Autonomics Flashcards
M1/M3/M5 second messenger?
Gq –> PLC –> DAG & IP3 –> Calcium release
M2/M4 second messenger?
Gi –> Inhibit AC –> Decreased cAMP; Kchannel –> Hyperpolarization
Alpha 1 second messenger?
Gq –> PLC –> DAG & IP3 –> Calcium release
Alpha 2 second messenger?
Gi –> inhibit AC –> Decreased cAMP; Kchannel –> Hyperpolarization
Use Gi as second messenger?
M2/M4 & Alpha 2
Use Gq as second messenger?
M1/M3/M5 & Alpha 1
B1/B2/B3 second messenger?
Gs –> Stimulate AC –> Increase cAMP
Bethanechol class?
Direct acting carbamic acid ester (direct acting muscarinic cholinomimetic)
Muscarine class?
Direct acting non-ester alkaloid (direct acting muscarinic cholinomimetic)
Pilocarpine class?
Direct acting non-ester alkaloid (direct acting muscarinic cholinomimetic)
Cevimeline class?
Direct acting non-ester alkaloid (direct acting muscarinic cholinomimetic)
Nicotine class?
Direct acting non-ester alkaloid (direct acting nicotinic cholinomimetic)
Bethanechol treats?
Post-op and neurogenic ileus; urinary retention (bowel & bladder smooth muscle ACh-innervated)
Pilocarpine treats?
Glaucoma (ACh activates sphincter & ciliary muscles of eye)
Cevimeline treats?
Dry mouth (Sjogren’s, post-radiation therapy) via increased salivation
Nicotine treats?
Smoking cessation via reduced cravings
Side effects of direct acting muscarinic cholinomimetics?
SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis
Direct acting muscarinic cholinomimetics?
Bethanechol, Muscarine, Pilocarpine, Cevimeline
Neostigimine class?
Indirect acting carbamate (AChE inhibitor)
Physosligmine class?
Indirect acting carbamate (AChE inhibitor)
Donepezil class?
Indirect acting non-ester (AChE inhibitor)
Edrophonium class?
Indirect acting non-ester alcohol (AChE inhibitor)
Echothiophate class?
Indirect acting organophosphate (AChE inhibitor)
Pralidoxime class?
Strong nucleophile and regenerates phosphorylated AChE
Sarin class?
Potent indirect acting organophosphate (AChE inhibitor)
Neostigmine treats?
Post-op and neurogenic ileus; urinary retention; myasthenia gravis; reversal of NMJ blockade
Neostigmine time?
Lasts 0.5-2 hours
Physostigmine treats?
Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Physostigmine time?
Lasts 0.5-2 hours
Donepezil treats?
Alzheimer’s (amplifies endogenous ACh in brain)
Edrophonium treats?
Myasthenia gravis (differentiating deficiency versus ACh crisis); ileus
Edrophonium time?
Lasts 5-15 minutes
Echothiophate treats?
Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Echothiophate time?
Lasts >100 hours
Pralidoxime treats?
Poisoning by nerve gas (also an insecticide)
Sarin can be used as?
Volatile nerve gas
Sarin can cause?
Death
Sarin toxicity treated how?
Treat with pralidoxime and atropine before aging
Side effects of AChE inhibitors?
SLUDGE + general increase in cholinergic neurotransmission; paralysis
Long acting AChE inhibitor?
Echothiophate
Short acting AChE inhibitors?
Neostigmine, Physostigmine, Edrophonium
Atropine class?
Tertiary amine antimuscarinic
Scopolamine class?
Tertiary amine antimuscarinic
Dicyclomine class?
Tertiary amine antimuscarinic
Tropicamide class?
Tertiary amine antimuscarinic
Tolterodine class?
Tertiary amine antimuscarinic
Benztropne class?
Tertiary amine antimuscarinic
Side effects of tertiary amine antimuscarinics?
General block of muscarinic functions
Tertiary amine antimuscarinics?
Atropine, Scopolamine, Dicyclomine, Tropicamide, Tolterodine, Benztropine
Atropine treats?
Mydriasis, cycloplegia
Scopolamine treats?
Prevent or reduce motion sickness
Dicyclomine treats?
Reduce transient hypermotility
Tropicamide treats?
Mydriasis, cycloplegia
Tolterodine treats?
Transient cystitis, post-op bladder spasms, incontinence
Benztropine treats?
Manifestations of Parkinson’s
Tertiary amine antimuscarinics that cross the BBB?
Scopolamine, Benztropine
Metabolism of scopolamine?
Slow
Metabolism of tropicamide?
Rapid
Quarternary amine antimuscarinics?
Ipratropium, Tiotropium
Ipratropium class?
Quarternary amine antimuscarinic
Tiotropium class?
Quarternary amine antimuscarinic
Which quarternary amine antimuscarinic is longer acting?
Tiotropium
Ipratropium and tiotropium treat?
Bronchodilation in asthma or COPD
Ipratropium and triotropium side effects?
General block of muscarinic effects
Ganglionic blockers?
Hexamethonium, Mecamylamine
Hexamethonium, Mecamylamine mxn?
Block Nn receptor and sympathetic tone
Hexamethonium, Mecamylamine treat?
Hypertenisve crisis (“Bloodless” field surgery)
Succinylcholine class?
Depolarizing blocker
How do depolarizing blockers work?
Overstimulation of nicotinic receptor, leading to desensitization of muscle unit to further ACh stimulation
Succinylcholine used for?
Brief procedures (tracheal intubation, reset dislocated joints?
Side effects of succinylcholine?
Respiratory paralysis, disturbance of autonomic function, flaccid paralysis within minutes
Tubocurarine class?
Nondepolarizing blocker (Block Nm receptor)
Mivacurium class?
Nondepolarizing blocker (Block Nm receptor)
Nm blockers?
Tubocurarine, Mivacurium
Tubocurarine, Mivacurium used for?
Muscle relaxant for surgery w/o deep anasthesia
Tubocurarine, Mivacurium side effects?
Respiratory paralysis, disturbance of autonomic function
Tubocurarine time?
Lasts 30-60 minutes
Mivacurium inhibitor?
Rapidly hydrolyzed, short-lasting
Botulinum toxin A class and mxn?
Local paralytic: Blocks vesicle fusion and ACh release on presynaptic terminal by degrading SNAP-25
Botulinum tonxin A treats?
Reduces frown lines and wrinkles, achalasia, strabismus, oromandibular dystonia
ANS activity in the SA node?
Symp accelerate B1,B2. Parasymp decelerate M2
ANS activity in the contractility of the heart?
Symp increase B1,B2. Parasymp decelerate M2 (atria).
ANS activity in the blood vessels?
Symp contract skin vessels alpha. Symp relax skeletal muscle vessels B2. Parasymp release EDRF relax vessels M3 (not innervated and responds only to circulating muscarinic agonists)
ANS activity in bronchiolar smooth muscle?
Symp relax B2. Parasymp contract M3.
ANS activity in GI?
Symp relax smooth muscle contract sphictors. Parasymp contract smooth muscle relax sphinctors + secretion.
ANS activity in GU smooth muscle?
Symp relax bladder wall B2, contract sphinctor a1. Parasymp contract bladder wall M3, relax sphinctor M3. Symp relax uterus B2, contract uterus a. Parasymp contract uterus M3.
ANS activity in the eye?
Symp dilate relax ciliary muscle B. Parasymp constrict contract ciliary muscle M3.
Beta 1?
Heart (Increase HR, Increase contraction). Kidney (Renin secretion)
Beta 2?
Arterioles (Dilate). Bronchial smooth muscle (Relax). Uterus (Relax). Increase metabolic effects.
Beta 3?
Increase lipolysis and thermogenesis.
Alpha 1?
Arterioles (Constrict). Veins (Constrict). Uterus (Constrict).
Alpha 2?
Presynaptic Nerve Endings (Inhibit NE Release and ACh release). Postsynaptic in CNS (Decreased peripheral Sympathetic Tone)
Dopamine?
Renal, mesenteric, cerebral arterioles (Dilate).
Tell me about skeletal muscle blood vessel receptors and response.
Alpha1 and Beta2. At physiological concentration (of epi), Beta2 predominates and vasodilation occurs. At pharmacological concentrations, Alpha2 predominates and vasoconstriction ocur.
B1 potency?
ISO > Epi ~ NE > DA
B2 potency?
ISO > Epi»_space; NE»_space; DA
A1 potency?
Epi ~ NE > DA > ISO
A2 potency?
CLON > Epi ~ NE»_space;ISO
Norepinephrine mxn?
Non-selective agonist of a1, a2, B1
Norepinephrine for?
Acute hypotension
Norepinephrine side effects?
HTN, Arrythmias, HAs
Epinephrine mxn?
Non-selective agonist of a1, a2, B1, B2
Epinephrine for?
Anaphylactic shock; combined with local anasthetic; glaucoma
Epinephrine side effects?
Palpitation, arrythmias, HAs, tremors
Amphetamine mxn?
Indirect acting adrenergic agonist, Increases NE release
Amphetamine for?
ADHD, narcolepsy, recreation
Amphetamine side effects?
HTN, insomnia, anxiety, arrythmias
Isoproterenol mxn?
Nonselective agonist of B1, B2
Isoproterenol for?
Shock, Heart block, Bronchodilator
Isoproterenol side effects?
Palpitation, Tachyarrhythmias, HAs
Dobutamine mxn?
Selective B1 agonist
Dobutamine for?
Cardiac decompensation, heart block, shock
Dobutamine side effects?
Tachyarrythmias, HTN
Albuterol mxn?
Selective B2 agonist
Albuterol for?
Mild asthma, COPD, prevent/reduce exercise-induced bronchospasm
Albuterol timing?
10-15 minutes for action, 6-12 hours duration
Albuterol side effects?
Tachycardia, muscle tremor, can mask progressively severe inflammation
Terbutaline for?
Selective B2 agonist
Terbutaline for?
Mild asthma, COPD, prevent/reduce exercise-induced bronchospasm
Terbutaline timing?
10-15 minutes for action, 6-12 hours duration
Terbutaline side effects?
Tachycardia, muscle tremor, can mask progressively severe inflammation
Phenylephrine mxn?
Selective a1 agonist
Phenylephrine for?
Postural hypotension, nasal congestion, possibly as an anorexic
Phenylephrine side effects?
HTN, Reflex bradcardia
Clonidine mxn?
Selective a2 agonist
Is clonidine a prodrug?
No
Can clonidine cross the BBB?
Yes
Clonidine for?
Hypertension, Drug W/D, Shock
Clonidine side effects?
Sedation, Retention of Na/H2O
a-Methyldopa mxn?
Selective a2 agonist, Metabolite (a-methylnorepinephrine) activates CNS a2 receptors
Is a-methyldopa a prodrug?
Yes
Can a-methyldopa cross the BBB?
Yes
a-Methyldopa for?
HTN
a-Methyldopa side effects?
Sedation
Dopamine mxn?
Mixed acting (Indirect/Direct) agonist of D1, a1, B1. NE release
Dopamine for?
Shock, renal failure, hypotension
Dopamine side effects?
Vasoconstriction at high doses
Dopamine at low dose?
Direct @ D1 –> dilation of renal vessels –> decrease in BP, increase in GFR/urine
Dopamine at medium dose?
Direct @ B1 –> Positive inotropic effect (increased heart contraction)
Dopamine at high dose?
Direct @ a1 –> Vasoconstriction
Fenoldopam mxn?
Selective Dopamine agonist (D1 only)
Fenoldopam for?
Increase blood flow at renal, mesenteric, cerebral arteries (HTN emergency, Anuria)
Fenoldopam half-life?
10 minutes
Phentolamine mxn?
Nonselective a1,a2 antagonist
Phentolamine for?
Pheochromocytoma, Raynaud’s, frostbite
Phentolamine side effects?
Postural hypotension, Inhibit ejaculation, Tachycardia
Phenoxybenzamine mxn?
Nonselective a1,a2 antagonist (non-competitive blocker)
Phenoxybenzamine for?
Pheochromocytoma, Raynaud’s, frostbite
Phenoxybenzamine side effects?
Postural hypotension, inhibit ejaculation, Tachycardia
Prazosin mxn?
Selective a1 antagonist
Prazosin for?
Primary HTN, BPH
Prazosin side effects?
Postural hypotension @ 1st dose, less side effects thatn phentolamine and phenoxybenzamine
Terazosin mxn?
Selective a1 antagonist
Terazosin for?
Primary HTN, BPH
Terazosin side effects?
Postural hypotension @ 1st dose, less side effects thatn phentolamine and phenoxybenzamine
Propranolol mxn?
1st generation nonselective B1,B2 antagonist
Propranolol for?
Angina, HTN, Arrythmias
Propranolol half-life?
4 hours
Propranolol side effects?
Bradycardia, Bronchoconstriction, Sexual dysfunction
Timolol mxn?
1st generation nonselective B1,B2 antagonist
Timolol for?
Glaucoma (Decrease secretion of aqueous humor from ciliary processes)
Timolol side effects?
Bradycardia, Bronchoconstriction, Sexual dysfunction
Timolol half life?
4 hours
Metoprolol mxn?
2nd generation B1 selective antagonist
Metoprolol for?
HTN, Angina, Arrythmias, CHF
Metoprolol side effects?
Bradycardia, Sexual dysfunction
Metoprolol half life?
4 hours
Atenolol mxn?
2nd generation B1 selective antagonist
Atenolol for?
HTN, Angina, Arrythmias, CHF
Atenolol side effects?
Bradycardia, Sexual dysfunction
Atenolol half life?
6-8 hours
Atenolol lipid soluble?
No, cannot access CNS
Bisoprolol mxn?
2nd generation B1 selective antagonist
Bisoprolol for?
HTN, Angina, Arrythmias, CHF
Bisoprolol side effects?
Bradycardia, Sexual dysfunction
Carvedilol mxn?
3rd generation nonselective B1, B2 antagonist
Carvedilol for?
CHF, HTN
Carvedilol side effets?
Bradycardia, fatigue
Labetalol mxn?
3rd generation nonselective B1, B2 antagonist
Labetalol for?
CHF, HTN
Labetalol side effects?
Bradycardia, Fatigue
Betaxolol mxn?
3rd generation selective B1 inhibitor
Betaxolol for?
HTN, CHF
Betaxolol side effect?
Bradycardia
Cocaine mxn?
Prevents NE reuptake
Cocaine for?
Local anasthetic, vasoconstricor
Cocaine side effects?
Insomnia, anxiety, arrythmias
Tyramine mxn?
Indirect acting adrenergic agonist, Increases cytoplasmic NE release (involved in exhange with NE across membrane)
Guanethidine mxn?
Nerve ending blocker: False NT – Vesicles are filled with guanethidine instead of NE
Guanethidine?
AntiHTN
Guanethidine side effects?
Many and serious – rarely used in US anymore
Reserpine mxn?
Nerve ending blocker: NE is not taken into vesicles because it binds uptake transporter and stops it
Reserpine for?
AntiHTN
Reserpine side effects?
Many and serious, including depression and suicide. Extremely cheap, but not used in the US. Used abroad.
a-methyl-tyrosine mxn?
Nerve ending blocker: Inhibits tyrosine hydroxylase and decreases NE synthesis
a-methyl-tyrosine for?
Inoperable pheochromocytoma
a-methyl-tyrosine side effects?
Many and serious: Used only for inoperable pheochromocytoma
Ephedrine mxn?
Mixed indirect/direct (B2) agonist
Ephedrine for?
Anorexic, Nasal decongestion