Autonomic-Cholinergic Pharmacology Flashcards Preview

Pharmacotherapeutics I > Autonomic-Cholinergic Pharmacology > Flashcards

Flashcards in Autonomic-Cholinergic Pharmacology Deck (66):
1

Cholinergic recptors

Muscarinic and nicotinic

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Muscarinic Receptors

M1, M2, M3, M4, M5

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M1

Neural areas- CNS, PNS, gastric parietal cells

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M2

Cardiac, bladder, lung

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M3

Glandular- exocrine glands, smooth muscle, bladder, and eye

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M1, M3, M5 coupled to G-Proteins

Activate second messenger systems responsible for the stimulation of phospholipase C

7

M2 and M4 coupled to G proteins

Responsible for adenyl cyclase inhibition and K+ channel activation

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Nicotinic receptors

N2 and Nn- autonomic ganglia
N1 or Nm- Neuromuscular junction (NMJ)-somatic motor end plates.

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Responses mediated by muscarinic receptors - Heart (AV node and Atria)

Decreased heart rate
Decreased AV nodal conduction

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Responses mediated by muscarinic receptors - Eyes

Contraction of sphincter muscle of iris and ciliary muscles

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Response mediated by muscarinic receptors- Gastrointestinal

Increased tone, mobility, and secretion

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Response mediated by muscarinic receptors- Urinary bladder

Relaxation of sphincter

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Response of muscarinic receptors- secretory glands (sweat, bronchial, salivary)

Increased secretion

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Pharmacological properties of choline esters on the Cardiovascular system

Vasodilation, decreased cardiac rate, decreased conduction rate, and decreased force of cardiac contraction

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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)

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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.

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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.

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Bethanechol side effects

sweating, salivation, flushing, HPOTN, N/D, abd pain and bronchospasm.

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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

20

Carbachol (Carbamylcholine) adverse reactions

Little to no side effects when used in the eye

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Methacholine

Receptors- M1, M2, M3
Used as diagnostic challenge for bronchial hyperreactivity and asthmatic conditions

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Cholinomimetic natural alkaloids and synthetic analogs

Pilocarpine, muscarine, and arecoline

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Muscarine

acts almost exclusively at muscarinic receptor sites

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arecoline

acts at nicotinic receptor sites

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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.

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Pilocarpine ADR

CNS effects, profuse sweating and salivation

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Major contraindications to use of choline esters

Asthma, hyperthyroidism, coronary insufficiency, and peptic ulcer disease.

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Ach and agonist antidote

Atropine

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Ach and agonist route of administration

Oral and subcutaneous for systemic. Sometimes in the eye for local.

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Undesirable effects of Ach

Flushing, sweating, abd cramping, sensation of tingling in the urinary bladder, difficult visual accommodation, HA, and salivation

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Indirect-acting Cholinomimetic drugs- Reversible

Water soluble
Physostigmine
Neostigmine
Pyrostigmine
Edrophonium (tacrine, donepezil, rivastigmine, and galantamine)

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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)

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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

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Neostigmine, pyridostigmine, edrophonium

Myasthenia gravis, helps w/ reversal of neuromuscular block
Action- amplified effects of Ach, increased muscle strength.

35

Isoflurophate and echothiopate

Glaucoma (not the 1st line therapy
Action- amplifies the effect of Ach

36

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

37

Excessive acetylcholine effects

D-Diarrhea
U-Urination
M-miosis
B-bronchoconstriction
E-Exitation (CNS or muscle)
L-lacrimation
S-sweating and salivation

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Nicotinic effects

M-Mydriasis, muscle twitching
T-tachycardia
W- weakness
tH- hypertension, hyperglycemia
F- fasciculations

39

Pralidoxime

Cholinesterase reactivator that breaks bonds between drugs and enzymes if the enzyme has not aged.

40

Effects of muscarinic blocking drugs- CNS

Drowsiness, antimotion sickness action, antiparkinson action, amnesia, delerium

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Effects of muscarinic blocking drugs- Eye

Clycoplegia, mydriasis, reduction of lacrimal secretion

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Effects of muscarinic blocking drugs- bronchi

bronchodilation

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Effects of muscarinic blocking drugs- GI

relaxation, slowed peristalsis

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Effects of muscarinic blocking drugs-Gu

Relaxation of bladder wall, urinary retention

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Effects of muscarinic blocking drugs-Heart

Initial bradycardia, then tachycardia

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Effects of muscarinic blocking drugs-glands

Decreased secretion

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Antimuscarinic drug- benztropine

Treats manifestation of Parkinson Disease

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Antimuscarinic drug- scopolamine

prevent or reduce motion sickness

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Antimuscarinic drug atropine

Produce mydriasis and cycloplegia

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Antimuscarinic drug- Ipratorium

Bronchodilate in ashtma

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Antimuscarinic drug- methscopolamine

Reduce transient mobility- used in combination with other antiulcer drugs

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Antimuscarinic drug- Oxybutinin

Treats transient cystitis and postoperative bladder spasms.

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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.

54

Cause anticholinergic toxicity

Antihistamines-diphenhydramine
Tricyclic antidepressants- amitryptyline
Atypical antipsychotics- olanzapine
Neuroleptic antipsychotics- chlorpromazine

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Ganglionic Blockers

Interfere w/ postsynaptic transmission
block action of Ach on nicotinic receptors

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Trimethaphan and Mecamylamine

competitive agonists of Ach at ganglionic nicotinic receptors.

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Non-depolarizing (competitive)

drugs that bind to nicotinic cholinergic receptors to induce a competitive blockade of Ach (affinity without efficacy)
D-tubocurarine

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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

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Long acting duration of action (DOA)

Curare and Pancuronium

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Intermediate actiong DOA

Cisatracurium and atacurium (metabolism not dependent on hepatic or renal function)

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Short acting DOA

Mivacurium and succinylcholine

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Properties of neuromuscular blocking agents- selevtivity

curare is not selective for NMJ

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Properties of neuromuscular blocking agents- ganglionic block

nicotinic antagonist induces tachycardia and hypotension

64

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.

65

Properties of neuromuscular blocking agents- histimine release

By action on mast cells. Induces bronchospasm, hypotension, airway secretion

66

Botulinum (Botox)

Toxin inhibits Ach release, thus interferes with nerve impulses and causes flaccid paralysis of muscles.