Anti-Muscarinic and Ganglionic

8/13/2019 Anti-Muscarinic and Ganglionic

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Acute nicotine poisoning



Onset of symptoms is rapidNicotinic receptors desensitize very quickly (w/in seconds)

Initial: salivations, nausea, vomiting, abdominal pain, diarrhea,loss of urine and feces, cold sweat, tachypnea, tachycardia,disturbed hearing and vision, headache, dizziness, mental

confustion, marked weakness

Progress to --> faintness and prostration, falling of BP, weak,irregular and rapid pulse, difficulty in breathing, tremors,convulsions --> death from respiratory failure within minutes



Acute OD of anti-muscarinic

How would death occur?



Think 3 C'sConvulsions, Coma, Cardiac

*for this to occur it can be quaternary compound...must betertiary so that it crosses BBB

Death due to respiratory failure, may follow after a period of ciculatory collapse and coma

In cases of serious poisioning, symptoms and signs appear

within 30-60 minutes and may last 2-7 days



Anti-muscarinic effect of

respiratory system



bronchial smooth musclerelaxation

decreased secretionsdecreased mucociliary

clearance





decreased secretion of sweat glands (atropine

fever)



Anti-muscarinic effect on

Eye



relax sphincter of iris --> mydriasisrelax ciliary muscle --> cycloplegia(hinders outflow of aqueous humorthrough Schlemm canal)

decreased secretion of lacrimal glands

Atropine given locally can last for 3 days

or more




Genitourinary system



relax pelvis, calyces, uretersdecrease ureteral

peristalsisrelax detrusor




GI



decrease gastric secretion

decrease tone, amplitude of contractions, peristaltic activity andsecretions of intestinal tractrelax LESmild relaxation of gallbladder and bile ducts



Antimuscarinictherapeutic dose on CV

vessels?High dose?



therapeutic dose --> negligible effects

on circulationin kids...can cause "dilitation" =atropine flush

high doses --> dilitation of cutaneous blood vessels (atropine flush)



AtropineScopolamineHomatropineDarifenacin

Benzotropine



Tertiary Amine (enters CNS)

Anti-muscarinic drugs

*Actually, atropine and scopolamineare natural alkaloids found in severalplants (jimsonweed, deadly nightshade)



BiotransformationExretion

Half-lives




50% atropine and 90% scopolamine are

metabolized by liver

60% atropine excreted by kidney

Atropine/scopolamine = 3 hour half lifeGlycopyrrolate = 10 hours



Carbachol

Cholinesterase inhibitorsSuccinylcholine

GlycopyrrolateIpratropiumTubocurarine



Drugs with significantganglionic activity as side

effects



Darifenacin

what class of drug is it? which receptor does it have

the highest affinity for?



Anti-muscarinic - tertiary amine

M3



EyeFor funduscopic examinationFor measurements of refractive errorsIritis, iridocyclitis, choroiditis

Gastrointestinal system

Irritable bowel syndrome Abdominal colic, biliary colic.DiarrheaSialorrheaMotion sickness prevention and treatment (scopolamine)

Urinary systemRenal colic, enuresisUrge incontinence

Respiratory systemPreoperative useBronchial asthma and chronic obstructive pulmonary disease (ipratropium)

Cardiovascular systemCardiopulmonary resuscitationSinus or nodal bradycardia

A-V block Preoperative use



Therapeutic uses of antimuscarinic drugs

again...just think logically about each one

ALSO:

Central nervous systemParkinson's disease (Trihexyphenidyl)

Other usesTo counteract the parasympathomimetic effects of neostigmine in myasthenicpatients.Poisoning by AchE inhibitors or by certain mushrooms containing muscarine.





Nicotine



Give 5adjectives forfeatures of poisinoning with anti-cholinergics



RED = vasodilation

HOT = vasodilation andhyperthermiaDRY = reduced sweating, salivation,

fluid intake & dehydrationBLIND = cycloplegia and mydriasisMAD = delirum



GlaucomaProstatic hypertrophy Urinary tract obstructionGastrointestinal tract obstruction Adynamic ileusGastric ulcerSevere infectious diarrheaReflux esophagitisUlcerative colitis, Crohn' disease (toxic megacolon can ensue)TachyarrhythmiasCoronary artery disease, cardiac failureHyperthyroidismChildrenElderly



List of contraindications andprecautions of antimuscarinic drugs

just think about what is going on witheach and think logically why you wouldnt want to give anti-muscarinic



Glycopyrrolate

Ipratropium



Quaternary ammoniumcompounds (no CNS)




Half life of nictoine





KAPLAN FACT

Someone on Atropine candevelop what in heart/ekg



Tachycardia (ventricular) (Inc.

QRS) (Inc. QT interval) (TorsaDe Pointes) --> cardiac toxicity

Treat torsa de pointes withMg!!!



KAPLAN FACT

What are some othercategories of drugs that haveanti-cholinergic side effects



Antihistamines

Tricyclic anti-depressants Anti-psychotics

Qunidine AmantadineMeperidine (opiate)



KAPLAN FACT:

Tropicamide



Anti-muscarinic drug used topically

eye drops --> shorter dilation of eye

preferred over Atropine b/c of shorter half-life



Lets Play a game: What branch of ANS provides the predominant tone? and what would happen if i used a ganglionic blocker

Heart Arterioles VeinsIrisCiliary MuscleGI TractUrinary bladderExocrine glandsEjectionEjaculation



Heart --> PNS --> Tachycardia Arterioles --> SNS --> vasodilation, orthostatic hypotension

Veins --> SNS --> vasodilation, venous pooling, decr COIris --> PNS --> MydriasisCiliary Muscle --> PNS --> cycloplegiaGI Tract --> PNS--> constipation, gas accumulation

Urinary bladder --> PNS --> urinary retentionExocrine --> SNS --> anhydrosisEjection --> PNS --> impairedEjaculation --> SNS --> impaired



Mecamylamine



Ganglionic blocking

drugs



Moderate dose of nicotinegiven

Effect on GI?

High dose?



anorexia, nausea, vomitingstimulation of peristalsis and

secretions

Toxic doses --> paralytic ileus



Moderate dose of nicotine? high dose?effect on Respiratory



stimulation of respiration bronchoconstriction and

increased secretions

Toxic --> apnea



Moderate doses of nicotinegiven:

What affect on CV system?

How bout high/toxic doses?



Increase CO and HR Constriction of skin and splnachnic vesselsDilation of muscular vessels

Increased BP

Toxic --> cardiovascular collapse



Name as many anti-muscarinic drugs as you

can



Atropine (natural)Scopolamine (natural)Homatropine (3)Darifenacin (3)

Benzotropine (3)Glycopyrrolate (4)Ipratropium (4)



Pharmacologic paralysis of accomodation with the useof atropine works restoring visual acuity in children with _________?

bl l ( h h



Amblyopia - lazy eye (which occurs in50% of kids withesotropia/strabismus/squint

Atropine eyedrops blur the healthy eye at near vision and force fixationof the amblyopic eye



Pharmacological Effects

of Nicotine on CNS

ti l t R h ll (i hibit i t f LMN )



stimulate Renshaw cells (inhibitory interneurons of LMNs)stimulate or depress reticular formationdirect and reflex stimulation of respiratory and vasomotorcentersreflex stimulation of the emetic centerdirect stimulation of the chemoreceptor trigger zonestimulation of ADH secretionMild Stimulation of attention and memory sedative-anxiolytic activity generalized stimulation of cerebrospinal axis which leads tohyperreflexia, tremors, convlusions



SCOPOLAMINE uses

( i i )



(tertiary amine)

Used for motion sicknessopthalmology sedation and short-term

memory block (anterogradeamnesia)



So if i give someone anantimuscarinic drug: how

would an intermediate doseaffect their CNS?

How about a high dose?

Intermediate:



Intermediate:mild central vagal stimulation

fatigue, sedation, drowsiness, dreamless sleepdepression of vestibular functionreduction of parksonian tremor and rigidity

High doseamnesia, malaise, restlessness, irritability,disorientation, hallucinations, delirium. Centralstimulation followed by depression (coma)



Someone has been poisoned by a antimuscarinic

drug...what are signs andsymptoms in each of the

different organs



Stimulation of sweat glands



Stimulation of sweat glandsmiosis

induction of mixed function oxidasesincreased platelet aggregation and bloodcoagulability loss of body wtincreased hand tremorsparalysis of skeletal muscle



Nicotine effects





Benztropine (tertiary

amine)



This ganglionic blockerMay be used to treatTourette's syndrome





This ganglionic blockingdug is a secondary amine

taken orally



Mecamylyamine



This is a short acting

ganglion blocker, IV only



Trimethaphan





Hexamethonium

(quaternary ammonium)





Ipratropium*wont change mucus

viscosity...just decreasesamount





Glycopyrrolate



Darifenacin



Darifenacin

M3 in detrussor --> increasesmotility and tone

M3 in trigone/sphincter -->relaxaton

True or false



True or false

Atropine's affinity forMuscarinic Receptors does

not change among thedifferent types (M1,M2,M3)



Trueso does Scopolamine

High affinity for M1, M2and M3



decreased diuresis



decreased diuresis

contraction of detrusormuscle

relaxation of trigone andinternal sphincter of urethra

What effect does an anti



What effect does an anti-

muscarinic have on the SA-Node atlow doses? intermediate doses?

antimuscarin on atria? av node? ventricles?

Low --> decrease heart rate



Low decrease heart rateIntermediate --> tachycardia

atira --> increase automaticity and contractility av node --> increase conduction and

automaticity; decrease in refrractoriness ventricles --> minimal direct effects onmyocardial cells



What is a ganglionic

blocking drug





What is the antidote of

Atropine OD



Physostigamine (tertiamy amine - crosses CNS)

this is acetylcholinesteraseinhibitor



Where are nictonic

receptors located?

autonomic gangliaj



nmj

presynaptic nerve terminalsadrenal medullacns

Nictonie also stimulates sensory receptors of carotid bodies, aortic arch, skin/tongue/lung...and pain receports

Which of the following would have



the highest affinity for a nicotinicreceptor?

atropineipratropiumdarifenacin

Ipratropium (also



Ipratropium (also

Glycopyrrolate)Think quaternary compounds

All 3 are anti-muscarinic



Which organs aresensitive to high dose

atrophine

Intestinal, bronchial, and



bladder smooth musclegastric glandsCNS (excitation)Heart, sphincter muscle of eye,ciliary muscle



Which organs are sensitiveto intermediate dose

atrophine

Heart (M2 receptors)



Sphincter muscle of irisCiliary Muscle

CNS (depression)lacrimal, salivary and sweat

glands



Which organs aresensitive to low dose

atropine?

Heart (M2 autoreceptors



( p

on parasympatheticterminals);

lacrimal, salivary and sweatglands

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Anti-Muscarinic and Ganglionic