L2, L4- Cholinergic Drug Overview Flashcards
compare direct and indirect cholinergic agonists
Direct- binds and activates muscarinic or nicotinic receptors
Indirect- inhibits AChE
therapeutic direct acting cholinergic drugs preferentially bind (nicotinic/muscarinic) receptors
muscarinic
list the direct effects of ACh on the cardiovascular system (ignore dosing)
-vasodilation (M3)
- dec cardiac rate (M2)
- dec rate of conduction in SA and AV nodes (M2)
- dec force of heart contraction (M2)
compare the cardiovascualar effects of ACh administered at low and high doses
Low: dec BP due to vasodilation (M3) –> reflex tachycardia: baroreceptors overpower low dose ACh
High: dec BP due to vasodilation (M3), bradycardia (M2): ACh effect»_space; baroreceptors
describe the effects of ACh on the following:
1) vasculature
(2) eyes (x2
(3) inc secretions from what glands?
(4) lungs
(5) heart
(6) GI tract
(7) bladder
1- (endothelial cells) NO release => vasodilation and dec BP
2- miosis (iris: pupil constriction), lens accommodation (ciliary muscle)
3- salivary, sweat, lacrimal glands
4- bronchial constriction and inc secretions
5- dec HR, dec conduction velocity
6- inc tone, peristalsis, secretions + sphincter relaxation
7- detrusor muscle contraction + relaxation of sphincter
(Note- erections for males, variable effects on uterus for females)
describe the effect of large doses of ACh given with atropine
-atropine is a muscarinic antagonist
-=> ACh produce a nicotinic response: inc BP, vasoconstriction
-due to stimulation of SNS ganglia and Epi. release via adrenal medulla stimulation
(Note- must be a significantly large dose)
what are the two forms choline agents come in and what does it indicate about its effects
- quaternary ammonium: polar, doesn’t cross BBB
- tertiary amine: nonpolar, crosses BBB (acts on CNS)
list the 4 choline esters
- ACh
- methacholine
- carbachol
- bethanechol
compare ACh metabolism with the rest of the choline esters
- ACh is metabolized rapidly (by plasma BChE and AChE, 5-20 sec)
- methacholine, carbachol, bethanechol are more resistant to hydrolysis by cholinesterases
list the generalized adverse effects of muscarinic agonists
- sweating
- salivation
- flushing
- low BP
- nausea, abdominal pain, diarrhea
- bronchospasm
describe the effect of nicotine at low doses
- ANS ganglia stimulation via depolarization => simultaneous SNS/PSNS activation
- CV (SNS): inc BP, HR
- GI/GU (PSNS): n/v/d, voiding of urine
- Secretions from SNS/PSNS
describe the effect of nicotine at high doses (and symptom of acute poisoning)
- ANS ganglia blockade + neuromuscular blockade
- Poisoning: n/v/d, abdominal pain, salivation, cold sweat, mental confusion, weakness’ BP falls, weak pulse => death via paralysis of respiratory muscles or central respiratory failure
compare the mechanisms of action of 3 types of anti-cholinesterases (aka the type of binding)
1) edrophonium: reversible non-covalent binding with AChE (short-lived: 2-10 mins)
2) carbamates: covalent binding with AChE (.5-6 hrs)
3) organphosphates: AChE phosphorylation => extremely stable covalent bond + very slow hydrolysis
organophosphates will (1) cholinesterases, which will in turn undergo a process called (2) in order to (3)
1- phosphorylate
2- ageing
3- strengthens the phosphorus-enzyme bond
compare the effects of low and high doses of liposoluble anti-cholinesterases
Low- inhibition => CNS activation
High- convulsions –> coma + respiratory arrest
describe the effects of anti-cholinesterases on the cardiovascular system (moderate and toxic doses)
-activates both SNS/PSNS + activates AChRs on cardiac and vascular smooth muscle
- PSNS effects in the Heart (at moderate doses): negative chronotropic / dromotropic / ionotropic effects => fall in CO, modest bradycardia
- SNS effects on vasculature (at moderate doses): inc systemic vascular resistance and BP
-Toxic doses: marked bradyardia, significant dec in CO, hypotension
describe the effects of anti-cholinesterases in the NMJ
- inc strength of contraction
- used to reverse action of non-depolarizing neuromuscular blockers (+ myasthenia gravis Tx)
(1) drugs related to ACh can be used in Alzheimer’s disease, this includes the following, (2), and has the purpose to (3)
- AChE inhibitors: donepezil, rivastigmine, galantamine
- slows the progression of Alzheimer’s, but does not reverse or treat it
(1) can be used to split the phosphorous-enzyme (P-AChE) bond made by organophosphates if given before (2). This is usuful in the treatment for (3).
1- pralidoxime
2- ageing
3- organophosphate insecticide poisoning (cholinesterase regenerator)
(Note- given after muscarinic antagonist like atropine)
list the types of cholinergic antagonists
- muscarinic receptor antagonists
- nicotinic receptor antagonists: ganglion blockers (Nn) and NMJ blockers (Nm)
- presynaptic acting drugs (M2)
list the effects of atropine on the following:
(1) eyes
(2) GI
(3) GU
(4) secretions
1- mydriasis, cycloplegia (ciliary muscle paralysis - loss of accommodation)
2- reduced gastric motility
3- dec hypermotility of bladder
4- dec salivary (dry mouth), dec sweat (=> hyperthermia), dec lacrimal (dry eyes) secretions
list the effects of atropine on the cardiovascular system at low and moderate/high doses
Low: presynaptic M2 receptor blockade increases ACh release => bradycardia
Moderate/High: atrial M2 receptor blockade => tachycardia; cutaneous vasodilation
list the adverse effects of atropine
- dry mouth (no salivary secretion), blurred vision (mydriasis, cycloplegia), sandy eyes (no lacrimal secretion), tachycardia (atrial M2 blockade), constipation (dec GI motility), urinary retention (inc bladder relaxation)
- CNS effects (b/c tertiary amine): restlessness, confusion, hallucinations, delirium —> depression, collapse of circulatory / respiratory systems —> death
what are the contrindications of using antimuscarinic agents
- angle closure glaucoma
- Pts with prostatic hypertrophy (worsens urinary retention)
- elderly: sensitive to neurological changes (especially dementia patients)
