Cholinergic agonist, direct acting vasodilation (M3), dec HR (M2), dec conduction rate in SA and AV nodes (M2), dec force of contraction (M2)
Acetylcholine effects on organ systems
Cholinergic agonist, direct acting vasodilation (NO release); eye contraction and miosis; contraction and accommodation to near vision; inc secretions; bronchoconstriction (inc secretions); bradycardia, dec conduction velocity, inc GI tone, relaxation of sphincters; contraction of detrusor, relaxation of sphincter; erection.
Cholinergic agonist, direct acting Acts on nicotinic and muscarinic receptors. Rapidly hydrolyzed
Cholinergic agonist, direct acting Strong muscarinic activity; NO nicotinic actions Not hydrolyzed by AchE (inactivated by other esterase)
Cholinergic agonist, direct acting Tmt of acute postoperative and postpartum urinary retention Neurogenic atony of urinary bladder with retention "Bethanechol for Bowel and bladder"
Direct cholinergic agonist Non-selective - both muscarinic and nicotonic agonist Not hydrolyzed by AchE
Direct cholinergic agonist Miosis during sx, reduces IOP after cataract sx "CARBon copy of Ach"
Direct cholinergic agonist More resistant to hydrolysis by AchE than Ach
Direct cholinergic agonist Diagnosis of bronchial airway hyperreactivity (Methacholine challenge test for dx of asthma)
Direct muscarinic agonist
Muscarinic and nicotinic agonist - direct acting cholinergic agonist
Direct cholinergic agonist Not hydrolyzed by AcheE Partial muscarinic agonist
Direct cholinergic agonist Second line for open angle glaucoma Management of acute angle-closure glaucoma "PILe on the sweat and tears"
Direct cholinergic agonist Affects NMJ and ganglia
Nicotine actions at low doses
Direct cholinergic agonist Ganglionic stimulation by depolarization -Response resembles simultaneous discharge of both parasympathetic and sympathetic
Direct cholinergic agonist CVS: sympathomimetic (d/t catecholamine release from adrenergic nerve terminals and adrenal medulla) - inc HR, inc BP GI/UT: parasympathomimetic - nausea, vomiting, diarrhea, voiding of urine Secretions: stimulation of salivary and bronchial secretions
Nicotine actions at high doses
Direct cholinergic agonist Ganglionic blockade and neuromuscular blockade
Nicotine acute poisoning - sx?
Direct cholinergic agonist Nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, mental confusion, weakness BP falls, weak pulse Death may occur from paralysis of resp muscles and/or central resp failure
Direct cholinergic agonist Smoking cessation therapy
AchE inhibitor (cholinergic agonist) Binds reversibly to active sit of AchE
AchE inhibitor (cholinergic agonist) Dx of MG - edrophonium IV leads to rapid increase in muscle strength Reverses neuromuscular block produced by non-depolarizing muscular blockers.
Physostigmine uses, cautions
AchE inhibitor (cholinergic agonist) Can enter and stimulate CNS Uses: Tmt of OD's of anticholinergic drugs (eg. atropine); glaucoma Should not be given for suspected TCA overdose - can aggravate depression of cardiac conduction "PHYS is for eyes"
AchE inhibitor (cholinergic agonist) Doesn't enter CNS Uses: stimulate bladder and GIT; antidote for competitive blockers of NMJ; symptomatic tmt for MG
AchE inhibitor (cholinergic agonist) Tmt of MG "pyRIDostigmine Gets RID of myasthenia gravis"
AchE inhibitor (cholinergic agonist) Used for glaucoma
Malathion & Parathion
AchE inhibitor (cholinergic agonist) Thiophosphate insecticides Must be activated in the body by conversion to oxygen analogs
Reactivator of AChE Cholinesterase regenerator for organophosphate insecticide poisoning If given before ageing has occurred, splits phosphorous-enzyme bond
Cholinergic muscarinic antagonist Binds competitively to muscarinic receptors
Cholinergic muscarinic antagonist Mydriasis, cycloplegia; reduced gastric motility; dec hypermotility of bladder; bradycardia at low doses (d/t blockade of presynaptic M2 that normally inhibit ACh release), tachycardia at mod to high dose (d/t blockade of atrial M2 receptors); secretions blocked (salivary, sweat, lacrimal) - high body temp.
Explain atropine flush
High doses of antimuscarinic agents may cause cutaneous vasodilation - mechanism is unknown.
Cholinergic muscarinic antagonist Mydriasis, cycloplegia; antispasmodic (GIT, bladder); antidote for cholinergic agonists; antidote for mushroom (muscarine) poisoning (Amanita muscaria, fungi); block RT before sx.
Atropine adverse effects
Cholinergic muscarinic antagonist Dry mouth, blurred vision, sandy eyes, tachycardia, constipation; restlessness, confusion, hallucinations, delirium, depression, collapse of circulatory and resp systems and death.
Cholinergic muscarinic antagonist Uses: Prevention of motion sickness, block short-term memory - sometimes used in anesthetic procedures.
Ipratropium ("I PRAy tropium")
Cholinergic muscarinic antagonist Quaternary ammonium Used in asthma and COPD "I PRAy I can breathe soon"
Cholinergic muscarinic antagonist Quaternary ammonium Used for COPD
Homatropine, Cyclopentolate, Tropicamide
Cholinergic muscarinic antagonist Tertiary amine Uses: Ophthalmology - preferred to atropine d/t shorter duration of action --> Mydriasis with cycloplegia
Cholinergic muscarinic antagonist Tertiary amine Uses: treat PARKinsonism and extrapyramidal effects of antipsychotic drugs "PARK my BENZ"
Cholinergic muscarinic antagonist Used orally: inhibit GI motility Used parentally: prevent bradycardia during sx
Cholinergic muscarinic antagonist Uses: overactive bladder "TOLd you to go before we left"
Contraindications of antimuscarinic agents
Angle-closure glaucoma pts Use with caution in prostatic hypertrophy (since urine retention aggravates BPH) and elderly
Ganglionic blockade by prolonged depolarization: drug example
Ganglionic blockade by antagonism of nicotinic receptors: drug examples
Hexamethonium, mecamylamine, trimethaphan
Mecamylamine, Trimethaphan, Hexamethonium MOA
Ganglion blockers Ganglion blockade by antagonism of nicotinic receptors
Malignant hyperthermia - d/t excessive calcium release from SR Combination of succinylcholine and halogenated anesthetic in most incidents TMT: dantrolene blocks release of calcium from SR
3 cholinergic drugs that act pre-synaptically
Hemicholinium, Vesamicol, Botulinum Toxin
Presynaptic cholinergic antagonist Inhibitor of ACh synthesis Blocks the CHT; prevents uptake of choline
Presynaptic cholinergic antagonist Inhibitor of ACh storage Blocks ACh-H antiporter
Presynaptic cholinergic antagonist Inhibitor of ACh release Uses: tmt of several diseases involving muscle spasms (at NMJ); cosmetic tmt of wrinkles
Direct adrenergic agonist Released by adrenal medulla Interacts with both alpha and beta receptors: low doses=beta (vasodilation); high doses=alpha (vasoconstriction)
Epinephrine: large dose CV effects
Direct adrenergic agonist Inc BP: -inc ventricular contraction (beta 1) -inc HR (beta 1) --> may be opposed by baroreceptor reflex -vasoconstriction (alpha 1)
Epinephrine: low dose CV effects
Direct adrenergic agonist -inc HR d/t beta 1 effects -beta 2 more sensitive to epi than alpha 1 --> dec peripheral resistance d/t beta 2, dec diastolic P --> mean BP may fall -no baroreceptor reflex since no inc in mean BP
Direct adrenergic agonist -bronchodilation (beta2) -hyperglycemia --> inc glycogenolysis in liver (beta 1), inc lipolysis (beta3)
Direct adrenergic agonist -Anaphylactic shock -acute asthmatic attacks -in local anesthetics --> inc duration of anesthetic with vasoconstriction (prevents dissipation of anesth) -glaucoma (not common)
Direct adrenergic agonist Acts on alpha and beta1 receptors, not on beta2
Norepinephrine CVS effects
Direct adrenergic agonist -vasoconstriction (alpha1 effect) -inc BP (beta1 effect) -CO is unchanged or dec -baroreceptor reflex bradycardia -->BP high, peripheral resistance high (alpha1), pulse rate low (baroreceptor reflex)
Direct adrenergic agonist Treat shock --> inc vascular resistance (inc BP) -dec blood flow to kidney (this is bad - dopamine is better)
Effect of atropine pre-treatment with norepinephrine
Tachycardia (d/t anti-muscarinic effect of atropine with additional NE-induced activation of alpha and beta1)
Direct adrenergic agonist -Activates D rec and alpha and beta rec -Substrate for MAO and COMT -ineffective when taken orally
Direct adrenergic agonist -drug of choice for shock (inc BP with beta1; inc kidney perfusion with D1)
Direct beta agonist (beta 1 and 2) -inc HR and force of contraction (beta1) -dilates skeletal muscle arterioles (beta2); dec peripheral resistance (beta2) -bronchodilation (beta2)
Isoproterenol CV effect
Direct beta agonist (beta 1 and 2) Inc HR from beta1; dec peripheral resistance from beta2 --> BP does not increase!
Direct beta agonist (beta 1 and 2) Stimulate heart in emergency
Direct beta1 agonist -inc CO in CHF -inc CO with little change in HR -does not significantly inc oxygen demands of myocardium (big advantage)
Albuterol, Terbutaline uses
Direct beta2 agonist -asthma --> acute episodes
Direct beta2 agonist -asthma --> long-acting agonist (NOT for breakthrough attacks); slow onset, lasts long (12 hrs)
Direct alpha1 agonist -vasoconstrictor --> used as nasal decongestant and mydriatic -used to inc BP and terminate episodes of supraventricular tachycardia -induces reflex bradycardia (IV)
Direct alpha2 agonist -antihypertensive --> acts centrally to inhibit sympathetic vasomotor centres
Direct alpha2 agonist -converted to alpha-methylnorepinephrine which activates central alpha2 adrenoceptors -dec BP -hypertension in pregnancy
Indirect adrenergic agonist -central stimulatory action -inc BP (alpha effect on vasculature); stimulate heart (beta effect)
Indirect adrenergic agonist -structural analogue of amphetamine -tmt of ADHD in kids
Indirect adrenergic agonist -found in fermented food like cheese and wine -oxidized by MAO --> if taking MAO inhibitors, can ppt vasopressor episodes (hypertensive crisis)
Mixed action adrenergic agonist -stimulates alpha and beta, release NE from nerve endings -long duration since not substrate for MAO or COMT -excellent oral absorption and penetrates CNS
Mixed action adrenergic agonist -OTC component of decongestant mixtures
non-selective alpha antagonist -irreversible antagonist -used in pheochromocytoma --> before sx removal of tumour, chronic management of inoperable tumours
non-selective alpha antagonist -reversible antagonist -Dx of pheochromocytoma by phentolamine blocking test -hypertensive crisis assoc with stimulant drug overdose -hypertensive crisis d/t sudden withdrawal of sympatholytic antihypertensives (eg. clonidine)
BP response to epinephrine given in presence of phenoxybenzamine
alpha1 blocked by phenoxybenzamine so epi acts on beta2 to vasodilate (ie. unopposed beta2 activation) ---> BP decreases
selective alpha1 antagonist Uses: -hypertensives (relaxes arterial and venous sm) -first dose--> hypotensive response and syncope -BPH (drug of choice) --> improve urinary flow
selective alpha1 antagonist Uses: (same as Prazosin) - HTN and BPH
selective alpha1 antagonist Uses: -BPH -not much effect on BP
selective alpha2 antagonist -blockade of alpha2 autoreceptors -> inc NE release -> stimulation of beta1 and alpha1 Uses: -tmt of ED (but PDE5 have replaced now)
Uses and actions of non-selective beta blockers
Propranolol is prototype -dec HR and dec myocardial contractility -dec glycogenolysis; dec glucagon secretion -lower BP by dec CO -dec IOP -prophylaxis of migraines (block vasodilation) -blunt hyperthyroidism-induced symp stimulation -dec oxygen requirement of heart - treat angina pectoris -treat atrial fibrillation -treat MI -treat performance anxiety -CNS effect --> sleep disturb, depression, sedation
Adverse effects of non-selective beta blockers
-bronchoconstriction (potentially lethal in asthmatics) -up-regulation of receptors --> stop therapy, inc receptors worsen angina or HTN
Propranolol uses and actions
non-selective beta blocker -dec HR and dec myocardial contractility -dec glycogenolysis; dec glucagon secretion -lower BP by dec CO -dec IOP -prophylaxis of migraines (block vasodilation) -blunt hyperthyroidism-induced symp stimulation -dec oxygen requirement of heart - treat angina pectoris -treat atrial fibrillation -treat MI -treat performance anxiety -CNS effect --> sleep disturb, depression, sedation
Propranolol adverse effects
non-selective beta blocker -bronchoconstriction (potentially lethal in asthmatics) -up-regulation of receptors --> stop therapy, inc receptors worsen angina or HTN
non-selective beta blocker -long duration of action -management of angina pectoris -management of HTN
non-selective beta blocker -tmt of intraocular HTN/open-angle glaucoma -tmt of HTN -prophylaxis of migraines