Anti-Muscarinic Drugs Flashcards
Naturally occuring alkaloids
Atropine
Scopolamine
Synthetic and Semi-synthetic alkaloids
Quaternary ammonium derivatives
Tertiary amine derivatives
Predilection of Atropine
Heart
GI
Bronchial smooth muscles
Predilection of Scopolamine
Iris sphincter
Ciliary muscle
Exocrine glands
CNS effect of Atropine
less BBB permeation (vs scopolamine)
CNS effect of Scopolamine
Increased permeation of BBB (vs atropine)
Atropine duration
7-14 days
Scopolamine duration
3-7 days
Effect of therapeutic dose (0.5-1 mg) of Atropine
Almost NO detectable effects (only mild vagal stimulation)
Effect of therapeutic dose (0.5-1 mg) of Scopolamine
Prominent central effects
Depression (drowsiness, amnesia, fatigue, dreamless sleep, reduced REM sleep, euphoria)
Occasional excitation (in presence of severe pain)
Which atropine isomeer is more potent?
L isomer is 100x more potent
Atropine effects decline rapidly in all organs EXCEPT which organ?
Eye (72 hours)
Effect of slow infusion of atropine
Paradoxical bradycardia
Drug combination to induce “twilight sleep”
Scopolamine + Meperidine (or Demerol)
Quaternary ammonium derivatives used as anti-spasmodic
Glycopyrolate (adjunct for reversal of NM blockade) Propatheline bromide Methantheline bromide Tricyclamol Anisotropine methylbromide Clindinium bromide Hexocyclium methylsulfate Mepenzolate bromide Oxyphenonium bromide Homatropine methylbromide
Quaternary ammonium derivatives used as bronchodilators
Ipatropium bromide
Oxytropium bromide
Tiotropium
Tertiary amine derivatives used as mydriatics and cycloplegics
Tropicamide
Cyclopentolate
Homatropine hydrobromide
Tertiary amines used as anti-spasmodics (and treatment of acid peptic disease, hypermotility and GU infections)
Dicyclomine hydrochloride / Dicloverine Tolterodine (on M3 receptor) Propiverine Trospium Oxybutinin chloride Methixene Thipenamil Piperidolate Oxyphencyclimine hydrochloride Flavoxate hydrochloride Tridihexethyl chloride
Anti-spasmodic tertiary amines used for treatment of overactive bladder
Tolterodine (on M3 receptor)
Propiverine
Trospium
Oxybutinin chloride
Tertiary amines used as anti-parkinsonism and anti-tremor drugs
Benzotropine mesylate (adjunct) Trihexyphenidyl (adjunct) Biperiden (adjunct) Procyclidin Diphenhydramine (anti-histamine) Carmiphen Orpehadrine citrate
Selective M1 inhibitors
Pirenzipine
Telenzipine
Cardiac muscarinic receptor selective
Methoctramine
Relative selectivity for glandular and smooth muscles
Hexahydrosiladifenidol
Selective M3 receptor blockers
Darifenacin
Solifenacin
Fesoteridine
Treatment use of selective M3 receptor blockers
Overactive bladder
General mechanism of action of antimuscarinics
Reversible COMPETITIVE surmountable blockade; Inhibits binding of Ach
Decreased cGMP –> Decreased intracellular calcium
Anti-muscarinics are more effective in blocking exogenous or endogenous Ach?
Exogenous
Place in decreasing order: Sensitivity of M-receptors to anti-muscarinic agents (atropine is the prototype drug)
1) Salivary, bronchial, sweat glands
2) Smooth muscles of eyes & heart
3) Smooth muscles of GIT & GUT
4) Gastric secretion
PK: Absorption
Tertiary amines: well absorbed from GIT & conjunctival membrane (scopolamine absorbed from skin)
Quaternary: only 10-30% absorbed from GIT
PK: Distribution
Tertiary: widely distributed in tissues/CNS (scopolamine with greatest effect in the CNS)
Quaternary: poorly taken up by brain, exists in free form
Metabolism & Excretion: Tertiary Amine
Lipid-soluble, penetrate BBB, efficient absorption in post-auricular area, metab in liver, 50% secreted unchanged in urine
Metabolism & Excretion: Quaternary
Poorly lipid soluble, Does not cross BBB
Better by inhalation, given at the site where it is needed
90% of dose taken orally appears in feces
Pharmacologic effects: CNS
Atropine: minimal effects
Scopolamine: CNS depressant, prevention of motion sickenss
Centrally-acting: Adjunct for Parkinsons (with levadopa), extrapyramidal side effects
Pharmacologic effects: Eyes
Mydriasis (not direct effect)
Cycloplegia
“Sandy eyes” (decreased lacrimation
Pharmacologic effects: CVS
Modest tachycardia (therapeutic doses) Myocardial depression (very high doses) Little effect on BP Atropine flush (toxic doses) Reduce PR interval
Pharmacologic effects: Respiratory System
Bronchodilation (d/t blockade of presynaptic receptors)
Reduced bronchial secretions
Pharmacologic effects: GIT
Decreased volume of secretions (in large doses)
Pharmacologic effects: GUT
Urinary retention
Pharmacologic effects: Sweat glands
Xerostomia (mouth)
Anhidrosis
Causing atropine fever (especially in children)
Therapeutic uses: Opthalmologic d/o
Examination of fundus
Anterior uveitis, acute iritis, keratitis, iridocyclitis
Therapeutic uses: Respiratory d/o
Hyperactive neural bronchoconstriction reflex (in asthmatics)
COPD
Bronchial asthma
Therapeutic uses: CVS d/o
Sinus bradycardia Heart block (d/t digitalis toxicity) Arrythmias in acute MI Angina of MI (parenteral) Hyperactive carotid sinus Idiopathic dilated cardimyopathy
Therapeutic uses: GIT d/o
NOT a first line treatment
Reflux esophagitis
Hypermotility and diarrhea
Therapeutic uses: CNS disturbance
Parkinson’s disease
Motion sickness
Therapeutic uses: Anticholinesterase poisoning
Medical emergency
Carbamate - Use atropine as antidote
Organophosphate - Atropine + pralidoxime
**Used for pretreatment
Therapeutic uses: Urinary d/o
Urolithiasis Enurisis Bladder spasms Urinary incontinence Overactive bladder
Therapeutic uses: Anesthesia
Adjunct to reverse skeletal muscle relaxation after surgery
Obstetrics
Therapeutic uses: Mushroom poisoning
Rapid onset: Parenteral atropine
Late onsent: Atropine NO value
Contraindications of anti-muscarinics
Narrow angle glaucoma
BPH
Obstructive conditions (GUT, GIT atony)
Gastric ulcer (do NOT use non-selective)
Which contraindication is an ABSOLUTE contraindication
Narrow angle glaucoma
Toxicology
DRY as a bone BLIND as a bat RED as a beet HOT as a hare MAD as a hatter
Treatment for anti-muscarinic poisoning
Supportive: artificial respiration hyperthermia control
Gastric lavage with activated charcoal (oral)
Physostigmine (not SOP)
Benzodiazepines (for convulsions)
Treatment for anti-muscarinic poisoning d/t quaternary ammonium compunds
ADD neostigmine, sympathomimmetics
Drug Interactions: Propantheline + TCA
Additive
Drug Interactions: Anti-parkinson
Anti-muscarinic effect ENHANCED
Other drug Interactions
Quinidine
Phenothiazines
Anti-histamines
Procainamide
