Lecture 38 Flashcards
What are the two types of cholinergic drugs?
cholinergic agonists and cholinergic antagonists
What are the two types of cholinergic agonists?
direct acting- bind to and activate
indirect acting- inhibit
What are the direct effects of ACh on the cardiovascular system?
- vasodilation (M3)
- decrease in cardio rate (M2)
- decrease in the rate of conduction by SA and AV nodes (M2)
- decrease force in contraction (M2)
How does a low dose of ACh impact the cardiovascular system?
A fall in blood pressure, but tachycardia occurs in response
How does a high does of ACh impact the cardiovascular system?
leads to a fall in blood pressure (M3) and bradycardia (M2)
How does ACh impact the vasculature?
release of NO and vasodilation
lower BP
How does ACh impact the eye?
miosis
How does ACh impact the ciliary muscle?
accommodation of lens to near vision
How does ACh impact glands?
increase secretion
how does ACh impact the bronchi?
constriction
how does ACh impact the heart?
decreased heart rate and conduction velocity
how does ACh impact the GI?
increased peristalic activity and relaxtion of sphincters
how does ACh impact the bladder?
Contraction of detrusor muscle; relaxation of
sphincter
What does atropine do?
a muscarinic antagonist
If muscarinic effects are blocked by a muscarinic antagonist such as atropine, large doses of acetylcholine produce nicotinic effects:
Vasoconstriction and increase in blood pressure
What are the two kinds of direct-acting cholinergic agonists?
- esters of choline
2. alkaloids
What are examples of choline esters?
- acetylcholine
- methacholine
- bethanechol
About choline esters?
they are quaternary ammoniums
poorly absorbed and distributed into the CNS
ACh is very rapid hydorlyzed
meth and beth are more resistant to hydrolysis
Acetylcholine
A muscarinic receptor and nicotinic agonist
used to produce an miosis effect during cataract surgery or other procedures where miosis is needed
Bethanechol
muscarinic agonist
uses:
- postoperative urinary retention
- atony of the bladder
methacholine
Muscarinic agonist
uses:
Diagnosis of bronchial airway hyperreactivity in
subjects who do not have clinically apparent
asthma.
What are the natural alkaloids (direct acting)?
- pilocarpine
2. nicotine
pilocarpine?
partial muscarinic agonist
tertiary amine
stable to hydrolysis by ACh enzyme
uses:
glaucoma
dry mouth due to radiotherapy
what are the adverse effects of muscarinic agonists?
- sweating
- salivation
- flushing
- low bp
- nausea
- abdominal pain
- diarrhea
- bronchospasm
nicotine?
tertiary amine
agonist at nicotinic receptors
Depending on the dose, nicotine depolarizes
autonomic ganglia, resulting first in stimulation
and then in paralysis.
low nicotine dose?
ganglionic stimulation by depolarization
high nicotine dose?
ganglionic and neuromuscular blockade
nicotine uses?
to stop smoking
indirect-acting cholinergic agents?
- edrophonium
- carbamates
- organophosphates
mechanism of edrophonium?
binds reversibly to the active site
of the enzyme. The inhibition is short-lived.
anticholinesterase
mechanism of carbamates?
form a covalent bond with the enzyme
anticholinesterase
mechanism of organophosphates?
phosphorylate the enzyme.
The covalent bond formed is extremely stable
and hydrolyzes very slowly
explain anticholinesterases
they increase the concentration of ACh since acetylcholinesterase is inhibited
effects are similar to direct acting cholinergic agonists
how do anticholinesterases impact the cardiovascular system?
In the vascular smooth muscle cholinesterase
inhibitors have minimal effects because most
vascular beds lack cholinergic innervation.
how do anticholinesterases impact the neuromuscular junction
increase the strength of the contraction
Useful to reverse action of nondepolarizing
neuromuscular blockers.
Useful in myasthenia gravis.
edrophonium uses?
does not enter CNS
quaternary ammonium
uses:
diagnosis of myasthenia gravis
Used to reverse the neuromuscular block produced by non-depolarizing muscular blockers
physostigmine uses?
tertiary amine
can enter the CNS
uses:
treatment of anticholinergic drug overdose
neostigmine uses?
quaternary ammonium
does not enter CNS
uses:
urinary retention
Reversal of effects of non-depolarizing
neuromuscular blockers after surgery.
Treatment of myasthenia gravis
pyridostigmine uses?
quaternary ammonium
does not enter CNS
uses:
treatment of myasthenia gravis
types of organophosphates?
malathion (insecticide)
sarin (nerve agent)
Types of cholinergic antagonists?
- muscarinic
- nicotinic
- drugs that act presynaptically
types of nicotinic receptor antagonists?
- ganglion blockers
2. NMJ blockers
what drugs are muscarinic receptor antagonists?
atropine and scopolamine
Atropine characteristics?
Reversible competitive antagonist at muscarinic
receptors.
Tertiary amine: both central and peripheral
muscarinic blocker
Atropine actions?
Eye: Mydriasis & cycloplegia (M3 blockade).
GI: Reduces gastric motility (M3 blockade).
Urinary system: Decreases hypermotility of urinary bladder (M3 blockade).
CV system: Moderate to high therapeutic doses cause tachycardia (Atrial M2 blockade).
Secretions: Salivary, sweat and lachrymal glands
are blocked. Inhibition of sweat glands may cause
high body temperature (M3 blockade).
Atropine uses?
antidote for cholinergic agonists
to block respiratory secretions prior to surgery
adverse effects of atropine?
Dry mouth, blurred vision, sandy eyes,
tachycardia, constipation, urinary retention.
Effects on CNS: restlessness, confusion,
hallucinations, delirium.
uses of scopolamine?
motion sickness
Ipratropium use?
used for the treatment of COPD and asthma
muscarinic antagonist
tropicamide use?
used as a mydriatic for fundoscopy
produces mydriasis with cycloplegia
muscarinic antagonist
What are the contraindications of using antimuscarinic agents?
Contraindicated in patients with angle-closure
glaucoma.
Should be used with caution in patients with
prostatic hypertrophy and in the elderly.
examples of ganglion blockers?
nicotinic antagonists
remove dominant control
- nicotine = prolonged depolarization
- hexamethonium = antagonism of nicotinic receptors
hexamethonium use?
was used for hypertension in the past
no longer used due to adverse effects
Tubocurarine?
nondepolarizing blocker
mechanism: competitive antagonist
use: As adjuvant drugs in anaesthesia during surgery
to relax skeletal muscle.
Succinylcholine?
depolarizing blocker
mechanism:
binds to the nicotinic receptor and depolarizes the junction. Persists in the synaptic cleft, stimulating the receptor: receptor desensitizes.
This leads to flaccid paralysis.
use:
Rapid endotracheal intubation.
ECT
Botulinum toxin?
inhibitor of ACh release
Injected locally into muscles for treatment of several diseases involving muscle spasms.
Also approved for cosmetic treatment of facial wrinkles.