CHOLINOCEPTORACTIVATING & CHOLINESTERASEINHIBITING DRUGS Flashcards Preview

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Flashcards in CHOLINOCEPTORACTIVATING & CHOLINESTERASEINHIBITING DRUGS Deck (55):
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 Mimic acetylcholine

CHOLINOMIMETIC DRUGS

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TYPE OF CHOLINOMIMETIC DRUGS Classified by
A. Spectrum of action (type of receptor activated)

1. Muscarinic
2. Nicotinic

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TYPE OF CHOLINOMIMETIC DRUGS Classified by
B. Mechanism of action

1. Direct-acting
 Binding/activate cholinoceptors
2. Indirect-acting
 Inhibiting the hydrolysis of endogenous
ACh

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CHOLINOMIMETIC DRUGS

 Divided on the basis of their chemical structure
 Directly bind to and activate muscarinic or
nicotinic receptors
 Many have effects on receptors like ACh

A. DIRECT-ACTING CHOLINOMIMETIC DRUGS

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BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS (2)

1. CHOLINE ESTERS
 Including ACh
2. ALKALOIDS
 Muscarine and nicotine

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BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
 4 important choline esters
 Permanently charged quaternary NH 4 group
 Relatively insoluble in lipids

CHOLINE ESTERS

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BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
Poorly absorbed
 Poorly distributed in the CNS
 Hydrophilic

CHOLINE ESTERS

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BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
 Hydrolyzed in the GIT
 Differ markedly in their susceptibility to
hydrolysis by cholinesterase

CHOLINE ESTERS

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Very rapidly hydrolyzed
 Large amounts must be infused IV to achieve
concentrations high enough to produce
detectable effects

ACETYLCHOLINE

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Addition of methyl CH3
 3x more resistant to hydrolysis compared to ACh

METHACHOLINE

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Carbamic acid ester derivative of ACh
 More resistant to hydrolysis by cholinesterase
 Longer duration of effect

CARBACHOL and BETANECHOL

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Addition of beta-methyl group (methacholine and
betanechol reduces the potency of these drugs at
nicotinic receptor sites

CARBACHOL and BETANECHOL

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Act mostly with muscarinic receptors
(muscarine, pilocarpine)
 Act with nicotinic receptors
(nicotine, lobeline)

2. ALKALOIDS

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Well absorbed from most sites of administration
 Excreted chiefly by the kidneys
 Acidification of urine accelerates clearance of
these amines

2. ALKALOIDS

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Liquid
 Sufficiently lipid-soluble to be absorbed across
the skin

NICOTINE

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Quaternary amine
 Less completely absorbed from the GIT
 Toxic when ingested
 Eg, in certain mushrooms, it even enters the brain

MUSCARINE

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BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Plant derivative
 Similar to nicotine

LOBELINE

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ORGAN SYTEM EFFECTS

 Instilled to the conjunctival sac
 Causes contraction of the sphincter muscle
of iris (miosis)
 Causes ciliary muscle contraction
(accommodation)

1. EYE

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ORGAN SYTEM EFFECTS

 Reduction in peripheral resistance and
changes in heart rate

2. CVS

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ORGAN SYTEM EFFECTS

 Contraction of the smooth muscles of the
bronchial tree
 Stimulate glands of the tracheobronchial
mucosa to secrete

3. RESPIRATORY SYSTEM

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ORGAN SYTEM EFFECTS

 Similar to the parasympathetic nervous
system stimulation
 Increase in the secretory and motor activity
of the gut

4. GIT

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ORGAN SYTEM EFFECTS

 Stimulation of the salivary and gastric glands
 Increase in peristaltic activity
 Relaxation of sphincters

4. GIT

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ORGAN SYTEM EFFECTS

 Endothelium Derived Relaxing Factor (EDRF)
is released to produce dilation
 Dilation of arteries
 Dilation of veins
 Constriction (high-dose direct effect)

5. BLOOD VESSELS

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ORGAN SYTEM EFFECTS

 Stimulate the detrussor muscle
 Relax the trigone and sphincter
 Promote voiding

6. GUT

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ORGAN SYTEM EFFECTS
Stimulate the thermoregulatory sweat,
lacrimal and nasopharyngeal glands

7. GLANDS

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CHOLINOMIMETIC DRUGS

 Primary effect by inhibiting acetylcholinesterase
which hydrolyzes acetylcholine to choline and
acetic acid

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

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CHOLINOMIMETIC DRUGS

 Increase endogenous ACh concentration
 Stimulates cholinoceptors to evoke increase
response

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

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CHOLINOMIMETIC DRUGS

 Parasympathetic effects
 Some have direct action at nicotinic receptors

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

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CHOLINOMIMETIC DRUGS

 Chief difference of the group are chemical and
pharmacokinetics
 3 chemical groups

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

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BASIC PHARMACOLOGY 0F INDIRECT-ACTING
CHOLINOMIMETICS

 Quaternary NH4 group
 2 to10 minutes
 Reversible

1. SIMPLE ALCOHOLS

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BASIC PHARMACOLOGY 0F INDIRECT-ACTING
CHOLINOMIMETICS

 Quaternary or tertiary NH4 group
 30 minutes to 6 hours
 Reversible

2. CARBAMIC ACID ESTERS OF ALCOHOL

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BASIC PHARMACOLOGY 0F INDIRECT-ACTING
CHOLINOMIMETICS

 Highly lipid soluble
 Very long duration
 Irreversible

3. ORGANIC DERIVATIVES OF PHOSPHORIC
ACID

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BASIC PHARMACOLOGY 0F INDIRECT-ACTING
CHOLINOMIMETICS

 Echothiophate
-Retains the very long duration of other
organophosphates
-More stable in aqueous solution

3. ORGANIC DERIVATIVES OF PHOSPHORIC
ACID

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ORGANIC DERIVATIVES OF PHOSPHORIC
ACID

 Used as insecticides

 Parathion and malathion (thiophosphates)

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 Primary action is to amplify the actions
of endogenous Ach
 Effects are similar, but not always identical,
to the effects of direct-acting cholinomimetics

ORGAN SYSTEM EFFECTS

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ORGAN SYSTEM EFFECTS
 Most prominent effects

 CVS
 GIT
 Eye
 Skeletal muscle neuromuscular junction

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CLINICAL PHARMACOLOGY OF CHOLINOMIMETICS

Pilocarpine
Echothiophate (long-acting effect)

1. EYE

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CLINICAL PHARMACOLOGY OF CHOLINOMIMETICS

POSTOPERATIVE ILEUS
URINARY RETENTION POST OP

2. GIT and GUT

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2. GIT and GUT
Clinical disorders that involve depression of smooth muscle activity without obstruction
Betanechol

CLINICAL PHARMACOLOGY OF
CHOLINOMIMETICS

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NEUROMUSCULAR JUNCTION

 Disease affecting the skeletal muscles
neuromuscular junction
 Autoimmune process

MYASTHENIA GRAVIS

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NEUROMUSCULAR JUNCTION

 Production of antibodies that decrease
the functional nicotinic receptors at the
postjunctional end plates
 Cholinesterase inhibitors are used for
therapy

MYASTHENIA GRAVIS

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MYASTHENIA GRAVIS
diagnostic test

 Edrophonium

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MYASTHENIA GRAVIS

long term therapy

 Neostigmine, pyridostigmine

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CLINICAL PHARMACOLOGY OF
CHOLINOMIMETICS

 SUPRAVENTRICULAR TACHYCARDIA
 Treated by short-acting cholinesterase inhibitor
(edrophonium)
 Replaced by newer drugs (calcium channel
blockers)

4. HEART

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5. ANTIMUSCARINIC DRUG INTOXICATION

 Lethal in children
 Causes prolonged severe behavioral
disturbances and arrhythmias in adults


ATROPINE INTOXICATION

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5. ANTIMUSCARINIC DRUG INTOXICATION

 Causes severe muscarinic blockade
 Physostigmine
Antidote to atropine poisoning

ATROPINE INTOXICATION

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CNS
 ALZHEIMER’S DISEASE
 With anticholinesterase activity
 With cholinomimetic action
 Used for therapy

Tacrine

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TOXICITY
A. DIRECT-ACTING MUSCARINIC STIMULANTS

 Nausea and vomiting
 Diarrhea
 Salivation
 Sweating
 Cutaneous vasodilatation
 Bronchial constriction
 Excitation
 Lacrimation

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A. DIRECT-ACTING MUSCARINIC STIMULANTS
BLOCKED BY

atropine

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DIRECT-ACTING NICOTINIC STIMULANTS

 40 mg or 1 drop of pure liquid is fatal
(2 cigarettes)
 Central stimulant action

ACUTE TOXICITY

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DIRECT-ACTING NICOTINIC STIMULANTS

 Convulsion
 Coma
 Respiratory arrest or paralysis
 Hypertension
 Arrhythmia

ACUTE TOXICITY

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DIRECT-ACTING NICOTINIC STIMULANTS

 Treatment is symptom directed
 Atropine
 Anticonvulsants

ACUTE TOXICITY

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DIRECT-ACTING NICOTINIC STIMULANTS

 Smoking

CHRONIC TOXICITY

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RISK OF chronic toxicity increased when

Vascular disease
 Peptic ulcers
 60 % carcinogenic

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C. CHOLINESTERASE INHIBITORS
Major source of intoxication is pesticid
Organophosphates
Treated with large doses of atropine

ACUTE TOXICITY

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