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Pharmocodynamics

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PHARMACOKINETICS

Drug Metabolism

1. Biotransformation (major site is liver)

Drug Metabolite
(Active) (Inactive)
Quetiapine fumarate (Seroquel®) Sulfoxide metabolite
PHARMACOKINETICS
Excretion of Drugs

Excretion of Drugs- Process by which a drug is eliminated from the body

• Renal Excretion (in the urine)


- Primary organ for removal of most drugs, especially those that are
water-soluble and non-volatile
• In the feces
• Exhalation (through the breath)
• Perspiration, Saliva or Milk
DRUG DOSAGE FORMS –
SOLIDS
PHARMACOKINETICS
Absorption of Drugs (Entry of drug into bloodstream)

Dosage forms:
• Liquids (solution, elixir, suspension)
• Tablets (for swallowing and/or chewing)
• Coated tablets
• Capsules
• Caplets
• Time-Release Capsules
• Immediate-Release Capsules
Drug forms-Solutions
Oral dosage forms comprise liquids (solutions, suspensions, and
emulsions), semi-solids (pastes), and solids (tablets, capsules, powders,
granules).

A solution
- is a mixture of 2 or more components that form a homogeneous
mixture.
Advantages of solutions over other dosage forms.
- absorbed faster
- cause less irritation of the GI mucosa.
- Oral solutions provide a convenient means of drug administration
to neonates and young animals.
Drug forms-Solutions
Disadvantages of solutions over other
dosage forms:
- susceptibility to microbial
contamination
- hydrolysis in aqueous solution of
susceptible active ingredients.
- In addition, the taste of some drugs is
more unpleasant when in solution.
Drug forms- Suspensions
A suspension is a coarse dispersion of
insoluble drug particles, generally with a
diameter exceeding 1 µm, in a liquid (usually
aqueous) medium. Particle size is an important
determinant of the dissolution rate and
bioavailability of drugs in suspension. In
addition to the excipients described above for
solutions, suspensions include surfactants and
thickening agents.
Drug forms- Suspensions
 Advantages of using suspensions over other dosage forms:
 - Useful for administering insoluble or poorly soluble drugs
 - or in situations when the presence of a finely divided form of
the material in the GI tract is required.
 - The taste of most drugs is less noticeable in suspension than
in solution, due to the drug being less soluble in suspension.
 - Surfactants wet the solid particles, thereby ensuring the
particles disperse readily throughout the liquid.

 Disadvantages : Suspensions rely on the use of thickening


agents and thickening agents reduce the rate at which particles
settle to the bottom of the container.
Drug forms - Tablets
 Tablet -uncoated or coated.
Uncoated tablets are generally chewable, effervescent,
lozenge, soluble and sublingual tablet.
Chewable tablet-
The tablet which is intended to be broken and chewed
in between the teeth before ingestion. Antacid and
vitamin tablets are usually prepared as chewable
tablets. It is also given to the children who have
difficulty in swallowing and to the adults who dislike
swallowing.
Drug forms - Tablets
Coated tablets are enteric coated, film coated,
implant, sugar coated and modified-release tablet.
A broken section of a coated tablet shows a core
which is surrounded by a continuous layer of a
different texture. The reasons for coating a tablet
are:
a) protection of the active ingredients from air,
moisture, light,
b) to mask the unpleasant tastes and odor; and
c) to improve appearance
Drug forms- Tablets
 Sugar coating
 - Maybe coated with coloured or uncoloured sugar layer.
 Coating is water soluble and quickly dissolves after swallowing.
 Advantages
 protects the enclosed drug from the environment and provides a barrier to
objectionable taste or order.
 - Enhances the appearance of the compressed tablet and permit imprinting
manufacturing’s information.
 Sugar coating provides a combination of insulation, taste masking,
smoothing the tablet core, colouring and modified release.

 Disadvantages
 - The disadvantages of sugar coating are the time and expertise required in
the coating process and thus increases size, weight and shipping costs.
Sugar coating increases the weight by 30-50%
Drug forms- Tablets
 Film Coating - Film coating is deposition of a thin
film of polymer surrounding the tablet core.
 -More favored over sugar coating. Weight increases by 2-
3%

 Advantages:
 - improved packaging efficiency,
 - prevention of cross contamination
 - reduced tablet breakage and chipping.

And with a large variety of pigmented and non-pigmented tablet


film coating systems available, the products can be coded in a
color of choice with a cost-effective coating that can also provide
protection from light, moisture and environmental gases.
Drug forms - Tablets
Enteric Coating
 This type of coating is used to protect tablet core from
disintegration in the acid environment of the stomach
for one or more of the following reasons:
 i) To prevent degradation of acid sensitive API (Active
pharmacological ingredient)
 ii) To prevent irritation of stomach by certain drugs like
sodium salicylate
 iii) Delivery of API into intestine

 iv) To provide a delayed release component for repeat


action tablet
Drug forms - Capsules
 What Is A Capsule?
- Capsules are easier to swallow and are
used by manufacturers when the drug
can’t be compacted into a solid tablet.
They are also useful when the drug needs
to be mixed with oil or other liquid to aid
absorption in the body. It is normally a
shell or container made of gelatin that
contains the drug.
Drug forms - Capsules
 There are two types of capsules, hard or soft.
- Hard capsules- Hard capsules, which are
more commonly seen, are made up of a
rigid shell in two pieces that fit together
and is then filled with the drug. This
formulation is normally more suitable for
drug powders and can only be used if the
drug will be easily dissolved in the
stomach.
Drug forms - Capsules
 Soft capsules
- formed in a single piece and are more suitable for oils e.g. Fish
oils, or drugs that need to be dissolved in oils or other liquids to
aid the drug to be absorbed in the stomach. In soft capsules the
drug is combined with an appropriate solvent in the centre of the
capsule and the capsule shell melts within minutes in the stomach.
Drugs are easily absorbed from these mixtures offering two distinct
advantages;
- 1) quicker effect, which is good for immediate pain relief,
- 2) Drug is absorbed more effectively, so lower doses can be used
which in turn means the soft capsules can be made smaller,
making swallowing easier
Drug forms - Caplets
A caplet is a tablet that has
shape of a capule, it is easier to
swallow compared to a tablet
and therefore is suitable when a
large dose of a drug needs to be
given
ROUTES OF DRUG ADMINISTRATION
Route of Drug administration
The route of administration (ROA), that is chosen may have a
profound (great) effect upon the speed and efficiency with which
the drug acts.
The ROA is determined
by the physical characteristics of the drug,
the speed which the drug is absorbed and/ or released,
as the need to bypass hepatic metabolism and achieve
high conc. at particular sites
No single method of drug administration is ideal for all drugs in all
circumstances
ROUTES OF DRUG ADMINISTRATION

Oral ingestion

• Most common and convenient


• Good for self administration
• May produce irritation leading to vomiting
• Most economical
• Many variations of dosage forms
• Food in stomach will effect absorption (/)
• Subject to first past effect
Oral dosage
Orally lot of different formulations can be administered
capsule, tablets, syrups
 Disadvantages

 -Sometimes inefficient - only part of the drug may be


absorbed

 First-pass effect - drugs absorbed orally are initially


transported to the liver via the portal vein

 Some times only 5 % of the drug is finally available because of


the first pass effect
First-pass Effect
First-pass Effect

The first-pass effect is the term used for the


hepatic metabolism of a pharmacological
agent when it is absorbed from the gut and
delivered to the liver via the portal circulation.
The greater the first-pass effect, the less the
agent will reach the systemic circulation when
the agent is administered orally
ROUTES OF DRUG ADMINISTRATION

Inhalation

• Drug administered via the lungs


• General anesthetics (gases)
• Solution of drugs in aerosol (for bronchial asthma)
• Almost instantaneous absorption
• Can’t regulate the dose of drug
• Drug can cause pulmonary irritation
ROUTES OF DRUG ADMINISTRATION
Parenteral Administration (by injection)

• Used when it is desired to bypass the GI tract


• Commonly implies the use of a syringe and a needle
Parenteral Administration
 All though all these routes use a syringe and needle , the place
where the needle is inserted is important, so in the next slide
you will see cross section of the skin. The skin has three
layers, epidermis, dermis and hypodermis, which is also
called the subcutaneous layer. Below these 3 layers is blood
supply and muscle, so if the needle by passes the three layers
and is inserted into the vein the route is called the intravenous
route. If the needle is inserted in the muscle it is called the
intramuscular route and if the needle is inserted in the third
layer of the skin it is called subcutaneous administration. So
technique wise which one do you think among these three is
the hardest?
 IV is the hardest, of course.
 IM and SC routes are used routinely by patients to self
administer.
ROUTES OF DRUG ADMINISTRATION

Intravenous (i.v.)

• Drug is placed directly into the blood stream by i.v. injection


• Rapid onset of action (within 30-60 seconds)
• Problem concerned with absorption are circumvented (avoided)
• Suitable for large volumes and for drugs that are irritating
(i.v. infusions in hospitals)
• Precise control of the dose
• Valuable for emergency use
• Increased risk of adverse effects
• Drug must be water soluble
• Once injected a drug can’t be removed
ROUTES OF DRUG ADMINISTRATION
Subcutaneous (s.c.)

• Injection underneath the skin


• Suitable for insoluble suspensions
• Subcutaneous implants- slow release medications
• If drug is irritating agent, pain may occur

The subcutaneous route is used for


many protein drugs because such
drugs would be digested in the
digestive tract if they were taken
orally.
ROUTES OF DRUG ADMINISTRATION

Intramuscular (i.m.)

• Injected into the muscle


• Irritating drugs may be given this way
• Pain at injection site for certain drugs

Muscle is less richly


supplied with sensory
nerves hence mild
irritants can be injected.
It has more vasculature
hence absorption is
faster
ROUTES OF DRUG ADMINISTRATION

Intradermal

• Injection into the layers of the skin


• Used for diagnostic tests
ROUTES OF DRUG ADMINISTRATION

Intrathecal

• Injection into the fluid surrounding the spinal cord


• Difficult to administer
• Drug has local and rapid effect in the CNS
• Spinal anesthesia administer this way
ROUTES OF DRUG ADMINISTRATION

Body Orifices (Openings)

• Eye, ear, nose drops


• Sublingual (underneath the tongue)
• Vaginal inserts
• Rectal suppositories
ROUTES OF DRUG ADMINISTRATION

Skin Application

• Ointments
• Sun protective lotion
• Local anesthetics
ROUTES OF DRUG ADMINISTRATION
Transdermal Systems

• Skin patch (worn on a convenient area of the body


from which the drug is absorbed into blood)
- Nitroglycerine
- Ortho Evra
ROUTES OF DRUG ADMINISTRATION
Implantable Drug Delivery Systems

• May reduce the risk of infection compared to the long-term use


of external systems
• Does not restrict daily activities
• Can adjust doses non-invasively, minimizing patient discomfort
• Can deliver different doses at various times of the day-
meeting patients' changing needs
- e.g. Norplant
Time for onset of drugs by various ROA

intravenous 30-60 seconds


inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular 10-20 minutes
subcutaneous 15-30 minutes
rectal 5-30 minutes
ingestion 30-90 minutes
Overview of Lectures

Physiological/pathological basis of
inflammation, fever and pain.

Pharmacology of nonprescription pain relievers.


Inflammation
The main function of inflammation
is to destroy or inactivate foreign
invaders and to set the stage for
tissue repair. The key mediators of
inflammation are the cells that
function as phagocytes -(WBC’s).
Physiology of Inflammation
 Inflammatory response can be caused by:
Microbial agents
Noxious chemicals
Thermal or other physical trauma

 Process involves dilation of blood vessels and


leakage of inflammatory cells into site of injury.

 Clinical signs: erythema (redness, Rubor), edema


(swelling, Tumor), heat (Calor) and pain (dolor).
Inflammation- Characteristics
1. Inflammation is the body’s local response to infection or injury.

2. Inflammation can be caused by a variety of reasons –

Microbial agents
Noxious chemicals
Thermal or other physical trauma
Anything ending with the word “itis” means inflammation so
inflammation in the brain is called meningitis, inflammation of
the liver is called hepatitis, and inflammation of the joints is
called arthritis.
Inflammation- Characteristics
3. Inflammation can also occur if you burn yourself or
have a physical injury.
4. Inflammation is characterized by redness, swelling,
heat and pain. All these characteristics of inflammation
are induced and regulated by a huge number of
chemical mediators.
5. Injuries due to noxious chemicals can also cause
inflammation - say for example harsh chemicals when
come in contact with the skin lead to irritant contact-
dermatitis.
Physiology of Inflammation
 Main mediators of inflammatory process are
biochemicals - histamine, 5-hydroxytryptamine,
prostaglandins and bradykinins.

 Vascular changes cause redness, local heat and


edema (Prostaglandins, bradykinin, histamine).

 Tissue components cause pain (due to combined


effects of bradykinin, 5-hydroxytryptamine,
prostaglandins and histamine).
Physiology of Inflammation
1. Our blood has three types of cells -WBC’s; RBC’s and platelets-
Functions
2. Our blood has special cells called the white blood cells, which are
traveling all over the body and trying to find out if a foreign
particle is trying to invade our body, they are like the army of
our body preventing any invasion to occur from outside. So
whenever they recognize a pathogen, the WBC’s release many
chemicals at the site of infection to destroy that pathogen.
3. There are other ways to damage body cells other than bacterial
infection, for example if you cut yourself. Platelets, the
components of the blood that are responsible for blood clotting,
release chemicals that not only cause clotting but also
inflammation – this is how you can have inflammation without
infection.
Physiology of Inflammation
4. Once the inflammation occurs, several things happen that
explain the symptoms that are associated with
inflammation.
5. Many of these chemical mediators are potent vasodilators
– cause the blood vessels to open to their widest
diameters. The process of vasodilatation increases the
blood flow to the inflamed area. Increased blood flow
allows more nutrients and more WBC’s to reach the
affected area and speeds the healing process.
6. Blood is red and hot and that explains the redness and
the heat that is associated with inflammation.
Histamine
 Chemical mediator of a wide variety of cellular
responses including allergic and inflammatory
reactions, and gastric acid secretion.
 High concentrations found in lungs, skin and the
gastrointestinal tract. Commonly stored in mast cells.
 Destruction of cells as a result of cold, bacterial
toxins, trauma, etc.
 Histamine is released in essentially every tissue of the
body if
- the tissue becomes damaged or inflamed
 - or is the subject to allergic reaction,
5-Hydroxytryptamine
 Serotonin (or 5-hydroxytryptamine) is derived from
the amino acid tryptophan.

 Present in gastrointestinal tract (about 90% of total


body serotonin is present in this tissue), platelets and
serves as a neurotransmitter in the central nervous
system.

 Major physiological/pharmacological action is the


stimulation of nociceptive (pain-mediating) sensory
nerve endings.
Bradykinin
 Bradykinin is a vasoactive peptide that may be
involved in the process of inflammation.

 Formed by the action of an enzyme on protein


substrates (kininogens) in the plasma.

 Can cause vasodilatation and increased vascular


permeability.

 Can stimulate pain nerve endings.

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