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)
list the 2 mechanisms of nicotinic ganglion blockers
1) prolonged depolarization (nicotine is agonist –> antagonist effects with prolonged exposure)
2) AChR-N antagonism (hexamethonium, mecamylamine)
what are the uses for ganglion blockers (nicotinic antagonists)
rarely used because there are many more selective autonomic agents available
list the effects of ganglionic blockade on the following:
(1) vasculature
(2) heart
(3) eyes
(4) GI tract
(5) bladder
(6) sweat glands
(7) salivary glands
1- (α1) vasodilation, venodilation, hypotension
2- (M2) inc HR
3- (M3) mydriasis, cycloplegia
4- (M3) reduced tone/motility, constipation, dec secretions
5- (M3) urinary retention
6- (M3) anhydrosis
7- (M3) xerostomia (dry mouth)
xerostomia =
dry mouth (absent salivary flow)
what is the biggest risk with using depolarizing blockers and what can be used to prevent it
(succinylcholine)
- Malignant hyperthermia: excessive Ca++ release from SR
- usually from combination of succinylcholine + halogenated anesthetic
- Tx with dantolene –> prevents Ca++ release from SR
(1) is prevents the synthesis of ACh by blocking (2) which functions to (3)
Hemicholium-3: blocks CHT (Na+/choline symporter), prevents uptake of choline necessary for ACh synthesis
(1) prevents the storage of ACh by blocking (2) which functions to (3)
Vesamicol: blocks VAChT (H+/ACh antiporter), prevents ACh storage w/in vesicles
