Cholinergic Antagonists Flashcards
Scopolamine hydrobromide (Transderm Scop™)
Class: Alkaloid derived from plant, muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors throughout body Indications: prevention of nausea and vomiting caused by motion sickness; for prolonged use, usually given as a transdermal patch; can also be given as oral tablet
PK: when given as a patch (1.5 mg), onset is in 4 h, peak 24 h, duration 72 h (apply new patch every 3 days)
Contraindications and ADRs: avoid in patients with acute angle-closure glaucoma, urinary or GI tract obstruction, ileus, toxic megacolon, or ophthalmic prep in patients with eye adhesions between iris and lens; can cause wide range of anticholinergic side effects, including agitation, confusion, delirium, blurred vision; avoid also in patients with BPH, in patients in hot or humid environments
Other facts: overdose can cause delirium and tachycardia; physostigmine is occasionally given for severe overdose
Dose: apply transdermal patch (1.5 mg) behind ear 4 hours before anticipated trip, apply new patch every 3 days
Tiotropium
Class: Synthetic, inhaled muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors in the respiratory tract, thus leading to bronchodilatation
Indications: bronchospasm in chronic bronchitis and emphysema; bronchospasm in asthma; rhinorrhea in allergic rhinitis or with common cold
PK: much of an inhaled dose is actually swallowed (only 10% gets to lungs); not well absorbed from the resp tract; drug is metabolized in liver, or excreted unchanged in feces
Duration: 24 hours
Contraindications and ADRs: avoid in patients with problems with atropine or similar drugs; use cautiously in patients with angle-closure glaucoma, BPH, bladder neck obstruction;
ADRs include bitter taste, blurred vision, dry moiuth, nausea, bronchospasm (perhaps from propellant)
Other facts: close relative is tiotropium (Spiriva™)
Dose: for bronchospasm, usual dose is 2 puffs (36 mcg per puff) qid not to exceed 12 puffs per 24h
Rocuronium Bromide (Zemuron™)
Class: Neuromuscular blocker; approved by FDA in 1994
MOA: Bind to and block NMJ cholinergic receptors (NM), denying access to ACh, and producing a flaccid paralysis; developed to have rapid onset of action, relatively short duration of action, and minimal release of histamine; sequence of paralysis begins with small muscles (eyes, face, neck), then large muscles (limbs, chest, abd wall) and finally diaphragm Indications: to facilitate routine or rapid-sequence intubation; to produce NM blockade during surgery or ventilation
PK: has a half-life of rapid distribution (1-2 min), slower distribution phase (14-18 min), and terminal half-life (2.4 h); cleared mostly via hepatic metabolism
Contraindications and ADRs: never give to patient allergic to bromide; can cause hypo- or hypertension, tachycardia
Other facts: Other than succinylcholine, has the most rapid onset of any neuromuscular blocker, so useful when you wish to avoid sux, but need a rapid induction and rapid paralysis; little histamine release, no ganglionic blocking effects (both of which minimize hypotension)
Dose: always given iv; varies with indication, and with which inhalational agent is being used
Atropine
Class: Alkaloid derived from belladonna, muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors throughout body
Indications: symptomatic bradycardia; pre-op patients to reduce bronchial secretions and to block vagal reflexes (e.g. during intubation); to block muscarinic effects of anticholinesterases given to reverse effects of neuromuscular blockers; antidote for poisoning by anticholinesterase insecticides or poisons (e.g. Sarin); to manage pupil size in patients with acute iritis or uveitis
PK: most commonly given iv, but also topically to eye; >50% metabolized in liver; after iv dose, onset immediate, peak 2-4 min, duration 4 h
Contraindications and ADRs: avoid in patients with acute angle-closure glaucoma, urinary or GI tract obstruction, ileus, toxic megacolon, or ophthalmic prep in patients with eye adhesions between iris and lens; can cause wide range of anticholinergic side effects, including agitation, confusion, delirium, blurred vision
Other facts: overdose can cause delirium and tachycardia; physostigmine is occasionally given for severe overdose
Dose: for bradycardia, 0.5 -1 mg iv push; for pre-op use, 0.4 mg IM 3o minutes before anesthesia; for insecticide poisoning, may need 2-6 mg iv, repeated every 5 minutes
Succinylcholine (Anectine™)
Drug class: Neuromuscular blocking agent, of the depolarizing type (only member of this class); approved by the FDA in 1952
MOA: binds to NM receptors (specifically) and causes inward Na current and depolarization of the muscle cell; this leads to influx of calcium and contraction, visible as muscle fasciculations; tight binding to receptor prevents Ach from binding to receptor; drug itself is not cleaved by AChE; eventually the cell extrudes calcium, and the fasciculations and contraction ceases, leading to a flaccid paralysis (remember, Ach can’t access the nicotinic receptor, it is blocked
Indications: to produce muscle paralysis quickly and briefly, as needed for emergency intubations, or for brief procedures such as ECT
PK: when given iv 90% of drug is eventually metabolized pseudocholinesterase, but not by the actual synaptic AChE; complete relaxation is produced within 30-60 sec, and lasts 2-10 minutes, with gradual recovery of muscle strength and ability to contract
Contraindications, ADRs: previous malignant hyperthermia, or prolonged paralysis (due to deficiency in pseudocholinesterase); avoid in patients with burns, trauma, or renal disease (prolonged half-life of succinylmonocholine); ADR’s include apnea, bradycardia, cardiac arrest, asystole, bronchospasm, malignant hyperthermia, salivation, hypotension
Other info: quickest onset of all muscle relaxants (makes intubation easier, more quickly); known to release histamine in some patients; reserved now for use in emergencies that require “crash intubation”
Dose and route: for iv route in adults, 1.0-1.5 mg/kg, up to 150 mg total dose
Trimethaphan (Arfonad)
Drug class: Ganglionic blocker (NN cholinergic receptor blocker)
MOA: binds to NN receptors (specifically) and prevents action of locally released ACh, thereby blocking neurotransmission in both parasympathetic and sympathetic ganglia; since usually the SNS has greater tone, this results primarily in drop in HR and BP; dose can be titrated to produce desired reduction in BP; drop is greater if patients is placed in head-up tilt (pooling of blood in leg veins)
Indications: to produce deliberate hypotension during some operative procedures; not used very often, as more precise blood pressure-lowering agents are now available
PK:
Contraindications, ADRs: should not be given to patients who are hemodynamically unstable, or who are already hypotensive; since there are many side effects, only given to anesthetized patients
Other info: oral formulation not available; harder to titrate than drugs such as nitroprusside
Dose and route: for iv route only,
Benztropine mesylate (Cogentin™)
Class: Synthetic muscarinic receptor blocker
MOA: Tertiary amine, therefore able to penetrate blood brain barrier to reach and block muscarinic receptors located in the CNS; changes the balance of CNS dopaminergic tone to cholinergic tone (reduced)
Indications: parkinsonism; to treat some drug (neuroleptic)-induced extrapyramidal reactions, including acute dystonic reactions
PK: absorbed from GI tract, metabolism unknown; excreted in urine as unchanged drug; with po use, onset 1-2 h, duration 24 h; with iv use, onset 15 min, duration 24 h
Contraindications and ADRs: avoid in patients with acute angleclosure glaucoma; in children < 3 yo; in hot weather; ADRs include confusion, psychosis, tachycardia, blurred vision, dilated pupils, constipation, dry mouth, ileus, urine retention nausea, bronchospasm (perhaps from propellant)
Other facts: avoid use in breast-feeding women
Dose: for parkinsonism, 0.5 to 6 mg po daily; for drug-induced extrapyramidal reactions, 1-4 mg po per day; for acute dystonic reaction, 1-23 mg iv, followed by 1-2 mg po bid to prevent recurrence
Ipratropium (Atrovent™)
Class: Synthetic, inhaled muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors in the respiratory tract, thus leading to bronchodilatation Indications: bronchospasm in chronic bronchitis and emphysema; bronchospasm in asthma; rhinorrhea in allergic rhinitis or with common cold
PK: much of an inhaled dose is actually swallowed (only 10% gets to lungs); not well absorbed from the resp tract; drug is metabolized in liver, or excreted unchanged in feces
Duration: 6-8 hours
Contraindications and ADRs: avoid in patients with problems with atropine or similar drugs; use cautiously in patients with angle-closure glaucoma, BPH, bladder neck obstruction;
ADRs include bitter taste, blurred vision, dry moiuth, nausea, bronchospasm (perhaps from propellant)
Other facts: close relative is tiotropium (Spiriva™)
Dose: for bronchospasm, usual dose is 2 puffs (36 mcg per puff) qid not to exceed 12 puffs per 24h
