04 Smooth Muscles

Vasoactive

Nitrates

• Dynamite: nitrates (e.g. nitroglycerine)

• Nitric oxide exhaust: nitrates are metabolized and release nitric oxide

• Grump: nitric oxide causes an increase in cGMP in vascular smooth muscle cells

• Chains constricting pants/shirts: MLCK usually causes vasoconstriction

• Cut P lock off chain: increased cGMP causes myosin light chain dephosphorylation, preventing its interaction with actin.

• Dilated blue pants: nitrates cause venous dilation and increased venous capacitance

• Modestly dilated red sleeves: nitrates cause some vasodilation of large arteries, but minimal dilation of arterioles

• preload: Nitrates decrease preload

• Folded tongue: sublingual administration of nitroglycerine avoids first pass metabolism (for acute symptom relief)

• Anvil: antianginal therapy

• Angina anvil:nitrates treat chronic stable angina

• Discarded oxygen mask: nitrates reduce myocardial oxygen requirements

• Anvil medal: nitrates treat Prinzmetal angina

• Broken heart strings: nitrates are useful in acute coronary syndrome (ACS) (unstable angina, NSTEMI, STEMI)

• Emergency shut-off: IV nitroglycerine can be used in hypertensive emergency

• Wet lung spots: nitroglycerine is an acute treatment for pulmonary edema

• Mouth cave: oral nitrate preparations have a longer duration of action

• Single nitro stick in cave: isosorbide mononitrate (oral)

• Double nitro stick in cave: isosorbide dinitrate (oral)

• Big pile of dynamite: oral nitrate preparations require larger dosing

• Fainting: nitrates can cause orthostatic hypotension (venous blood pool in extremities)

• Heart reflex hammer: nitrate induced hypotension causes reflex tachycardia

• muted beta bugle: beta blockers help prevent reflex sympathetic activation

• Nitrates can cause throbbing headaches and flushing

• Oxidized iron wheels: nitrates can cause methemoglobinemia

• No tolerance for 24 hr work day: avoid tolerance with daily nitrate free intervals

• "Monday disease" - with workplace nitrate exposure, tolerance disappears over weekend (decreased drug exposure at work) causing headache and dizziness recur on monday

• No right turn: nitrates should be avoided in right sided MI (reduce right ventricular preload, use IV fluid to enhance preload)

• Fill* station on blocked track: patients on PDE-5 inhibitors (e.g. sildenafil) should avoid nitrate therapy for 24 hrs, avoid severe hypotension

• Obstructed heart smokestack: nitrates are contraindicated with hypertrophic obstructive cardiomyopathy (HOCM), worsens on decreased preload

Migraine

• Pounding head shaped bell: migraine therapy

• Three gems on hat: migraine pain due to activation of trigeminal nerve afferents in the meninges

• Dilated sleeves: trigeminal afferents release vasoactive peptides (e.g. CGRP, substance P, neurokinin A) onto meningeal vessels -> vasodilation and protein extravasation

• Sumowrestler: triptans (e.g. sumatriptan) are an acute treatment for migraines

• "b" and "d" shaped fingers: triptans (e.g. sumatriptan) are 5-HT1b and 5-HT1d receptor agonists

• Smiley face on headband: 5-HT1b and 5-HT1d receptors are located on the meningeal vessels

• Tightening red headband: triptans (e.g. sumatriptan) cause vasoconstriction of cerebral and meningeal vessels. Decreases stretch of pain receptors

• Sumo taking out the 3 gems: triptans also activate 5-HT1b and 5-HT1d receptors on the trigeminal nerve, preventing release of vasoactive peptides

• Hair stem: triptans also activate 5-HT1b and 5-HT1d receptors in the brain stem, inhibiting pain pathways

• Constricted coronary crown: triptans can cause coronary vasospasm

• Anvil in the sumo's shadow: triptans are contraindicated in patients with angina

• Anvil medals in the sumo's shadow: triptans are a known trigger of Prinzmetal angina

• Lantern cluster: triptans (and inhaled oxygen) are also an acute treatment for cluster headaches

• Fire extinguisher: NSAIDs are an acute treatment for migraine

• Calci-Yum icecream nozzles: calcium channel blockers can be used for migraine prophylaxis

• Muted beta bugle: beta blockers can be used for migraine prophylaxis

• festiVAL PRO: valproic acid (an antiepileptic) can be used for migraine prophylaxis

• Toupee: topiramate (an antiepileptic) can be used for migraine prophylaxis

• Tricycle: tricyclic antidepressants (e.g. amitriptyline) can be used for migraine prophylaxis

Prostaglandins

• Head and assistant coaches: COX-1 and COX-2 produce prostanoids (e.g. prostaglandins)

• Pro slugger: prostaglandins

• "E": PGE1 and PGE2

• Dill pickle: alprostadil (PGE1)

• Erect bat: alprostadil treats erectile dysfunction

• Dilated red sleeves: alprostadil is a vasodilator

• Opening air duct: alprostadil maintains patent ductus arteriosus

• Closing air duct: NSAIDs (e.g. indomethacin) promote closure of ductus arteriosus

• Missed swing: misoprostol (PGE1)

• Gastric protective equipment: misoprostol promotes protective mucus secretion by gastric mucosa

• Missed swing hitting fire extinguisher: misoprostol can prevent NSAID-induced peptic ulcer

• Opening uterus bag: misoprostol promotes uterine contraction to facilitate labor or terminate pregnancy

• Flooded bathroom: misoprostol can cause diarrhea

• Dino helmet: dinoprostone (PGE2)

• Opening uterus bag: dinoprostone promotes uterine contraction and ripens the cervix to facilitate labor or terminate pregnancy

• "F": PGF2a

• Cardboard box: carboprost (PGF2a)

• Opening uterus bag: carboprost promotes uterine contraction to control postpartum hemorrhage or terminate pregnancy

• LA tan sandals: latanoprost (PGF2a)

• World traveler boots: travoprost (PGF2a)

• Leaking eyeballs: latanoprost and travoprost treat glaucoma by increasing aqueous humor outflow (not production)

• Brown sunglasses: latanoprost and travoprost can produce brown pigmentation in iris

• High tension pulmonary rackets: pulmonary hypertension

• Dilated pro-cycler: prostacyclin analogs cause vasodilation (e.g. iloprost, epoprostenol)

• iLOW - ePRO setting: iloprost and epoprostenol (prostacyclin analogs) treat pulmonary hypertension

• Fainting: iloprost and epoprostenol may cause flushing, headache, hypotension

• FILL: -fill suffix of phosphodiesterase isoform 5 (PDE-5) inhibitors (e.g. sildenafil, tadalafil)

• Don't phoster disinterest: phosphodiesterase isoform 5 (PDE-5) inhibitors (e.g. sildenafil tadalafil

• Grump: PDE-5 inhibitors increase cGMP

• Erect bat: PDE-5 inhibitors (e.g. sildenafil, tadalafil) treat pulmonary hypertension and erectile dysfunction

• Boss man Stan: bosentan treats pulmonary hypertension

• End o' the line: bosentan is an endothelin inhibitor

• Dilated red sleeves: bosentan (an endothelin inhibitor) causes vasodilation

• Liver spot: bosentan is associated with fatal hepatotoxicity

Allergy and Pulmonary

Histamines

• beehive: histamine sequestered inside the granules of mast cells

• "Q" dandelion: H1 histamine receptor is coupled to Gq protein (mediates allergic inflammation)

• Honeypot with 2 "S" handles: H2 histamine receptor is coupled to Gs protein, increased cAMP

• Golden gastric honey looks like stomach: H2 histamine receptor mediates gastric acid secretion

• Dripping nose sap: histamine increases nasal and bronchial mucus production (H1 receptor activation)

• Dripping vascular sap: histamine increases vascular permeability (H1 receptor activation) (urticaria/hives)

• Constricted lung branch: histamine causes constriction of bronchial smooth muscle (H1 receptor activation)

• Brain tree: histamine functions as a neurotransmitter (H1 receptor regulates sleep and arousal)

• fairy rubbing nose: allergic rhinitis

• Bee swatter: H1 receptor blocker (antihistamine) treats allergy

• Dragonfly fairy: diphenhydramine and dimenhydrinate (1st-generation H1 receptor blockers)

• Color fairy: chlorpheniramine (1st-generation H1 receptor blocker)

• Fairy cuiSINE: hydroxyZINE, mecliZINE, promethaZINE (1st-generation H1 receptor blockers)

• Fairy dust and dander: histamine mediates type-1 allergic reaction -> hives, allergic rhinitis (H1 receptor blockers are first line therapy)

• Seasick fairy sailors: 1st-generation H1-blockers treat vestibular nausea or motion sickness (lipophilic -> enter CNS -> act on vestibular system and brainstem)

• Falling "extra parking" cone: 1st-generation H1-blockers treat extrapyramidal side effects caused by antipsychotics, e.g. acute dystonia (antimuscarinic effects re-establish dopaminergic-cholinergic balance)

• Sleeping under brain tree: 1st-generation H1-blockers cause drowsiness (lipophilic -> cross BBB -> central effects)

• Antimuscarinic tea party: 1st-generation H1-blockers antagonize peripheral and central muscarinic receptors (e.g. pupillary dilation, dry mouth, urinary retention, constipation, exacerbation of glaucoma, and delirium)

• Cut smiley face cake: 1st-generation H1-blockers antagonize serotonin receptors in the CNS

• Stuffed fairy: 1st-generation H1-blockers stimulate appetite and weight gain (anti- serotonergic effects)

• Extinguished single alpha candle, fainted fairy: 1st-generation H1-blockers antagonize alpha-1 receptors -> dizziness and hypotension

• Delirious elderly man: 1st-generation H1-blockers cause cognitive impairment in the elderly (central antihistamine and antimuscarinic effects)

• Fox, satyr, and rat: 2nd-generation H1-blockers: fexofenadine, cetirizine, loratidine

• Fox, satyr, and rat stand outside of brain tree: 2nd-generation H1-blockers are less lipophilic -> do not cross BBB -> less sedating (also less antimuscarinic, antiserotonergic, or anti-alpha adrenergic properties)

Asthma Drugs

• Dilated beta 2 tuba: selective beta-2 agonists (e.g. albuterol) treat bronchoconstriction in asthma

• ROL call: "-rol" suffix of the selective beta-2 agonists (e.g. albuterol, pirbuterol)

• "Do not disturb": terbutaline (a selective beta-2 agonist) treats bronchoconstriction in asthma

• Inhaler: selective beta-2 agonists (e.g. albuterol) are available as metered dose inhalers for acute symptom relief

• Moon face: inhaled corticosteroids (e.g. beclomethasone, budesonide, fluticasone) can be added as daily maintenance therapy for persistent symptoms

• Moon eclipsing inflammatory sun: corticosteroids treat asthma by blocking later inflammation and cellular infiltration

• Canadian snow: Candida albicans

• Snow cone tongue: inhaled corticosteroids (e.g. beclomethasone, budesonide, fluticasone) can cause oropharyngeal candidiasis

• AA league: arachidonic acid (AA) is the precursor of leukotrienes (and prostanoid) synthesis

• Lacrosse Coach Lox: lipoxygenase (LOX) converts AA into leukotrienes

• Lacrosse players: leukotrienes LTB4, C4, D4, and E4 are important regulators of inflammation

• B4 attracting first-responders: LTB4 is a chemoattractant for inflammatory cells (e.g. neutrophils

• First responders: neutrophils

• Hand clamping lacrosse stick bronchi: LTC4, D4, E4 increase airway vascular permeability, mucus production, and bronchoconstriction

• Lacrosse goal CysLT1: receptor for LTD4 (most potent bronchoconstrictor)

• Monte the broadcaster: "-kast" suffix of LTD4-receptor antagonists (e.g. montelukast, zafirlukast)

• Blocked D4 shot: LTD4-receptor antagonists (e.g. montelukast, zafirlukast) are an alternative therapy for mild persistent asthma

• Dilated scarf: LTD4-receptor antagonists cause bronchodilation

• Open mouth: LTD4-receptor antagonists are administered orally

• Godzilla falling on Coach Lox: zileuton (a direct lipoxygenase inhibitor) is an alternative therapy for mild persistent asthma

• Liver spot: zileuton has a risk of hepatotoxicity

• ASA umpire grabbing Coach Cox: inhibition of COX shifts the AA metabolism to the LOX leukotriene pathway (exaggerated in aspirin-induced asthma)

• Salute formation: salmeterol and formoterol (long acting beta-2 agonists) treat moderate or severe persistent asthma

• Long tapering flag: salmeterol and formoterol (beta-2 agonists) have a long duration of action

• Inhaler: long acting beta-2 agonists (salmeterol, formoterol) are administered as a daily controller inhaler

• Higher moon face: an increased dose of inhaled corticosteroids treats moderate or severe persistent asthma

• Xanthine energy drink: methylxanthines (e.g. theophylline) are an alternative therapy for mild to severe persistent asthma

• Xanthine energy drink: methylxanthines (e.g. theophylline) are an alternative therapy for mild to severe persistent asthma

• "flyin'": theophylline (a methylxanthine)

• Caffeine: methylxanthines are related to caffeine

• "Don't phoster disinterest": methylxanthines (e.g. theophylline) are phosphodiesterase inhibitors

• "Camping'": methylxanthines increase cAMP, bronchodilation

• Open mouth: theophylline is administered orally

• Shaking kid: methylxanthines (e.g. theophylline) have CNS side effects including nervousness and tremor

• Holding up heart watch: methylxanthines (e.g. theophylline) can cause tachycardia

• Chrome bumper hitting energy drinks: methylxanthines (e.g. theophylline) are metabolized by the cytochrome P-450 system

• Treat overdose with activated charcoal

• Bee hive: mast cell degranulation is important to the pathogenesis of asthma

• IgE gun shooting hive: antigen binding to IgE on mast cells causes degranulation and release of inflammatory mediators (e.g. histamine)

• Limousine: omalizumab (an anti-IgE monoclonal antibody) is an adjunctive therapy for moderate or severe persistent asthma

• Grabbing end of IgE gun: omalizumab is a monoclonal antibody directed against the Fc portion of IgE, preventing mast cell sensitization

• chrome Lynn's bee control dispenser: cromolyn sodium

• Bee sedating smoke: cromolyn sulfate inhibits mast cell degranulation (preventing release of histamine)

• Beta-2 tuba: inhaled short-short acting beta-2 agonists (e.g. albuterol) treat an acute severe asthma exacerbation

• Moon face: systemic corticosteroids treat acute severe asthma exacerbation

• Ivy: corticosteroids are administered IV or orally during an acute severe asthma exacerbation

• Cat-ipra-pillar: nebulized ipratropium bromide (anticholinergic) can be added to treat an acute severe asthma exacerbation

• Epic: subcutaneous or intramuscular epinephrine can be used to treat an acute severe asthma exacerbation