Directing acting Cholinomemetics Flashcards
Describe Choline esters
- Cationic quaternary ammonium compounds = INSOLUBLE IN LIPIDS (poor absorption in GI)
–> does not enter CNS; actions chiefly peripheral
- ACh has VERY SHORT HALF LIFE
- Methacholine and bethanechol have LONGER half lifes
- Effects based on receptor they activate (M2 vs M3 vs M1)
Acetylcholine
- RAPID Destruction by AChE = short half-life
- has muscarinic and nicotinic effects
- LOW DOSE = VASODILATION and DECREASED TOTAL PERIPHERAL RESISTANCE followed by reflex tachycardia (due to M3 receptor)
- HIGHER DOSE:
–> M2 = decreased HR, conduction velocity, ventricular contraction (heart)
–> M3 = lungs (bronchospasms, increased bronchial secretions), Bladder (release of urine), glands (increase salivary, tear and sweat) Eye (SHORT LASTING MIOSIS
Methacholine (provocholine)
- similar effects to ACh, but LONGER HALF-LIFE (due to methyl group)
- USES: DIAGNOSTIC TOOL:
–> Bronchiolar hypersenstivity: upon inhalation of aerosilized methacholine at much lower doses would show bronchoconstriction
–> belladonna alkaloid poisoning: in people affected, subcutaneous dose shows NO cholinoceptor activation
Carbachol
- activates both nicotinic and muscarinic receptors (nicotinic effects seen at level of autonomic ganglia, adrenal medulla and skeletal muscle
- USES:
–> topically in glaucoma to decrease intraocular pressure by enlarging canal of schlemm to increase drainage of acqeous humor
- ADVERSE EFFECTS:
–> High doses = muscarinic effects on the heart which include CARDIAC ARREST
Bethanechol (urecholine) (B goes with Bladder)
- NOT SUSCEPTIBLE TO DESTRUCTION BY AChE
- NO NICOTNIC ACTION
- ACTION (mainly M3)
–> Genitourinary = forces urination (increase detrusor tone, decreases outlet resistance of internal sphincter)
–> Gastrointestinal = increase motility and secretion
USES: gastric emptying abnormatlities and urinary retention (when no urinary obstruction is present)
Muscarine
- alkaloid (found in mushrooms)
- DIRECTLY activates muscarinic receptors with 100x POTENCY of Ach
- Is NOT destroyed by AChE –> much longer half life
- DOES NOT contain NICOTINIC ACITIVTY
- No therapeutic uses –> involved in poisoning
–> SYMPTOMS of POISONING
describe muscarine poisoning
- SYMPTOMS:
–> Increased salivation, sweating, tear flow WITHIN MINUTES
–> LARGER DOSES –> abdominal pain, nausea, diarrhea, blurred vision and dyspnea
–> intoxication subsides with 2 hours
–> severe cases lead to cardiac and respiratory failure/death
Pilocarpine (pilo=eye)
- isopto carpine, salagen
- Alkaloid (found in leaves in south america)
- Tertiary amine
- produces muscarinic effects similar to ACh
- ACTION:
- OPTHALAMIC EFFECTS (M3) predominate:
–> contracts iris sphincter muscles –> miosis
–> frees entrace to canal of schlemm (therapy for narrow-angle glaucoma)
–> enhances tone of trabecular network
–> contracts the ciliary muscle = accommodation and loss of far vision
- STIMULATES CORTICAL NEURONS
Nicotine
- nicotinic alkaloid
- ACTION on Nm subtype receptors (neuromusclar endplate)
= skeletal muscle contraction, fasciulations, spasms, depolarizing blockade
- ACTION on Nn subtype (both sympathetic and parasympathetic)
–> Cardiac = increased heart rate (more sympathetic)
–> Vascular peripheral vasoconstriction (more sympathetic)
–> GI = increased gut motility/secretion
–> Carotid bodies = increased respiratory rate
–> medulary emetic chemoreceptors = nausea and comiting
What are the contradictions to use of cholinoceptor agonists
- peptic ulcers
- GI tract disorders
- Asthma
What are some drugs that interact (block) effects of muscarinic agonists
- Quinidine (antiarrhythmics)
- Procainamide (antiarrhythmics)
- tricyclic antidepressants
