Autonomic-Cholinergic Pharmacology Flashcards
Cholinergic recptors
Muscarinic and nicotinic
Muscarinic Receptors
M1, M2, M3, M4, M5
M1
Neural areas- CNS, PNS, gastric parietal cells
M2
Cardiac, bladder, lung
M3
Glandular- exocrine glands, smooth muscle, bladder, and eye
M1, M3, M5 coupled to G-Proteins
Activate second messenger systems responsible for the stimulation of phospholipase C
M2 and M4 coupled to G proteins
Responsible for adenyl cyclase inhibition and K+ channel activation
Nicotinic receptors
N2 and Nn- autonomic ganglia
N1 or Nm- Neuromuscular junction (NMJ)-somatic motor end plates.
Responses mediated by muscarinic receptors - Heart (AV node and Atria)
Decreased heart rate
Decreased AV nodal conduction
Responses mediated by muscarinic receptors - Eyes
Contraction of sphincter muscle of iris and ciliary muscles
Response mediated by muscarinic receptors- Gastrointestinal
Increased tone, mobility, and secretion
Response mediated by muscarinic receptors- Urinary bladder
Relaxation of sphincter
Response of muscarinic receptors- secretory glands (sweat, bronchial, salivary)
Increased secretion
Pharmacological properties of choline esters on the Cardiovascular system
Vasodilation, decreased cardiac rate, decreased conduction rate, and decreased force of cardiac contraction
Pharmacological properties of choline esters on GI
Increase tone, amplitude of contraction, peristaltic activity of stomach and intestines, enhanced secretory activity, and enhanced mobility (accompanied by Nausea, vomiting, belching, intestinal cramping, and defecation)
Pharmacological properties of choline esters on urinary tract
Increased ureteral peristalsis, contract of the detrusor muscles of urinary bladder, increased maximal voluntary voiding pressure, and decreased capacity of the bladder.
Bethanechol- cholinergic agonist
Acts on receptors M1, M2, M3
Poor substrate for AchE
Sites- smooth musculature of the bladder and GI
Actions- increased intestinal motility and tone, and stimulates detrusor muscles of the bladder while the trigone and sphincter are relaxed causing expulsion of urine.
Therapeutic action- stimulates atonic bladder in postpartum or postoperative urinary renention.
Bethanechol side effects
sweating, salivation, flushing, HPOTN, N/D, abd pain and bronchospasm.
Carbachol (carbamylcholine)
Poor substrate of AchE with DOA of as long as 1hr
Action- M1, M2, M3 and wak nicotinic agonist-CV and GI systems- may first stimulate then depress, can also cause release of epinephrine for adrenal medulla by its nicotinic acitons.
Therapeutics- used seldomly, sometimes as miotic for gluacoma
Carbachol (Carbamylcholine) adverse reactions
Little to no side effects when used in the eye
Methacholine
Receptors- M1, M2, M3
Used as diagnostic challenge for bronchial hyperreactivity and asthmatic conditions
Cholinomimetic natural alkaloids and synthetic analogs
Pilocarpine, muscarine, and arecoline
Muscarine
acts almost exclusively at muscarinic receptor sites
arecoline
acts at nicotinic receptor sites
Pilocarpine
Dominant muscarinic response at M1, M2, M3
Tertiary amine and less potent
Action- rapid miosis and contraction of the ciliary muscle
Therapeutic use- emergency lowering of the intraocular pressure of both narrow and wide-angle glaucoma.
Pilocarpine ADR
CNS effects, profuse sweating and salivation
Major contraindications to use of choline esters
Asthma, hyperthyroidism, coronary insufficiency, and peptic ulcer disease.
Ach and agonist antidote
Atropine
Ach and agonist route of administration
Oral and subcutaneous for systemic. Sometimes in the eye for local.
Undesirable effects of Ach
Flushing, sweating, abd cramping, sensation of tingling in the urinary bladder, difficult visual accommodation, HA, and salivation
Indirect-acting Cholinomimetic drugs- Reversible
Water soluble Physostigmine Neostigmine Pyrostigmine Edrophonium (tacrine, donepezil, rivastigmine, and galantamine)
Indirect-acting Cholinomimetic drugs- irreversible/Organophosphates (covalent binding; lipid soluable/cross BBB)
Echothiopate (tx for open angle glaucoma)
Tabun, sarin, soman, parathion, malathion (typically pesticides)
Physostigmine
Glaucoma (miosis in the eye); increased intestinal and bladder motility, reverse CNS and cardiac effects of TCA (tricyclic antidepressant); reverse CNS effects of atropine.
Action- amplifies effect of Ach
Neostigmine, pyridostigmine, edrophonium
Myasthenia gravis, helps w/ reversal of neuromuscular block
Action- amplified effects of Ach, increased muscle strength.
Isoflurophate and echothiopate
Glaucoma (not the 1st line therapy
Action- amplifies the effect of Ach
Effects of severe acetylcholinesterase inhibition
Indirect agonists “amplify” action of endogenous acetylcholine.
GI-Diarrhea, urination, salivation
Eye-miosis
Respiratory- bronchoconstriction, increased bronchial secretion
CNS- tremor, anxiety, convulsion, and coma
SKeletal muscle- fasciculation
CV- hypotension
Excessive acetylcholine effects
D-Diarrhea U-Urination M-miosis B-bronchoconstriction E-Exitation (CNS or muscle) L-lacrimation S-sweating and salivation
Nicotinic effects
M-Mydriasis, muscle twitching T-tachycardia W- weakness tH- hypertension, hyperglycemia F- fasciculations
Pralidoxime
Cholinesterase reactivator that breaks bonds between drugs and enzymes if the enzyme has not aged.
Effects of muscarinic blocking drugs- CNS
Drowsiness, antimotion sickness action, antiparkinson action, amnesia, delerium
Effects of muscarinic blocking drugs- Eye
Clycoplegia, mydriasis, reduction of lacrimal secretion
Effects of muscarinic blocking drugs- bronchi
bronchodilation
Effects of muscarinic blocking drugs- GI
relaxation, slowed peristalsis
Effects of muscarinic blocking drugs-Gu
Relaxation of bladder wall, urinary retention
Effects of muscarinic blocking drugs-Heart
Initial bradycardia, then tachycardia
Effects of muscarinic blocking drugs-glands
Decreased secretion
Antimuscarinic drug- benztropine
Treats manifestation of Parkinson Disease
Antimuscarinic drug- scopolamine
prevent or reduce motion sickness
Antimuscarinic drug atropine
Produce mydriasis and cycloplegia
Antimuscarinic drug- Ipratorium
Bronchodilate in ashtma
Antimuscarinic drug- methscopolamine
Reduce transient mobility- used in combination with other antiulcer drugs
Antimuscarinic drug- Oxybutinin
Treats transient cystitis and postoperative bladder spasms.
Toxicity of antimuscarinic drugs
Red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare
Flushing, dry skin and mucous membranes, mydriasis w/ loss of accommodation, AMS, and fever.
Cause anticholinergic toxicity
Antihistamines-diphenhydramine
Tricyclic antidepressants- amitryptyline
Atypical antipsychotics- olanzapine
Neuroleptic antipsychotics- chlorpromazine
Ganglionic Blockers
Interfere w/ postsynaptic transmission
block action of Ach on nicotinic receptors
Trimethaphan and Mecamylamine
competitive agonists of Ach at ganglionic nicotinic receptors.
Non-depolarizing (competitive)
drugs that bind to nicotinic cholinergic receptors to induce a competitive blockade of Ach (affinity without efficacy)
D-tubocurarine
Depolarizing (Non-competitive)
Resistant to AchE so they persist in the synaptic cleft and continually depolarize the neuromuscular end-plate thus the action potential cannot be elicited.
Decamethonium
Long acting duration of action (DOA)
Curare and Pancuronium
Intermediate actiong DOA
Cisatracurium and atacurium (metabolism not dependent on hepatic or renal function)
Short acting DOA
Mivacurium and succinylcholine
Properties of neuromuscular blocking agents- selevtivity
curare is not selective for NMJ
Properties of neuromuscular blocking agents- ganglionic block
nicotinic antagonist induces tachycardia and hypotension
Properties of neuromuscular blocking agents-Vagolytic
Muscarinic antagonist induces because you are blocking at the ganglia and it stops the end result of muscarninc receptoryou see the muscarinic block.
Properties of neuromuscular blocking agents- histimine release
By action on mast cells. Induces bronchospasm, hypotension, airway secretion
Botulinum (Botox)
Toxin inhibits Ach release, thus interferes with nerve impulses and causes flaccid paralysis of muscles.
