Cholinergics Flashcards
Hemicholinium
inhibits choline transport so you wont be able to make Ach
What are the responses mediated by muscarinic receptors when Ach binds?
Heart: decreased HR, AV node conduction
Eyes: contraction of sphincter muscle of iris and ciliary muscle
Gi: increase tone, motility and secretion
bladder: relaxed sphincter
secretory glands: increased secretions (sweat, bronchial, salivary)
M1 receptor
stomach-increased acid and pepsin secretion
ganglion-stimulation
CNS-neurotransmission
M2 receptor
SA node- increase K+ conduction, slow diastolic depolarization, bradycardia
Atria- decreased contractility, conduction velocity, and refractory period
AV node- slows conduction, AV block
Lung: bronchoconstriction, increased secretions
stomach- increased motility
bladder- contract detrusor, relax sphincter
penis- erection
M3 receptor
Eyes- meiosis, accommodation
glands- increase secretions
Direct-acting cholinomimetic drugs
Receptor agonists (all of the following): Choline esters: Ach, bethanecol, carbachol, methacholine
alkaloids: pilocarpine
Indirect-acting cholinomimetic drugs
Cholinesterase inhibitors (all of the following) Carbamates: physostigmine, neostigmine, pyridostigmine, edrophonium
phosphates: isoflurophate (irreversible)
Nicotinic receptor
skeletal muscle-contract
ganglion-stimulation
CNS-neurotransmission
Bethanechol
stimulates the atonic bladder in postpartum or postoperative urinary retention
-actions: increases intestinal motility and tone, stimulates detrusor muscle of bladder while trigone and sphincter are relaxed, causing expulsion of urine.
-Sites: smooth muscle of bladder and GI
direct Ach agonist. Poor substrate for AchE so not broken down well.
-unique: used to promote salivation in Sjogren syndrome (an alternative to pilocarpine)
Carbachol (carbamylcholine)
Rarely used; sometimes used as miotic for glaucoma.
Action: direct cholinomimetic, weak nicotinic agonist. Can cause release of epinephrine from adrenal medulla by nicotinic actions. Poor substrate for AchE so it has a longer time to work.
DOA: ~1hr
ADR: little to no side effects when used in the eye
Methacholine
Used as DIAGNOSTIC (not medicinally). “Methacholine challenge” for bronchial hyperreactivity and asthmatic conditions.
Cholinomimetic natural alkaloids and synthetic analogs
Pilocarpine(muscarinic action)
muscarine (acts at muscarinic receptor sites)
arecoline (acts at nicotinic receptors)
Pilocarpine
Emergency lowering of intraocular pressure of both narrow and wide-angle glaucoma. Opens canal of Schlemm, decreases pressure through increased drainage of aqueous humor.
Action: rapid miosis/contraction of ciliary muscle.
ADR: CNS effects, profuse sweating, salivation (some systemic absorption through eye)
Atropine
Anti-muscarinic. ANTIDOTE for Ach and Ach agonist toxicity.
This is an anticholinergic—muscarinic receptor antagonist.
Major contraindications to use of choline esters
- Asthma (bronchoconstrictor action can precipitate asthma attack)
- Hyperthyroidism(=A.fib)
- Coronary insufficiency (hypotension=decreased coronary blood flow)
- Peptic ulcer disease
Reversible Anticholinesterases
water-soluble.indirect-acting cholinomimetics
- physostigmine
- neostigmine
- pyridostigmine
- edrophonium
- tacrine, donepezil, rivastigmine, galantamine
Physostigmine
Meiosis: used in glaucoma; increases intestinal and bladder motility; reverses CNS and cardiac effects of tricyclic antidepressants; reverses CNS effects of atropine
Action: amplifies effects of Ach by stopping its’ breakdown.
This is a water-soluble indirect-acting cholinomimetic drug.
neostigmine
pyridostigmine
edrophonium
Used: Myesthenia Gravis, reversal of neuromuscular block. Used in surgery.
Action: amplifies effects of Ach, increases muscle strength.
Water-soluble. reversible.
Isoflurophate
Echothiophate
Used: glaucoma (not first line of therapy. used if rxn to other drugs). Administered topically, so no systemic effects.
Action: amplifies effects of Ach.
Lipid-soluble=irreversible b/c it crosses the blood-brain barrier.
Effects of excessive Ach
DUMBELS mnemonic
D-diarrhea U-urination M-meiosis B-bronchoconstriction E-excitation (CNS, skeletal muscle) L-lacrimation S-sweating, salivarion
nicotinic manifestations
M T W t(H) F mneumonic
M-mydriasis, muscle twitching T-tachycardia W-weakness tH- HTN, hyperglycemia F-fasciculations
Pralidoxime
choinesterase reactivator that breaks bond between drug and enzyme (ANTIDOTE)
Treatment for poisoning with organophosphate insecticides. Carried by military in case of exposure.
Effects of muscarinic blocking drugs
- CNS: amnesia, delirium, drowziness, anti-parkinsons actions, antimotion sickness action
- eyes: lens accommodation inhibited, mydriasis, reduction in lacrimal secretions
- bronchodilation
- GI: relaxation, slowed peristalsis
- urinary: relaxed bladder wall, urine retention
- heart: bradycardia (initially from blocking M2 receptor in heart), then tachycardia (from blocking vagus)
- Glands: secretions decrease
Antimuscarinic drugs for CNS and applications
- Benztropine: treat manifestations of Parkinson’s disease
- scopolamine- prevent/reduce motion sickness
