ACETYLCHOLINE

AUTONOMIC DRUGS
Dr. Paguirigan (August 23, 2019)
 is a prototype of drug that acts directly at both
4 GROUPS: the muscarinic and nicotinic receptors
1. CHOLINOCEPTOR-ACTIVATING &  spectrum of action: both Muscarinic and
CHOLINESTERASE INHIBITING DRUGS Nicotinic receptors
2. CHOLINOCEPTOR-BLOCKING DRUGS  rapidly hydrolyzed by cholinesterase
3. ADRENOCEPTOR-AGONIST &  duration of action: 5 - 30 seconds
SYMPATHOMIMETIC DRUGS METHACOLINE
4. ADRENOCEPTOR-ANTAGONIST DRUGS
 acetyl-β-methylcholine
CHOLINOCEPTOR-ACTIVATING &  pharmacologically similar to Acetylcholine
CHOLINESTERASE INHIBITING DRUGS
CARBACHOL
2 GROUPS:
 spectrum of action: both Muscarinic and
1. DIRECT-ACTING CHOLINOCEPTOR Nicotinic
STIMULANTS  resistant to cholinesterase
2. INDIRECT-ACTING CHOLINOMIMETICS/  orally active
CHOLINESTERASE INHIBITORS  has poor lipid solubility
 duration of action: 30 minutes – 2 hours
DIRECT-ACTING CHOLINOCEPTOR STIMULANTS
BETHANECOL
 also called direct-acting cholinomimetic agents
 they bind to and they activate the Muscarinic  spectrum of action: both Muscarinic and
or Nicotinic receptors Nicotinic; but more on Muscarinic receptor
 further subdivided into 2 subgroups:  has the same pharmacologic feature as
Carbachol
CHOLINE ESTERS
o include: PILOCARPINE
 Acetylcholine  spectrum of action: Muscarinic
 Methacoline- acetyl-β-  not an ester; more of an alkaloid
methylcholine  has a good lipid solubility
 Carbachol- carbanoyl choline  duration of action: 30 minutes – 2 hours
 Bethanecol- carbanyl-β-
methylcholine NICOTINE

CHOLINOMIMETIC ALKALOIDS  also acts on the Periperheral Nervous System

o either muscarinic or nicotinic  there is an initial stimulation and
o include: subsequently there is a major persistent
 Muscarine depression of all the autonomic ganglia
 Pilocarpine  also causes the release of cathecolamine in a
 Nicotine number of isolated organs
 Lobeline  effects on the neuromuscular junction are
similar to those of the ganglia
 also stimulates a number of sensory receptors
and this includes:

Acebedo, Cruz, Davis, Duran, Salucon, Uy 1

 o Methanoreceptor- respond to stretch or  if it is given via IV bolus injection it can cause
pressure on the skin, the mesentery in the transient bradycardia; otherwise it will
tongue, lungs, stomach produce reflex tachycardia
o Chemoreceptors- in the carotid body
o Thermal receptors- in the skin and tongue
and also some pain receptors INDIRECT-ACTING CHOLINOMIMETICS/
 perfectly stimulates the Central Nervous CHOLINESTERASE INHIBITORS
Sytem (CNS)
 on the Cardiovascular System, it increases the  has primary effect at the active site of
heart rate and the blood pressure acetylcholinesterase while some ahve direct
 on the Gastrointestinal Tract, it increases the actions at the Nicotinic receptors
tone and motor activity of the bowel  drugs include:
 in the exocrine glands, Nicotine has an initial  Neostigmine
stimulation of the salivary and bronchial  Physostigmine
secretion followed by inhibition  Carbaryl
 readily absorbed from the respiratory tract  Edrophonium
(major source of Nicotine is cigarette) from the  Ambenonium
buccal mucosa and skin  Demecarium
 about 80-90% of the Nicotine that we take in  NEOSTIGMINE, PYRIDOSTIGMINE, and
is altered in the body mainly in the liver but AMBENONIUM
some are also metabolized in the kidney and o are standard anticholinesterase drugs that
lungs are used as symptomatic treatment for
 half life after inhalation or parenteral “myasthenia gravis”; these are reversible
administration is about 2 hours anticholinesterase drugs
 both Nicotine and its metabolite are rapidly o also used in the reversal of neuromuscular
eliminated by the kidney via renal elimination blocking
 the rate of urinary secretion is dependent on o dosage:
the pH of the urine; there is decreased rate of Neostigmine = 7.5mg
elimination if the urine is alkaline Pyridostigmine = 30mg
 the major metabolite of Nicotine are Cotinine Ambenonium = 2.5mg
and nicotine-N-oxide
 Nicotinic toxicity:  has 2 major chemical classes:
o stimulation of the CNS and ganglion
o neuromuscular end plate depolarization CARBAMIC ACID ESTERS/ CARBAMATES
which will lead to fasciculations and o prototype: NEOSTIGMINE
paralysis o are hydrolyzed; and the carbamate
Muscarinic Toxicity: residue is released by cholinesterase
o stimulation of CNS (uncommon) over a period of 2-8 hours
o produces myosis
o spasm of accommodation PHOSPHORIC ACID ESTERS/
o bronchoconstriction ORGANOPHOSPHATES
o increase GIT and urinary tract smooth o prototype: ECHOTHIOPHATE
muscle activity  long acting cholinesterase inhibitors
o increase activity in the sweat glands,  include:
airways and GIT  ECHOTHIOPHATE
 PARATHION

Acebedo, Cruz, Davis, Duran, Salucon, Uy 2

  MALATHION PYRIDOSTIGMINE
 SOMAN
 PARAOXON  use:
 MALAOXON o for myasthenia gravis
 form an extremely stable phosphate  duration of action: 3-6 hrs
complex with the enzyme
 released over a period of many days or CARBARYL
even weeks
 effects: cause an increase in the  used as an insecticide
concentration and half-life of acetylcholine
especially in the synapses where EDROPHONIUM
acetylcholine is realeased physiologically  not an ester but an alcohol
 these cholinesterase inhinbitors do not  uses:
have therapeutic actions in parts of the o for the diagnosis of “myasthenia gravis”
body where acetylcholine is not normally o Ileus
released
o Arrhythmia
Other group:  duration of action: 5-15 mins

ALCOHOL ECHOTHIOPHATE
o EDROPHONIUM
 amplifies the effects of acetylcholine
 use:
o anti-glaucoma drug
DRUGS USED AS CHOLINESTERASE INHIBITORS  duration of action: 100 hours
NEOSTIGMINE MALATHION
 is a typical ester  is an insecticide but it is used as scabicide for
 amplifies the endogenous acetylcholine medical use (for scabies)
 uses:
o post-operative and neurogenic ileus PARATHION
o urinary retention
 one of the most toxic
o reversal of neuromuscular blocking
 rapidly fatal if the exposure is not immediately
o Ileus
recognized and treated
o Myasthenia gravis
 if there is an inadvertent exposure to this
 duration of action: 30 min- 2 hrs
drug, treatment used is a Regenerator
PHYSOSTIGMINE Compound like PRALIDOXIME
o this can be used if given early
 naturally-occurring carbamate  signs and symptoms of toxicity are the same
 amplifies the effects of acetylcholine as the toxicity during direct-acting drugs
 use: except for the following: Parathion may cause
o for glaucoma o Vasodilation- late and uncommon
 duration of action: 30 minutes- 2 hours o Bradycardia and CNS stimulation- more
common

Acebedo, Cruz, Davis, Duran, Salucon, Uy 3

METRIFONATE B. DIRECT-ACTING MUSCARINIC ALKALOIDS
(SYNTHETICS)
 antihelminthic drug
PILOCARPINE
 Effects of indirect-acting cholinomimetics/
cholinesterase inhibitors :  like Bethanechol--partial agonist

D -diarrhea CEVIMELINE

U -urination  synthetic M3 selective

 similar to Pilocarpine
M - miosis

B - bronchoconstriction
C. DIRECT-ACTING NICOTINIC AGONISTS
E – excitation of skeletal muscles and CNS
NICOTINE
L - lacrimation
 agonist of both Nn and Nm receptors
S - salivation
VARENICLINE
AMBENONIUM
 selective partial agonist of both alpha-4 and
 use: beta-2 nicotinic receptors
o Myasthenia gravis  use: exclusively for smoking cessation
 duration of action: 4-8 hours

DEMECARIUM
D. SHORT- ACTING CHOLINESTERASE INHIBITORS
 use: (ALCOHOLS)
o Glaucoma
EDROPHONIUM
 Duration of Action: 4-6 hrs
 only drug under this category
DRUGS THAT ARE USED FOR CHOLINOMIMETIC
 alcohol
EFFECTS
 binds briefly to the active site of
A. DIRECT-ACTING CHOLINE ESTERS acetylcholinesterase and prevents the access
of acetylcholine
BETHANECHOL

 muscarinic agonists

CARBACHOL

 non-selective muscarinic and nicotinic agonist

Acebedo, Cruz, Davis, Duran, Salucon, Uy 4

E. INTERMEDIATE- ACTING CHOLINESTERASE CHOLINOCEPTOR BLOCKING DRUGS
INHIBITORS (CARBAMATES)
ANTIMUSCARNIC DRUGS
NEOSTIGMINE
ATROPINE
 forms a covalent bond with
acetylcholinesterase but it is hydrolyzed and it  prototype of naturally occurring compounds
is released with antimuscarinic effects

PYRIDOSTIGMINE PROPANTHELINE

 like Neostigmine in pharmacologic action  quaternary amine

 but has longer action, longer-acting
PIRENZEPINE
 duration of action: 4-6 hrs
 use: for myasthenia gravis  tertiary amine
 use: peptic ulcer diseases
PHYSOSTIGMINE
TROPICAMIDE
 like neostigmine but a natural alkaloid
 a tertiary amine  tertiary amine
 enters the CNS  use:
o mydriatic action
o cycloplegic action
F. LONG- ACTING CHOLINESTERASE INHIBITORS
GLYCOPYRROLATE
(ORGANOPHOSPHATES)
 quaternary amine
ECHOTHIOPATE
DICYCLOMINE
 like Neostigmine, but released more slowly
 tertiary amine
MALATHION
 use:
 insecticide but relatively safe for mammals o peptic ulcer diseases
and birds o GI hypermotility

PARATHION TIOTROPIUM

 insecticide and very dangerous to all animals  quaternary amine

 use: asthma
SARIN
BENZTROPINE
 nerve gas
 use: exclusively for warfare and terroristic  tertiary amine
activities  use: Parkinson’s disease

Acebedo, Cruz, Davis, Duran, Salucon, Uy 5

 ANTIMUSCARINIC DRUGS USED IN MUSCARINIC ANTAGONISTS (MUSCARINIC
OPTHALMOLOGY BLOCKERS)

1. ATROPINE A. NON-SELECTIVE
2. SCOPOLAMINE a. ATROPINE – prototype
3. HOMATROPINE b. SCOPOLAMINE
4. CYCLOPENTOLATE c. GLYCOPYRROLATE
5. TROPICAMIDE d. IPRATROPIUM
e. CYCLOPENTOLATE
ANTIMUSCARINIC DRUGS USED IN
f. BENZTROPINE
GASTROINTESTINAL AND GENITOURINARY
g. HOMATROPINE
CONDITIONS
h. METHYLSCOPOLAMINE
A. QUATERNARY AMINES i. TROPICAMIDE
a. ANISOTROPINE B. M1 SELECTIVE
b. CLIDINIUM a. PIRENZEPINE
c. GLYCOPYRROLATE b. TELENZEPINE
d. ISOPROPAMIDE
ATROPINE
e. MEPENZOLATE
f. METHANTHELINE  Prototype drug
g. METHYLSCOPOLAMINE  alkaloid found in Atropa belladonna and many
h. OXYPHENONIUM other plants
i. PROPANTHELINE  tertiary amine
j. TRIDIHEXETHYL  relatively lipid-soluble
k. TROSPIUM  readily crosses the membrane barrier
B. TERTIARY AMINES  well distributed in the CNS and other organs
a. ATROPINE  eliminated by hepatic or liver metabolism and
b. DARIFENACIN partly by renal excretion
c. DICYCLOMINE  elimination half-life: about 2 hours
d. OXYBUTYNIN  duration of action: 4-8 hours except in the
e. OXYPHENCYCLIMINE eyes where the action lasts for 72 hours or
f. PROPIVERINE longer
g. SCOPOLAMINE  moa: muscarinic blocking drug that acts as a
h. SOLIFENACIN competitive(or surmountable) pharmacologic
i. TOLTERODINE antagonists
o blocking effect could be overcome by
GANGLION-BLOCKING DRUGS
increasing the concentration of
1. HEXAMETHONIUM muscarinic agonist
2. MECAMYLAMINE  effects: same ocular, GI, genitourinary and
3. TETRAETHYLAMMONIUM secretory effects as cholinoceptor blocking
4. ACETYLCHOLINE drugs

Acebedo, Cruz, Davis, Duran, Salucon, Uy 6

 CNS  Sedation effects and very low/few
 Amelioration of motion antimuscarinic effect
sickness outside the lungs
 Reduction of signs of because it is poorly
Parkinsonism absorbed and is rapidly
CVS  Initial bradycardia followed by metabolized
tachycardia
 Reduction of AV conduction
time D. GENITOURINARY TRACT
EYES  Cycloplegia
 Mydriasis ATROPINE  Reduce acid
LUNGS  Bronchodilation METHSCOPOLAMINE secretion but less
SECRETIONS  Reduction of salivation, PROPANTHELINE effective than
lacrimation, sweating and other H2 blockers
gastric secretion like Cimetidine
SKELETAL  No effect PIRENZEPINE  New muscarinic
MUSCLES drug
 Selective
muscarinic blocker
CLINICAL USES OF MUSCARINE BLOCKERS  Use: Peptic Ulcer
Diseases
A. CNS

SCOPOLAMINE  Motion sickess E. GIT

BENZTROPINE  Parkinsonism  Muscarinic blocker that reduces cramping and
BIPERIDEN hypermotility in transient diarrhea but
TRIHEXYPHENIDYL DIPHENOXYLATE or LOMOTIL is more effective
BENZTROPINE (given  Acute dystonic caused
parenterally) by antipsychotic F. BLADDER
medications

GLYCOPYRROLATE  Reduce the

B. EYES OXYBUTYNIN urgency and
ATROPINE 72 hrs Dilate the METHYLSCOPOLAMINE mild cystitis
HOMATROPINE 24 hrs pupil
 Reduce bladder
CYCLOPENTOLATE 2-12 hrs
spasm followed
TROPICAMIDE 30 min-4 hrs
by neurologic
surgery
C. BRONCHI
ATROPINE  Reduce the airway
secretion especially Mnemonics for Atropine Toxicity:
during surgery
IPRATROPIUM  Inhalation: reduce “Dry as a bone, red as a beet, mad as a hatter,
bronchoconstriction in blind as a bat”
asthma and COPD
 Has less arrhythmic side
Acebedo, Cruz, Davis, Duran, Salucon, Uy 7
*These descriptions will reflect both predictable  Classified into 2 groups:
antimuscarinic effect and some of the
unpredictable actions of Atropine” 1. Drugs that initially stimulate the ganglia by
ACh-like action then blocks the ganglia
The predictable toxic reactions are because of persistent depolarization
Eg. Nicotine – most popular drug that
 Hyperthermia or atrophic fever because of the
gives this action
blockade of the thermoregulatory sweating
 prolong application results in
mechanism. This effect can be fatal in infants.
desensitization of cholinergic
 In adults, sweating salivation and lacrimation
receptor sites and there will be
are all significantly reduced or even stopped
continuous blockade
by Atropine
 In the elderly, it can also produce acute angle drugs that do not involve prior ganglionic
glaucoma and urinary retention stimulation or change in the ganglionic potential
 Constipation and blurred vision are seen in all
age groups 2. Drugs that impair transmission either by
competing with ACh or ganglionic
Other toxic reactions of Atropine cholinergic receptor sites or blocking the
channels when it is open (drugs that do not
A. CNS
involve prior ganglionic stimulation or
 Sedation
change in the ganglionic potential)
 Amnesia
Eg. Hexamethonium, Trimethaphan -
 delirium or hallucination (“mad as a
prototypes
hatter”)
 convulsions HEXAMETHONIUM & RELATED DRUGS
B. CVS
 intraventricular conduction blockade  Effects on CVS
 dilation of the cutaneous blood vessels  postural hypotention, sympathetically-
especially in the arm, head, neck and mediated vasomotor reflexes that are
trunk --Atropic flash (this sign may be inhibited and they also reduce the cold
diagnostic for overdose of Atropine); pressor response
“red as a beet”  Mild tachycardia that accompanies
hypotension
Contraindication/Cautions  Reduced cardiac output as a result of
diminished venous return due to
 Infants – danger of hyperthermia
venous dilatation and peripheral
 Patients with glaucoma (especially closed
pooling of blood
angle glaucoma)
 In Hypotension – CO, SV and left
 Men with Prostatic Hyperplasia
ventricular work are all diminished
 Total systemic vascular resistance is
decreased but the blood flow and
NICOTINIC ANTAGONISTS vascular resistance (vascular beds are
variable)
 Skin temperature is elevated mostly in
GANGLION BLOCKING DRUGS
head and feet
 Impair the actions of primary nicotinic  Blood flow into limbs is increased
receptors

Acebedo, Cruz, Davis, Duran, Salucon, Uy 8

  Reduced cerebral blood flow – minimal NEUROMUSCULAR BLOCKING DRUGS
unless the mean systolic BP falls below
50-60 mmHg A. Non-depolarizing Group
 Skeletal muscle blood flow is unaltered  Includes Tubocurarine, Pancuronium,
 Splanchnic and renal blood flow are Atrocurium – neuromuscular blocking
decreased drugs
 Ganclion blocking drugs are not anymore
 Renal vascular resistance is increased
clinically used because of severe serious
 Glomerular filtration is decreased
side effects like:
 Cyclopegia
 severe constipation
 Other effects  reduced bladder contractility
 GIT secretions are decreased  impairment of erection and
 Tone and motility of GIT are reduced ejaculation
 Partial impairment of voiding and  tachycardia
contraction of the urinary bladder  reduced CO
 Penile erection and ejaculation are  reduced venous tone
impaired  decreased BP
 Mydriasis partial loss of  orthostatic hypotension
accommodation  reduced salivation
 Sweating is reduced  lacrimation
 sweating
 Clinical Uses  GI secretion
 Used as an emergency drug in
hypertensive crisis  The neuromuscular blocking drugs are
 Initial control of BP in acute dissecting important for producing complex skeletal
aortic aneurysm muscle relaxation especially during surgery
 Production of controlled hypotension
Other drugs:
TRIMETHAPHAN  Vecuronium
 Gallamine
 management of autonomic hyperreflexia
TUBOCURARINE

 prototype
OTHER GANGLIONIC BLOCKING DRUGS
 causes flaccid paralysis that can last for 30 – 60
minutes
1. Mecamylamine
2. Trimethaphan PANCURONIUM, ATROCURIUM, VECURONIUM
3. Pempidine
4. Pentolinium  shorter acting non-depolarizing blockers

GALLAMINE

 old drug that is now rarely used

Acebedo, Cruz, Davis, Duran, Salucon, Uy 9

B. Depolarizing Group  Also classified according to MOA and spectrum
of activity
SUCCINYLCHOLINE

 only member of the group that is used 1. ENDOGENOUS CATECHOLAMINES

clinically  Epinephrine
 produces fasciculations during induction of  Norepinephrine
paralysis  Dopamine
 hydrolyzed by pseudocholinesterase or plasma
cholinesterases
 Half life: few minutes 2. DIRECT – ACTING SYMPATHOMIMETICS
 duration of action: may be prolonged in PHENYLEPHRINE
patients with genetically determined
abnormality in cholinesterase  longer duration of action than the
catecholamines
 Effective mydriatic and decongestant
In case of cholinesterase overdose, you can use a
cholinesterase regenerator: MIDODRINE

PRALIDOXIME  prodrug
 selective alpha-1 receptor agonist
 prototype drug
 Used in cholinesterase overdose METHOXAMINE
 cholinesterase regenerators are not receptor
antagonist but are chemical antagonists  predominantly direct-acting alpha-1 receptor
 contain an “–oxime” group which has an agonist
extremely high affinity for phosphorous atom CLONIDINE, METHYLDOPA, GUANFACINE,
in organophosphate insecticides GUANABENZ
 Because of high affinity for phosphorous
excess that of the enzyme active site, these  alpha selective agonist
agents will be able to bind to inhibitor and  used in treatment of hypertension
displace the enzyme – so the active enzyme
will be regenerated MOXONIDINE OR RILMENIDINE

 also used for HTN

DEXMEDETOMIDINE
ADRENOCEPTOR ANTAGONISTS AND
SYMPATHOMIMETIC DRUGS  produces sedation
 initial sedation needed for intubated patients
 Sympathomimetic drugs – these drugs mimic
or imitate stimulation of sympathetic ANS TIZAMIDINE
 Classified as:
 Endogenous Catecholamines  central muscle relaxant
 Direct – acting Sympathomimetics XYLOMETAZOLINE AND OXYMETAZOLINE
 Mixed – acting Sympathomimetics
 Indirect-acting sympathomimetics  direct acting alpha agonist
 Dopamine Agonists  used only as topical decongestant

Acebedo, Cruz, Davis, Duran, Salucon, Uy 10

ISOPROTERENOL (ISOPRENALINE)  Duloxetine
 Milnasipram
 very potent beta receptor agonist with very  Cocaine
little effect on alpha agonist

DOBUTAMINE AND PRENALTEROL ATOMOXETINE

 frequently seen to cause ORTHOSTATIC
 Beta – 1 selective agonist (Prenalterol – partial TACHYCARDIA
agonist)
REBOXETINE
RITODRINE AND TERBUTALINE  like Atomoxetine pharmacologically
 Beta – 2 selective agonist
SIBUTRAMINE
 used for the treatment of asthma
 an APPETITE SUPPRESSANT
3. MIXED – ACTING SYMPATHOMIMETICS
DULOXETINE
 Ephedrine
 an ANTIDEPRESSANT
 Pseudoephedrine
 Phenylpropanolamine
MILNASIPRAM
 used to RELIEVE PAIN in cases of
4. INDIRECT ACTING SYMPATHOMIMETICS
FIBROMYALGIA
 Either: Amphetamine-like or
Catecholamine Reuptake Inhibitors
COCCAINE
 mainly acts on CNS
 AMPHETAMINE-LIKE
 used to INHIBIT DOPAMINE REUPTAKE in the
SYMPATHOMIMETICS
neurons or more specifically the pleasure
 Amphetamine
center of the brain
 Methamphetamine
 Phenmetrazine
5. DOPAMINE AGONISTS
 Methylphenidate
 Includes:
 Modafinil
 Levodopa
 Tyramine
 Dopamine agonists with central
action
AMPHETAMINE
 has a very strong CNS STIMULANT effect like
LEVODOPA
Methamphetamine
 is converted to Dopamine in the body
MODAFINIL
LEVODOPA AND DOPAMINE AGONISTS WITH
 used for NARCOLEPSY
CENTRAL ACTION
 used for Parkinson’s Disease and
TYRAMINE
prolactinemia
 acts as Norepinephrine
 Sympathomimetic drugs can also be classified
according to their MOA and spectrum of
 CATECOLAMINE-REUPTAKE INHIBITORS
activity
 Atomoxetine
 Reboxetine
 Sibutramine
Acebedo, Cruz, Davis, Duran, Salucon, Uy 11
  ACCORDING TO MOA: ISOPROTERINOL
 prototype for drugs that act on the beta
AMPHETAMINE  can cause the release of receptors
DERIVATIVES stored catecholamines so
AND TYRAMINE they have an indirect DRUGS THAT ACT ON THE DOPAMINE RECEPTORS
action
I. CATECHOLAMINE
COCCAINE AND  inhibit the uptake of  Epinephrine
TRICYCLIC catecholamine by the  Norepinephrine
ANTIDEPRESSA nerve terminals so they  Isoproterinol
NTS increase the synaptic  Dopamine
activity of the released  Dobutamine
transmitter, so they also
have an indirect action II. NON-CATECHOLAMINE
 Amphetamine
 They can also act to block  Ephedrine
the metabolism of the  Mephentermine
drug like the blockade of  Hydroxyamphetamine
catechol-O-methyl  Metaraminol
transferase (COMT) and  Phenylephrine
the monoamine oxidase  Methoxamine
(MAO)  Prenalterol

 They have little direct

effect on the autonomic A. CATECHOLAMINE
activity but the bound (?)
inhibition will increase SELECTIVE BETA-1 AGONISTS
the stores of
catecholamine in the DOBUTAMINE
storage vesicles  resembles dopamine chemically
 a direct acting drug with the selectivity to beta
 They can potentiate the 1 receptors
action of indirectly acting  relatively more effective in enhancing the
sympathomimetics contractile force of the heart than increasing
the heart rate
 it does not affect the atrial conduction velocity
 ACCORDING TO SPECTRUM OF ACTION: but it augments the conduction velocity
through the AV node
EPINEPHRINE  there is little or no effect on ventricular
 the prototype for drugs that act on all impulse conduction
adrenoceptors  does not produce renal vasodilation
 plasma half life: approximately 2 mins only
PHENYLEPHRINE  not effective orally
 prototype for drugs that act on the alpha  usual dose: 2.5-10 nanograms per kilogram
receptors body weight per minute

Acebedo, Cruz, Davis, Duran, Salucon, Uy 12

 rapidly metabolized in the liver to an inactive  tachycardia
conjugate with glucoronic acid and 3-O-methyl  anginal pain
dobutamide  arrhythmia
 should not be used in patients with atrial  headache
fibrillation  hypertension
 the less frequent SE:  vasocontriction
 nausea  Contraindications: MAO inhibitors
 headache
 palpitation  Therapeutic uses:
 SOB  treatment of some types of shock
 anginal pain  oliguria and those with low or normal
peripheral vascular resistance
 Therapeutic Uses:  cardiogenic and bacteremic shock and
 Congestive heart failure profound hypertension following removal
 Cardiogenic shock of pheochromocytoma
 Contraindications:
 Patients with marked obstruction to
cardiac ejection like in idiopathic B. NON CATECJHOLAMINES
hypertrophic subaortic stenosis
DOPAMINE AMPHETAMINE

 is the immediate metabolic precursor of NE  has a powerful CNS stimulant action in

and epinephrine addition to the peripheral alpha and beta
 a central neurotransmitter actions that are common to indirect acting
 possesses important intrinsic pharmacologic sympathomimetic drugs
properties  effective for oral administration
 a substrate for both MAO and COMT  effect lasts for several hours
 ineffective when administered orally  the effects on the system raises both systolic
 Cardiovascular effects: and diastolic BP
 positive inotropic effect on myocardium  heart rate is reflexly slow and cardiac
 acting as an agonist at the beta-1 receptor arrhythmias can occur
 capable of causing the release of NE from  L-isomer is slightly more potent than D-isomer
nerve terminals preparation of amphetamine (as far as its
 tachycardia is less compared to one that is cardiovascular action is concern)
produced by isoproterenol  one of the most potent sympathomimetic
 it can increase the systolic pressure and amines with respect to the stimulation of CNS
pulse pressure  stimulates the medullary respiratory center
 increases GFR, renal blood flow and and lessens the degree of central depression
sodium excretion caused by various drugs
 depresses appetite, but found out that weight
 Overdose: loss in obese patient treated with
 attributable to the excessive amphetamine is almost entirely due to
sympathomimetic activity reduced food intake and only in small
 encountered during dopamine infusion: measures due to increased metabolism
 nausea
 vomitting

Acebedo, Cruz, Davis, Duran, Salucon, Uy 13

 EPHEDRINE  the actions of this drug are similar to that of
Ephedrine except that the drug almost entirely
 stimulates both alpha and beta receptors lacks a CNS stimulant activity
 clinical uses are related to both its action on  the only current clinical use of
alpha and beta receptors hydroxyamphetamine now is as a mydriatic
 cardiovascular action persists 10x longer than (an agent that makes the pupil of the eye
that of Epinephrine dilate or open up)
 the bronchial muscle relaxation that is
produced by Ephedrine is less prominent but METARAMINOL
is more sustained compared to that produced
by Epinephrine  is used almost exclusively for the treatment of
 mydriasis occurs after local application of the hypotension or hypotensive states
drug to the eyes  it has both a direct and indirect action
 activity of the human uterus is usually reduced  its overall effects are similar to those of
by Ephedrine Norepinephrine but it is much less potent and
 less effective than epinephrine in elevating the has a more prolonged action
concentration of glucose in the blood  it does not have any CNS stimulant effect
 CNS effect are similar to those Amphetamine  it is absorbed after oral administration, but for
but are considerably less marked equal effects, the oral dose must be 5-6 times
 Therapeutic uses: greater than the dose when you give it by IM
 Bronchospasm or IV
 Stoke Adams syndrome  the pressor effect on an IM dose is 5 mg and it
 Decongestant (Nasal decongestant) will last for 1 and a half hour
 Allergic disorders  the principal use clinically by Metaraminol is
 Pressor agent during spinal anesthesia as a pressor agent in certain hypotensive
 Central stimulant in cases of narcolepsy states.

MEPHENTERMINE PHENYLEPHRINE

 used in various hypotensive conditon  a powerful alpha-1 receptor stimulant with

 prolonged duration of action, can be up to very little effect on the beta receptors of the
4hrs heart
 cardiac contraction is enhanced  its direct action on the receptors accounts for
 cardiac output and the systolic and diastolic the greater part of its effect and only small
pressures are also increased part being due to its ability to release
 there is a marked mucosal vasoconstriction if norepinephrine
applied locally  however, the central stimulant effect on the
 used mainly as pressor (producing an increase CNS is very minimal
in blood pressure by stimulating constriction of  the responses to the drug persist for about 20
the blood vessels) drug in various hypotensive minutes after IV injection and it can persist for
states or conditions as long as 50 minutes after subcutaneous
injection.
HYDROXYAMPHETAMINE  The effects of phenylephrine are:
 marked reflex bradycardia
 slight increase in the heart rate
 slightly decreased cardiac output

Acebedo, Cruz, Davis, Duran, Salucon, Uy 14

  peripheral resistance is considerably PRENALTEROL
increased
 increased coronary blood flow  a selective beta-1 adrenergic agonist
 pulmonary blood vessels are constricted  it is used as a cardiac stimulant
 elevated pulmonary arterial pressure  useful in the management of chronic
congestive heart failure
 Therapeutic uses of phenylephrine:
 as a nasal decongestant
 used for hypotension  TYPES OF ADRENOCEPTORS
 used as a mydriatic
 used as a local vasoconstrictor when given 1. alpha 1
together with a local anesthetic 2. alpha 2
 used to relieve paroxysmal atrial 3. beta 1
tachycardia 4. beta 2
5. beta 3
6. dopamine 1
METHOXAMINE 7. dopamine 2
 ORGAN SYSTEM EFFECTS OF STIMULATION OF
 the pharmacologic properties of this drug are ADRENOCEPTORS
almost exclusively those that characterize an A. CNS
alpha receptor stimulant
 it acts directly on the sit AMPHETAMINE  can enter the CNS
 the actions of methoxamine are similar to  it starts its effect with a
those of Phenylephrine mild alerting effect
 the outstanding effect of this drug is increased  there is anorexia,
in the blood pressure due entirely to euphoria, and insomnia
vasoconstriction  high doses of
 there is no stimulant action on the heart and it amphetamine will cause
also lacks beta receptor action on smooth marked anxiety,
muscles aggressiveness, paranoia,
 it does not have any CNS stimulation effect and sometimes
 Reflex bradycardia is a prominent action so it convulsions (high doses)
is used clinically to relieve attacks of
paroxysmal atrial tachycardia B. EYES
 it does not appear to precipitate cardiac
arrhythmia PHENYLEPHRINE  cause mydriasis
 it can prolong the ventricular muscle action & OTHER ALPHA-  can reduce intraocular
potentials and the refractory period so it can AGONISTS pressure
slow the AV conduction time
C. BRONCHI
 Therapeutic uses of methoxamine
 a pressor agent in hypotensive states BETA-2  cause bronchodilation
 used to end attacks of paroxysmal atrial AGONISTS
tachycardia

Acebedo, Cruz, Davis, Duran, Salucon, Uy 15

 D. GASTROINTESTINAL TRACT Dopamine-1 receptor  cause vasodilation
 there will be an activation of the alpha agonist in the splanchnic
and beta receptors causing relaxation and renal vascular
of the smooth muscles bed but at higher
Alpha-2 agonists  decrease salt and water doses beta
secretion in the GIT receptors are
activated and at
even higher doses
E. GENITOURINARY
alpha receptors are
also activated
ALPHA RECEPTORS  cause contraction of
the urinary
G. HEART
sphincter
 there will be an increased rate of
BETA-2 AGONISTS  will cause significant
cardiac pacemaker
uterine relaxation in
 the AV node conduction and the
women near term
cardiac force will be increased
 on the other cardiovascular actions,
there is increased blood pressure and a
F. VASCULAR SYSTEM
reflex bradycardia because of increased
vagal outflow
PHENYLEPHRINE (alpha-  constrict the skin
1 agonist) and splanchnic
H. METABOLIC AND HORMONAL EFFECTS
blood vessels and
 increase the
Beta-1 agonists  increase renin
peripheral vascular
secretion
resistance and
venous pressure
Beta-2 agonists  increase insulin
secretion
CLONIDINE (alpha-2  if given by IV or as
agonist) nasal spray, it will
cause  they will also increase glycogenolysis in
vasoconstriction the liver and they can also stimulate
 but if it is given lipolysis
orally, it will cause
reduced
sympathetic  CLINICAL USES:
outflow and blood
pressure EPINEPHRINE
TERBUTALINE (beta-2  significantly reduce  used in anaphylaxis, glaucoma, asthma, and as
agonist) the arteriolar tone a vasoconstrictor
in the skeletal
muscle vascular NOREPINEPHRINE
bed  will cause vasoconstriction and hypotension
 can reduce
peripheral vascular ISOPROTERENOL
resistance and  used for asthma and AV block although it is
arterial blood rarely used
pressure
Acebedo, Cruz, Davis, Duran, Salucon, Uy 16
DOPAMINE  small doses of these sympathomimetics can
 for most type of shock and heart failure cause nervousness, anorexia, and insomnia
 higher doses can cause anxiety, aggressiveness
DOBUTAMINE or paranoid behavior
 also for shock and heart failure  convulsions can also occur

ALPHA-1 AGONIST
AMPHETAMINE and PHENMETRAZINE  can cause hypotension
 for narcolepsy, obesity and for attention-
deficit disorder BETA-1 AGONIST
 can cause sinus tachycardia and serious
EPHEDRINE cardiac arrhythmias
 used for urinary incontinence and hypotension
BETA-2 AGONIST
 can cause skeletal muscle tremor
PHENYLEPHRINE COCAINE
 will cause mydriasis, vasoconstriction, and as a
 can cause addiction, cardiac arrythmia,
decongestant
infarction, and convulsion
ALBUTEROL, METAPROTERENOL, and
TERBUTALINE SUBCLASSES OF SYMPATHOMIMETIC DRUGS
 used in asthma
 premature labor A. ALPHA-1 AGONISTS

OXYMETAZOLINE AND XYLOMETAZOLINE

MIDODRIN
 used as long-acting nasal decongestant
 activates phospholipase C resulting in the
COCAINE increase intracellular calcium and
 will cause vasoconstriction vasoconstriction
 used also as local anesthetic
PHENYLEPHRINE
 TOXICITY  when used by IV for short a term period, is
used to maintain BP for acute hypotension
 CATHECOLAMINES – has little CNS toxicity
although they cause:  intranasally as decongestant
o excessive vasoconstriction
o cardiac arrhythmias B. ALPHA-2 AGONISTS
o myocardial infarction  Clonidine
o pulmonary edema  Methyldopa
o hemorrhage  Guanfacine
 Guanabenz
 OTHER SYMPATHOMIMETICS
 Dexmedetomidine
PHENYLISOPROPYLAMINE  Tizanidine
 Apraclonidine
 will cause light to moderate CNS toxicity  Brimonidine

Acebedo, Cruz, Davis, Duran, Salucon, Uy 17

CLONIDINE
 inhibit adenyl cyclase and interacts with other METHYLDOPA
intracellular pathways thus it lowers BP  exerts its effect via central mechanism
 antihypertensive agent that paradoxically,  enters cns readily and is decarboxylated to α-
possesses primarily alpha-2 adrenergic methyldopamine and beta hydroxylated to α-
agonist properties methylnorepinephrine which occurs at the
 owes its antihypertensive effect to a central adgrenergic neurons
predominant action on the CNS thus, a o α-methylnorepinephrine- is a potent
centrally acting antihypertensive agonist at alpha-2 receptors in the CNS
 decreases the sympathetic outflow from the and like clonidine, it will inhibit central
brain sympathetic outflow; more potent
 possible site of action on the nucleus tractus stimulator at the alpha-2 receptors
solitarius in the lower brainstem (region rich in than in the alpha-1 receptors
cell bodies and nerve terminals that contain  alpha-methyldopa, marketed as Aldomet
epinephrine and norepinephrine)  used mainly for pre-eclampsia
 Possible SE:  SE:
 sedation  sedation
 rebound hypertension (especially when  hemolytic anemia
withdrawn suddenly-taper the use  positive Coomb’s test
before total discontinuation to avoid
this) APRACLONIDINE, BRIMONIDINE
 dry mouth  both sympathomimetics
**treatment for rebound hypertension,  alpha-2 selective
due to inadvertently stopping the use of  increase secretion of aqueous humor by
Clonidine, using PHENTOLAMINE activating the alpha-2 adrenergic receptors
 for glaucoma
GUANFACINE & GUANABENZ  SE: dry mouth
 central sympatholytic; also act on CNS  blurred visin
 used for hypertension  conjunctivitis
 same pharmacologic properties as Clonidine
C. BETA-1 AGONIST
DEXMEDETOMEDINE
 sedative effect DOBUTAMINE
 adjunct for anesthesia  activates adenyl cyclase
 increase in myocardial contaractility
TIZANIDINE  positive ionotropic effect
 muscle relaxant

APRACLONIDINE & PRIMONIDINE

 for glaucoma

Acebedo, Cruz, Davis, Duran, Salucon, Uy 18

D. BETA-2 AGONISTS  used for treatment of reversible obstruction of
the airway
ALBUTEROL  selective beta-2 agonist
 activates adenyl cyclase causing bronchial  not methylated by COMT
smooth muscle to dilate  after a 5 mg dose- produce bronchodilation
 used for asthma after 1 hour and lasts for 7 hours;
subcutaneous- effect starts within 5 minutes
METAPROTERENOL and lasts for 4 hours
 chemically similar to Isoproterenol  SE:
 resistant to methylation by COMT  Nervousness
 effective orally  muscle tremors
 longer duration of action than Isoproterenol  headache
 primarily a beta-2 adrenergic agonist  tachycardia
 when administered by inhalation, it has little  palpitation
effect on the beta-1 receptors in the heart  drowsiness
 after inhalation/ oral adminstration- there is  nausea
an increased force expiratory volume (FEV)  vomiting
and maximal rate of force expiratory flow  sweating
(FEF) and decreased in airway resistance
 after oral dose - improvement of airway  used in children below 12yo is not
function will be demonstrable for a period of recommended
at least 4 hours  subcutaneous dose: 0.25 mg
 after inhalation - improved respiratory  inhalation: 2 sprays every 4-6 hours;
function will be apparent for 3-4 hours  tablet: 2.5 mg or 5 mg depending on body size;
 approx. 40% of Metaproterenol will be  injection: 1 mg (prep of 1mg/ml)
absorbed after oral dose  aerosol: 0.2 mg per spray
 excreted in the urine as a conjugate with
glucuronic acid ALBUTEROL
 Adverse effects:  selective beta-2 adrenergic agonist
 tachycardia  same pharmacologic properties and
 hypertension therapeutic indications with Terbutaline
 tremor  inhalation: effect starts after 15 mintes and
 palpitation lasts for 3-4 hours
 nervousness  preparations available:
 nausea and vomiting o 2mg tab and 4mg tab for oral use,
 therapeutic use: as a bronchodilator o aerosol preparation also available,
initial dose: 2-4 mg 3x or 4x a day
TERBUTALINE  Total daily dose of 32 mg should not be
 synthetic sympathomimetic drug exceeded
 routes: oral, subcutaneous, inhalation

Acebedo, Cruz, Davis, Duran, Salucon, Uy 19

RITODRINE
 selective beta-2 adrenergic agonist
 used to delay or prevent premature
parturition
 rapidly but incompletely absorbed (30%)
following oral dose
o 90% excreted in the urine as inactive
conjugate
o 50% excreted unchanged after IV
administration

Acebedo, Cruz, Davis, Duran, Salucon, Uy 20