VPT Agonist

General Pharmacology
Oswald Schmiedberg Father of Pharmacology
Col. Ramnath Chopra Father of Indian Pharmacology
Sir James Black Father of Modern Pharmacology
John Jacob Abel Father of American Pharmacology
Paul Ehrlich Father of chemotherapy
Paracelsus Father of Toxicology
M.J.B. Orifila Father of Modern Toxicology / Modern

Father of Toxicology / Father of
Experimental toxicology
Scientist and their contributions
Otto Loewi : Direct proof of transmission across nerve junctions

to be mediated by neurotransmitters
Lundy : Coined the term balanced anaesthesia
Guede : Described 4 stages of anaesthesia with Ether
William Withering : Published his work on medicinal uses of Foxglove

(digitalis), Cardiac glycoside
Ehrlich : ✓ Coined the term chemotherapy.

✓ Used the idea Selective toxicity
✓ Salvarsan (As) compound Vs Syphilis
Domagk : Discovered Sulphonamides (1935)
Fleming : Discovered Penicillin (1928)
Walksman : Discovered Streptomycin (1944)
1 | A.E VPT AGONIST - in view of TNPSC 2020

First of its kind
First antibiotic : Penicillin
First local anaesthetic Cocaine for ocular anaesthesia
First i.v anaesthetic : Thiopentone
First anti-tubercular drug : PAS followed by streptomycin
William Withering : Published his work on medicinal uses of

Foxglove (digitalis), Cardiac glycoside
Ehrlich : ✓ Coined the term chemotherapy.

✓ Used the idea Selective toxicity
✓ Salvarsan (As) compound Vs Syphilis
Domagk : Discovered Sulphonamides (1935)
Fleming : Discovered Penicillin (1928)
Walksman : Discovered Streptomycin (1944)
Placebo is a vehicle for cure by suggestion and is surprisingly often successful though
only temporarily. It can be used as a control in scientific evaluation of drugs and to
benefit or please a patient not by pharmacological actions but by psychological means
(Latin: Placebo – I shall be pleasing or acceptable).
Posology is the study of the medicine dosages, which varies with the species of animals,
the intended effect of the drug and the individual tolerance or susceptibility.
Pro-drugs are drugs that are inactive or have a low order of activity in the form
administered and are metabolised to the active form in the body.
Prodrug Active drug

Aspirin : Salicylic acid
Protonsil : Sulphanilamide
Febentel : Fenbendazole + Oxfendazole
Codeine : Morphine

Pharmacognosy is the study of the source of drugs. It also deals with the physical and
chemical properties of drugs.
Empirical therapy is the use of certain agents that prove successful in a series of cases
of the same disease, although, it is not possible to explain their actions. Their value has
been demonstrated by experience.
Iatrogenic disease means physician caused disease
Pharmacogenomics means individual variation in drug action
Pharmacokinetics
✓ Pharmacokinetics is also called ADME study as it deals with Absorption,

Distribution, Metabolism and Excretion of a drug.
Processes involved in pharmacokinetics

Routes of administration
• Oral route is safer and economical but several drugs are not effective by this
route because of high first pass metabolism in the liver and intestinal wall.
• Sublingual route avoids first pass metabolism as in the IV route, can be used in
emergencies, can be self administered Eg., Nitroglycerine, isosorbide dinitrate,
clonidine, nifedipine etc.
• Inhalational route is the route by which the rate of drug delivery can be
controlled like i.v. infusion. (Eg., Salbutamol for Asthma and inhalational
anaesthetic agents like nitrous oxide)
• Rectal route avoids first pass metabolism to 50% extent. Eg. Diazepam for
unconscious animals
Passage of drug across membrane
✓ Only the nonionized (uncharged) form of a drug crosses biomembranes; When
medium is same, drugs can cross the membrane because of high degree of
non-ionization. Thus, acidic drugs can cross the membranes in acidic medium;
Alkaline drugs can cross the membranes in acidic medium.

✓ Weak bases are poorly absorbed from the stomach since they exist mostly in
theionized state (low lipid solubility) because of the acidic conditions. Weak
basesare better absorbed from the small intestine due to the higher
environmental pH.
✓ In monogastric animals with a low stomach pH, weak acids such as aspirin (pKa=
3.5) tend to be better absorbed from the stomach than weak bases because of
the acidic conditions. In ruminants, the pH varies with feeds and the pH is often
high.
Different methods
.
• Passive transfer
✓ Simple diffusion
✓ Filtration
• Specialized transport
✓ Facilitated diffusion
✓ Active transport
✓ Endocytosis / Phagocytosis
Characteristics Simple diffusion Facilitated Active transport
Incidence Commonest Less common Least common
Process Slow Quick Very Quick

Movement Along Along Against
concentration concentration concentration
gradient gradient gradient
Carrier Not needed Needed Needed
Energy Not required Not required Required
• Endocytosis / Phagocytosis: It is the process by which the large

molecules are engulfed by the cell membrane and releases them
intracellularly e.g. protein, toxins (botulinum, diphtheria) - Energy needed

Henderson Hasselbach equation
It is used to calculate the percent of a drug that exists in ionized form or to

determine the concentration of a drug across the biologic membrane.
concentration of nonionized acid

For weak acid, pKa = pH + log -------------------------------------
concentration of ionized acid
concentration of ionized base

For weak base, pKa = pH + log --------------------------------
concentration of nonionized base
Acid drugs Basic drugs

Pencilllin Histamine
Sulfonamide Serotonin
Chlorthiazide Procainamide
Ethacynic acid Neostigmine
Frusemide Atropine
Probenecid
Salicylate
Phenylbutazone
Cephalosporin
Bioavailability
✓ It is the fraction ofadministered drug that reachesthe systemic circulation in
theunchanged form.
✓ Intravascular administration (e.g., IV) does not involve absorption, andthere is no

loss of drug. Bioavailability = 100%.
First-Pass Effect
✓ With oral administration, drugs are absorbed into the portal circulation and
initially distributed to the liver. For some drugs, their rapid hepatic metabolism
decreases bioavailability, i.e., the “first-pass” effect. Examples include lidocaine (IV
vs. PO) and nitroglycerin (sublingual).

✓ With extravascular administration (e.g., per os [PO; oral], intramuscular[IM],
subcutaneous [SC], inhalation), less than 100% of a dose may reach the systemic
circulation because of variations in bioavailability.
✓ AUC tells about the extent of absorption of the drug.

✓ Tmax. tells about the time to reach maximum concentration, rate of
absorption
✓ Cmax is the maximum concentration of a drug that can be obtained
Bioequivalence
✓ Many different pharmaceutical companies can manufacture same compound
(with same dose as well as dosage form).
✓
In general
✓ The more lipid soluble (less polar) a drug is, the better it is absorbed from the
gut and the more widely it is distributed in the body.
✓ Weak acids are absorbed best from the stomach
✓ Weak bases are absorbed best from the intestine
✓ However, it is also true that most drug absorption from the gut occurs in the
proximal duodenum.
✓ Absorption is a dynamic process; absorbed drug is rapidly carried away by

blood or lymph
✓ Most drugs are sufficiently water-soluble to be carried away by blood. This

blood enters the protal vein and goes to the liver where some or all the drug
may be metabolized.
✓ Extremely lipid soluble compounds enter the lymphatics
Distribution
✓ Drugs which are lipid soluble are more likely to cross the blood vessel wall and
thus have high volume of distribution.
✓ If a drug is highly bound to plasma proteins, (e.g., warfarin, benzodiazepines,
furosemide, calcium channel blockers, digitoxin etc.) it will behave like a large
molecule and more likely to stay in the plasma.

✓ Therefore, less will go to tissues resulting in reduced volume of distribution.
Therefore, plasma protein binding makes a drug long acting by reducing its
metabolism.
Amount of drug in the body

Vd= ------------------------------------------- expressed as L/Kg
Concentration of drug in the plasma
Dose = Vd x Plasma concentration
Vd is the main determinant of loading dose.
Drug reservoirs – Sites other than the site of action can act as reservoirs for the drug if
enough amount of the drug is sequestered there. For example
1. Plasma proteins – digoxin, phenytoin

2. Fat – thiopental, organochlorine pesticides
3. Cells – quinacrine (liver cells)
4. Bone – tetracyclines, lead
5. GI tract – weak bases
6. Keratinous tissues – arsenic, griseofulvin
Metabolism
• Detoxification means decreased activity following metabolism. But it is not true

in some cases as the activity of the metabolite is not decreased.
• Metabolism is the term used to denote normal anabolic and catabolic reactions
of the body.
• Biotransformation is probably the best term useful for describing the biological
fate of foreign compounds. Liver is the most important organ for
biotransformation, but athe lungs, kidney and gastrointestinal epithelium also
play a role.
• In general all of these reactions are grouped into two major categories as Phase I
and Phase II reactions.

• The primary site of metabolism is liver.
• Function of phase I reactions is to attach a functional groupto the drug
molecule whereas phase II reactions serve to attach a conjugate to the drug
molecule.
• After phaseI reaction, drug may be water soluble or lipid soluble whereas after
phase II reaction, all drugs become water soluble (lipid insoluble).
• Glucuronidation is most common phase II metabolic reaction. Glucoronide
conjugation is catalyzed by microsomal enzymes but not by cytochrome p450
enzymes.
• CYP3A metabolizes 50% drugs, most common
Enzymes responsible for metabolism of drugs:

✓ Microsomal enzymes: Present in the smooth endoplasmic reticulum of the liver,
kidney and GIT e.g. glucuronyl transferase, dehydrogenase , hydroxylase and
cytochrome P450
✓ Non-microsomal enzymes: Present in the cytoplasm, mitochondria of different
organs. e.g. esterases, amidase, hydrolase
✓ Enzyme inducers - rifampicin, phenobarbitone, phenytoin, griseofulvin,

phenylbutazone and chloral hydrate.
✓ Enzyme inhibitors - ketoconazole, cimetidine, erythromycin and metronidazole.
Excretion
✓ The major route of excretion is kidney. Lithium, KI and rifampicin aresecreted in

saliva
✓ Excretion through kidneys occurs by glomerular filtration, tubular reabsorption
and tubular secretion.

Glomerular filtration:
✓ It is a process, which depends on the concentration of drug in the plasma,
molecular size, shape and charge of drug and glomerular filtration rate.
✓ Glomerular filtration does not depend on the lipid solubility and it depends on
the plasma protein binding and renal blood flow.
✓ Only the drug which is not bound with the plasma proteins can pass through
glomerulus. All the drugs which have low molecular weight can pass through
glomerulus e.g. digoxin, ethambutol, etc.
Tubular reabsorption:
✓ Tubular reabsorption depends on the lipid solubility.
✓ The reabsorption of drug from the lumen of the distal convoluted tubules into
plasma occurs either by simple diffusion or by active transport.
✓ When the urine is acidic, the degree of ionization of basic drug increase and their
reabsorption decreases. Conversely, when the urine is more alkaline, the degree
of ionization of acidic drug increases and the reabsorption decreases.
Tubular secretion:
✓ It does not depend on lipid solubility or plasma protein binding.
✓ Drugs utilizing the sametransporter may show drug interactions e.g. probenecid
decreases the excretion of penicillin.
• Excretion can be enhanced for drugs eliminated primarily by the kidneythrough

altering the pH of the urine. For practical purposes this is limited toweak acidic or
weak basic drugs with a pKa of 5–8.
Acidification of urine → increases ionization of weak bases →
increasesrenal elimination.
Alkalinization of urine → increases ionization of weak acids →
increasesrenal elimination.
Kinetics of Elimination
CL = Rate of Elimination / Plasma concentration

T1/2 = 0.693 X Vd/CL
Maintenance dose is determined by Clearance (CL)

First order Zero order
Constant fraction of drug is eliminated Constant amount of the drug is
per unit time. eliminated per unit time.
Rate of elimination is proportional to Rate of elimination is independent of
plasma concentration. plasma concentration.
Clearance remains constant Clearance is more at low concentrations
and less at high concentrations
Half life remains constant Half life is less at low concentrations
and more at high concentrations.
Most of the drugs follow first order Very few drugs follow pure zero order
kinetics. kinetics e.g. alcohol, Warfarin, Phenetoin
✓ Time to reach steady state depends on t½. It takes approximately 5 half lives.
✓ Steady state plasma concentration acheived depends on dose rate.
Loading dose = Vd × Target plasma concentration

Maintenance dose = CL × Target plasma concentration
Pharmacodynamics
✓ Mechanism of action (What the drug does to the body).
✓ Drugs may act by physical mechanism (e.g. osmotic diuretics), chemical action
(e.g.antacids), stimulation or inhibition of enzymes (competitive and non-
competitive inhibition) or via receptors.
Receptors
These are the binding sites of the drug with functional correlate. Two important terms
related to the receptors are affinity and intrinsic activity (IA).
Affinity is the ability of a drug to combine with the receptor. Drugs with high affinity can
be used in low concentrations.
After binding to the receptor, the ability to activate the receptor is called its intrinsic
activity (IE) . It varies from –1 through zero to +1.

For agonist, IE = +1; Partial agonist IE = Between 0 to +1; Antagonist, IE = 0; Inversal
agonist IE = -1 (βcarboline is an inverse agonist at BZD receptors)
✓ Agonist – affinity and intrinsic activity

✓ Antagonist- only affinity – prevent the action of agonist
Antagonist
These may be physical, chemical, physiological or pharmacological.
✓ Physical antagonist binds to the drug and prevents its absorption like charcoal
binds to the alkaloids and prevents their absorption.
✓ Chemical antagonist combines with a substance chemically like chelating agents

bind with the metals.
✓ Physiological antagonist produces an action opposite to a substance but by

binding to the different receptors e.g. adrenaline is a physiological antagonist of
histamine because adrenaline causes bronchodilation by binding to b2 receptors,
which isopposite to bronchoconstriction caused by histamine through H1
receptors.
✓ Pharmacological antagonists produce opposite actions by binding to the same

receptor e.g. beta blockers.

Classification of Receptors
The receptors are classified into four types based on the signal transduction
mechanisms.
G Protein Coupled Receptors (Metabotropic receptors)

• These are heptahelical (serpentine) receptors i.e. have seven transmembrane
spanningsegments. Drugs bind to the receptor which in turn activates a G protein
(GTP activatedprotein) – slow acting
• G-proteins consist of three subunits; Cyclic AMP, IP3 and DAG act as second
messengers, whereas Ca2+ is a third messenger.
• Examples include muscarinic acetylcholine receptors and adrenergic
receptors, GABA B
Ligand gated Channels - Inotropic Receptors

• The drug binds directly to the receptor located on an ion channel without
mediation byG proteins. These are the fastest acting receptors. It includes
GABA A, Nicotinic, NMDA(receptors of glutamate) and 5-HT3 receptors.

Enzymatic Receptors
✓ This type of receptor has two sites, the drug binds on the extracellular site
and the intracellular site has enzymatic activity (mostly tyrosine kinase).
This enzyme can be activated via JAKSTAT pathway.
✓ Example: Insulin, growth hormone, prolactin and cytokines act via
enzymatic.
.
Intracellular Receptors
o These types of receptors are slowest acting. These may be present in the
cytoplasm (glucocorticoids, mineralocorticoids, and vit. D) or in the
nucleus (T3, T4, Retinoic acid, PPAR, estrogen, progesterone and
testosterone).
o Both type of receptors finally act by nuclear mechanisms (i.e. by affecting
transcription).

Dose Response Curve (DRC)
• It is a graph between the dose of a drug administered (on X-axis) and the
effect produced by the drug (on Y-axis). It consists of two components;
dose-plasma concentration curve and plasmaconcentration-response curve.
As plasma concentration is more closely related to response, the graph
between plasma concentration and response is usually called DRC.
• Two types of DRC can be described: Quantal and graded.
Quantal DRC
When the response is an ‘all or none’ phenomenon (e.g. antiemetic drug stopping
the vomiting or not), the y-axis (response axis) shows the number of person responding
and X-axis shows the plasma concentration. It is used to calculate ED50 and LD50.
Median Effective Dose (ED50): It is the dose that will produce the half of the maximum
(50%) response. More is ED50, lower is the potency and vice a versa.
Median Lethal Dose (LD50): It is the dose that will result in death of 50% of the animals
receiving the drug. More is LD50, safer is the drug.
Therapeutic Index (T.I.): It is a measure of the safety of a drug. It is calculated as a ratio

of LD50 to ED50. Drugs having high T.I. are safer whereas those having low T.I. are more
likely to be toxic.
Graded DRC
When the response can be graded (e.g. reduction in BP), the y-axis shows the magnitude
ofresponse.DRC is usually hyperbola in shape. As curved lines cannot give good
mathematical comparisons, so usually the dose is converted to log dose to form log
DRC, which gives a sigmoid shaped curve.
Three important parameters (potency, efficacy and slope of curve) can be determined
from DRC.
Potency
It is the measure of the amount of a drug needed to produce the response. Drugs
producing the same response at lower dose are more potent whereas those requiring large
dose are less potent.In DRC, more a drug is on left side of the graph, higher is its potency
and vice a versa. In Fig,drug A is more potent than drug B.

It is the maximum effect produced by a drug. More the peak of the curve greater is
the efficacy. It is clinically more important than potency. In Fig, drug B is more efficacious
than drug A.
Slope
If the DRC is steeper, that means the response will increase dramatically with
slight increase in dose. Thus, drugs having steeper DRC have narrow therapeutic index
(like barbiturates) than those having less steep curves (e.g. benzodiazepines).
Therapeutic Index = LD50/ED50
Standard safety margin = (LD1 − ED99 / ED99) X100
• Efficacy is clinically more important than potency.

• Drugs having steep DRC have narrow therapeutic index (like barbiturates)
than those having less steep curves (e.g. benzodiazepines).
• In case of competitive inhibitor, dose response curve will shift to right
whereas In case of non competitive inhibitor, there will be flattening of
DRC
Species variation:
• Xylazine (an α2-adrenergic agonist) is a much more potent sedative in cattle
than other species; the reason that ruminants are more sensitive to α2-agonists
such as xylazine is because the difference is at the pharmacodynamics level;
ruminants have α2D-receptors and nonruminants have α2A-receptors.
• Morphine (a μ-opoid agonist) is more potent in cats than dogs. In dogs, the
dose is 1 mg/kg where it consistently produces sedation. In cats, the dose for
analgesia is 0.1 mg/kg. Higher doses in cats may produce excitement.

• Great Dane and Irish Setters are more sensitive to bloat following xylazine
administration due to aerophagia.
• Ivermectin can cause CNS depression in collies and hence contraindicated at

normal doses due to a defect in the P-glycoprotein transporter which excludes
ivermectin from the brain.
• Ivermectin should not be used in tortoises or crocodiles because of potential

toxic effects; it is possible that the BBB in these species against ivermectin
maintained by the P-glycoprotein is not secure.
• Succinlycholine, a depolarizing muscle relaxant, can be used in horses

relatively in higher doses than in the cattle. In horses, broken down rapidly by
the plasma esterases, but in ruminants where the esterase levels are much lower
require only 0.02 mg/kg, but horses require 0.1 mg/kg.
• Cats have a low level of glucuronyl transferase so that the t1/2 of many
drugs that are conjugated to glucuronide by the liver is much longer. The
classic example is aspirin where the t1/2 in cats is 25–35 hours compared to 8
hours in dogs and 1 hour in horses.
• GI absorption will differ between nonherbivores animals and ruminant herbivores.

The GI transit time in monogastrics animals means that oral suspensions are
swept out of the intestine within 24 hours. The benzimidazoles are examples of
drugs where the GI transit time in herbivores is longer than in nonherbivores.
In most cases, benzimidazoles are administered once to herbivores, but to
nonherbivores, in daily doses over a period of 3–5 days.
• Most lipophilic organic bases, like ivermectin, lincosamide, tulathromycin,

erythromycin, tylosin, ketamine, metronidazole, enroﬂoxacin, theophylline, and
trimethoprim have larger volumes of distribution in ruminants than in
monogastrics animals because of alkaline environment.

LOCAL ANAESTHETICS (LA)
Mechanism of Action:
All LAs are weak bases. These drugs act by penetrating the axonal
membrane (in unionized form) and blocking the voltage gated sodium
channels from within (in ionized form).
• Sodium bicarbonate speeds the onset of action of LAs by increasing

the unionized form (weak bases are unionized in the alkaline medium)
that can penetrate the axonal membrane.
• Vasoconstrictors like adrenaline can prolong the duration of action

of LA and decrease the systemic toxicity. Alternative vasoconstrictor
felypressin (synthetic vasopressin) can also be used with LAs in order to
avoid cardiovascular complications due to adrenaline.
• Hyaluronic acid can increase the spreading of LA’s action.
Types:
Local anaesthetics (LAs) can be classified into amide and ester types.
Amides are usually long acting and chances of allergic reactions are less whereas
esters are short acting (due to metabolism by esterases present in the plasma).
Ester LAs can cause allergic reactions and also antagonize the action of
sulfonamides due to degradation of PABA.

Amide class Ester class
✓ Lignocaine ✓ Cocaine
✓ Prilocaine ✓ Procaine
✓ Bupivacaine ( Second longest) ✓ Chlorprocaine (Shortest acting)
✓ Dibucaine (Longest acting) ✓ Tetracaine (Amethocaine)
✓ Mepivacaine ✓ Benzocaine
✓ Etidocaine
✓ Ropivacaine
(If the name of the local anaesthetic contains the 2 “i” in the name then it is an
amide type local anaesthetic and if only one “i” it is an ester type of drug)
▪ All LAs are vasodilators except cocaine (act as sympathomimetic

due to inhibition of nor-adrenaline reuptake) which is a
vasoconstrictor. Therefore all LAs decrease BP except cocaine
(increases).
▪ Lignocaine is the most commonly used LA and is the drug of

choice for ventricular tachycardia. It can precipitate malignant
hyperthermia due to release of calcium.
▪ Dibucaine is the most potent, longest acting and most toxic LA

whereas chlorprocaine is the shortest acting LA.
▪ Epidural block – In this method the drug is injected into the

epidural space of the spinal canl at the level of the lumbosacral
region, lumbosacral space or 1st and 2nd intercoccygeal space.
Drugs act on posterior spinal nerve before leaving the vertebral
column. Drugs like chloroprocaine, lidocaine, mepivacaine,
bupivacaine, etidocaine and prilocaine are used.
Lidocaine (lignociane) – This is an amide type drug used widely in veterinary

and human medicine. Being an amide type it is resistant to plasma esterases.
Metabolised in the liver.
Large doses may produce death due to ventricular fibrillation or cardiac
arrest. Advantages are freedom from tissue irritation, rapid onset of action, better
diffusing ability and longer duration.

• Ophthalmic application – Benoxinate is used to reproduce anaesthesia of
the cornea. It may have antibacterial and antifungal properties.
• Mucous membrane and skin application – Dyclonine and hexylcaine are

used for topical anaesthesia.
NEUROMUSCULAR BLOCKING DRUGS
According to the mechanism of action neuromuscular blockers are classified as
1. Competitive or non-depolarizing agents – d-tubocurarine

Gallamine
Pancuronium
2. Non competitive or depolarizing agents - Succinylcholine

Decamethonium
GENERAL ANAESTHETICS
Anaesthesia is the reversible loss of response to noxious stimuli. It may be

general anaesthesia (if associated with loss of consciousness) or local anaesthesia
(consciousness is maintained).
Four main features of balanced anaesthesia are:

✓ Unconsciousness
✓ Muscle relaxation
✓ Analgesia
✓ Abolition of compensatory reflex responses
Amino acid neurotransmitters
✓ Excitatory amino acids – L-glutamate, Aspartate
✓ Inhibitory amino acids – GABA, Glycine, Dopamine
✓ An example for GABA agonist is muscimol and GABA antagonist is

bicuculine.

Stages of anaesthesia
The stages of anaesthesia are divided into distinct packages, each correlating with a
particular set of physiological responses or reflexes. The organisational scheme includes
four stages of anaesthesia.
Stage I This stage is also known as the stage of analgesia or stage of voluntary
excitement or stage of analgesia and amnesia.
This period begins from the beginning of induction to the loss of

consciousness.
The patient exhibits voluntary resistance to restraint and to anaesthetic

vapours.
Stage II This stage is also known as the stage of delirium or stage of involuntary
excitement or stage of uninhibited action.
This period begins from the loss of consciousness to onset of automatic

respiration. There will be apparent excitement. Patient may show struggle,
hold the breath, muscle tone increases, jaws are tightly closed, breathing is
jerky, vomiting, involuntary micturition and defecation noticed. Pupillary
dilatation, increase in heart rate and blood pressure due to sympathetic
stimulation are noticed.
Stage III This stage is also known as the stage of surgical anaesthesia. It is divided
into four planes as Plane 1, Plane 2, Plane 3 and Plane 4.
This period begins from the onset of automatic respiration to respiratory

arrest.
Plane 1 – Light surgical anaesthesia – roving eye balls and plane ends with
eyes becoming fixed
Plane 2 – Moderate surgical anaesthesia – loss of corneal and laryngeal

reflex
Plane 3 – Deep surgical anaesthesia – Pupil starts dilating and light reflex is
lost
Plane 4 – Excessive surgical anaesthesia – intercostal paralysis, shallow

abdominal breathing

Stage IV This stage is also known as the stage of medullary paralysis or
respiratory paralysis.
This period is between respiratory arrest and cardiac arrest.
• Not all anaesthetics display all the stages of anaesthsia.
Ether : all stages
Ultra short acting barbiturates : Stages I, III and IV
Dissociative anaesthetics : Stages I and II
Halothane, Isoflurane : Stages I, III and IV
Preanaesthetic medication
1. Alleviate or minimize pain

2. Allay apprehension
3. Facilitate handling
4. Minimize undesirable reflex autonomic nervous system activity
(a) Parasympathetic – Vagal nerve stimulation
Secretions – salivary, bronchial
(b) Sympathetic - Arrhythmia

Arterial blood pressure alteration
5. Supplement general anaesthesia

(a) Add to level of analgesia, sedation, muscle relaxation
(b) Reduce anaesthetic requirement
6. Minimize undesirable post anaesthetic recovery complication
7. Prevent infection
8. Continue treatment of intercurrent disease
9. Major classes of drugs used as preanaesthetics
10. Tranquilizer – sedatives Acepromazine, Diazepam, Midazolam,
Droperidol, Azaperone
11. Hypnotic – sedatives Pentobarbital, Chloral hydrate
12. Opioid drugs Morphine, Meperidine, Butorphanol
13. α2 adrenergic agonist Xylazine, Detomidine, Metomidine
14. Dissociatives Ketamine
15. Commercially prepared combinations Telazol, Innovar
16. Parasympatholytics Atropine, Glycopyrrolate
Mode of action of general anaesthetics
There have been many attempts to explain the mechanism of general

anaesthetics at a molecular level. But, this is not possible because
1. The rate at which anaesthesia can be induced and wakefulness resumed focuses
attention on short term biochemical events
2. Wide variation in the structure of anaesthetic drugs
3. Ability of anaesthetics to cause superimposed selective and specific anaesthetic
side effects such as reductions in myocardial contractility.
Theories of Anaesthesia:
Meyer and Overtone theory: According to this theory, to be an anaesthetic it must be

soluble in oil. The higher the solubility in oil, the greater was its anaesthetic
potency. Ether and chloroform fit conveniently into the above hypothesis, but at present
there are many objections to this theory.
Colloidal theory: This theory states that, colloids of nerve protoplasm form a loose
compound with the anaesthetic.
Surface tension theory: According to this theory, a reduction in the surface tension of
neuronal membrane is brought about by the anaesthetics.
Permeability theory: General anaesthetics are said to impair the permeability of

neuronal membranes as a result of which depolarization and subsequent activation fail
to occur.
Pauling and Miller theory: Pauling and Miller theory states that microcrystals
(clatharates) are formed by the anaesthetic vapour. These in turn reduce the
conductance.
Reduced energy formation theory: This theory states that general anaesthetics depress
the formation of high energy bonds.
Cell membrane expansion theory: This theory states that inhalation anaesthetics are
hydrophobic and therefore distribute to sites in which they are removed from aqueous
environment and because of the close correlation between potency and lipophilicity, it is
theorized that these anaesthetics act on the cell membrane lipid layer.

It is thought that their presence distorts the membrane structure, which in turn
causes occlusion of the pores through which ions pass (example – sodium channel). This
theory also explains the pressure reversal of anaesthesia.
Properties:
Minimum Alveolar Concentration (MAC):
It is the minimum concentration of an inhalational agent required in the alveoli to

produce unresponsiveness to the skin incision in 50% of the patients. It is the measure of
potency of an agent. Greater is the MAC, lesser is the potency.
• Nitrous oxide is a gas with maximum MAC and thus least potency. Its MAC is
104% i.e. even with pure (100%) nitric oxide alone, we cannot get complete
anaesthesia. This is thus, not a complete anaesthetic agent.
• Methoxyflurane is the most potent agent (having least MAC).
Blood gas partition coefficient:
It is determined by solubility of an agent in the blood. It determines the speed of

onset and recovery of an anaesthetic drug. Greater is blood gas partition coefficient,
lesser is the speed of onset and recovery and vice versa..
• Desflurane is the fastest acting agent as it has minimum blood gas partition
coefficient.
• Methoxyflurane is the slowest acting agent (maximum blood gas partition

coefficient).
• Ether also has a very high value of this coefficient; therefore it is also a slow
acting agent. Due to its slow onset of action, we can differentiate the four
stages of general anaesthesia whereas with modern anaesthetics like
desflurane, these stages are hardly discernible.
Oil/gas partition coefficient – This describes the ratio of concentration of an

anaesthetic in oil and gas phases at equilibrium. The oil/gas partition coefficient
correlates inversely with anaesthetic potency and describes the capacity of lipids for
anaesthetics.

Inhalant Oil/Gas Potency Rank Blood/Gas
Anesthetic Partition Partition
Coefficient Coefficient
Isoflurane 91.0 1 1.46
Sevoflurane 47.0 2 0.68
Desflurane 18.7 3 0.42
Nitrous oxide 1.4 4 0.47
Inhalation anaesthetic agents
Drugs used as inhalation anaesthetics are classified as gases and volatile liquids.
Based on their use, they are also calssified as follows.
Group I Agents in current clinical use
Major use – Halothane, Isoflurane
Minor use – Enflurane, methoxyflurane, nitrous oxide, ether
Group II New agents – Desflurane, sevoflurane
Group III Agents of historical interest
Chloroform, cyclopropane, fluroxene, trichloroethylene
Halothane: Is the most widely used agent, highly lipid soluble, potent. It causes
arrhythmia, hangover and the risk of liver damage is high if used repeatedly.
Nitrous oxide: Oderless and colourless gas. It is rapid in action and also an effective
analgesic agent. Its potency is low, hence must be combined with other agents. It is a
relatively free of serious unwanted effects (Second gas effect)
Enflurane: Halogenated ether (similar to halothane). Poorly metabolized in the liver,

thus less toxic than halothane. It is faster in its action, less liable to accumulate in the
body fat compared to halothane. It causes seizure during induction and following
recovery from anaesthesia.

Ether:
✓ Has analgesic and muscle relaxant properties. It is highly explosive, causes

respiratory tract irritation, postoperative nausea and vomiting.
✓ It is not widely used currently.
Sevoflurane: has a low blood:gas partition coefficient; therefore, induction and recovery
are rapid.
INTRAVENOUS ANESTHETICS
Intravenous anesthetics act much more rapidly, producing unconsciousness in

about 20 seconds, as soon as the drug reaches the brain from the site of its injection.
These agents used for induction of anaesthesia followed by inhalation agent. The main
induction agent in current use is: thiopentone, etomidate, propofol, ketamine and short
acting benzodiazepine (midazolam).
Thiopentone: Thiopentone is a barbiturate with very high lipid solubility. After

intravenous administration the drug enters to tissues with a large blood flow (liver,
kidneys, brain, etc) and more slowly to muscle. Uptake into body fat occurs slowly
because of the low blood flow to this tissue, which may cause prolonged effect if given
repeatedly. It causes cardiovascular depression.
Barbiturates
Barbiturates are derived from the nondepresssant barbituric acid or melonylurea.

Melonylurea is obtained by combining urea to malonic acid. Barbiturates are bitter
tasting white powders. Salts containing sulfur have a yellowish tint.
In USA ‘al’ is substituted in the name of barbiturates for ‘one’ (For example in
USA thiopentone is known as thiopental).
Classification of barbiturates
Barbiturates are classified based on their duration of action as follows.

Long acting - Phenobarbital sodium, Barbital sodium
Intermediate acting - Amobarbital sodium
Short acting - Pentobarbital sodium, Secobarbital sodium
Ultra short acting barbiturate - Thiopental sodium, Thiamylal sodium,
Thiobarbital sodium, Methohexital sodium

Mechanism of action
• Barbiturates bind to GABA receptors, decreasing the rate of dissociation of the
inhibitory neurotransmitter from the receptor. Barbiturates decrease the
excitatory effects of neurotransmitter glutamate
• In large animals, ultra-short acting barbiturates are used in combination with

glycerol guaiacolate (also called guaifenesin).
Thiopental (Pentothal) – Thiopental is classified under Schedule II, is a barbiturate with

very high lipid solubility. After intravenous administration the drug enters to tissues with
a large blood flow (liver, kidneys, brain, etc) and more slowly to muscle. Uptake into
body fat occurs slowly because of the low blood flow to this tissue, which may cause
prolonged effect if given repeatedly. It causes cardiovascular depression.
Methohexital – This drug is twice as potent as thiopental.
Pentobarbital (Nembutal) – This was the most widely used anaesthetic in small animal
surgery. After the introduction of methoxyflurane and halothane its use declined.
Etomidate - a non-barbiturate, is more quickly metabolized and the risk of

cardiovascular depression is less compared to thiopentone. Etomidate suppresses the
adrenal cortex, which has been associated with an increase in mortality in severely ill
patients.
Benzodiazepines - prolong the postanesthetic recovery period but also cause a high
incidence of amnesia for events occurring after the drug is administered.The
benzodiazepines are useful in anesthesia as premedication and intraoperative sedation.

✓ Barbiturates bind to another site on this channel to exert GABA mimetic (direct
activation of GABA A receptors) as well as GABA facilitatory (increase the binding
of GABA to GABA A receptors) actions. Bemegride (Megimide) – This drug is a
CNS stimulant and is the specific antagonist to barbiturate group of drugs.
✓ Benzodiazepines bind to a different site (BZD receptor) and increase the binding
of GABA to GABA A receptor (GABA facilitatory action). These drugs increase the
frequency of Cl– channel opening.
Antidote for BZD compounds:

✓ Bicuculline binds to GABA A receptor and acts as a competitive inhibitor of GABA
and non competitive inhibitor of benzodiazepines.
✓ β-carboline acts as an inverse agonist at benzodiazepine site and thus produces
convulsions due to stimulation of the brain.
✓ Flumazenil acts as a competitive antagonist at BZD site and therefore inhibits the
action of benzodiazepines as well as b-carboline
Opioid analgesic anesthesia
• Opium is the air-dried milky exudates obtained from the incised unripe seed
capsules of the poppy plant Papaver somniferum. Opioid analgesics can be used
for general anesthesia, in patients undergoing cardiac surgery and fentanyl and
its derivates are commonly used for these purposes.
• The pharmacological effects result from interactions with one or more of the four
opioid receptors (mu, sigma, kappa and delta).
• Antagonists – Nalorphine and naloxone are used as antagonists to morphine.

Nalorphine is a mixed agonist-antagonist, while naloxone is a pure antagonist.
Dissociative anaesthetics
The drugs that cause the patient to feel dissociated from or unaware of the
surroundings during induction are called dissociative anaesthetics. Dissociative
anaeasthetics depress the cerebral cortex before causing medullary depression.
Ketamine – NMDA receptor antagonist - Can be administered by intramuscular or

intravenous routes. Adverse effects produced by phencyclidine are less pronounced with
ketamine. Used in combination with other anaesthetics.

Miscellaneous agents
Chloralose – This drug is metabolised to chloral hydrate and chloral and this chloral
hydrate is in turn metabolised to trichloroethanol. Hypnosis and anaesthesia produced
by chloral hydrate and chloralose are similar.
Etomidate – Etomidate is an intravenous, ultra-short-acting, nonbarbiturate hypnotic

drug. Etomidate has been used for intravenous anesthesia induction in dogs, cats and
humans.
Propofol – Propofol is a substituted phenol. Propofol is a nonbarbiturate, non-

dissociative intravenous anesthetic agent. Propofol is not a controlled substance.
Althesin - This drug is steroidal preparation which produces immediate induction of
anaesthesia of short duration when administered intravenously. Vastly used in birds.

CHEMOTHERAPY
Mechanism of chemotherapeutic agents:
The principle underlying chemotherapeutic action is selective toxicity, that is,

the drug should be toxic to the microorganisms and non – toxic to the host.
Antibacterial drugs can be grouped as follows based on their mechanism of action.
1. Inhibitors of cell wall synthesis : Pencillins, Cephalosporins, Cycloserine,

Bacitracin and Vancomycin
2. Inhibitors of protein synthesis : Tetracyclines, Erythromycin,

Chloramphenicol, Spectinomycin,
Lincomycin, Viginamycin and
Aminoglycosides
3. Agents affecting cell membrane : Polymixin B, Nystatin, Colistin, Tylosin,

Amphotericin B, Natamycin and Monensin
4. Anti metabolites : Sulfonamides, Paramino salycilic acid and

Trimethoprim
5. Agents affecting nucleic acid metabolism : Griseofulvin, Nitroimidazoles, Nitrofurans,

Quinolones, Rifamycin and Novobiocin

Sources of antibiotics:
Group produced Microorganism Antibiotic

Bacteria Bacillus licheniformis Bacitracin
Bacillus collistnus Colistin
Bacillus polymyxa Polymixin
Streptomyces Streptomyces grieseus Streptomycin
(filamentous Streptomyces aureofaciens Chlortetracycline
bacteria) Streptomyces fradiae Tylosin
Streptomyces erytherus Erythromycin
Streptomyces noursei Nystatin
Streptomyces venezulae Chloramphenicol
Fungi Penicillium notatum Penicillin
Penicillium chrysopgenum Penicillin
Penicillium griseofulvum Griseofulvin
Penicillium cephalosporium Cephalothin
Fermentative Micromonospora puprppurea Gentamicin
products Streptomyces tenebrans Apramycin
Streptomyces orientalis Vancomycin
Streptomyces lincolaensis var
linconensis Lincomycin
Streptomyces spectabilis Spectinomycin
Concentration-dependent killing
• Rate and extent of killing increase with increasing drug

concentrations
• Maximizing peak concentrations increases efficacy and decreases
selection of resistant bacteria
• Examples -- aminoglycosides, fluoroquinolones (Presence of Post-
antibiotic effect: Persistent suppression of bacterial growth after
limited exposure to an antimicrobial agent is known as post-antibiotic
effect)
Time-dependent killing
• Increasing concentrations above MBC do not result in proportionate

increases in killing
• Killing continues as long as concentrations are above MBC
• Lack post-antibiotic effect and should be maintained above MIC for
entire dosage interval
• Example: beta-lactams, vancomycin
Additive or indifferent effect – the combined effect of the drugs equals the sum of
their independent activities measured separately
Synergistic effect – the combined effects are significantly greater than the independent
effects
Antagonistic effect – the combined effects are significantly less than their independent
effects.
Synergism may occur if the combination involves –
• Sequential inhibition of successive steps in metabolism E.g.: Trimethoprim +

Sulfonamides
• Facilitation of drug entry of one antibiotic by another. E.g.: Betalactam and

aminoglycosides – the cell wall synthesis is inhibited by beta lactams. So there is
better penetration of aminoglycoside and in turn effective inhibition of protein
synthesis.
• Inhibition of inactivating enzymes E.g.: Amoxicillin + Clavulanic acid – clavulanic

acid has good affinity for majority of plasmid mediated beta lactamases while
amoxicillin is susceptible for beta lactamases.
• Sequential inhibition of cell wall synthesis. E.g.: Methicillin + Ampicillin
• Prevention of emergence of resistant populations. E.g.: Erythromycin +

Rifampicin, Streptomycin + Isoniazid
Drug resistance
Drug resistance in bacteria may be natural or acquired. Development of acquired

resistance may be due to single step mutation (as seen with streptomycin and rifampicin)
or multi step mutation (erythromycin, tetracycline and chloramphenicol).
Drug resistance can be transferred from one microorganism to other by gene

transfer (also called infectious resistance) via conjugation, transduction or
transformation.

• Conjugation: It is due to the physical contact between bacteria and is responsible
for multidrug resistance. This is a very important mechanism for the development
of resistance against chloramphenicol and streptomycin. (Most common route
of resistance)
• Transduction: It is the transfer of resistance gene through bacteriophage e.g.

penicillin, erythromycin and chloramphenicol.
• Transformation: It is the transfer of resistance gene through environment and is

not significant clinically e.g. penicillin G.
Antimicrobial susceptibility testing: Agar disc diffusion method, Kirby Bauer method
Super infection - Metronidazole is the drug of choice (alternative drug is vancomycin)
MIC (Minimum Inhibitory Concentration) - This gives a quantitative measure of the

sensitivity of a particular bacterium to a particular antibiotic. It is a measurement
obtained in vitro and so may correlate poorly with the results in vivo. The lowest
concentration which prevents visible growth of bacteria is taken as MIC.
MBC (Minimum Bactericidal Concentration) – It is the lowest concentration causing

complete bactericidal activity (99.99%)
MAC (Minimum Antibacterial Concentration) – It is also defined as the lowest

concentration of drug required for inducing morphologic changes.
Combined Use of antibiotics
✓ Bacteriostatic effect is one in which there is inhibition of growth of the organism

which in time results in failure of the organism to multiply. Hence this inhibited
growth in time equals death.
✓ Bactericidal effect is one that when initiated almost invariably results in cell
death. Cidal drugs preferred in immunocompromised patients and in serious, life
threatening infections.

Bacteriostatic Bactericidal
Chloramphenicol Penicillins
Spectinomycin Cephalorsporins
Erythromycin Aminoglycosides
Clindamycin Quinolones
Lincomycin Vancomycin
Tetracyclines Colistin
Sulfonamides Bacitracin
Trimethoprim Cycloserine
Methanamine
Polymixin B
Fiamycin
Nalidixic acid
Nitrofuranzole
Metronidazole
• Two bacteriostatic agents often show additive effect.
• Two bactericidal agents are synergistic if the organism is sensitive to both e.g.
isoniazid and rifampicin in tuberculosis.
• Combination of a bactericidal with a bacteriostatic drug is additive if the

organism has low sensitivity to the cidal drug e.g. streptomycin + tetracycline for
brucellosis.
• Combination of bactericidal with bacteriostatic agent is antagonistic if the

organism has high sensitivity to cidal drug e.g. penicillin + tetracycline (or
chloramphenicol) for pneumococci.
▪ Bactericidal + Bactericidal = Synergistic effect

▪ Bacteriostatic + Bacteriostatic = Additive effect
▪ Bactericidal + Bacteriostatic = Antagonistic effect

MAJOR ROUTES OF DRUG ELIMINATION
Renal ( majour Route) Hepatic / Biliary
Aminoglycosides Metronidazole , Ceftriaxone, Cefotaxime,

Amphotericin B Cefperazone, Doxycycline, Macrolides,
Beta lactams Clindamycin , rifampicin , Chloramphenicol
Quinolones
Sulfonamides
Tetracyclines
DRUGS EFFECTIVE AGAINST ANAEROBIC ORGANISMS
• Clindamycin Cefotetan Moxifloxacin Cefmetazole Trovafloxacin Cefoxitin

Metronidazole
• Chloramphenicol Vancomycin
• (Aminoglycosides are not effective against anaerobic microorganisms)
DRUGS EFFECTIVE AGAINST PSEUDOMONAS

1. Beta lactam antibiotics
✓ Carboxypenicillins (Carbenicillin, ticarcillin)

✓ Ureidopenicillin (Piperacillin, azlocillin and mezlocillin)
✓ Carbapenems (Imipenem, doripenem, meropenem)
2. Monobactams (Aztreonam)
✓ Cephalosporins (Ceftazidime, cefoperazone, moxalactam, cefepime, cefpirome).
Fluoroquinolones (Ciprofloxacin, Pefloxacin)
3. Polypeptide Antibiotics (Colistin, Polymixin )
4. Aminoglycosides
DRUGS EFFECIVE AGAINST MRSA
✓ Vancomycin Telavancin Streptogramins Linezolide Daptomycin

Cotrimoxazole Rifampicin Tetracyclines
✓ No β-lactam is effective against MRSA except 5th generation cephalosporins

MOST IMPORTANT MECHANISM OF DRUG RESISTANCE
Plasmid mediated;
• Beta Lactams - Inactivating Enzyme (Beta Lactamase)
• Tetracyclines - Efflux pump (decreased concentration in the cell)
• Chloramphenicol - Inactivating enzyme (acetyl transferase)
• Aminoglycosides - Inactivating enzyme
• Macrolides – Decreased permeability or efflux pumps
• Sulfonamides Form large amount of PABA Decreased activity of folate synthase
Chromosomal mediated; (Only one)

• Fluoroquinolones Altered DNA gyrase with reduced affinity.
I. CELL WALL SYNTHSIS INHIBITORS
Drug Step in cell wall synthesis involved

Beta – lactam 1. Inhibition of transpeptidase enzyme (Last
1. Penicillin step or Third step of cell wall synthesis -
2. Cephalosporin Transpeptidation reaction)
3. Carbapenam 2. Inhibition of Autoysin inhibitors
4. Monobactam
Bacitracin Inhibition of Dephosphorylation of
bactoprenol cell
Cycloserine Inhibition of Alanine racemase and alanine
ligase enzyme
Vancomycin Inhibition of Transglycosylase enzyme
(Second step of cell wall synthesis –
Transglycosylation reaction)
1. PENICILLINS
• The structure of penicillins includes a β-lactam ring and a thiazolidone

ring.
• Cleavage of the β-lactam ring destroys antibiotic activity.
• Amidase cleavage of the amide bond side chain yields the 6-amino-
penicillanic acid (6-APA) nucleus used in producing semisynthetic
penicillins.
Mechanism of action: Penicillins bind to and inhibit the transpeptidase involved in the
cross-linking of the bacterial cell wall, the third and final step in cell-wall synthesis
Therapeutic uses of various penicillins

1. Natural penicillins
a. Penicillin G (benzylpenicillin) – acid liable is used in all species for the treatment of
infections caused by Gram(+), nonpenicillinase producing pathogens. It is the most
potent penicillin for these organisms.
b. Penicillin V – acid stable now used infrequently for long-term oral therapy of
Gram(+) bacterial infections in dogs, cats, and horses.
2. Penicillinase-resistant penicillins include methicillin, oxacillin, and cloxacillin. Their

use is suited for severe staphylococcal infections caused by β-lactamase-
producingorganisms (some bovine mastitis) but they are less effective against
Streptococcus than the natural penicillins.
3. Broad-spectrum penicillins
a. Aminopenicillins. Ampicillin and amoxicillin are active against many Gram(–) aerobes
(E. coli, Proteus, Haemophilus spp.) as well as Gram(+) pathogens. They are used in all
species for the treatment of susceptible infections. They are acid stable but are not
penicillinase stable. GI absorption of amoxicillin is better than ampicillin.
b. Anti-pseudomonal penicillins
✓ Carbenicillin and ticarcillin are carboxypenicillins that have antipseudomonal

actions when used alone or in combination with or gentamicin or tobramycin.
They are useful for ear and skin infections in dogs caused by Pseudomonas spp.
✓ Mezlocillin, Azlocillin, Piperacillin is an ureidopenicillin that has an extended

Gram(-) spectrum including Pseudomonas, Enterobacter, and Klebsiella spp. Cost
limits its use to the treatment of severe Gram(–) bacterial infections in dogs and
cats.

4. Potentiated penicillins(Penicillin + β-lactamase inhibitor) :
✓ Clavulanic acid has minimal antibacterial action but it inhibits many of the β-
lactamases produced by penicillin-resistant organisms. It is combined with
amoxicillin or ticarcillin in commercial preparations.
✓ Sulbactam has an action similar to clavulanic acid and is combined with
ampicillin. The potentiated penicillins are used in small animals for extended
spectrum antimicrobial action. Tazobactam is another β-lactamase inhibitor.
✓ (The phenomenon of β-lactamase inhibitors inhibiting B lactamase enzyme is

called as suicidal inhibition)
Administration:
✓ Penicillins are generally administered IM. The acid-stable penicillins are
administered orally 2–3 times a day.
✓ Procaine penicillin G is slowly absorbed from IM sites and may provide
therapeutic levels for 24 hours with a single dose.
✓ Benzathine penicillin G is even more slowly absorbed over 48–72 hours but blood
levels attained are relatively low.
Adverse effects.
✓ Allergic reactions to penicillin may occur in animals, especially cattle.
✓ Procaine salts of penicillin should not be used in birds, snakes, turtles, guinea
pigs, or chinchillas because these species are sensitive to procaine.
✓ Procaine penicillin G should not be used in race horses 30 days before racing.
2. CEPHALOSPORINS
• Mechanisms of action and resistance: identical to penicillins
• Assume complete cross-allergenicity between individual cephalosporins and

partial cross-allergenicity with penicillins
• Hence, Most authorities recommend avoiding cephalosporins in patients allergic

to penicillins (for gram-positive organisms, consider macrolides; for gram-
negative rods, consider aztreonam)

.
3. CARBAPENAMS
• Meropenem is a more recent derivative that is more DHP-1 stable that does not
need cilastatin to inhibit kidney metabolism.

4. MONOBACTAMS
• Aztreonem binds to penicillin binding proteins present in Gram(–) aerobic
bacteria and disrupt cell wall synthesis (Figure 15-3). It is stable to most β-
lactamases.
• No cross reaction with other β-lactam antibiotics. Hence, we can administer
monobactams in penicillin allergic animals.
• Aztreonem is used replace aminoglycosides, which are more toxic when used
with macrolides and lincosamides.
• It may be used as a reserve antibiotic in veterinary medicine to treat severe

Gram(–) infections.
5. VANCOMYCIN
• Vancomycin blocks the second step of bacterial cell wall synthesis by inhibiting
polymer release from the cell membrane via bactoprenol by hindering (Second
step of cell wall synthesis ) the transglycosylation reactions (and indirectly
preventing transpeptidation). It is bactericidal for Gram(+) organisms.
• RESERVE ANTIBIOTIC for MRSA infections
• Adverse effects: “Red man syndrome” (histamine release), Nephrotoxicity

II. INHIBITORS OF FOLIC ACID SYNTHESIS
SULPHONAMIDES
• Synthetic organic chemicals. - first chemotherapeutic agents used
systemically for prevention and treatment bacterial infections - first
discovered from prontosil dye by Domagk in 1935.
• Antibacterial activity of prontosil is due to the release of metabolite, the

sulphanilamide.
Classification
I. Systemically acting Sulphonamides
1. Short acting sulphonamides (duration <12 hours): sulphadiazine,
sulphafurazole, sulphameraaine,.sulphachlorpyridazine, sulphathiazole and
sulphamlamlde.
2. Intermediate acting sulphonamides (duration 12-24 hours): sulphadimidine,
sulphamethoxazole, sulphamoxole and sulphaphenazole.
3. Long-acting sulphonamides (duration 24 48 hours): sulphadimethoxine,
sulphaethoxypyridazine, sulphamethoxypyridazine and sulphabromomethazine.
II. Locally acting sulphonamides

1. Gut-acting sulphonamides: succinylsulphathiazole, phthalylsulphathiazol‘
phthalylsulphacetamide , sulphasalazine.

2. Topically acting Sulphonamides: Sulphacetamide, Mafenide, silver
sulphadiazine
Antibacterial spectrum - primarily bacteriostatic against many gram-positive and gram-

negative bacteria
Mechanism of Action – Inhibition of folic acid synthesis – Bacteria cannot utilize

preformed folic acids
Therapeutic uses:
• Sulfamethazine is used in cattle, sheep, and swine. It is slowly excreted and
therapeutic levels are maintained in plasma for 24 hours with a single dose.
• Sulfadimethoxine is a long-acting sulfonamide. It is more soluble and less
toxic than sulfamethazine. The plasma t 1/2 is 10–15 hours.
• Sulfachlorpyridazine is a rapidly absorbed and rapidly excreted sulfonamide
used orally in calves under 1 month of age and in swine for the treatment of
respiratory and enteric infections, especially colibacillosis. Peak levels occur in
1–2 hours in nonruminants and in preruminant calves. The plasma t 1/2 is 1.2
hours.

• Sulfamethoxazole is used to treat urinary tract infections in small animals. It
is rapidly excreted and very soluble. Thus high concentrations may be attained in
urine with minimal danger of renal crystalluria.
• Sulfacetamide is the only sulfonamide that can be prepared as the sodium

salt at neutral pH and thus can be used in ophthalmic preparations.
• Sulfasalazine is an “enteric” sulfonamide employed in the therapy of colitis

and inflammatory bowel disease in dogs and cats. It consists of a molecule of
sulfapyridine linked to a molecule of 5-aminosalicylic acid (5-ASA) by a diazo
bond. This prevents absorption in the small intestine and allows drug transit to
the large bowel where it is cleaved by gut bacteria to sulfapyridine and 5-ASA.
These have antibacterial and anti-inflammatory actions, respectively.
• Silver sulfadiazine for burns.
Adverse effects
• Renal crystalluria due to precipitation of sulfonamides in neutral or acidic urine
may occur with large or prolonged doses or inadequate water intake, especially
with the older, less soluble sulfonamides such as sulfathiazole.
• Therapeutic regimens generally do not extend beyond 5 days and renal
crystalluria is rare.
• Keratoconjunctivitis sicca (KCS) may be observed in dogs treated with
sulfonamides, such as sulfadiazine
• Hypoprothrombinemia, thrombocytopenia, and anemia occur rarely and are
probably immune-mediated reactions.
• Sulfonamides should not be used in animals with preexisting bleeding disorders.
Potentiated sulphonamides (Sulfa + trimethoprim = 5:1)

✓ sulfadiazine plus trimethoprim (Co-trimazine)
✓ sulfamethoxazole plus trimethoprim (Co-trimaxoazole)
✓ sulfadimethoxine plus ormetoprim.
The combination also broadens the antibacterial spectrum and covert the complex
as bactericidal

III. DIRECT INHIBITORS OF NUCLEIC ACID (DNA) SYNTHESIS
FLUROQUINOLONES
Classification:
• First-generation quinolones: Nalidixic acid, oxolinic acid, flumequine, cinoxacin,
pipemidic acid, piromidic acid and rosoxacin
• Second-generation quinolones: Enrofloxacin, ciprofloxacin, danofloxacin,
marbofloxacin, norfloxacin, ofloxacin, pefloxacin, sarafloxacin
• Third-generation quinolones: levofloxacin, sparfloxacin,
• Fourth-generation quinolones: Moxifloxacin, gatifloxacin, besifloxacin,
clinafloxacin, garenofloxacin, gemifloxacin, sitafloxacin, trovafloxacin and
prulifloxacin
Veterinary specific FQ:

• Enrofloxacin
• Difloxacin
• Pradofloxacin
• Ibafloxacin
Therapeutic uses
• Enrofloxacin is used in the treatment of dermal, respiratory, and urinary tract
infections (including prostatitis) in dogs, cats, and birds and in respiratory
infections in cattle.

• Danofloxacin is used for the treatment of bovine respiratory infections including
Mannheimia species.
• Difloxacin is used for treatment of dermal, respiratory, and urinary tract infections
in dogs.
• Orbifloxacin and Marbofloxacin are used for the treatment of dermal, respiratory,
and urinary tract infections of dogs and cats. Orbifloxacin is used for susceptible
Gram(–) infections in horses.
• Extralabel use of fluoroquinolones in food animals is prohibited.
Mechanism of action:
• In gram-negative bacteria the major target of FQ action is a DNA gyrase
(Topoisomerase II) which nicks and separates daughter DNA strands after DNA
replication.
• In gram-positive bacteria the major target of FQ action is a similar enzyme
topoisomerase IV which nicks and separates daughter DNA strands after DNA
replication.
Antimicrobial spectrum:
• First-generation quinolones (e.g. nalidixic acid), which are used less often today,
have well effective against gram positive, moderate gram-negative activity
and minimal systemic distribution.
• In general, second-generation quinolones have expanded gram-negative
activity and atypical pathogen coverage, but limited gram-positive activity.
These agents are most active against aerobic gram negative bacilli.
• Third-generation quinolones retain expanded gram negative and atypical
intracellular activity but have improved gram-positive coverage.
• Fourth-generation agents show improved gram-positive coverage, maintain
gram-negative coverage, and gain anaerobic coverage.
Drug Interactions
• As a potent chelator of divalent and trivalent cations – should not be
administered with antacids, multimineral supplements – up to 4 hrs
• Synergistic effect with beta-lactam, aminoglycosides, clindamycin or
metronidazole
Enrofloxacin:
• Exclusively for use in animals
• AB Spec: Gr+ve, Gr-ve, including Pseudomonas, Brucella, Chlamydia and
Mycobacterium species
• Long ‘concentration dependent’ post-antibiotic effect of 5 to 8 hours

• Eliminated in urine as metabolised to ciprofloxacin (25%) and unchanged
(75%)
Clinical uses:
• infections of skin, urinary tract and soft tissues in dogs and cats
• Respiratory disease in cattle, enzootic pneumonia in pigs
• Recommended in infections in exotic species
• Dose: 2.5 to 5 mg/kg PO- to most of the species
Moxifloxacin
• Spectrum against – Gr+ve, Gr-ve and anaerobes
Adverse effects.
• Erosion of articular cartilage in young dogs and foals, particularly, if they are
used at high doses for longer than 14 days in rapid growth phase.
• Phototoxicity - Retinal degeneration has been reported due to acute and diffuse
retinal damage in cats.
IV. PROTEIN SYNTHESIS INHIBITORS
Drug Step in Protein

synthesis inhibited
Inhibition of 30 s Aminoglycosides 1. Interfere with formation of
subunit of initiation complex.
ribosomes 2. Misreading of codon
Tetracyclines Block the attachment of
aminoacyl tRNA to A site
Inhibition of 50 s Chloramphenicol Inhibits peptidyl transferase
subunit of that results in the inhibition
ribosomes of peptide bond formation and
transfer of peptide chain from
P to A site (-static in action)
Macrolide Inhibit translocation of
Lincosamide peptidyl-tRNA from A to P site
Linezolid (−static in action)
Streptogramins

AMINOGLYCOSIDES
• Aminoglycosides consist of two or three amino sugars joined to a hexose

(aminocyclitol) by glycosidic bonds.
• Mostly Gram –ve infections
• Bactericidal, accumulated intracellularly in microorganisms via an O2 -dependent

uptake → anaerobes are innately resistant
• Very polar and basic in character. These are not absorbed orally and do not cross
blood brain barrier.
✓ Poor oral availability

✓ Predominantly gram negative activity
✓ Cause eight cranial nerve toxicity and kidney damage
✓ Bactericidal action
✓ Rapid induction of resistance.
• All aminoglycosides are produced by the soil actinomycetes

➢ Streptomyces sp. derived aminoglycoside carry suffix –mycin e.g.
streptomycin
➢ Microsmonospora sp. derived aminoglycosides carry suffix – micin,
e.g. Gentamicin - Micromonospora purpurea ,
Therapeutic uses.
The aminoglycosides are used in the treatment of Gram(–) infections in all species.
• Streptomycin and dihydrostreptomycin are the oldest members of this class of

antibiotics. Their use has declined with the advent of broader spectrum
aminoglycosides such as gentamicin and amikacin.
• Neomycin is used orally for the treatment of enteric infections and topically for
treating skin, ear, and eye infections. Topically neomycin sulfate is used as
solution or ointment for dressing wounds and eye infections

• Gentamicin and amikacin are expanded spectrum aminoglycosides with activity
against Pseudomonas, Proteus, Staphylococcus, and Corynebacterium spp., as well
as Gram(–) aerobes. They are used in all species for the treatment of susceptible
infections of the skin, respiratory tract, ear, eye, urinary tract, and septicemia.
Tobramycin is similar to gentamicin but has more potent antipseudomonal
activity and reduced nephrotoxicity.
• Kanamycin has an antimicrobial spectrum similar to gentamicin except it is

not effective against Pseudomonas spp..
• Aminoglycosides tend to accumulate in the renal cortex and otic endolymph,

which predisposes these tissues to their toxicity
• Thus amikacin and netilmicin may be effective against organisms resistant to

other aminoglycosides.
• Spectinomycin : Aminocyclitol antibiotic structurally related to Aminoglycosides

Adverse effects
• The aminoglycosides are relatively more toxic than other classes of

antimicrobials.
• Should not be used with other ototoxic or nephrotoxic drugs such as furosemide
or amphotericin B.
Irreversible Ototoxicity - Reversible Nephrotoxicity - Neuromuscular blockade.
TETRACYCLINES
• The tetracyclines are polycyclic compounds that are amphoteric and that
fluoresce when exposed to ultraviolet light. Most are prepared as the
hydrochloride salt.
• They form insoluble chelates with cations such as Ca2+, Mg2+, Fe3+, and Al3+
and They accumulate in growing teeth and bones.
• They are bacteriostatic and broad spectrum. Their antimicrobial spectrum

includes Gram(+) and Gram(–) aerobes and anaerobes, Rickettsiae, Spirochetes,
Chlamydiae, Mycoplasma, and some protozoans such as Anaplasma spp. and
Haemobartonella spp.

Classification:
Short acting: Oxytetracycline, chlortetracycline and tetracycline
Intermediate acting: Demethylchlortetracycline and methacycline
Long acting: Doxycycline and Minocycline.
• Doxycycline and minocycline are more lipid soluble than tetracycline,

chlortetracycline, or oxytetracycline and penetrate the CNS, eye, and
prostate at therapeutic concentrations.
• All tetracyclines are excreted primarily in the urine except doxycycline.

Doxycycline is excreted in the feces and thus can be used in the presence of renal
failure
• A recent derivative of the glycylcyclines, tigecycline, has been developed that has
an effect against methicillin-resistant S. aureus (MRSA).

Adverse effects
• Kidney Failure (All are contra-indicated except doxycycline)

• Photosensitivity (Maximum with demeclocycline) – Type I Photosensitivity
• Dentition and Bone defects (contra-indicated in pregnancy and young ones )
• Expired drugs can cause Fanconi’s syndrome
• Superinfection or Pseudomembranous colitis
CHLORAMPHENICOL
• It is the first antibiotic to be synthesized commercially.
• Para-nitro group in the structure is responsible for pharmacological activity
• In addition to a wide spectrum of gram positive and negative bacteria,

chloramphenicol is active against such organisms as Rickettsia.
• In the mid 1950s, it was discovered that chloramphenicol caused aplastic anemia
and other blood dyscrasias in a small proportion of patients
• One of cytochrome P450 inhibitor.
• Chloramphenicol causes bone marrow toxicity. This toxicity can be of two types.
1. Dose dependant reversible suppression of bone marrow activity. This occurs

when the dose is high.
2. Small doses can cause irreversible bone marrow depression leading to aplasia
and fatal anaemia.
• Newer derivative, Florfenicol is not known to produce aplastic anemia.

• “Gray baby” syndrome in neonates (↓ glucuronosyl transferase)
MACROLIDES
• The macrolide antibiotics include erythromycin, azithromycin, clarithromycin,

tulathromycin, tylosin, and tilmicosin.
• Erythromycin base is destroyed by gastric acid; Motilin receptor agonist –

Prokinetic activity.
• Spectrum: They are mainly effective against Gram + ve bacteria; Also in

mycoplasma, chlamydia, helicobacter, listeria.

• Tylosin is used in cattle, sheep, swine and poultry for the treatment of local and
systemic infections caused by Mycoplasma and Gram(+) bacteria. It is also added
to feed as a growth promotant in these species.
• Erythromycin, Azithromycin is used as an alternative for erythromycin for R. equi

pneumonia in foals
• Spiramycin: . It is a macrolide and used to treat contagious bovine

pleuropneumonia to prevent toxoplasmosis abortion and in mastitis.
• Telithromycin: a ketolide active against macrolide-resistant S. pneumonia
Uses
• Chlamydial infections
• Mycoplasma and Legionella
Adverse effects:
• Cholestatic jaundice
• Gastro intestinal motilin agonist – diarrhea (Erythromycin have prokinetic
activity also)
• Interactions : Erythromycin inhibits CYP-450; Azithromycin not.
LINCOSAMIDES – Lincomycin and Clindamycin
• Not a macrolide, but has the same mechanisms of action and resistance.
• Narrow spectrum: gram-positive cocci (including community-acquired MRSA)

and anaerobes (but not against Cl. Difficile) , including B. fragilis (backup drug)
• Lincosamides are contraindicated in horses, rabbits, hamsters, and guinea

pigs because they may produce a severe, often fatal, diarrhea due to altered
GI flora.
• Cross-resistance between lincosamides and macrolides is common
• Major adverse effect is resp. for pseudomembranus colitis (by Cl. difficile) and
Super-infection.

V. OTHER ANTI-BACTERIALS
METRONIDAZOLE
• It is bactericidal against most obligate anaerobes and is active against protozoa,

including Giardia and Trichomonas spp.
• Mainly against Cl.difficile (resp. for pseudomembranus colitis and Super-

infection) and MRSA (Same action we can see for Clindamycin also)
IONOPHORE ANTIBIOTICS - monensin, lasalocid, laidlomycin, salinomycin, and narasin
• They complex with Na+ in the cell membrane to produce passive extracellular
transport of K+
and intracellular influx of H+, which kills bacteria and coccidian by lowering
intracellular pH.

POLYMIXINS: - acts by altering the permeability of cell membrane
Polymixins are products of Bacillis polymyxa. Originally these antibiotics are used for
their action against Pseudomonas aeuroginosa.
Polymixin E is also known as Colistin.
ANTIFUNGAL AGENTS
Classification of antifungal drugs based on their mechanism of action
✓ Drugs altering membrane permeability

1. Azoles
• Triazoles e.g. Fluconazole, itraconazole, voriconazole,
terconazole, posaconazole.
• Imidazoles e.g. Ketoconazole, miconazole, clotrimazole,
econazole, butoconazole, oxiconazole, sertaconazole,
sulconazole.
2. Allylamine: e.g. Terbinafine, butenafine, naftifine.
3. Polyenes Antibiotics e.g. Amphotericin B, nystatin, hamycin
✓ Drugs blocking nucleic acid synthesis e.g. Flucytosine
✓ Drugs disrupting microtubule function e.g. Griseofulvin
✓ Drugs inhibiting cell wall synthesis e.g. Caspofungin, nikkomycin.

• Drugs used for the Treatment of Systemic Fungal Infections: These include
amphotericin B (Highly nephrotoxic), flucytosine, triazoles, ketoconazole and
echinocandins
• Systemic Drugs for Superficial Fungal Infections: Griseofulvin (for ring worm
infection), Allylamines, Ketoconazole, fluconazole and itraconazole
• Topical: Terbinafine, Benzoic acid (6%) with salicylic acid (3%) - Whitfield’s
ointment
• Flucytosine is combined with amphotericin B for synergistic action in the

treatment of cryptococcosis (especially meningeal cryptococcosis) in dogs and
cats.
ANTIVIRAL DRUGS
Classification based on mechanism of action:

Anti Influenza Drugs
These include amantadine, rimantadine, oseltamivir and zanamavir.
✓ Amantadine and Rimantadine

These drugs prevent uncoating of influenza A virus (not influenza B). These
drugs decrease the duration of symptoms of influenza if used
prophylactically. Rimantadine is longer acting
than amantadine.
✓ Oseltamivir and Zanamavir

These drugs act as neuraminidase inhibitors and prevent the virion
release by causing clumping of mature virions.
Oseltamivir is drug of choice for bird flu (currently strain causing
pandemic is H5N1) as well as swine flu (by H1N1) – TAMIFLU
Anti herpes virus drugs - Acyclovir is a guanosine derivative with selectivity for
particular herpes.
Anti HIV virus drug - Zidovudine is frequently used NRTI in the treatment of HIV
infections. It can also be used for the prophylaxis of needle stick injury patients and for
the prevention of vertical transmission of HIV from mother to fetus.
ANITI-CANCER DRUGS
• The kinetics of chemotherapy drug-induced cell kill is first-order—a constant

percentage (not a constant number) of cells is killed with each dose.
• Rapidly multiplying and growing cells are most susceptible to drug effects. These
include the normal cells of the hair follicles, gastrointestinal tract, and bone
marrow.
• Thus, hair loss, vomiting and diarrhea, and leucopenia and thrombocytopenia are
common side effects of therapy

Drugs Affecting Cell Cycle
Determination of dose on the basis of body surface area
Surface area = B.Wt.0.67 x K/104
Surface area is in square meter (m2) and b.wt. in g
K is constant with value of 10.0 and 10.1 for cats and dogs respectively
Anti cancer drugs - Classification
1. Alkylating Agents (Cell cycle Non specific - CCNS)
Nitrogen mustards: Mechlorethamine, cyclophosphamide,

ifosfamide, melphalan, chlorambucil
Ethylenimines: Thio-TEPA, hexamethylmelamine

(altretamine)
Alkyl sulfonates: Busulfan
Nitrosoureas: Carmustine, lomustine, streptozocin
Triazines : Procarbazine, dacarbazine, temozolomide

2. Platinum compounds - Cisplatin, carboplatin, oxaliplatin.
(Cell cycle Non specific - CCNS)
3. Antimetabolites (S-phase of cell cycle - CCS drugs)
Pyrimidine analogs : 5-FU, cytarabine, gemcitabine
Purine analogs: 6-MP, 6-thiogunanine, pentostatin,
cladribine
Folic acid analogs: Methotrexate, pemetrexed
4. Natural products
All natural anticancer products can cause bone marrow suppression except bleomycin
and vincristine.
Vinca alkaloids: Vincristine, vinblastine, vinorelbine
(M-phase of cell cycle - CCS drugs) Inhibits tubule polymerization
Taxanes: : Paclitaxel, docetaxel
(M-phase of cell cycle - CCS drugs) Inhibits tubule depolymerization
Epipodophyllotoxins: Etoposide, teniposide
Camptothecins: Topotecan, irinotecan
Antitumor antibiotics: Anthracyclines (daunorubicin, doxorubicin,
epirubicin, idarubicin, mitoxantrone),
bleomycin, dactinomycin, mitomycin-C
Enzymes: L-asparaginase
5.Hormones and related agents
6. Miscellaneous Agents
Vincristine
✓ Vincristine is the most commonly used mitotic inhibitor in veterinary medicine. It
is employed in the treatment of lymphoreticular neoplasms, carcinomas, and
sarcomas in dogs and cats and transmissible venereal tumors (TVT) in dogs.
✓ Bone marrow suppression will be minimal compare to other group drugs.
✓ The vinca alkaloids, especially vincristine, may produce a peripheral neurotoxicity.

Taxanes
✓ Paclitaxel and docetaxel interfere with mitotic spindle formation by preventing
disassembly of microtubules.
Distinctive toxicities of natural anticancer drugs
✓ Bleomycin - Pulmonary fibrosis (Marrow sparing)
✓ Anthracyclines (Doxorubicin) - Cardiotoxicity

ANIPARASITICAL DRUGS
1. Drugs affecting energy production

• Inhibitors of fumarate reductase and glucose uptake, and binding of tubulin
in microtubules
o Benzimidazoles, and benzimidazoles pro-drugs: albendazole,

ca,mbendazole, febanel, febendazole, flubendazole, luxabendazole,
mebendazole, netobimin, oxfendazole, oxibendazole, parbendazole,
thiabendazole and thiphanate.
• Inhibitors of (mitochondrial) phosphorylation

o Salicylanilides, substituted phenols and halogenated hydrocarbons:
niclofolan, niclosamide, nitroxynil, oxyclozanide, rafoxanide, resorantel
and tribromosalicylanilide.
• Inhibitors of glycolysis
o Clorsulon and thiacetarsamide.
2. Drugs causing paralysis

• Cholinergic agents (Spastic paralysis)
o levamisole, methyridine, morantel, pyrantel and tetramisole
• GABA agonists (Flaccid paralysis)

o Avermectins (ivermectin), milbimycins an dpiperazines
• Muscle hyperpolarizer (Flaccid paralysis)

o Piperazine ( may also affect GABA)
• AchE inhibitors (Spastic paralysis)

o Organophosphosphates, coumaphos, crufomate, dichlorvos, fenchlorphos
3. Disruption of tegument
Affecting permeability of cells and vacuolation of tegument - Praziquantel

SOME DIAGRAMMATIC REPRESENTATIONS
Benzimidazole (BZD)-induced inhibition of microtubule synthesis in helminthes.
✓ Benzimidazoles (BZDs) - Thiabendazole is the prototypical agent.
✓ Albendazole is contraindicated in pregnant animals, but fenbendazole is safe

for pregnant animals
✓ Netobimin- is a pro drug of albendazole effective against nematodes and their

larvae, tapeworms and flukes. It may be administered as injection.
✓ Febantel - Febantel is a pro-benzimidazole which yields both fenbendazole and

oxfendazole
For other drugs

✓ Ivermectin is effective against all major GI worms and lungworms. It is
administered at 0.2 mg/kg orally or SC, and 0.5 mg/kg topically. It has shown to
block neurotransmission by stimulating release of the neurotransmitter GABA
(Gama amino butyric acid) which keeps chloride channels open.
Mechanisms of action of ectoparasiticides that interfere with

parasite nervous system.

ETHNOVETERINARY PRACTICES
Plant Secondary Metabolites:

• The substances that have no known direct function in growth
• Most of the SM are involved in defence reactions
• Eg., alkaloids, phenolics, terpenoids, sterols, steroids, essential oils and
lignins.
MEDICINAL PLANTS AND ITS PHARMACOLOGICAL ACTIONS

Rauwolfia serpentine
Active principle Reserpine
Pharmacological Tranqulizer and Antihypertensive

action
Vinca rosea
Active principle Vincristine and Vinblastine
Pharmacological Anticancer drug – common used for the treatment of transveneral tumour
action in dogs.
Withania somnifera
Active principle Somniferine
Pharmacological General tonic and Immunostimulant

action
Laptadenia reticulate
Active pricinple Laptadine
Pharmacological Galactagogue
action
Gingiber officinalis
Active principle Gingerol
Pharmacological Carminative and Stomachic

action
Ricinus communis
Active principle Ricin
Pharmacological Purgative
action

INDIGENOUS ANTIBACTERIAL AGENTS
• Curcuma longa
• Azadirachta indica
• Allium sativum
• Ocimum sanctum
• Zingiber officinalis
INDIGENOUS ANTIFUNGAL AGENTS

• Curcuma longa
• Pongamia glabra
• Azadirachta indica
• Cassia alata
INDIGENOUS ANTHELMINTIC AGENTS

• Areca catechu
• Azardirachta indica
• Carica papaya
• Punica grantum
INDIGENOUS ARTHROPODE REPELLANTS/ INSECTICIDAL AGENTS
Acorus calamus Repellant of Ixodid ticks
Azadirachta indica wide range insecticidal
Curcuma longa Against ticks and mites
Chrysanthemum indicum Against scabies
Pongamia glabra Against sarcoptic mange
Ricinus communis Against mites
Tinospora cardifolia Against scabies

VETERINARY TOXICOLOGY
• The major disasters of poisoning include,
✓ Ergotism in France and Spain in 992,

✓ Nuclear accident in Pennsylvania in 1979,
✓ Bhopal gas tragedy due to METHYL ISOCYANATE in 1984
✓ Chernobyl nuclear accident in 1986.
✓ Use of thalidomide in pregnant women for treating morning
sickness caused PHOCOMELIA condition in newborn infants during
1960s in Europe.
• In the term toxicology, the word ‘toxicon’ (Greek) means POISON.
• The branch of toxicology, which is involved in establishing safety limits for

chemical exposure is REGULATORY TOXICOLOGY.
• Investigating and controlling the toxic effects of various substances on the

community is dealt by TOXICOVIGILANCE.
• The branch of toxicology, which investigates vetero-legal cases of death,

poisoning and drug abuse is FORENSIC TOXICOLOGY.
• The study of toxicity produced by substances of plant, animal and microbial

origin (termed as toxins) is termed as TOXINOLOGY.
• Paracelsus is often quoted for his statement ‘All substances are poisons; there is
none which is not a poison. The right dose differentiates a poison and a remedy’.
Guidelines for the classification of relative toxicities (Sterner-Hodge scale)

Extremely toxic <1mg/kg
Highly toxic 1-50 mg/kg
Moderately toxic 50-500 mg/kg
Slightly toxic 0.5-5 g/kg
Practically non toxic 5-15 g/kg
Relatively harmless > 15 g/kg

Types of poisoning / Toxicity
Type Exposure time Parameter could be

found out
Highly toxic Single or multiple exposure 1-50 mg/kg
within 24 hours
Sub-acute Repeated exposure from 1 day to LD50
toxicity within 30 DAYS or LESS
Sub-chronic Repeated exposure from 1 to 3 NOEL< NOEL
toxicity months
Chronic Repeated exposure from 1 to 3 NOEL, NOAEL
toxicity months
Relatively Repeated exposure more than 3 Cumulative toxicity

harmless months
• The type of toxicity which results due to progressive accumulation of a toxicant in

the body is known as CUMULATIVE TOXICITY. (Several toxicants such as heavy
metals, alcohol, DDT etc cause cumulative toxicity.)
• The amount of toxicant in food and water, which can be consumed daily over a
life time without any significant health risk, is known as ACCEPTABLE DAILY
INTAKE (ADI).
• LD refers to the ‘lowest dose’ of the toxicant administered directly to the animal
in any route. LC refers to the ‘lowest concentration’ of toxicant present in feed
and water. (In LD, the compound is administered directly to the animal on mg/kg
bd wt basis, whereas, in LC the toxicant is present in feed or water (mg/kg of feed
or Liter of water). (LD > LC)
• NOEL (No observed effect level) is the highest dose, which will not produce any
effect, whereas, NOAEL (No observed adverse effect level) is the highest
concentration, which will not produce any adverse effect. (NOAEL > NOEL)
• Maximum acceptable/ permitted amount of a drug present in feed and foods is

known as MAXIMUM RESIDUE LEVEL (MRL). (For pesticides – MAXIMUM RESIDUE
LIMIT).

• The highest dose of a compound, which produces adverse effects but no
mortality is called MAXIMUM TOLERATED DOSE (MTD). (MTD is also referred to
as LD0 (Zero) as it will cause adverse effects but no mortality).
LD > LC > MTD > NOAEL > NOEL > ADI > MRL
• DDT (Dichloro diphenyl trichloro ethane), which is used to control malaria and
typhus was discovered by PAUL MULLER.
Poisons - Classification
Based on their toxic effects in the body as:
1. Poisons which cause death by anoxia

• Poisons which make haemoglobin incapable of
transporting oxygen
E.g. Carbon monoxide, nitrites
• Poisons which inhibit cellular respiratory enzymes, E.g.
Cyanides
• Poisons which destroy haemopoietic organs, E.g.
Radioactive substances.
2. Poisons, which on contact cause irritation or corrosiveness of the

organs (skin) or damage the organ through which they are excreted
(GI tract, respiratory tract, urinary tract) e.g. Irritant gases, alkaline
corrosives, corrosive inorganic acids, corrosive organic acids and
heavy metals.
3. Poisons, which damage protoplasm or parenchyma. These poisons

produce local irritation and after absorption cause damage to the cells
and capillaries e.g. Phosphorus and carbon tetrachloride.
4. Poisons, which affect the nerve cells and fibres e.g. Hypnotics,
narcotics, anesthetics, alcohol, some alkaloids and glycosides.
Metabolism, Mechanisms and Factors Affecting Toxicity
• Unlawful or criminal killing of animals through administration of poisons is known

as MALICIOUS POISONING.

• Unintentional addition of toxicants or contaminants to feed and water is known
as ACCIDENTAL POISONING.
• Man-made sources of toxicants are referred to as ANTHROPOGENIC sources.
• Genetically determined abnormal reactivity of an individual to a chemical is

known as IDIOSYNCRACY.
• Failure to elicit a response to an ordinary dose of a substance due prior exposure

is known as TOLERANCE.
• The phenomenon in which toxic substances elicits beneficial effects at low doses
is known as HORMESIS.
• In oral route of exposure, and liver are responsible for elimination prior to entry
into circulation and hence Pre-systemic elimination is possible
• The common process involved in the absorption of xenobiotics across the cell
membrane is PASSIVE DIFFUSION.
• In body, heavy metals such as mercury, lead, cadmium tend to accumulate in

KIDNEY (organ of the body). (However, the major site for accumulation of lead in
the body is bone and teeth).
• Organo-chlorine insecticides such as DDT tend to accumulate in ADIPOSE TISSUE

(organ of the body).
• Arsenic tends to accumulate in HAIR and SKIN (organ of the body). (Hence,
bacterial decomposition of carcass is absent resulting in preserved carcass)
• Major route of excretion for xenobiotics is RENAL EXCRETION.
• The process of chemical transformation (conversion from one form to another)

occurring in the body is known as BIOTRANSFORMATION.
• The major site for biotransformation of xenobiotics in body is LIVER.

• Major biotransformation reaction occurring in Phase I is OXIDATION and in Phase
II is CONJUGATION.
• Phase I Oxidation reactions are mainly catalyzed by MICROSOMAL ENZYMES

(MFO).
• All Phase II conjugation reactions are catalyzed by non-microsomal enzymes

except for GLUCURONIDE CONJUGATION, which is catalyzed by microsomal
enzymes.
• The metabolic reaction that is deficient in dogs is ACETYLATION; in cats is

GLUCURONIDE CONJUGATION, and in pigs is SULFATION. (Hence,
sulphonamides which undergo acetylation cause toxicity in dogs and similarly,
paracetamol, which undergoes glucuronide conjugation, causes hepatotoxicity in
cats).
• The process of conversion of non-toxic substance into a toxic metabolite through

biotransformation is known as LETHAL SYNTHESIS.
• Rodents are preferred for oral toxicity testing as they lack VOMITION reflex.
• Organo-chlorine insecticides such as DDT, BHC tend to be more toxic in oily

vehicles due to INCREASED ABSORPTION.
• The species of animal that is resistant to the toxic effects of consuming Atropa
belladonna (Belladonna) leaves is RABBIT. (Rabbits contain the enzyme
atropinase, which destroys atropine).
• The breed of dog that is more susceptible to the toxic effects of ivermectin is
COOLIE BREED. (In coolies, ivermectin easily crosses blood brain barrier and
causes neurological symptoms).
• Asprin and sulphonamides cause hemolysis in individuals deficient in the

metabolic enzyme GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) – Example
for Idiosyncrasy

• Greyhounds are more susceptible to the toxic effects of barbiturates (when used
for anesthesia). Barbiturates mainly distribute to adipose tissue. Since,
Greyhounds, have little body fat, higher circulating concentration of barbiturates
causes toxicity.
Diagnosis & Treatment of Poisoning
• The type of evidence obtained at the scene of poisoning is referred to as

CIRCUMSTANTIAL EVIDENCE.
• The most common feed contaminant that can be expected during improper
storage is MYCOTOXINS (Aflatoxin).
• Pink colouration of urine is suggestive of poisoning with PHENOTHIAZINES.
• Phenols and cresols produce GREEN colouration of urine.
• The symptom or lesion that is characteristic to a particular toxicant is known as

PATHOGNOMONIC (symptom or lesion).
• The evidence that is obtained during postmortem examination is known as

PATHOLOGICAL evidence.
• Bitter almond smell of ruminal contents is suggestive of CYANIDE POISONING.

(Bitter almond smell

• Poisoning with phosphorus results in GARLIC-LIKE odour during postmortem
examination.
• Detection of toxic material in body using laboratory methods constitutes

ANALYTICAL evidence.
• The evidence that is obtained by feeding suspected material (feed) to healthy

animals to ascertain the presence of a toxicant is known as EXPERIMENTAL
EVIDENCE.
• The aim of treatment during poisoning is to INCREASE the threshold of the

toxicant. (Measures are directed to create a situation where more toxicant is
required to produce the toxicity)
• The time versus concentration curve of toxicant in the body is BELL OR INVERTED
‘U’ shaped.
• The ascending phase (Absorption phase) of the time-concentration curve of the

toxicant represents ABSORPTION.
• The descending phase (elimination phase) of the time-concentration curve of the

toxicant represents EXCRETION.
• Hence, the aim of treatment in poisoning should be Decreasing the slope of

ascending phase (AP) and increasing slope of descending phase (DP).

• Emesis is not indicated for the compounds like Volatile compounds, Corrosives,
Convulsants, CNS stimulants, for the unconscious patients and in cases of
respiratory distress or debilitated animals.
• The safest alternative when emesis is contraindicated is GASTRIC LAVAGE.
• The most commonly used adsorbing agent for binding toxicants in GIT is
ACTIVATED CHARCOAL.
• The type of diuretics or purgatives that are preferred in cases of poisoning are
OSMOTIC/SALINE TYPE. However, for prompt action, furosemide, which is a loop
diuretic is also used.
• The mechanism involved in the enhanced elimination of acidic agents in alkalized
urine and basic agents in acidified urine is ION TRAPPING. (Ion trapping for basic
drugs occurs in the acidic pH of rumen - due to the production of volatile fatty
acids).
• The antidote for paracetamol (acetaminophen) toxicity is N-ACETYL CYSTEINE.
• The agents that are used during CNS depression and respiratory arrest are called
as ANALEPTICS. (Eg. Doxapram).
Chelating agents:
Chelating agents are used in the treatment of poisoning with heavy metals. They
incorporate the metal ion into an inner ring structure in the molecule by means of
chemical groups called ligands (Greek word chele = claw, Latin word ligare = to bind).
✓ British Anti-Lewisite (BAL) or Dimercaprol - BAL is far from an ideal antidote as it

is rapidly inactivated, irritant and unstable.
✓ DMSA (Mesodimercaptosuccinic acid) - probably the preferred chelator as it is

much safer than BAL.
✓ Unithiol (DMPS – Dimercapto propane sulphonate) - It is analogue of BAL with
reduced toxicity and high water solubility. This agent effectively chelates lead
and mercury.
✓ Sodium calcium edentate - It is the calcium chelate of the disodium salt of

ethylene diamine-tetra-acetic acid. Its effectiveness is due to its capacity to
exchange calcium for lead in lead poisoning.

✓ D - Penicillamine ( Dimethylcycteine ) - It is a metabolite of penicillin that
contains –SH groups; it may be used to chelate lead and also copper.
Universal antidote (ATMK)
✓ Universal antidote containing 10 g activated charcoal, 5g kaolin, 5g tannic

acid and 5 g magnesium oxide in the form of a slurry with 200 ml of water
can be administered.
METALS
Lead Poisoning (Plumbism)
• Lead is ubiquitous in nature .Most of the animals live close to ground level and
hence gets more exposure.
• In Pica condition, animals tends to lick walls, chew on dry peelings of paint, eat
wall posters etc. Since, paints are lead based, the animals are affected with lead
poisoning.
• The species that are most susceptible to lead poisoning are DOG, CATTLE and
HORSES.
• The species that is considered as indicator for lead in the environment is DOG,
Since dogs live close to soil are have the habit of frequent digging of soil.
• The species that is very resistant to lead poisoning is SWINE.
• As >90% of ingested lead is eliminated from GIT without absorption and even
after absorption, as only <1% of lead is in free form. Hence, acute lead toxicosis is
not common.
• The organ that is considered as sink for lead is BONE (95% of body’s lead burden
is found in bone).
• Lead toxicity is
✓ result of binding with –SH groups of proteins and enzymes.
✓ decreases ‘haeme’ synthesis through the inhibition of the enzyme δ-
AMINO LEVULINIC ACID SYNTHETASE (ALA-D synthase), Haem synthatase
etc.,
• lead poisoning, basophilic stipplings (BS) are commonly seen in DOGS.
• Lesions are MICROCYTIC HYPOCHROMIC ANAEMIA, BLUE LINES IN GUM
• The characteristic histological picture of lead poisoning in tubular cells of kidney
is INTRANUCLEAR INCLUSION BODIES. (Eosinophilic)
• Neurological symptoms accompanied by GIT symptoms possibly indicate LEAD
poisoning.

• In lead poisoning, roaring in horses is caused by RECURRENT LARYNGEAL nerve
paralysis (Stertorous sounds).
• Specific antidote for lead toxicosis is CALCIUM DISODIUM EDTA.
Mercury (Hydrargyrism)
• Calomel is Mercurous chloride.

• MINAMATA DISEASE AND NIGATTA DISEASE (Both are seashore places) in Japan
was caused by the consumption of fish contaminated with METHYL MERCURY.
• The species that is more sensitive to Hg poisoning is CATTLE. (Cow & Calves).
• The process of accumulation of Hg in marine animals to a very high
concentration over a period of time is known as BIO-ACCUMULATION or BIO-
MAGNIFICATION.
• The mechanism of toxicity of mercury involves binding with –SH, THIOL groups of
proteins and enzymes.
• Antidote: BAL, Sodium thiosulphate
ARSENIC
• ‘King of poisons and Poison of kings’ is ARSENIC
• Arsenites (As3+ or trivalent) are 5-10 times more toxic than Arsenates (As5+ or
pentavalent) due to higher solubility.
• Most toxic gaseous form of arsenic which is released during charging of storage
batteries is ARSINE.
• The species that is more sensitive to arsenic poisoning is CAT.
• The mechanism of toxicity of arsenic involves binding to SULPHYDRYL GROUPS

(–SH) (Eg: Lipoic (thioctic) acid).
• The primary symptom of acute arsenic toxicity is GASTROENTERITIS.
• The nature of diarrhoea in acute arsenic poisoning is described as RICE WATERY

Diarrhea.
• The characteristic coloration of mucosa in chronic arsenic poisoning is BRICK RED.
• Organic arsenicals cause nervous symptoms in swine (DOG SITTING SWINE).
• Only arsenical that can cause blindness is Arsenillic acid

• Samples that should be collected in suspected cases of arsenic toxicity are HAIR
and NAILS.
• Specific antidote for arsenic poisoning is BRITISH ANTI-LEWISITE (BAL). or

DIMERCAPROL.
• Superior water soluble derivatives of BAL are MESO-DIMERCAPRO-SUCCINIC

ACID (MDSA) and DI-MERCAPTO-SUCCINIC ACID (DMSA).
Copper Vs Molybdenum
• Copper has inverse inter-relationship with Molybdenum and Sulphur.
• Hence, when the animal is associated with copper deficiency, the same animal
always having the chances to be in Molybdenum Toxicity condition. (Vice Versa)
Copper
• The species that is more susceptible of copper poisoning is SHEEP.
• The species that is highly resistant to copper poisoning is CHICKEN.
• The ideal ratio of copper to molybdenum in feeds should be 6:1.
• The breed of dog that is highly susceptible to copper toxicosis due to genetic
predisposition is BEDLINGTON TERRIER. (Autosomal recessive gene causes
copper retention in liver as a result of failure of excretion).
• Major symptoms of copper toxicosis are HEPATOTOXICITY and HEMOLYTIC

ANAEMIA.
• The characteristic appearance of kidneys in copper poisoning is GUNMETAL.
• In copper poisoning, elevation of liver marker enzymes (AST, SDH, and LDH)
occurs prior to HEMOLYTIC CRISIS (about 3-6 weeks before). Hence, though
marker enzymes are elevated, the level of Cu in blood is not increased until a day
or two before development of hemolysis.
• Specific chelating agent used to treat copper poisoning is D-PENICILLAMINE.
• Zinc induces the synthesis of mucosal metallothionins in GIT, which bind to

copper and prevent Cu absorption. Hence, ZINC SUPPLEMENTATION DECREASES
THE DEVELOPMENT OF COPPER TOXICITY.

Molybdenum
• In molybdenum poisoning, deficiency of COPPER (mineral) is observed. (Hence,

most of the symptoms in Mo poisoning resemble copper deficiency).
• Peat scours or teart or shooting diarrhea is a characteristic symptom of

MOLYBDENOSIS.
• Light coloured hair and depigmentation around eyes in molybdenum poisoning

causes SPECTACLE-EYE appearance. (Due to Cu deficiency, melanin production is
reduced due to decreased in activity of Cu containing enzyme, tyrosinase, which
converts tyrosine to melanin. Spectacle-eye is prominently visible in buffaloes due
to dark colouration of the animal).
• Molybdenosis in sheep is manifested as ENZOOTIC ATAXIA or SWAY BACK.
• The treatment of molybdenum poisoning involves administration of COPPER

SALTS
Cadmium Poisoning (ITAI ITAI DISEASE)

• Cadmium-metallothionein promotes renal accumulation and causes severe
NEPHROTOXICITY.
• Calcium disodium EDTA is useful for chelation.
• Selenium administration competes with cadmium and protects the kidneys.
• BAL IS CONTRAINDICATED BECAUSE OF NEPHROTOXICITY IN CADMIUM

POISONING.
IRON POISONING
• Toxicity is usually noticed in pigs. Toxicity is more in piglets born to selenium and
vitamin E deficient pigs.
• In baby pigs pale skin, corrosion of mucosa, dark faeces, diarrhea and
tachycardia.
• Yellowinsh brown discolouration and oedema of the tissues especially near the
injection site.
• Specific antidote: Desferrioxamine can be administered slowly by intravenous

route.

SELENIUM
• OBLIGATE (PRIMARY) ACCUMULATORS or INDICATOR PLANTS - Eg: Astragalus

sps, Stanleya sps, Oonopsis sps etc.
• FACULTATIVE ACCUMULATORS - Eg: Acacia sps, Aster sps, Astriplex sps,

Artemisia sps etc.
• NON- ACCUMULATORS - Eg: Maize, Wheat, Barley etc
• The pH of the soil that favours selenium accumulation is ALKALINE (>7.0).
• In selenium poisoning, the characteristic odour is GARLIC-LIKE. (Phosphorus also

produces garlic-like odour)
• The vitamin that aggrevates selenium poisoning is VITAMIN E.
• Sub-acute toxicity of selenium is also known as BLIND STAGGERS.
• Chronic selenium toxicity is also called as ALKALI DISEASE - cracked and

overgrown hooves .
• In horses, loss of hair from the mane is the primary symptom of SELENIUM
poisoning.
• In selenium toxicity, depleted glutathione levels can be restored by administering

ACETYL CYSTEINE during treatment.
• The use of DIMERCAPROL (BAL) metal chelator is contraindicated in selenium

toxicity.

NON METALS
Common salt
• Salt poisoning is commonly associated with deprivation of water – Water

deprivation syndrome
• The most susceptible species for salt poisoning are POULTRY and PIGS. (Poultry
have poor sense of taste and indiscriminate feeding behavior).
• Salt toxicity is consequent to the development of HYPEROSMOLALITY or

HYPERTONICITY in blood and CSF.
• Nervous symptoms in salt poisoning are a result of edema of BRAIN.
• Dragging of hind limbs and knuckling of fetlock joints is characteristic feature of

SALT poisoning in cattle.
• In salt poisoning, pathognomonic histological appearance in brain is

EOSINOPHILIC MENINGIOENCEPHALITIS. (Perivascular cuffing of eosinophils is
observed in cerebral cortex and meninges).
• There is no specific treatment. Slat free fresh water must be given initially in small
quantities at more frequent intervals. Isotonic or hypertonic saline
intraperitoneally.
Urea
• Urea is added to the diets of ruminants as a source of NITROGEN. (Urea contains

46.7% nitrogen and 1 g of urea is equivalent to 2.92 g of protein).
• Urea is permitted in the diets of ruminants and horses due to the presence of
UREASE microbial enzyme in rumen and caecum respectively.
• Calf age group (Young ruminants) is more resistant to urea toxicity, since rumen
microbial is not well developed.
• The feed component that is required for efficient utilization of urea is

CARBOHYDRATES or TOTAL DIGESTIBLE NUTRIENTS (TDN).
• The recommended ratio of urea to molasses for straws and other high fiber diets
is 1:5.

• Ruminal pH above 7.5 is diagnostic of urea / non-protein nitrogen (NPN)
poisoning.
• pH of the blood is acidic in urea poisoning.
• The treatment in urea poisoning includes infusion of 5% ACETIC ACID (VINEGAR)

and COLD WATER into rumen.
• 4-Methyl-imidazole (4-MI) in ammoniated feeds produces CNS symptoms in

cattle known as BOVINE BONKER’S SYNDROME.
Fluoride
• Acute fluoride poisoning is common in DOG, whereas, chronic poisoning is

common in HERBIVORES. (Dogs are poisoned from fluoride containing pesticides
whereas herbivores from eating contaminated pastures).
• The level of fluoride in drinking water that can cause fluorosis in animals is >2
PPM.
• Fluoride accumulates in BONE and TEETH in the body. (Bone acts as sink for
fluoride similar to lead. However, accumulation of fluoride in teeth occurs only
during formative stages i.e., young age only).
• The corrosive effects of fluoride in GIT are due to the formation of

HYDROFLUORIC ACID in the acidic medium of stomach.
• Hyperkalemia in fluoride poisoning is a result of inhibition of Na+-K+ ATPase

enzyme.
• Brown or black discolouration of teeth in fluorosis is a result of oxidation of

ENAMEL
• Chronic fluorosis is manifested as SKELETAL and DENTAL forms ( In young animal

both the forms are appeared and In adults, only skeletal form is appeared)
• In fluorosis, the density of bones INCREASES.
• Soft tissue that accumulates highest amount of fluoride is PINEAL GLAND.
• Death in fluoride toxicity is due to the development of HYPERKALEMIA and

HYPOCALCAEMIA.
• The salts of CALCIUM are employed in treatment of fluorosis.

Phosphorus
• White and yellow (most toxic) phosphorus are soluble and readily absorbed.
Hence cause toxicity. Whereas red phosphorus is insoluble, hence is non-toxic.
• Excess feeding of wheat bran rich in phosphorus causes BRAN DISEASE in horses.
• Garlic-like odour of breath and luminous stomach contents suggest

PHOSPHORUS poisoning.
• The immediate symptom upon oral ingestion of phosphorus is EMESIS

(Hematemesis).
• Necrosis of jaw that is observed in chronic phosphorus poisoning is called as

PHOSSY JAW.
• On opening of gizzard in poultry during PM, Phosporus fumes will be noticed.
• Death Due to hypocalcemia.
• The salts of CALCIUM are employed in treatment of Phosporous.
PHYTOTOXINS
Nitrate and Nitrite
• Toxicity of nitrate is due to its conversion into NITRITE by rumen micro flora.
(Nitrites [NO2-] are 10 times more toxic than nitrates [NO3-]).
• The use of NITRATE fertilizers increases the concentration of nitrates in plants.
• Cereal grasses, Maize, Sunflower and Sorghum are nitrate accumulators.
• Silage making reduces nitrate content in forages.
• The species that are more susceptible to nitrate poisoning are RUMINANTS.
• The nitrate content in young plants is MORE than mature plants.
• Addition of SOLUBLE CARBOHYDRATES (TDN) to feed improves tolerance to

nitrate toxicity.
• The antibiotic used as feed additive that enhances conversion of nitrates to

nitrites causing poisoning is MONENSIN.

• Watering of animals immediately after consuming nitrate rich plants DECREASES
the chances of nitrate poisoning.
• Nitrite combines with hemoglobin (in1:2 ratio) to form METHEMOGLOBIN.
• The colour of blood in nitrate poisoning is CHOCOLATE BROWN / COFEE

COLOUR . (Due to methemoglobin formation).
• Physiologically formed methemoglobin (1 to 2 %) is converted back to

hemoglobin by the enzymes DIAPHORASE – I & II. (Diaphorase – I is NAD
dependent whereas DIAPHORASE – II is NADP dependent).
• When 20% of haemoglobin is converted to methaemoglobin, toxic

symptoms are noticed.
• When 80% of haemoglobin is converted, anoxia and clinical signs are
noticed and death occurs.
• Vasodilation and hypotension observed in nitrate poisoning is due to
smooth muscle relaxation caused by NITRIC OXIDE (NO).
• The respiratiory rate in nitrate poisoning is INCREASED (RAPID).
• DIPHENYLAMINE TEST – Diagnosis of Nitrate poisoning
• Specific treatment for nitrate poisoning is 1% METHYLENE BLUE.
Cyanide
• Cyanide from plant sources is present in the form of CYANOGENIC

GLYCODSIDES. (Cyanogenic glycosides are present in epidermal cells).
• Plant enzyme responsible for the release of hydrocyanic acid from cyanogenic
glycosides is β-GLYCOSIDASE. (β-glycosidase is present in mesochymal cells).
• During chopping and cutting or chewing of plants increases cyanide toxicity.
• The species that are susceptible to cyanogenic glycoside poisoning are

RUMINANTS.

• Hydrocyanic acid or prussic acid is most toxic and rapidly acting.
• The sodium and potassium salts of cyanide are slightly toxic.
• Young and immature plants, plants growing rapidly after drought, wittled
and frost bitten plants are more toxic.
• Drying the plant or making silage reduces the toxic potential of the plant.
• The use of NITRATE fertilizers increases cyanide toxicity.
• Watering animals after feeding on cyanogenic plants INCREASES toxicity.
Metabolism
• The metabolite of cyanide, which is excreted through urine is
THIOCYANATE.
• Cyanide is converted to non-toxic thio-cyanate by the enzyme

RHODANESE.
• Good reserves of SULPHUR in the body reduces the toxic effects of

cyanide.
• Cyanide inhibits cellular respiration by binding with CYTOCHROME

OXIDASE (cyta3). (Cyanide has more affinity towards metallo-porphyrin
(Fe) containing enzymes).

• The colour of blood in cyanide poisoning is BRIGHT RED. Due to non-utilization
by tissues, oxygen stays in blood giving bright colour.
• The characteristic smell of rumen contents that is suggestive of cyanide

poisoning is BITTER ALMOND.
• Chronic form of cyanide toxicity observed in humans due to consumption of

cassava root is called as KONZO.
• PICRATE PAPER TEST – Diagnosis of Cyanide toxicity
• Specific treatment for cyanide toxicity is SODIUM NITRATE followed by SODIUM

THIOSULPHATE.
Oxalate Containing Plants
• Important oxalate containing plants responsible for oxalate poisoning in animals

are HALOGETON GLOMERATUS and OXALIS PESCAPRAE.
• Halogeton species contains 34% of oxalates on dry matter basis.
• The species that is commonly affected by oxalate poisoning is SHEEP.
• The primary clinical sign in oxalate poisoning is HYPOCALCAEMIA.
• The deposition of insoluble calcium oxalate crystals in renal tubules causes

OXALATE NEPHROSIS.
• The common site for urinary obstruction in bulls and rams due to oxalate stones
is SIGMOID FLEXURE. (In rams, the oxalate crystals also deposit in urethral
process).
• In oxalate poisoning, CALCIUM salts are used as a part of the treatment.

Thiamine Deficiency Causing Plants
• Bracken fern poisoning is a result of consuming the plant PTERIDIUM

AQUILINUM.
• Cattle most commonly affected. Reports of poisoning in horses, swine, and sheep
are less frequent.
✓ Nonruminants - Horses - Mainly neurologic syndromew – B1
deficiency
✓ RUMINANTS - Cattle - Mainly bone marrow damage - Aplasia of
bone marrow – Aplastic anemia – Enzootic haematuria
• Bracken fern produces permanent blindness in SHEEP species.
• Specific treatment for bracken fern induced thiamine deficiency is
THIAMINE (Vit B1).
Abrus precatorius and Ricinus communis
• The toxicity due to seeds of Abrus precatorius is commonly referred to as SUI/
NEEDLE poisoning.
• The toxic principle in the seeds of Abrus precatorius is ABRIN and Castor is Ricin -
a type of toxalbumin /lectin (inhibit protein synthesis)
• Swallowing of seeds of abrus and castor is not toxic.
• The species that is more susceptible to abrin and ricin poisoning is HORSE.
Datura, Ipomea, Nerium
• Major tropane alkaloids present in Datura stramonium are HYOSCINE

(Scopolamine) and ATROPINE (dl-hyoscyamine).
• The toxic principles in datura are localized in SEEDS and FLOWERS.
• The species that is more sensitive to datura poisoning is PIG.
• The species that is resistant to Atropa belladonna is RABBIT. (Rabbits contains the
enzyme atropinase enzyme, which destroys atropine)
• Tropane alkaloids (atropine) act by inhibiting MUSCARINIC receptors in the body

– ATROPINE FEVER
• The toxic principle in Ipomoea turpethum (Indian jalapa or morning glory) is

TURPETHIN
• Toxic principle in Nerium oleandrum (White oleander) is OLEANDRIN, Nerin –

Cardiac glycosidal activity
Strychnous nuxvomica
• The toxic principle in Strychnous nuxvomica is STRYCHNINE.
• Strychnine is localized in SEEDS part of S.nuxvomica.
• Post synaptic neuronal Inhibition of GLYCINE neurotransmitter causes spinal

stimulation in strychnine poisoning - Increased Ach release – Spastic paralysis
• The site of action of strychnine in spinal cord is RENSHAW cells. (Recurrent

inhibitory interneuron cells of reflex arc of spinal cord).
• The characteristic appearance of animal in strychnine poisoning is SAW HORSE.

(Saw horse appearance is due to continuous tetanic seizures, which causes
rigidity. Tetanus similarly produces saw horse appearance)
Cotton seed
• The toxic principle in cotton seeds or seed cake is GOSSYPOL.
• Ruminants are not usually affected. Young calves, swine and poultry are affected.
• Gossypol binds with IRON mineral inhibiting heame synthesis and causing
anemia.
• Gossypol induced infertility is a result of LUTEOLYTIC effect on ovary.
• Presence of ferrous sulphate in the diet prevents toxicity

Calotropis gigantea
• This contains caloctin, calotropin and calotixin as toxic principles.
• It is an irritant to the gastrointestinal tract and is considered to be a
cerebrospinal poison.
Parthenium spp.,
• It is a photdynamic susbtance causing primary photosensitization, due to
the presence of toxin parthenin.
PHOTOSENSITIZATION
• The type of photosensitivity resulting from direct ingestion of photodynamic

substances or metabolically activated agents is called PRIMARY
photosensitization.

• Example for Primary photosensitization - Plants: Hypericin- Hypericium species;
Fagopyrin – Fagopyrum species; Parthenium sps; Drugs -phenothiazines,
tetracyclines, sulphonamides, acridine dyes etc)
• The type of photosensitivity resulting from hepatic damage consequent to

ingestion of hepatotoxic plants or substances is called SECONDARY /
HEPATOGENOUS photosensitization. (Eg. Pyrrolizidine alkaloid containing
plants- Senicio sps, Heliotropium sps,; Lantana camara; Mycotoxins-
Sporodesmins; Blue green algae – Microcystis sps)
• The photodynamic substance formed due to bacterial break down of chlorophyll

that is responsible for secondary photosensitization is PHYLLOERYTHRIN.
TOXICOLOGY OF AGROCHEMICALS

Organochlorine (OC) compounds
• Chlorinated hydrocarbons are known as ORGANOCHLORINE (OC) insecticides.

(Eg. DDT, BHC, Endrin etc).
• OC insecticides are not degradable and are persistent in the environment. And
due to high lipid solubility, they accumulate in the food chain and enter human
and animal bodies. Hence, OC compounds are being discouraged.
• Endosulfan and Methoxychlor are the OC insecticides is not persistent in

environment.
• The most susceptible species for OC insecticide poisoning is CAT.
• OC insecticides accumulate mainly in ADIPOSE tissue of the body.
• The only OC insecticide that does not accumulate in adipose tissue and bio-
degradable by microbes is ENDOSULFAN.
• The only isomer of benzene hexachloride (BHC) that is biodegradable is LINDANE

(Gamma isomer).
• OC compounds produce CNS excitation by prolonging DEPOLARIZATION

phase of action potential and also act by inhibiting GABA receptors.
• The sedatives of choice used in OC insecticide induced CNS excitation is

BENZODIAZEPINES (Eg. Diazepam). (Benzodiazepines also increases the affinity of
GABA to its receptors, which was previously inhibited by OC insecticides).
• Death in OC compound poisoning is due to RESPIRATORY failure.
Organophosphate (OP) compounds
• OP insecticides act as irreversible inhibitors of ACETYL CHOLINE ESTERASE

(AChE) enzyme. (AChE inhibition causes excess Ach accumulation producing
cholinergic symptoms).
• OP compounds are biodegradable and are easily destroyed by sunlight, water,

microbes, alkalis, metals etc. Hence, within 2-4 weeks of application, OP
compounds are destroyed. However, they have considerable toxicity for
mammals if consumed directly.

• DIRECT ACTING OP COMPOUNDS - have P=O (Oxon) group, hence act without
metabolic activation. Eg. TEPP, Dichlorovas, Sarin, Tabun
• INDIRECT ACTING OP COMPOUNDS - have P=S (Thionate bond) which should be

converted to P=O (Oxon) form before inhibiting AChE. Eg. Malathion, Parathion,
Chlorpyrifos (Parathion to Paraxon – Example for lethal synthesis).
• The species of animal that is highly sensitive for delayed neuropathy caused by
OP compounds (OPIDN) is CHICKEN. (Chicken brain has higher specific activity of
NTE, hence is more susceptible).
• OP compounds bind with AChE at ESTERATIC site causing irreversible inhibition.
• Phosphorylation of AChE by OP compounds resulting in irreversible bonding due

to the loss of alkyl group is called AGEING.
• The agents, which are used to reactivate AChE inhibited by OP compounds are
called OXIME REACTIVATORS (Eg. 2-PAM – Pralidoxamine).
• Oxime reactivators are ineffective in reactivating AChE inhibited by OP

compounds after AGEING stage.
• The specific antidote for OP poisoning is ATROPINE. (Atropine inhibits cholinergic

symptoms by blocking muscarinic receptors). 22. Oxime reactivators (2-PAM,
DAM) should be used within 24-36 h time before ageing of AChE.
• Use of atropine is contraindicated in CATS species, as it causes cyanosis.
Carbamates
• Carbamates have broad spectrum of activity, low in mammalian toxicity and

undergo rapid degradation in environment. Hence, carbamates are preferred for
veterinary use. (Eg. Carbaryl, Propoxur, etc).
• Insecticides that cause reversible inhibition of AChE are CARBAMATES.
• Carbamates bind with AChE at the both sites., Anionic and Esteratic.
• Specific antidote for carbamate poisoning is ATROPINE.
• Oxime reactivators are contraindicated in CARBAMATE insecticide poisoning.

(Carbamates bind with both sites of AChE leaving no room for oxime
reactivators).

Pyrethroids
• Pyrethroids are natural insecticides obtained from CHRYSANTHEMUM

flowers.
• Type I pyrethroids resemble NATURAL PYRETHRINS in their structure and

activity. (Eg. Allethrin, Pyrethrin, Permethrin etc) – T (tremor) SYNDROME
• Type II pyrethroids contain α-CYANO group in their structure and are more
active and toxic. (Eg. Deltamethrin, Cypermenthrin, Fenvalarate etc - CS
SYNDROME (Choreoathetosis and Salivation).
• The first commercial mosquito repellant pyrethroid still in use is ALLETHRIN.
• The roots of plants belonging to Derris genus are the source of natural insecticide
ROTENONE. Rotenone is highly toxic for FISH species.
RODENTICIDES
Zinc phosphide (Zn3P2)
• Toxicity of Zinc phosphide (Zn3P2) is due to the release of PHOSPHINE (PH3) gas.
• The characteristic smell of phosphine gas, which can be used for diagnosis of zinc
phosphide toxicity, is FISH LIKE or ACETYLENE.
• Zinc phosphide releases phosphine gas in Acidic pH.
• Zinc phosphide is more toxic on full stomach.
Anticoagulant rodenticides
• Bait shyness is not observed with ANTICOAGULANT rodenticides.
• Warfarin inhibits clotting factors that are dependent on VITAMIN K for synthesis.
(Vitamin K dependent clotting factors are II (Prothrombin), VII, IX and X).
• Anticoagulant rodenticides decrease vitamin K synthesis through the inhibition of

VITAMIN K EPOXIDE REDUCTASE enzyme.
• The specific treatment for anticoagulant poisoning is PHYTOMENADIONE

(Vitamin K1).

• Anticoagulant rodenticides effective against warfarin-resistant rats are SECOND
GENERATION anticoagulants. (Hence, they are also called super-warfarins. Eg.
Bromadiolone, Brodifacoum etc)
Fluoroacetate
• Fluoroacetate lowers energy production in the body by inhibiting TCA or KREBS
CYCLE.
• Fluoroacetate develops toxicity after a lag period. Hence, the rodent forgets the
exposure. Hence, Fluoroacetate rodenticide is devoid of bait shyness.
• The prominent symptoms in fluoroacetate poisoning are NEUROLOGICAL.
VITAMIN D (cholecalciferol)
• The mechanism of toxicity of vitamin D compounds (cholecalciferol) rodenticides
through the induction of HYPERCALCEMIA.
• Hypercalcemia causes calcification of visceral organs like kidney, blood vessels,
heart and lungs.
• Treatment for vitamin D rodenticide poisoning is CORTICOSTEROIDS and
CALCITONIN.
ANTU (alpha-napthyl-thio- urea)

The phrase ‘drowning in one’s own fluids’ is associated with ANTU (alpha-
napthyl-thio- urea) rodenticide poisoning. (ANTU causes leakage of fluid into
lungs leading to froth formation and death)
• Bait shyness and tolerance develops very rapidly for ANTU rodenticide.
• The main symptom in ANTU poisoning is PULMONARY EDEMA.
• Difference between pulmonary toxicity caused by ANTU (rodenticide) and

Paraquat (herbicide): ANTU causes pulmonary edema which is fatal, whereas,
paraquat causes pulmonary fibrosis which is not fatal.
Red squill
• Red squill, which is used as a rodenticide is obtained from the plant URGENIA
MARITIMA. (In south India, toxicity due to Indian squill (Urgenia indica) is more
common)
• Toxic glycosidic principle present in red squill is SCILLIROSIDE.

VENEMOUS ANIMALS
• The antigenic component in honey bee venom that causes allergies or
anaphylaxis is MELLITIN.
• The potent cytotoxin present in ant venom is FORMIC ACID.
• The piperidine alkaloid component of fire ant venom is SOLENOPSIN.
• The most potent neurotoxin in the venom of black widow spider (Lactrodectus
mactans) is α-LACROTOXIN.
• The most susceptible species for tick paralysis is DOG and the type of paralysis
seen induced by ticks is ASCENDING FLACCID.
• The most toxic toad is BUFO MARINUS – Bufo toxin
• The type of toxins present in the venom of elapidae snakes (Cobra, Krait, Mamba,
Coral snakes) are NEUROTOXINS.
• The type of toxins present in the venom of viperidae snakes (Viper, Rattle snake,
Adder) are HAEMOTOXINS.
• The neurotoxin present in the venom of kraits is α-BUNGAROTOXIN.
• The most potent among all marine toxins is TETRADOTOXIN (TTX). In snakes, the
venomous glands are homologues to PAROTID glands in other animals.
MYCOTOXINS
• Molds generally grow in stored fed stuffs containing a moisture content more
than 15%. (The other factors being a relative humidity of >85% and optimum
temperature of25-30oC i.e., without refrigeration.
• Mycotoxins may be grouped as based on their major toxic effects as
✓ mycotoxins that affect the liver – aflatoxins, sterigmatocystin, rubratoxin,

sporodesmin, penicillinic acid
✓ mycotoxins that affect the kidneys – ochratoxins, citrinin
✓ mycotoxins that cause neurological effects – fumonisins, salframin,
citreoviridin and patulin
✓ mycotoxins causing reproductive damage – zearalenone, zearalenol, and
T-2 Toxin
✓ mycotoxins producing circulatory disturbances – ergot alkaloids

Aflatoxin
• Turkey X disease is caused by AFLATOXIN mycotoxins.
• Aflatoxins are produced by ASPERGILLUS FLAVUS and A.PARASITICUS
• The most potent among the aflatoxins is AFB1.
• The order of toxicity is B1>G1>B2>G2 . Metabolites of B1 and B2 are excreted in

milk and are termed as M1 and M2 .
• Aflatoxins are heat resistant but are unstable in UV LIGHT.
• The domestic species that are highly susceptible to aflatoxicosis DUCKLINGS.
• The metabolite of aflatoxins excreted through milk and urine is AFM1.
• The carcinogenic metabolite of aflatoxins is AFLATOXIN 8, 9-EPOXIDE.
• The type of carcinoma caused by aflatoxins is HEPATOCELLULAR CARCINOMA.
Rubratoxin
• Rubratoxins are produced by PENICILLIUM RUBRUM and P.PURPUROGENUM.
• The most toxic metabolite of rubratoxins is RUBRATOXIN B. (Rubratoxin B is

hepatotoxic, mutagenic and teratogenic)
Ochratoxin
• Nephrotoxic mycotoxins responsible for mold nephrosis or mycotoxic

nephropathy are OCHRATOXINS.
• Ochratoxins are produced by ASPERGILLUS OCHRACEUS and PENICILLIUM

VIRIDICATUM.
• The most toxic among the ochratoxins is OCHRATOXIN A.
• The most susceptible species for ochratoxicosis are BIRDS and PIG.
• The site of action of ochratoxins in the nephron is Proximal Convoluted Tubule.
• The level of ochratoxin in feed should not exceed 10 PPB.

Sporodesmin
• Source : Pithomyces chartarum, formerly called Sporodesmium baker

• Facial eczema in sheep.
Zearalenone
• Estrogenic mycotoxin responsible for reproductive disorders is ZEARALENONE (F-

2). 33. Zearalenone (F-2) mycotoxins are produced by FUSARIUM ROSEUM
mold.
• The most susceptible species for zearalenone toxicosis is PIG.
• Vulvo-vaginitis or hyper-estrogenic syndrome in pigs is caused by
ZEARALENONE mycotoxin.
• The maximum permitted level of zearalenone in feed is 10 PPB.
Trichothecene
• Alimentary toxic aleukia (ATA) in human being
Ergotoxins
• Ergotoxins are produced by the mold CLAVICEPS PURPUREA. (Important ergot

alkaloids are ergotamine and ergometrine).
• Acute egotism is manifested as NERVOUS form while chronic ergotism is
manifested as GANGRENOUS form.
• In buffaloes, fusarium mycotoxins cause DEGNALA disease, which is similar to
chronic ergot posioing.
BACTERIAL TOXINS
• Botulism is most commonly seen in CHICKEN species.

• In birds, limber neck - due to paralysis of neck muscles - is caused by
BOTULINUM toxins.
• Botulinum acts as a neurotoxin by inhibiting the release of ACETYL CHOLINE

neurotransmitter. (Due to inhibition of ACh release, flaccid paralysis is seen).
• The most susceptible species for tetanus is HORSE and the species resistant to
tetanus is chicken.
• ‘Saw-horse’ or ‘Wooden-horse’ condition in horses is caused by TETANUS.

MISCELLANEOUS
• The ionizing radiation that has least penetrating capacity is ALPHA (α)-
PARTICLES.
• The ionizing radiation that has highest penetrating capacity is GAMMA (γ) RAYS.
• The SI unit of radiation is GRAY (Gy) and the CGS unit is RAD (rad).
• One Gray is equal to 100 rad. (or 1 rad = 0.01 Gy).
• ‘Chinese restaurant syndrome’ is caused by the food additive MONOSODIUM

GLUMATE (MSG).
• Antibiotics approved for use as growth promoters in food producing animals are
IONOPHORE ANTIBIOTICS. (Monensin, lasalocid and salinomycin are the
commonly used ionophore antibiotics). The most sensitive species for ionophores
toxicity is HORSE – Cardiomyopathy
• Pollutants released directly into atmosphere either through natural or

anthropogenic sources are called PRIMARY pollutants. (Eg. Carbon monoxide,
carbon dioxide etc)
• Pollutants synthesized as a result of interaction of primary pollutants in the

atmosphere are known as SECONDARY pollutants. (Eg. Ozone, Peroxyacetyl
nitrates [PAN])
• ‘Silo-fillers disease’ or ‘Silage gas’ poisoning is caused by NITROGEN DIOXIDE

(NO2).
• ‘Chick oedema’ is a characteristic clinical condition produced by PCB pollutants.
• The species that is highly sensitive for polychlorinated biphenyls (PCB) toxicity is
MINK.

SPECIFIC ANTIDOTES IN VETERINARY PRACTICE
INDICATION ANTIDOTE
Acetaminophen (Paracetamol) poisoning N-Acetylcysteine
Copper poisoning D – Penicillamine;
Ammonium molybdate
and tetrathiomolybdate
Reversal agent for Yohimbine, Atipamezole HCl
medetomidine, xylazine, and
potentially amitraz
Organophosphate poisoning Atropine sulfate, 2 PAM
Carbamate insecticide Atropine sulfate,

Lead, zinc poisoning Calcium-disodium EDTA, BAL
Cholecalciferol rodenticide Calcitonin
poisoning; vitamin D toxicosis
Iron, aluminum poisoning Deferoxamine, Mesylate
Digitalis, Digoxin poisoning; Bufo toads, Digoxin specific Antibody fragment
plants- eg., foxglove (Digitalis purpurea),
oleander (Nerium oleander)
Mercury poisoning Dimercaprol (BAL)
Ethylene glycol poisoning Fomepizole
Methemoglobinemia- Nitrate, chlorate 1% Methylene blue
poisoning; Phenol poisoning (dog and
cat)
Narcotic overdose/ poisoning Naloxone
Anticoagulant rodenticide Phytonadione (vitamin K1)
poisoning; sweet clover
(dicumarol) poisoning
Arsenic poisoning BAL, Sodium thiosulfate
Lead, mercury, arsenic poisoning Succimer (DMSA)

SAMPLE / SPECIMEN COLLECTED FOR ANALYTICAL EVIDENCES
Sample / Amount Comments

Specimen
Antemortem
Blood 5-10 ml Useful for detecting exposure to most metals, trace elements, cholinesterase, pesticides and
ethylene glycol and also for evaluating erythrocyte and leucocyte morphology
Serum 5-10 ml Useful for evaluation of electrolytes, urea nitrogen, ammonia nitrogen and organ function;
exposure to metals, drugs and vitamins. Serum should be removed from clotted blood, taking
care to avoid hemolysis
Urine 50 ml Useful for detecting exposure to alkaloids, metals, electrolytes, antibiotics, drugs,
sulphonamides and oxalates
Faeces 250 g Useful for detecting recent oral exposures or drugs or toxicants excreted primarily in bile
Vomitus 250 g Useful for detecting ingested poisons of all types, especially those that cannot be measured in
tissue ( e.g. organophosphorous compounds, ionophores)
Hair 5-10 g Useful for detecting dermal exposure to pesticides, chronic accumulation of some metals like
arsenic, selenium.
Postmortem
Liver 100 g Major oragn of biotransformation. Accumulates metals, pesticides, alkaloids, phenols and
some mycotoxins. Bile may be usesul for detecting toxicants concentrated by bile like lead.
Usually frozen till analysis
Kidney 100 g Major organ of excretion for antibiotics and other drugs, metabolized toxicants, alkaloids,
herbicides, some metals, phenolic compounds and oxalates
Stomach 500 g Confirmation of recent oral exposure of toxicant

contents
Rumen 500 g Confirmation of recent oral toxicant exposure. Rumen may degrade some toxicants like
contents nitrates and mycotoxins. Quantitative analysis is difficult as a result of variability of
concentrations and lack of correlation with toxic levels in the tissues. Samples should be
collected from several locations in the rumen and kept frozen till analysis.
Fat 250 g Useful for detection of cumulative fat-soluble toxicants like chlorinated pesticides and dioxins
Ocular fluids Entire Useful for evaluating electrolytes like sodium, calcium, potassium and magnesium, ammonia
eye nitrogen, nitrates and urea nitrogen. Ocular potassium and urea have been used to estimate
time since death. Both aqueous and vitreous humor are useful, but should be collected
separately
Brain Entire Useful for detecting some neurotoxins like chlorinated pesticides, pyrethrins, sodium, mercury.

brain Brain should be separated by midline sagittal section and the caudate nucleus collected for
cholinesterase determination. Half of the brain should be frozen and half fixed in 10% buffered
formalin
Environmental
Feeds 2 kg Multiple representative samples should be taken and then either combined and mixed for a
composite sample or retained as individual samples to detect variability in the source or both
Forages (e.g. 5 kg Samples should be taken from multiple locations in a pasture or storage facility using a forage
pasture, sampler for baled hay or stacks. Silage should be frozen to prevent mold and deterioration
hay,silage)
Baits All Entire suspected bait and label should be submitted if available
Water 0.5 – 1 L Useful for detection of nitrates, sulphates, total solids, metals, algae and pesticides. Water
should be allowed to run to clear pipes before collecting from well or storage tank. Bodies of
water from the probable site of exposure should be sampled. Water should be kept
refrigerated until analysis.
Soil /mud/ 1 kg Soil should be collected from root zone depth if plant contamination is suspected. Sampling
sediment from multiple sites may be appropriate. A soil scientist or agronomist may be contacted, if
possible.
REFERENCES
• Handbook of Veterinary Pharmacology, by Walter H. Hsu.

• Veterinary Toxicology, by Satish K. Garg
• Concepts and Concepts and Applications in Veterinary Toxicology - An
Interactive Guide bu P.K. Gupta
• Illustrated Objective Toxicology, by Alpharaj
• Veterinary Pharmacology and Therapeutics – Edited by Jim E. Riviere
• Basic and Clinical Pharmacology, by Katzung.
• Pharmacology - Exam preparatory manual for undergraduates, by G. R .Garg
& S. Gupta
• From the contents of TANUVAS E-learning.

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General Pharmacology

Oswald Schmiedberg Father of Pharmacology

Col. Ramnath Chopra Father of Indian Pharmacology

Sir James Black Father of Modern Pharmacology

John Jacob Abel Father of American Pharmacology

Paul Ehrlich Father of chemotherapy

Paracelsus Father of Toxicology

M.J.B. Orifila Father of Modern Toxicology / Modern

Scientist and their contributions

Otto Loewi : Direct proof of transmission across nerve junctions

Lundy : Coined the term balanced anaesthesia

Guede : Described 4 stages of anaesthesia with Ether

William Withering : Published his work on medicinal uses of Foxglove

Ehrlich : ✓ Coined the term chemotherapy.

Fleming : Discovered Penicillin (1928)

Walksman : Discovered Streptomycin (1944)

1 | A.E VPT AGONIST - in view of TNPSC 2020

First antibiotic : Penicillin

First local anaesthetic Cocaine for ocular anaesthesia

First i.v anaesthetic : Thiopentone

First anti-tubercular drug : PAS followed by streptomycin

William Withering : Published his work on medicinal uses of

Ehrlich : ✓ Coined the term chemotherapy.

Fleming : Discovered Penicillin (1928)

Walksman : Discovered Streptomycin (1944)

Prodrug Active drug

2 | A.E VPT AGONIST - in view of TNPSC 2020

Iatrogenic disease means physician caused disease

Pharmacogenomics means individual variation in drug action

✓ Pharmacokinetics is also called ADME study as it deals with Absorption,

Processes involved in pharmacokinetics

3 | A.E VPT AGONIST - in view of TNPSC 2020

4 | A.E VPT AGONIST - in view of TNPSC 2020

Characteristics Simple diffusion Facilitated Active transport

Incidence Commonest Less common Least common

Process Slow Quick Very Quick

Energy Not required Not required Required

• Endocytosis / Phagocytosis: It is the process by which the large

5 | A.E VPT AGONIST - in view of TNPSC 2020

It is used to calculate the percent of a drug that exists in ionized form or to

concentration of nonionized acid

concentration of ionized base

concentration of nonionized base

Acid drugs Basic drugs

✓ Intravascular administration (e.g., IV) does not involve absorption, andthere is no

6 | A.E VPT AGONIST - in view of TNPSC 2020

✓ AUC tells about the extent of absorption of the drug.

✓ Weak acids are absorbed best from the stomach

✓ Weak bases are absorbed best from the intestine

✓ Absorption is a dynamic process; absorbed drug is rapidly carried away by

✓ Most drugs are sufficiently water-soluble to be carried away by blood. This

✓ Extremely lipid soluble compounds enter the lymphatics

7 | A.E VPT AGONIST - in view of TNPSC 2020

Amount of drug in the body

Dose = Vd x Plasma concentration

Vd is the main determinant of loading dose.

1. Plasma proteins – digoxin, phenytoin

• Detoxification means decreased activity following metabolism. But it is not true

8 | A.E VPT AGONIST - in view of TNPSC 2020