Cholinergic Drugs Flashcards
Biperiden
a. Antimuscarinic drug
Carbachol
a. Direct-acting cholinomimetics
b. treats glaucoma; produce miosis during surgery
c. both nACh and mACh agonist
carACHOL glauCOMA - alcohol puts you in a comma
What are common compounds with anticholinergic properties?
anticholinergic agents (atropine), antihistamines, tricyclic antidepressants, sleep aids, cold preparations
Solifenancin
a. mAChR (M3) antagonist
b. used to treat GU excess problems with longer acting ability, and less side effects (dry mouth and constipation)
What do quaternary AChE inhibitors act on? organophosphates and tertiary AChE inhibitors?
a. mainly skeletal muscle (no CNS activity, and less effect at autonomic effects sites and ganglia)
b. ubiquitous effects at both peripheral and central cholinergic sites,
Tolterodine
a. mAChR (M3) antagonist
b. used to treat GU excess problems with longer acting ability, and less side effects (dry mouth and constipation)
Endrophonium
a. Cholinesterase inhibitor (1)
Pilocarpine
a. Direct-acting cholinomimetics
b. treats dry mouth; can also treat glaucoma
c. pure mAChR agonist
Neostigmine
a. Cholinesterase inhibitor (2)
b. used to treat MG; NAChR agonist; charged, and doesn’t go to the CNS
What do we see in children that are given a normal dose atropine?
“atropine fever” (body temperature is elevated only if large doses are administered in adults)
Trihexyphenidyl
a. Antimuscarinic drug
b. treat PD tremor
What is miosis?
pupil constriction
What drugs are choline esters?
a. acetylcholine, bethanechol, carbachol, methacholine
b. CHARGED
c. hydrolyzed by AChE (a>m>b=c)
Drugs used for respiratory disorders (asthma, COPD)
- Ipratropium (first line tx for asthma/COPD)
- Tiotropium (longer bronchodilator action than ipratropium)
What do we see with ODs of pilocarpine and choline esters?
predictable muscarinic effects (nausea, vomiting, diarrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, bronchial constriction) and are blocked by antimuscarinic compounds such as atropine
Trospium
a. Antimuscarinic drug (non selective)
b. used to treat GU excess problems
How do you treat Direct-acting cholinomimetic toxicity?
treat toxicity with atropine or anticonvulsants (diazepam or benzodiazepine)
Pralidoxime
a. cholinesterase regenerator
b. antidote for organophosphate warfare
c. regenerates active enzyme from the organophosphorus-cholinesterase complex via removal of the phosphorous group from the active site of the enzyme
What drugs are alkaloids?
a. muscarine, nicotine, pilocarpine
b. uncharged (except muscarine)
c. muscarine is highly toxic when ingested (mushrooms) and enters the brain
Pyridostigmine
a. Cholinesterase inhibitor (2)
How do Direct-acting cholinomimetic work?
they mimic ACh - bind to mAChR and nAChRs
a. Choline Esters -
Galantamine
a.
b. treat AD
Oxybutynin
a.
b. used to treat GU excess problems
What M R do you select to treat urinary problems?
M3
Ambenonium
a. Cholinesterase inhibitor
Benzotropine
a. Antimuscarinic drug
b. tertiary amine; tx PD tremor
Physostigmine
a. Cholinesterase inhibitor (2)
b. treat AD; antidote to anticholinergic agents OD (crosses BBB); uncharged, and goes into CNS
Procyclidine
a. Antimuscarinic drug
Darifenancin
a. mAChR (M3) antagonist
b. used to treat GU excess problems with longer acting ability, and less side effects (dry mouth and constipation
Drugs used in ophthalmology
- Atropine
- Cyclopentolate
- Homatropine
- Scopolamine
- Tropicamide
Antimuscarinic agents are contraindicated in what patients?
glaucoma, acid peptic dx
*used with caution in men with hx of prostatic hyperplasia (bc of urinary retention)
Varenicline
a. Direct-acting cholinomimetics
b. helps with smoking cessation
c. nACH agonist (partial); binds Rs in brain to stimulate receptor-mediated activity, but at a substantially lower level than nicotine
d. aka Chantix
Dicyclomine
a. Antimuscarinic drug
What are the three subgroups of AChE inhibitors?
a. alcohols: short acting - 2-10 min; + charged
b. carbonic acid esters (long acting - .5-6 hours); + charged or neutral
c. organophosphates (irreversible); neutral
Orphenadrine
a. Antimuscarinic drug
Of the subgroups of AChE inhibitors, which can cause CNS problems?
organophosphates, and some carbonic esters
- others have no CNS distribution
Ipratropium
a. Antimuscarinic drug
b. inhalation agent to tx asthma and COPD (only used for this)
What are neostigmine and edrophonium preferred for?
to reverse paralysis induced by neuromuscular blocking drugs during surgery
*AChE Inhibitors
Methacholine
a. Direct-acting cholinomimetics
b. causes bronchial hyperactivity, and is used in asthma testing (would exacerbate symptoms)
c. no nACh activity
Atropine
a. Antimuscarinic drug
b. antidote for organophosphate warfare; tertiary amine; causes mydriasis and decrease lacrimal secretion; most sensitive tissues are salivary, bronchial, and sweat glands
c. Atropine or glycopyrrolate is paired with neostigmine to block parasympathetic effects during reversal of skeletal muscle relaxation
What is the MOA of ganglion blockers?
competitively block the action of ACh and similar agonists at nAChRs of both parasympathetic and sympathetic autonomic ganglia (block all autonomic outflow)
*Urination hesitancy and possible urinary retention in men with prostatic hyperplasia;
Erection and ejaculation may be prevented
Acetycholine
a. Direct-acting cholinomimetics
b. causes mitosis
Mecamylaine
a. ganglion blocker (uncharged)
b. treat hypertension and is being investigated for use in smoking cessation therapy
Cevimeline
a. Direct-acting cholinomimetics
b. treats dry mouth
c. Metabolized via P450 pathways and eliminated in urine
Homatropine
a. mAChR antagonist
b. used to prevent synechia formation in uveitis and iritis
Bethanechol
a. Direct-acting cholinomimetics
b. treats non-obstructive GU/GI problems; heartburn
c. can produce UTI if sphincter doesn’t relax
Can an uncharged or charged drug enter the CNS?
uncharged
What happens when succinylcholine is given with an AChE inhibitor? corticosteroids with AChE inhibitor?
a. enhance phase 1 block and antagonize phase 2 block
b. may enhance muscle weakness seen in patients with myasthenia gravis
Pyridostigmine
a. Cholinesterase inhibitor (2)
b. pretreatment with pyridostigmine reduces the incapacitation and mortality associated with nerve agent poisoning
What types of parasympathetic receptors does the brain contain? SC?
a. mAChRs mainly
b. nAChRs mainly
Scopolamine
a. Antimuscarinic drug
b. tx motion sickness
c. has marked CNS effects (drowsiness and amnesia)
Oxybutynin
a. mAChR (M3) antagonist
b. used to treat GU excess problems
How do the parasympathetics innervate the smooth muscle of BVs?
they don’t –> they release EDFR, which is largely NO –> activation of guanylyl cyclase and increased cGMP –> relaxation
Donepezil
a. Cholinesterase inhibitor
b. treat AD
Tacrine
a. Cholinesterase inhibitor
b. used to treat AD, but not anymore
What are contraindications for Direct-acting cholinomimetics?
acid peptic disease, asthma, hyperthyroidism, coronary insufficiency
Pralidoxime
a. cholinesterase regenerator
b. antidote for organophosphate warfare
What organophosphate does NOT get to the CNS?
echothiophate - due to its charge
Hyoscyamine
a. Cholinesterase inhibitor
What do we see with nicotinic poisoning?
a. acute - effects include CNS stimulation (convulsions progressing to coma and respiratory arrest), skeletal muscle end plate depolarization leading to depolarization blockade and respiratory paralysis, and hypertension and cardiac arrhythmias
b. chronic - increased risk of vascular disease, sudden coronary death, and ulcer recurrences in smokers with peptic ulcer
Glycopyrrolate
a. cholinergic antagonist
b. helps reverse paralysis with neostigmine, helps GI problems
