Antimuscarinic Agents and nicotinic block Flashcards by Maria Gasque

What are the muscinarinic receptor antagonists

Tertiary amine esters - atropine, scopolamine, hyoscyamine and homatropine; these are nonpolar and well absorbed from GI tract, cross BBB

Quarternary ammonium antagonists - methscopolamine, iprotrapium, tiotropium, glycopyrrolate, umaclidinium
these are poorly absorbed and barely cross BBB

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Action of Ach antagonists

Block ACh binding to M receptors, nonselective- binds all of them.

-M receptors are constitutively active and most antimuscarinic drugs are inverse agonists that stabalize the receptor in the inactive state.

binds pre and post synaptic receptors at both parasympathetic and sympathetic muscinaric synapses, peripheral ganglia and CNS

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Atroptine dose-related effects

Too Low dose - 0.5mg paradoxical bradycardia, slight cardiac slowing, some dryness of mouth and inhibition of sweating

1 mg — dry mouth, tachycardia, mild dilation of pupils

Higher doses:
2mg - rapid heart rate, blurred vision, dilated pupils

5mg - 10 mg: difficulty speaking and swallowing, difficulty with urination, GI ileus, progression into hot skin causing atropine flush, ataxia, restlessness, hallucinations and delerium, coma.

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Effects of muscarinic antagonist

Decreased REM sleep and fatigue, tachycardia, bronchodilation, dry mouth, delayed gastric emptying and constipation, problems with microurition, blurred vision, dry eyes, hyperthermia

With too low doses - paradoxical bradycardia

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What are the therapeutic uses of atropine?

Mydriasis and cycloplegia 
As a preanesthesia 
To counteract over-vagal stimulation of the heart - lowered HR; used in this manner primarily as a short-term intervention
Cholinergic poisoning - too much Ach 
Treatment of peptic ulcer disease 
as an antispasmodic

used along with scopolamine, glycopyrrolate, preoperatively to reduce bronchotracheal secretions and spasm.

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Therpuetic use of ipratropium and tiotropium

They are bronchdilators, inhalded
also, umeclidinium
Used for management of COPD
Ipratropium can be in a nasal spray as well, short acting

muscinarinic antagonists

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Oxybutnin

Oral, treatment of overactive bladder, somewhat selective M3 receptor inhibitor, cyp3A4 metabolism, antimuscinaric side effects

atropine-like drugs in general induce urinary retention by blocking Ach binding to it’s receptor and causing detruser muscle contration.

other drugs - tolterodine, darifenacin, soliffenacin. fesoterodine, and trospium

not for use in men with prostatic hyperplasia

muscinarinic antagonists

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Cyclopentolate and tropicamide

Used topically for mydriasis and cycloplegia for visualization of optic nerve, retina and lens

Shorter duration and preffered over atropinee and scopolamine

muscinarinic antagonists

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Benztropine and trihexyphenidyl

Adjunctive Rx Parkinson’s disease - treatment of drug induced extrapyramidal symptoms

muscinarinic antagonists

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What are the contraindications for atropine like agents?

Narrow-angle glaucome - obstruct aqueous humor outlow

Prostatic hyperplasia - exarcerbate urinary retention

Tachycardia - aggravates

GI obstruction, paralytic ileus, severe ulcerative colitis

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Toxicity of anticholinergic drugs

Red as beet — flushed with hot skin, sweating is inhibited, capillary vasodialation as an attempt to give off excess heat

Dry as a bone — salviary and other secretion are inhibited, dry mouth, dry skin, reduced GI secretions
-constipation, dyspepsia

Blind as a bat — large, nonreactive pupils and blurred vision

Hot as hades — hyperthermia, tachycardia, and hypertension

Mad as a hatter — confusion, disorientation, hallucinations, seisuzes and coma

Reversal with physostigmine

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what are the effects of ganglion blockers?

They supress homeostatic reflexes that typically moderate autonomic functions

nondepolarizing block of AChR’s of both ANS systems (para and sym) - inhibits ganglionic transmission

Can give knowlegde of effector organ responses to autonomic stimulation and help determine the predominant resting tone.

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What organ systems have a primarily sympathetic tone at rest?

Arterioles - drug causes vasodilation and hypotension
veins - drug causes dilation, pooling of blood in periphery and decreased venous return
sweat glands - drug causes anhidrosis
Genital tract - drug causes sexual impairment

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Which organ systems have a predominately parasympathetic tone at rest?

Heart - drug causes tachycardia
iris - drug causes mydriasis
ciliary muscle - causes cycloplegia (farsightedness)
GI tract - causes reduced tone and motility and decrease in gastric and pancreatic secretions.
urinary bladder - urinary retention
salivary glands - xerostemia
genital tract

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previous therapeutic uses of ganglionic inhibitors

Was used classically for chronic hypertension, acute hypertensive crisis and controlled hypotension

Discontinued because of lack of selectivity leading to a broad range of undesirable effects

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What are the contraindication and drug interactions of ganglionic inhibitors?

Contraindications - cononary insuffciency, pyloric stenosis, glaucoma, uremia, recent MI, unreliable or uncontrollable patients

Drug interactions - patients on ganglionic blocks are still responsive to autonomic drugs acting on mAChRs, alpha and beta receptors leading to exaggerated or reversed ANS responses

what are the types of neuromuscular nicotinic receptor antagonists?

Succinylchoine
Benzylisoquinolines
Aminosteroids

Quarternary ammonium compounds, depolarizing agenst and non—depolarizing agents

Does not cross BBB, IV with poor absorption.

Succinylcholine

A depolarizing agent - fexible structure

Metabolized by plasma cholinesterase

Works almost instantly and lasts for mere minutes… metabolized quickly (4 to 6 min)

first causes fasciculations (because of channel opening) followed by flaccid paralysis

People deficient in plasma cholinesterase will have the drug active longer causing prolonged apnea at therapuetic doses

can be used to facilitate endotracheal intubation, unlikely to cause hypoxia in a pre-oxygenated patient

Amino sterols

metabolized heptically and renally - active metabolites

Intermediate acting drugs - rocuronium and vecuronium

Long acting - pancuronium

Nondepolarizing

Benzylquinolines

Non-hepatic metabolism

Short acting - mivacurium (plasma cholinesterase)

Intermediate — atracurium (metabolite laudanosine crosses BBB) and Cisatrcurium (spontaneous metabolism)

Long acting - doxacurium and Tubocurarine (renal metabolism)

Non-depolarizing nicotinic antagonists

Rocuronium

Amino steroid, onset in 1-2 minutes and lasts for 36 to 73 minutes

least potent NM blocker

rapid-induction anesthesia and relaxing laryngeal and jaw muscles for tracheal intubation, can be used to relax muscles for patients on mechanical ventilation

causes hypersensitivity reactions more commonly than the other drug versions

Cisatracuruim

benzylquinoline, intermediate acting
onset in 2 - 8 minutes
duration for 45 to 90 minutes

does not cause histamine release and less is metabolized to laudanosine. clincally used in place of atracurium.

Does not accumulate and degrades in plasma without aid of enzymes

facilitation of endotracheal intubation, skeletal muscle relaxation during surgery or mechanical ventilation

Vecuronium

amino steroid
onset - 2 to 3 minutes
duration - 40 to 45 minutes

Intermediate-acting agent; facilitation of endotracheal intubation, skeletal muscle relaxation during surgery or mechanical ventilation

Pancuronium

long acting amino steroid

onset: 3 to 5 min
duration: 85 to 100 min

more potent than the short-acting versions. Difficult to achieve reversal post-op

facilitation of endotracheal intubation, skeletal muscle relaxation during surgery or mechanical ventilation

slightly increases HR

Atracurium

intermediate acting benzyquinoline onset in 3 min duration is 45 min spontaneous decomposition with an active metabolite - laudanosine: crosses BBB and decreases seizure threshold. Can accumulate in patients with biliary obstruction or prolonged use of atracurium. (excreted both in renal and biliary systems) causes histamine release

General therapuetic uses of neuromuscular blocks

as an adjuvant to surgical anesthesia facilitate intubation - endotracheal intubation, laryngoscopy, bronchoscopy and esophagoscopy control of ventilation used in orthopedic procedures pain and consciousness is still intact with these NM blockers - to be used with anesthesia

What would you administer to reverse a competitve nondepolarizing neuromuscular blocking drug?

Neostigmine - inhibits degradtion of Ach, allowing the Ach to accumulate and outcompete the NM blocking agent pyridostigmine, edrophonium - same mechanism also, sugammadex

What is purpose of sugammadex?

Reversal of steriodal NM blocking agents - rocuronium and vecuronium Forms a tight 1:1 complex that is excreted in the urine

Name the adverse affects on succinylcholine?

Prolonged apnea - especially in patients with low or absent plasma cholinesterase Maligant hyperthermia - paitents with congenital myopathies Bradycardia - in children, requires pretreament with atropine Others - histamine release, hyperkalemia, myalgia, myoglobinuria and increase intra gastric and intraocular pressure regurgitation and aspiration secondary to increase intragastric pressure - a complication is more likely to occur in patients with delayed gastric empying (diabetes, traumatic injury, esophageal dysfunction and obesity)

What are the contraindications of succinylcholine?

Myopathies or UMN disease -> malignant hyperthermia, or personal/family history of -> other muscular dystrophies; paraplegia or quadroplegia spinal cord injuries, multiple trauma Burn patients - increased risk of hyperkalemia Patients with spinal or ocular injury Children Older age because of a decrease in renal clearance

Scopolamine

Transdermally for motion sickness, preanesthesia, mydraisis and cyclopllegia — gets into CNS at low doses (which is why it is used for motion sickness) spreads widely and quickly to CNS and rest of body, CNS effects are greater than other antimuscarinic's

therpeutic use of methscopolamine

decreases GI secretions and peristalsis, used in peptic ulcer disease but for the most part have been replaced by proton pump inhibitors (omeprazole) and H2 receptor blockers (ranitidine)

antispasmotics - antimuscarinics

symptomatic treatment of IBS, spastic colitis hypermotility, biliary or renal colic (use with morphine or other opiods) drugs - dicyclomine, hyoscyamine, belladonna alkaloids

ophthalmic therapeutic uses of antimuscarinics

induction mydriasis for fundascopic exam, eye surgery, iridocyclitis and keratitis therapy alternate with a miotic to prevent or break adhesions between iris and lens

reversal of antimuscarinic toxicity

rx physostigmine - increases levels on Ach in synapsis which outcompetes the antimuscarinic drug (anti cholinesterase inhibitor) other required measures - respiratory and cardiovascular support, detoxification and seizure treatment with denzodiazepine

what structure allow specificity for neuromuscular blockade?

2 ammonium groups separated by 10 Carbon atoms, (succinylcholine, pancorium etc) ANS blocking agents (the no longer used ganglionic blockers) have 2 ammonium groups separated by 6 C's

treatment for malignant hyperthermia

dantrolene - blocks the ryanodyne receptor in skeletal muscle (RyR1) which blocks the opening of the calcium channel on the sacroplasmic reticulum does not effect cardiac and smooth muscle

Tubocurarine

long duration, non-deplorizing NM blocker, associated with the greatest amount of histamine release and hypotension not used clinically.

drug interactions of NM blockers - which one is favorable?

volatile halogenated anesthetics - favorable, stabalizes the effect aminoglycoside antibiotics - potentiates NM Blockade other antibiotics - tetracycline, clindamycin, vancomycin, colistin and polymyxin B