01 Autonomics

Sympathomimetics

• NE acts as NT (e.g. BP); E acts as hormone (e.g. stress induced)

• fight or flight Sympathetic mime: sympathomimetic

• QISS: alpha-1, alpha-2, beta-1, beta-2 receptors are coupled to Gq, Gi, Gs, Gs respectively

• Alpha scouts: alpha receptor agonists

• Single lit alpha candle: alpha-1 agonist

• 3 "dags": alpha-1 receptor coupled to Gq -> IP3-DAG cascade

• "Dag" with bone: IP3-DAG cascade-> increased intracellular calcium (smooth muscle cell in vasculature/sphincters)

• Alpha-1 scout pulling red leashes: alpha-1 activation increases peripheral arterial resistance (vasoconstriction at small arteries, arterioles, precapillary sphincters)

• Alpha-1 scout elevating MAP: alpha-1 activation increases mean arterial pressure (MAP)

• Alpha-1 scout pulling blue leashes: alpha-1 activation increases venous return (venoconstriction) (good for increase CO)

• Alpha-1 scout binoculars: alpha-1 activation at pupillary dilator muscle causes mydriasis (pupillary dilation)

• Alpha-1 scout pulling pants string: alpha-1 activation causes urethral sphincter and prostatic smooth muscle contraction

• Full bladder canteen: alpha-1 activation causes urinary retention

• Two lit alpha candles: alpha-2 agonist

• "No sympathy": alpha-2 agonists are sympatholytics (act centrally to decrease sympathetic tone)

• Packed up alpha-2 camp tent: alpha-2 receptor coupled to Gi -> decreased cAMP

• Alpha-2 scout packing up presynaptic wire: presynaptic alpha-2 receptors cause inhibition of neurotransmitter release

• Welcome INSIDE mat: insulin

• Rolled up welcome INSIDE mat: alpha-2 activation at pancreatic islet cells decreases insulin release

• Alpha-2 scout dousing roasting pig: alpha-2 activation inhibits lipolysis and release of fatty acids

• Alpha-2 scout emptying water from eyeball hat: activation of alpha-2 at ciliary body decreases aqueous humor production (glaucoma meds)

• Brim of eyeball hat: brimonidine is an alpha-2 agonist used to treat chronic open angle glaucoma (decreases aqueous humor production)

• βand cAMP: beta receptor agonists increase cyclic AMP (cAMP)

• Beta-1 horn: beta-1 agonist

• "I heart βand cAMP": beta-1 receptors are found on cardiac myocytes (including SA and AV nodes)

• "I heart βand cAMP": beta-1 activation causes increased cyclic AMP -> increased intracellular calcium

• Elevated heart clock: beta-1 activation increases heart rate (SA node)

• Buff contracted bicep: beta-1 activation increases cardiac contractility

• Heart hydrant: beta-1 activation results in increased cardiac output

• Open rain umbrella: beta-1 activation increases renin release (JGA cells), increase BP/volume

• Beta-2 tuba: beta-2 activity

• "ROL" call sheet: beta-2 agonists used for bronchodilation have -"rol" suffix (albuterol, formoterol, salmeterol)

• Beta-2 camper taking big breath: beta-2 activation leads to bronchoDILATION (increased cyclic AMP -> activates PKA)

• Beta-2 camper with dilated sleeves: beta-2 activation causes coronary and skeletal muscle vasoDILATION -> decreases systemic vascular resistance (SVR)

• Beta-2 camper roasting pig: beta-2 activation stimulates lipolysis and release of free fatty acids

• Beta-2 camper producing marshmallows from liver-shaped bag: beta-2 receptor activation at the liver promotes gluconeogenesis

• Beta-2 camper carrying s'mores INSIDE tent: beta-2 activation at pancreatic islet cells stimulates insulin release-> moves glucose into cells

• Banana peels: beta-2 activation can cause hypokalemia (due to increased insulin activity)

• Beta-2 camper filling eyeball balloon: beta-2 activation at ciliary body increases aqueous humor production (β antagonist for glaucoma)

• Sleeping beta-2 camp counselor: beta-2 agonists relax uterine smooth muscle

Drugs

• Flannel friends: phenylephrine (alpha-1 agonist)

• Flannel friend holding single alpha candle: phenylephrine is an alpha-1 agonist

• Flannel friend's nasal spray: phenylephrine treats nasal congestion (alpha-1 mediated local vasoconstriction reducing edema)

• Flannel friend's binoculars: phenylephrine causes mydriasis (activates alpha-1 at pupillary dilator muscle)

• map: Phenylephrine increases MAP (alpha-1 increase in SVR)

• 1st line: Phenylephrine increases systolic pressure (alpha-1 arteriolar constriction)

• 2nd line: Phenylephrine increases diastolic pressure (alpha-1 venous constriction)

• Flannel friend's low dangling heart watch: phenylephrine causes reflex bradycardia (response to alpha-1 increase in MAP)

• Pts with reduced autonomic function (diabetic neuropathy) can't have baroreceptor reflex = very high pressure in response

• North compass: NORepinephrine (alpha>beta1 agonist) - a1, a2

• North scout blowing beta-1 bugle: norepinephrine has some beta-1 activity (primarily an ALPHA AGONIST)

• Norepinephrine increases MAP (alpha-1 increase in SVR)

• Norepinephrine increases systolic pressure (alpha-1 arteriolar constriction)

• Norepinephrine increases diastolic pressure (alpha-1 venous constriction)

• North scout's low dangling heart watch: norepinephrine causes reflex bradycardia (response to alpha-1 increase in MAP)

• North scout's buff contracted bicep: norepinephrine increases cardiac contractility (activates beta-1), although bradycarida

• Norepinephrine increases pulse pressure (b2 activity)

• Norepinephrine increases PULSE PRESSURE, difference between systolic and diastolic (beta-1 increase in contractility)

• Septic tank: septic shock (phenylephrine and norepinephrine increase SVR and venous return to treat distributive/hypovolemic shock)

• "Just DO BUgling": DOBUtamine (beta-1>beta-2 agonist)

• Beta-1 bugle: dobutamine is primarily a beta-1 agonist

• "Just DO BUgling" friend's beta-2 tuba: dobutamine has some beta-2 activity (primarily a BETA-1 AGONIST)

• "Just DO BUgling" winding up heart flashlight: dobutamine increases heart rate, contractility, and cardiac output (beta-1 effects)

• "Just DO BUgling" friend's dilated sleeves: dobutamine causes vasodilation -> decreases SVR (effects mild due to minimal beta-2 activity)

• Dobutamine increases PULSE PRESSURE, difference between systolic and diastolic (beta-1 increase in contractility)

• Dobutamine increases systolic pressure (beta-1 increase in CO)

• Dobutamine can decrease diastolic pressure (beta-2 arteriolar dilation)

• Batteries fallen out of heart flashlight: dobutamine can be used in cardiogenic shock

• Dead heart batteries: cardiogenic shock (dobutamine increases contractility and CO to treat cardiogenic shock)

• Dobutamine used for stress test (make heart work more without exercise )

• "Iso-pro-tunnel" between beta-1 and beta-2 camps: isoproterenol (beta-1=beta-2 agonist)

• Tunnel camper's elevated heart watch and contracted bicep: isoproterenol increases heart rate and contractility (beta-1 effects)

• Tunnel camper's dilated sleeves: isoproterenol causes vasodilation -> decreases SVR (beta-2 effects)

• Tunnel camper's dangling DIAmond earrings: isoproterenol decreases DIAstolic pressure (beta-2 vasodilation and decreased SVR)

• Isoproterenol increases PULSE PRESSURE, difference between systolic and diastolic (beta-1 increase in contractility)

• Isoproterenol decreases MAP (beta-2 decrease in SVR)

• Isoproterenol decreases diastolic pressure (beta-2 arteriolar dilation)

• dangling DIAmond earrings: decreased DIAstolic pressure (beta-2 vasodilation and decreased SVR)

• "Do not disTURB": TERButaline prevents premature labor (beta-2 relaxes the uterus)

• "I DREAM of band camp": ritoDRINE prevents premature labor (beta-2 relaxes the uterus)

• EPIC kiss between alpha and beta camps: EPInephrine (beta>alpha agonist)

• Low side of EPIC raft: at LOW doses, epinephrine's BETA AGONIST effects predominate

• EPIC DIAmond falling off LOW side of raft: at LOW doses, epinephrine decreases DIAstolic pressure (beta-2 vasodilation and decreased SVR)

• EPIC elevated heart watch and buff contracted bicep: epinephrine increased heart rate and cardiac contractility (beta-1 effects)

• High side of epic raft: at HIGH doses, epinephrine's ALPHA AGONIST effects predominate

• Epinephrine increases MAP (alpha-1 increase in SVR)

• Epinephrine increases systolic pressure (alpha-1 arteriolar constriction)

• Epinephrine can decrease diastolic pressure (beta-2 arteriolar dilation)

• Epinephrine increases PULSE PRESSURE, difference between systolic and diastolic (beta-1 increase in contractility)

• Beta-2 tuba girl's EPIC inhaler: epinephrine causes bronchodilation (beta-2 effects)

• "Anna + Phil": anaphylactic shock (epinephrine increases SVR and bronchodilates to treat anaphylactic shock) a1 for vasoconstriction, b1 for blood flow to tissues, b2 for bronchodilation

Indirect Sympathomimetics

• Indirect view of sympathetic mime: Indirect sympathomimetics

• Catfish: catecholamines (epinephrine, norepinephrine, dopamine)

• Dock: adrenergic nerve terminal (site of action of indirect sympathomimetics)

• Retrieving tire: tyrosine (the amino acid precursor to catecholamines) is transported to nerve terminal

• L-shaped rope handle: tyrosine is converted to L-DOPA

• Dope rope: L-dopa is converted to dopamine

• Sea vessel: vesicle containing neurotransmitters in the presynaptic neuron

• "V" mat: vesicular monoamine transporter (VMAT)

• Catfish transported to sea vessel: catecholamines are transported by VMAT into presynaptic vesicle

• North-facing compass on sea vessel: dopamine is converted to norepinephrine in the vesicle

• Hauled in catfish NET: norepinephrine transporter (NET) transports norepinephrine (and dopamine) back into the presynaptic neuron

• NET DAT catfish: dopamine transporter (DAT) transports dopamine back to the presynaptic neuron

• "My tire!": metyrosine (a tyrosine analog) prevents conversion of tyrosine to L-DOPA

• Hot cocoa: cocaine

• Hot cocoa scout ignoring catfish net: cocaine inhibits the norepinephrine transporter (NET and dopamine transporter (DAT)

• Stimulated hot cocoa scout: cocaine can cause agitation, pupillary dilation, hypertension and tachycardia

• Bloody nose: cocaine can cause nasal mucosal atrophy or septal perforation to due vasoconstriction

• Constricted red crown: cocaine can cause coronary vasospasm and myocardial ischemia

• Constricted net on anvil: cocaine induced coronary vasospasm can cause angina

• High pressure blocked bugle: beta-blockers can cause severe hypertension in cocaine intoxication (unopposed alpha-1 stimulation)

• Atom next to empty net: atomoxetine (NET inhibitor)

• Distracting HD TV: atomoxetine treats attention deficit and hyperactivity disorder (ADHD)

• Serpent blocking "V" mat: reserpine inhibits VMAT, depleting neurotransmitter stores

• A FRIEND of MINE releasing catfish: amphetamines displace catecholamines (norepinephrine, dopamine) into synapse; good for attention to tasks

• Distracted by HDTV while catfish are released: amphetamines can be used to treat ADHD

• Friend Date on HDTV: methylphenidate (an amphetamine derivative) treats ADHD

• Untouched dinner: stimulants (e.g. amphetamines, methylphenidate, modafinil) suppress appetite

• Sleeping scout hitting "sleep mode": modafinil is a stimulant used to treat narcolepsy

• Untouched dinner: stimulants (e.g. amphetamines, methylphenidate, modafinil) suppress appetite

• Untouched dinner: stimulants (e.g. amphetamines, methylphenidate, modafinil) suppress appetite

• Single rope swing: D1 receptor

• Double rope swing: D2 receptor

• Dope rope SwIng: D1 and D2 are coupled to Gs and Gi, respectively

• Low kidney tied to single rope: low doses of dopamine act on D1 receptors to increases renal blood flow

• Beta bugler in the middle: medium doses of dopamine activate beta-1 receptors (cardiac activation)

• Alpha scout up high: high doses of dopamine activate alpha-1 receptors (pressor effects)

• Brain helmet on double rope swing: D2 receptors are found in the CNS

Alpha drugs

• Claw weapon: clonidine (alpha-2 agonist)

• 2 lit alpha candles: alpha-2 receptor agonist

• Brain-shaped platform: alpha-2 agonists given systemically affect the CNS (inhibition of sympathetic tone -> reduced blood pressure)

• Crossed out "sympathy": alpha-2 agonists (e.g. clonidine) are sympatholytics

• High pressure pipes: clonidine treats hypertension (reduced sympathetic tone)

• Urgent pressure: clonidine is useful in the treatment of hypertensive urgency

• Distracting mirror: clonidine can be used to treat ADHD

• Tourette's marionette: alpha-2 agonists (e.g. clonidine) are useful in the management Tourette's syndrome

• Alpha shaped rope: a-methyldopa (alpha-2 agonist)

• 2 lit alpha candles: alpha-2 receptor agonist

• Brain-shaped platform: alpha-2 agonists given systemically affect the CNS (inhibition of sympathetic tone -> reduced blood pressure)

• High pressure pipes: a-methyldopa treats hypertension (reduced sympathetic tone)

• Pregnant: a-methyldopa is primarily used to treat gestational hypertension

• Lupus wolf: a-methyldopa can cause a lupus-like syndrome

• To X-tine: tizanidine (alpha-2 agonist)

• 2 lit alpha candles: alpha-2 receptor agonist

• Relaxing chair: tizanidine (alpha-2 agonist) is a muscle relaxant

• Phantom: phentolamine (reversible alpha-1 and alpha-2 receptor antagonist)

• Extinguished single and double alpha candles: alpha-1 and alpha-2 antagonist

• Dilated sleeves: phentolamine causes vasodilation (alpha-1 antagonist effect)

• Hot cocoa: alpha antagonists (e.g. phentolamine) can be used to treat cocaine toxicity (avoid beta blockers due to unopposed alpha vasoconstriction)

• Mousetrap protecting wine and cheese: MAO inhibitors can prevent the metabolism of tyramine -> hypertensive crisis (treat with alpha blockers e.g. phentolamine)

• Irreversible phoenix tattoo: phenoxybenzamine (irreversible alpha-1 and alpha-2 receptor antagonist)

• Hot cocoa: alpha antagonists (e.g. phentolamine) can be used to treat cocaine toxicity (avoid beta blockers due to unopposed alpha vasoconstriction)

• Wine and aged cheese contain the sympathomimetic tyramine (metabolized by monoamine oxidase-A (MAO-A))

• Mousetrap protecting wine and cheese: MAO inhibitors can prevent the metabolism of tyramine -> hypertensive crisis (treat with alpha blockers e.g. phentolamine)

• Frozen colorful dessert: pheochromocytoma (catecholamine secreting tumor of the adrenal medulla)

• Brain freeze: catecholamine excess in pheochromocytoma causes headaches, hypertension, palpitations, sweating (use alpha blockers (e.g. phentolamine) preoperatively to control blood pressure)

• Tiltable: alpha receptor antagonists can cause orthostatic hypotension (alpha-1 antagonist effect)

• Heart shaped reflex hammer: alpha blocker induced hypotension causes reflex tachycardia

• Dilated sleeves: alpha-1 antagonists "-osins" cause vasodilation

• Opera singer: "-osin" suffix of alpha-1 selective antagonists (e.g. prazosin, terazosin, doxazosin, tamsulosin)

• Extinguished single alpha candle: alpha-1 receptor antagonist

• Banister compressing prostate: alpha-1 antagonists (e.g. terazosin) treat symptoms of BPH (relax smooth muscle in the urethra and prostate)

• Praying opera singer: prazosin (alpha-1 antagonist)

• PTSD dog tags: prazosin can be used to treat PTSD

• 2 extinguished alpha candles: alpha-2 receptor antagonist

• Mirth and Misery: mirtazapine (atypical antidepressant with antagonist effects at alpha-2 and other a receptors)

• Happy face: mirtazapine enhances serotonin release and treats depression

Beta drugs

• Muted beta-1 bugle and beta-2 tuba: beta adrenergic receptor antagonists (beta blockers)

• Brahm's LOLlaby : "-lol" suffix of beta blockers (e.g. propranolol, metoprolol, atenolol)

• Weak arm: beta blockers decrease cardiac contractility (by antagonizing beta-1 receptors in the myocardium) (ionotropy)

• Music notes: beta blockers suppress activity at the SA and AV nodes (by antagonizing beta-1 receptors) (chronotropy)

• Low dangling heart watch: inhibition of SA node activity can cause bradycardia

• A-BEAM spotlight on beta-1 bugler: beta-1 selective antagonists (e.g. Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol) A through M

• Nebivolol

• A-BEAM spotlight on heart: the beta-1 selective antagonists primarily suppress adrenergic stimulation of the heart (cardioselective)

• Broken heart strings under A-BEAM spotlight: cardioselective beta blockers are useful in the acute treatment of MI and other acute coronary syndromes (ACS)

• Failing heart balloon in the A-BEAM spotlight: cardioselective beta blockers are useful in the management of chronic heart failure

• Extinguished alpha candle on CARVED candleholder: carvedilol is a nonselective beta blocker and alpha-1 blocker

• CARVED candleholder next to failing heart: carvedilol (in addition to cardioselective beta blockers) is useful in the management of chronic heart failure.

• Angina anvil: beta blockers are useful in the management of chronic stable angina. Slow Hr, increase diastolic time, decrease contractility

• Discarded oxygen line: beta blockers treat angina by reducing myocardial oxygen demand (decreased heart rate and contractility)

• Angel: beta blockers (e.g. carvedilol and cardioselective agents) reduce mortality in chronic heart failure and post-MI

• Remodeling: beta blockers reduce cardiac remodeling by protecting the heart from excess circulating catecholamines

• Big obstructed heart bag: beta blockers are useful in the management of hypertrophic obstructive cardiomyopathy. Slow down heart, allow more filling

• Rhythm inducing record: beta blockers have antiarrhythmic properties

• High pressure pipes: beta blockers are useful in the treatment of hypertension (especially in patients with heart failure or post-MI). Decrease CO

• Closed rain umbrella with blocked beta-1 bugle: beta blockers inhibit production of renin (antagonize beta-1 receptors at the JGA)

• Alpha and beta organ stops with extinguished alpha candle: labetalol ("alpha-beta-lol") is a nonselective beta blocker and alpha-1 blocker

• Dilated sleeves: labetalol antagonizes alpha-1 receptors causing vasodilation

• Pregnant organist: labetalol treats hypertension in pregnancy

• Emergency stop: labetalol is useful in hypertensive emergency (due to combined alpha and beta blocking effects)

• Dissected organ pipe with ivy: IV beta blockers (e.g. labetalol, propranolol, esmolol) are useful in the acute management of aortic dissection

• Ivy: IV beta blockers (e.g. labetalol, esmolol) treat hypertensive emergency

• Dissected organ pipe with ivy: IV beta blockers (e.g. labetalol, propranolol, esmolol) are useful in the acute management of aortic dissection

• Pounding head bell: beta blockers can be used for migraine prophylaxis

• Big stormy bowtie: beta blockers are useful for the symptomatic treatment of thyroid storm (blocks increased sympathetic activity) (treat with propanolol, propylthiouracil, prednisolone)

• Shaking baton: beta blockers treat essential tremor

• Draining the muted beta-2 tuba: topical nonselective beta blockers (e.g. timolol) treat glaucoma (antagonize beta-2 receptors on the ciliary epithelium -> decreased aqueous humor production)

• Droopy trombone: beta blockers can cause impotence in men

• Remain un-blocked: beta blockers can cause or exacerbate heart block (due to excessive suppression of AV node conduction)

• Wheezing beta-2 tuba player: nonselective beta blockers can exacerbate asthma and COPD (antagonize beta-2 mediated bronchodilation). Block b1 and b2 causing vasoconstriction

• Agonizing plastic bugle: acebutolol (a selective beta-1 antagonist with partial agonist activity)

• Agonizing pin: pindolol (a nonselective beta blocker with partial agonist activity)

• Popping failing heart: beta blockers with partial agonist activity (e.g. pindolol, acebutolol) should be avoided in patients with heart failure or a history of MI

• Glucagon packets: glucagon treats beta blocker toxicity (stimulates heart via glucagon receptors)