Autonomic DRUGS

PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG S SECTION II 243

` P HAR MACOLOGYAUTONOM IC DR UG S

Central and peripheral nervous system

Medulla

ACh AChM

AChM

AChN

ACh

ACh

ACh

ACh

Spinalcord

N

N

N

D

D1

N

N

NE

Voluntary motor nerve

SomaticSkeletal muscle

Sympathetic

Sympathetic

Sympathetic

Parasympathetic

Renal vasculature,smooth muscle

Cardiac and smooth muscle,gland cells, nerve terminals

Cardiac and smooth muscle,gland cells, nerve terminals

Sweat glands

Adrenalmedulla

Epi, NE

Note that the adrenal medulla and sweat glands are part of the sympathetic nervous system but are innervated by cholinergic fibers.

Botulinum toxin prevents release of neurotransmitter at all cholinergic terminals.

ACh receptors Nicotinic ACh receptors are ligand-gated Na+/K+ channels; NN (found in autonomic ganglia) and NM (found in neuromuscular junction) subtypes.

Muscarinic ACh receptors are G-proteincoupled receptors that usually act through 2nd messengers; 5 subtypes: M1, M2, M3, M4, and M5.

Epi is not a NT like NE, so it can act even if there is no innervation. B2 receptors are not innervated. So NE doesnt act on it but Epi can act on it. NE even if intravenously given cannot act on B2 coz it doesnt have the right chemical structure.

Ganglion Blocking Drugs:- hexamethonium- Mecamylamine

- Reduce the predominant autonomic tone- Prevent baroreceptor reflex changes in heart rateGANGLION BLOCKING DRUGS ARE USED TO PRODUCE CONTROLLED HYPOTENSION TO MINIMISE HEMORRHAGE DURINGORTHOPEDIC AND LARGE VESSEL (AORTA) SURGERY

!decreases the predominant tone in each system

So a ganglion blocking agent can differentiate whether the tachycardia is due to a reflex or dueto a B1 agonist. Because tachycardia due to reflex will stop but the tachycardia due to B1 agonist will not.

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BARORECEPTOR REFLEX OCCURS THROUGH AUTONOMIC

GANGLION (NICOTINIC RECEPTORS)

PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG SSECTION II244

G-proteinlinked 2nd messengersRECEPTOR G-PROTEIN CLASS MAJOR FUNCTIONS

Sympathetic

1 q q vascular smooth muscle contraction, q pupillary dilator muscle contraction (mydriasis), q intestinal and bladder sphincter muscle contraction

2 i r sympathetic outflow, r insulin release r lipolysis, q platelet aggregation 1 s q heart rate, q contractility, q renin release, q lipolysis 2 s Vasodilation, bronchodilation, q heart rate, q contractility, q lipolysis,

q insulin release, r uterine tone (tocolysis), ciliary muscle relaxation, q aqueous humor production

Parasympathetic

M1 q CNS, enteric nervous system

M2 i r heart rate and contractility of atria M3 q q exocrine gland secretions (e.g., lacrimal, salivary, gastric acid), q gut

peristalsis, q bladder contraction, bronchoconstriction, q pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation)

Dopamine

D1 s Relaxes renal vascular smooth muscle D2 i Modulates transmitter release, especially in brain

Histamine

H1 q q nasal and bronchial mucus production, q vascular permeability, contraction of bronchioles, pruritus, and pain

H2 s q gastric acid secretionVasopressin

V1 q q vascular smooth muscle contraction

V2 s q H2O permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)

Qiss (kiss) and qiq (kick) till youre siq (sick) of sqs (super qinky sex).

Receptor

Lipids PIP2

GqH1, 1, V1, M1, M3

IP3

DAG Proteinkinase C

Phospholipase C

Gs1, 2, D1,H2, V2

Protein kinase A

ATPReceptor

Adenylyl cyclase

M2, 2, D2

Gi cAMPReceptor

HAVe 1 M&M.

MAD 2s.

[Ca2+]in (heart)

Myosin light-chain kinase (smooth muscle)

[Ca2+]in Smooth muscle contraction

-ve feedback to decNE release presynaptic

through PLC

cAMP mediated inc in Ca2+ influx via Ltype Ca channel

smooth muscle relaxation also via cAMP

B1 R are found in cardiac and JG cells. so B1 blockers also blockcatecholamine-induced renin release by kidney

dec PR intervalnene


Autonomic drugs

CHOLINERGIC

AChNE

Choline

Choline+Acetyl-CoA

Ca2+

Choline + acetate

AChE

AChreceptor

Vesamicol

DOPA

Dopamine

NORADRENERGIC

Reuptake

Diffusion,metabolism

Adrenoreceptors or

Botulinum

Bretylium,guanethidine

Cocaine,TCAs, amphetamine

Hemicholinium-

-

+-

Metyrosine -

Ca2++

-

+

-

-AChE inhibitors

Amphetamine

AXON

POST-SYNAPTIC MEMBRANE POST-SYNAPTIC MEMBRANE

Tyrosine

ACh

Tyrosine

2

AT II

Reserpine - Release-modulatingreceptors

Negative feedb

ack

AXON

ChAT

-+

Circles with rotating arrows represent transporters. Drugs in italics are generally not clinically used.

Release of norepinephrine from a sympathetic nerve ending is modulated by norepinephrine itself, acting on presyn aptic 2-autoreceptors, angio tensin II, and other substances.

Sphincter muscle - M receptor, Radial muscle - alpha 1 receptor, Ciliary muscle - M receptorIf sphincter muscle contracts - pin point pupil - miosisIf radial muscle contracts - dilated pupil - mydriasisIf ciliary muscle contracts - near vision - blurred vision for far awayIf ciliary muscle relaxes - blurred vision for near - far away visionMiosis: contraction of sphincter muscle - M agonists or alpha 1 blockers (no blurred vision)Mydriasis: contraction of radial muscle - M antagonists or alpha 1 agonists (no blurred vision)

Botulinum toxin - local injection- muscle paralysis - decrease ACH @ Nm - used to treat:

- blepharospasm (sustained, forced involuntary closing of the eyelids)- dystonia- strabismus- wrinkles (cosmetics)

- decrease secretion - decrease Ach @ M- treat hyperhydrosis (excessive sweating)


Cholinomimetic agentsDRUG CLINICAL APPLICATIONS ACTION

Direct agonists

Bethanechol Postoperative ileus, neurogenic ileus, and urinary retention

Activates bowel and bladder smooth muscle; resistant to AChE. Bethany, call (bethanechol) me, maybe, if you want to activate your bowels and bladder.

Carbachol Glaucoma, pupillary constriction, and relief of intraocular pressure

Carbon copy of acetylcholine.

Pilocarpine Potent stimulator of sweat, tears, and salivaOpen-angle and closed-angle glaucoma

Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma); resistant to AChE. You cry, drool, and sweat on your pilow.

Methacholine Challenge test for diagnosis of asthma Stimulates muscarinic receptors in airway when inhaled.

Indirect agonists (anticholinesterases)

Neostigmine Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative)

q endogenous ACh. Neo CNS = No CNS penetration.

Pyridostigmine Myasthenia gravis (long acting); does not penetrate CNS

q endogenous ACh; q strength. Pyridostigmine gets rid of myasthenia gravis.

Physostigmine Anticholinergic toxicity (crosses blood-brain barrier p CNS)

q endogenous ACh. Physostigmine phyxes atropine overdose.

Donepezil, rivastigmine, galantamine

Alzheimer disease q endogenous ACh.

Edrophonium Historically, diagnosis of myasthenia gravis (extremely short acting). Myasthenia now diagnosed by anti-AChR Ab (anti-acetylcholine receptor antibody) test.

q endogenous ACh.

Note: With all cholinomimetic agents, watch for exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients.

Cholinesterase inhibitor poisoning

Often due to organophosphates, such as parathion, that irreversibly inhibit AChE. Causes Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, and Salivation.

DUMBBELSS.Organophosphates are components of

insecticides; poisoning usually seen in farmers.Antidoteatropine (competitive inhibitor) +

pralidoxime (regenerates AChE if given early).

ACh has short half life so no clinical use

acts at the M receptor

can differentiate myasthenia gravis from cholinergic crisis

tertiary amine so crosses BBB

neo and pyridostigminequaternary amines so noCNS penetration

lipid soluble so CNS entry

malthion and parathion - insecticidesechothiophate - Rx glaucomanerve gas - sarin

neo and pyrido in reversal of non depolarisingNM blockade by curare like drugs

all of the above are acute toxicitychronic toxicity has nothing to do with Ach inhibition

- peripheral neuropathy causing muscle weakness and sensory loss - foot drop, wrist drop, diplopia, etc..- demyelination like in MS not due to AchE inhibition (these are very lipid soluble and myelin is a lipid - so the organophosphates act as haptens and cause an immune mediated destruction of myelin)- cannot be treated with atropine or pralidoxime - no treatment - occurs in farmers with chronic low level exposure to insecticides


Muscarinic antagonistsDRUGS ORGAN SYSTEMS APPLICATIONS

Atropine, homatropine, tropicamide

Eye Produce mydriasis and cycloplegia.

Benztropine CNS Parkinson diseasePark my Benz.Scopolamine CNS Motion sickness.Ipratropium, tiotropium

Respiratory COPD, asthma (I pray I can breathe soon!).

Oxybutynin, darifenacin, and solifenacin

Genitourinary Reduce urgency in mild cystitis and reduce bladder spasms. Other agents: tolterodine, fesoterodine, trospium.

Glycopyrrolate Gastrointestinal, respiratory Parenteral: preoperative use to reduce airway secretions.

Oral: drooling, peptic ulcer.

Atropine Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications.

ORGAN SYSTEM ACTION NOTES

Eye q pupil dilation, cycloplegia Blocks DUMBBeLSS. Skeletal muscle and CNS excitation mediated by nicotinic receptors. See previous page.

Airway r secretionsStomach r acid secretionGut r motilityBladder r urgency in cystitis

TOXICITY q body temperature (due to r sweating); rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation

Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants

Side effects:Hot as a hareDry as a boneRed as a beetBlind as a batMad as a hatter

Jimson weed (Datura) p gardeners pupil (mydriasis due to plant alkaloids)

blurred vision

can cause tachycardia, increase QRS and QT on EKG andcause torsades de pointes (can be treated with Magnesium)

- ventricles have only sympathetic innervationcan cause convulsions and coma if it crosses the BBBcan cause sedation

can cause 3Cs:cardiotoxicity, convulsion, and coma

other classes of drugs with antimuscarinic pharmacology:- antihistamines - can cause sedation and also used to treat motion sickness coz have strong antimuscarinic effects-tricyclic antidepressants-antipshychotics-quinidine- amantadine- meperidine

Treatment of acute intoxication:- symptomatic +/- physostigmine

Tropicamide mainly used in opthamology topically

no CNS entry, no change in muscus viscosity

sedation and anterograde memory block(amnesia of events after drug is taken)

lipid soluble

in acute extrapyramidal symptoms induced by antipsychotics

P HA RMACO LOGY `PHARMACOLOGYAUTONOMIC DRUGSSEC TION II252

Tetrodotoxin Highly potent toxin that binds fast voltage-gated Na+ channels in cardiac and nerve tissue, preventing depolarization (blocks action potential without changing resting potential).

Causes nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes.

Treatment is primarily supportive.

Poisoning can result from ingestion of poorly prepared pufferfish (fugu), a delicacy in Japan.

Ciguatoxin Causes ciguatera fish poisoning. Opens Na+ channels causing depolarization. Symptoms easily confused with cholinergic poisoning. Temperature-related dysesthesia (e.g., cold feels hot; hot feels cold) is regarded as a specific finding of ciguatera.

Treatment is primarily supportive.

Caused by consumption of reef fish (e.g., barracuda, snapper, moray eel).

Scombroid poisoning Acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruritus, headache. May cause anaphylaxis-like presentation (i.e., bronchospasm, angioedema, hypotension).

Treat supportively with antihistamines; if needed, antianaphylactics (e.g., bronchodilators, epinephrine).

Caused by consumption of dark-meat fish (e.g., bonito, mackerel, mahi-mahi, tuna) improperly stored at warm temperature. Bacterial histidine decarboxylase converts histidine phistamine. Histamine is not degraded by cooking. Frequently misdiagnosed as allergy to fish.


SympathomimeticsDRUG EFFECT APPLICATIONS

Direct sympathomimetics

Epinephrine > Anaphylaxis, open angle glaucoma, asthma, hypotension; effects predominate at high doses

Norepinephrine 1 > 2 > 1 Hypotension (but r renal perfusion)

Isoproterenol 1 = 2 Electrophysiologic evaluation of tachyarrhythmias. Can worsen ischemia.

Dopamine D1 = D2 > > Unstable bradycardia, heart failure, shock; inotropic and chronotropic effects predominate at high doses

Dobutamine 1 > 2, Heart failure (inotropic > chronotropic), cardiac stress testing

Phenylephrine 1 > 2 Hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)

Albuterol, salmeterol, terbutaline

2 > 1 Albuterol for acute asthma; salmeterol for long-term asthma or COPD control; terbutaline to reduce premature uterine contractions

Indirect sympathomimetics

Amphetamine Indirect general agonist, reuptake inhibitor, also releases stored catecholamines

Narcolepsy, obesity, attention deficit disorder

Ephedrine Indirect general agonist, releases stored catecholamines

Nasal decongestion, urinary incontinence, hypotension

Cocaine Indirect general agonist, reuptake inhibitor Causes vasoconstriction and local anesthesia; never give -blockers if cocaine intoxication is suspected (can lead to unopposed 1 activation and extreme hypertension)

vasoconstrictor to prolong anesthetic actionreleased from adrenal medulla - not a NT

inc rate of Phase 4 depol more in systole than diastole thus inc HR while still maintaining blood flow (most blood flow occurs during diastole)

Ergonovine is an ergot alkaloid and constricts smooth muscle cells by stiimulatiing both a adrenergic and 5ht R > provocative test forPrinzemetal angina > induce coronary vasospasm, chest pain and ST elevations in hypercontractile segments

clonidine stimulates central a2 R > dec SANS> dec circulating catecholamines

hemodynamic actions of epinephrineHR > dose dep inc > B1SBP > inc > B1 + A1DBP > dec (low dose) > B2>A1DBP > inc (high dose) > A1>B2


Norepinephrine vs. isoproterenol

Norepinephrine causes q in systolic and diastolic pressures as a result of 1-mediated vasoconstriction p q mean arterial pressure p bradycardia. However, isoproterenol (no longer commonly used) has little effect but causes 2-mediated vasodilation, resulting in r mean arterial pressure and q heart rate through 1 and reflex activity.

Bloo

d pr

essu

reH

eart

rate

SystolicMean

Diastolic

Norepinephrine ( > )

(Reflex bradycardia)

Isoproterenol ( > )

150

100

50

100

50

Pulsepressure

1

1

1

2

1

Sympatholytics (2-agonists)DRUG APPLICATIONS TOXICITY

Clonidine Hypertensive urgency (limited situations); does not decrease renal blood flow

ADHD, severe pain, and a variety of off-label indications (e.g., ethanol and opioid withdrawal)

CNS depression, bradycardia, hypotension, respiratory depression, and small pupil size

-methyldopa Hypertension in pregnancySafe in pregnancy

Direct Coombs ! hemolytic anemia, SLE-like syndrome


-blockersDRUG APPLICATIONS TOXICITY

Nonselective

Phenoxybenzamine (irreversible)

Pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis

Orthostatic hypotension, reflex tachycardia

Phentolamine (reversible)

Give to patients on MAO inhibitors who eat tyramine-containing foods

1 selective (-osin ending)

Prazosin, terazosin, doxazosin, tamsulosin

Urinary symptoms of BPH; PTSD (prazosin); hypertension (except tamsulosin)

1st-dose orthostatic hypotension, dizziness, headache

2 selective

Mirtazapine Depression Sedation, q serum cholesterol, q appetite

-blockade of epinephrine vs. phenylephrine

Epinephrine (large dose) Epinephrine (large dose)Before blockade After blockade

PhenylephrinePhenylephrine

Bloo

d pr

essu

reBl

ood

pres

sure

Net pressor effect Net depressor effect

Net pressor effect Suppression of pressor effect

Shown above are the effects of an -blocker (e.g., phentolamine) on blood pressure responses to epinephrine and phenylephrine. The epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the response) to a net decrease (the 2 response). The response to phenylephrine is suppressed but not reversed because phenyl ephrine is a pure -agonist without action.

irreversible alkylating agentcompetitive

A2 blockade presynaptically inc NE release = tachycardia (B R is still unblocked) > so undesirable as antihypertensives

minimal cardiac effects - a1 selectivity

prostate hyperplasia to reduce urinary hesistancy

pheocromocytoma - excess catecholamines - use beta blocker to protect heart and alpha blocker to prevent HTN pre-surgery. BUT USEALPHA BLOCKER FIRST - AND THEN BETA BLOCKER TO PREVENT REFLEX TACHYCARDIA AS WELL AS ANS STIMULATION!!!!!!!!!pheochromocytoma - 10% tumor: 10%malignant, 10% extrarenal, 10% in childhood, 10% familial, 10% recur after resection.

promethazine an H1 histamine antagonist w/ potent hypnotic effects also has alpha blocking effects. when standing up - hypotension and alpha R cause sympathetic vasoconstriction - since alpha is blocked - orthostatic hypotension and reflex tachycardia due to pooling ofblood in lowe extremities

dont cause much reflex tachycardia coz presynalpha 2 inhibition is not blocked


-blockers Metoprolol, acebutolol, betaxolol, carvedilol, esmolol, atenolol, nadolol, timolol, pindolol, labetalol.APPLICATION EFFECTS NOTES

Angina pectoris r heart rate and contractility, resulting in r O2 consumption

MI -blockers (metoprolol, carvedilol, and bisoprolol) r mortality

SVT (metoprolol, esmolol)

r AV conduction velocity (class II antiarrhythmic)

Hypertension r cardiac output, r renin secretion (due to 1-receptor blockade on JGA cells)

CHF Slows progression of chronic failureGlaucoma (timolol) r secretion of aqueous humor

TOXICITY Impotence, cardiovascular adverse effects (bradycardia, AV block, CHF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthmatics/COPDers (may cause exacerbation)

Avoid in cocaine users due to risk of unopposed -adrenergic receptor agonist activity

Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated

SELECTIVITY 1-selective antagonists (1 > 2)acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol

Selective antagonists mostly go from A to M (1 with 1st half of alphabet)

Nonselective antagonists (1 = 2)nadolol, pindolol (partial agonist), propranolol, timolol

Nonselective antagonists mostly go from N to Z (2 with 2nd half of alphabet)

Nonselective - and -antagonistscarvedilol, labetalol

Nonselectives - and -antagonists have modified suffixes (instead of -olol)

Nebivolol combines cardiac-selective 1-adrenergic blockade with stimulation of 3-receptors, which activate nitric oxide synthase in the vasculature

propanolol shows considerable 1st pass metabolism. It is also lipophilic and readily crosses BBB (used for migraines and ass w/ nightmares)ALL ARE METABOLISED BY CYP2D6 EXCEPT ESMOLOL (BY RBC ESTERASES). ATENOLOL IS ALSO 40% RENAL EXCRETION SOUSED IN PATIENTS W/ RENAL DYSFUNCTION.CARVEDILOL AND METOPROLOL IS ALSO USED IN HEART FAILURE. METOPROLOL IS B1 ANTAGONIST BUT THERE IS ALSOVASOCONSTRICTION IN HEART FAILURE > SO COMBINE W/ A1 BLOCKER. BEWARE OF BRADYCARDIA. (MUST BE IN FLATPART OF FRANK- STARLING CURVE)> REDUCE MYOCARDIAL O2 CONSUMPTION. ALSO BLOCKING B1 R UPREGULATES IT> BETTER CARDIAC FUNCTION.ESMOLOL HAS A VERY SHORT HALF LIFE.

BETA BLOCKER OVERDOSE - GLUCAGON IS THE DRUG OF CHOICE (BETA BLOCKERS CAUSE A DECREASE IN CAMP > GLUCAGONACTS ON GPCR > INC IC Ca2+ DURING MUSCLE CONTRACTION > INC HR AND CONTRACTILITY)

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Specific antidotes TOXIN ANTIDOTE/TREATMENTAcetaminophen N-acetylcysteine (replenishes glutathione)

AChE inhibitors, organophosphates Atropine > pralidoximeAmphetamines (basic) NH4Cl (acidify urine)

Antimuscarinic, anticholinergic agents Physostigmine salicylate, control hyperthermia

Benzodiazepines Flumazenil

-blockers GlucagonCarbon monoxide 100% O2, hyperbaric O2Copper, arsenic, gold Penicillamine

Cyanide Nitrite + thiosulfate, hydroxocobalamin

Digitalis (digoxin) Anti-dig Fab fragments

Heparin Protamine sulfate

Iron Deferoxamine, deferasirox

Lead EDTA, dimercaprol, succimer, penicillamine

Mercury, arsenic, gold Dimercaprol (BAL), succimer

Methanol, ethylene glycol (antifreeze) Fomepizole > ethanol, dialysisMethemoglobin Methylene blue, vitamin C

Opioids Naloxone, naltrexone

Salicylates NaHCO3 (alkalinize urine), dialysis

TCAs NaHCO3 (plasma alkalinization)

tPA, streptokinase, urokinase Aminocaproic acid

Warfarin Vitamin K (delayed effect), fresh frozen plasma (immediate)

Drug reactionscardiovascularDRUG REACTION CAUSAL AGENTS

Coronary vasospasm Cocaine, sumatriptan, ergot alkaloids

Cutaneous flushing Vancomycin, Adenosine, Niacin, Ca2+ channel blockers (VANC)

Dilated cardiomyopathy

Anthracyclines (e.g., doxorubicin, daunorubicin); prevent with dexrazoxane

Torsades de pointes Class III (e.g., sotalol) and class IA (e.g., quinidine) antiarrhythmics, macrolide antibiotics, antipsychotics, TCAs

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Drug reactionsendocrine/reproductiveDRUG REACTION CAUSAL AGENTS NOTES

Adrenocortical insufficiency

HPA suppression 2 to glucocorticoid withdrawal

Hot flashes Tamoxifen, clomiphene

Hyperglycemia Tacrolimus, Protease inhibitors, Niacin, HCTZ, Corticosteroids

Taking Pills Necessitates Having blood Checked

Hypothyroidism Lithium, amiodarone, sulfonamides

Drug reactionsGIDRUG REACTION CAUSAL AGENTS NOTES

Acute cholestatic hepatitis, jaundice

Erythromycin

Diarrhea Metformin, Erythromycin, Colchicine, Orlistat, Acarbose

Might Excite Colon On Accident

Focal to massive hepatic necrosis

Halothane, Amanita phalloides (death cap mushroom), Valproic acid, Acetaminophen

Liver HAVAc

Hepatitis Rifampin, isoniazid, pyrazinamide, statins, fibrates

Pancreatitis Didanosine, Corticosteroids, Alcohol, Valproic acid, Azathioprine, Diuretics (furosemide, HCTZ)

Drugs Causing A Violent Abdominal Distress

Pseudomembranous colitis

Clindamycin, ampicillin, cephalosporins Antibiotics predispose to superinfection by resistant C. difficile

Drug reactionshematologicDRUG REACTION CAUSAL AGENTS NOTES

Agranulocytosis Ganciclovir, Clozapine, Carbamazepine, Colchicine, Methimazole, Propylthiouracil

Gangs CCCrush Myeloblasts and Promyelocytes

Aplastic anemia Carbamazepine, Methimazole, NSAIDs, Benzene, Chloramphenicol, Propylthiouracil

Cant Make New Blood Cells Properly

Direct Coombs-positive hemolytic anemia

Methyldopa, penicillin

Gray baby syndrome Chloramphenicol

Hemolysis in G6PD deficiency

Isoniazid, Sulfonamides, Dapsone, Primaquine, Aspirin, Ibuprofen, Nitrofurantoin

Hemolysis IS D PAIN

Megaloblastic anemia Phenytoin, Methotrexate, Sulfa drugs Having a blast with PMS

Thrombocytopenia Heparin

Thrombotic complications

OCPs, hormone replacement therapy


PHA RMACOLOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TSPH AR MACOLOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TS SEC TION II 259

Drug reactionsmusculoskeletal/skin/connective tissueDRUG REACTION CAUSAL AGENTS NOTES

Fat redistribution Protease inhibitors, Glucocorticoids Fat PiG

Gingival hyperplasia Phenytoin, Ca2+ channel blockers, cyclosporine

Hyperuricemia (gout) Pyrazinamide, Thiazides, Furosemide, Niacin, Cyclosporine

Painful Tophi and Feet Need Care

Myopathy Fibrates, niacin, colchicine, hydroxychloroquine, interferon-, penicillamine, statins, glucocorticoids

Osteoporosis Corticosteroids, heparin

Photosensitivity Sulfonamides, Amiodarone, Tetracyclines, 5-FU

SAT For Photo

Rash (Stevens-Johnson syndrome)

Anti-epileptic drugs (especially lamotrigine), allopurinol, sulfa drugs, penicillin

Steven Johnson has epileptic allergy to sulfa drugs and penicillin

SLE-like syndrome Sulfa drugs, Hydralazine, Isoniazid, Procainamide, Phenytoin, Etanercept

Having lupus is SHIPP-E

Teeth discoloration Tetracyclines

Tendonitis, tendon rupture, and cartilage damage

Fluoroquinolones

Drug reactionsneurologicDRUG REACTION CAUSAL AGENTS NOTES

Cinchonism Quinidine, quinine

Parkinson-like syndrome

Antipsychotics, Reserpine, Metoclopramide Cogwheel rigidity of ARM

Seizures Isoniazid (vitamin B6 deficiency), Bupropion, Imipenem/cilastatin, Enflurane

With seizures, I BItE my tongue

Tardive dyskinesia Antipsychotics, metoclopramide

Drug reactionsrenal/genitourinaryDRUG REACTION CAUSAL AGENTS NOTES

Diabetes insipidus Lithium, demeclocycline

Fanconi syndrome Expired tetracycline

Hemorrhagic cystitis Cyclophosphamide, ifosfamide Prevent by coadministering with mesna

Interstitial nephritis Methicillin, NSAIDs, furosemide

SIADH Carbamazepine, Cyclophosphamide, SSRIs Cant Concentrate Serum Sodium


PH ARMACOLOGY `PHARMACOLOGYMISCELLANEOUSP HARMACO LOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TSS E C TIO N II260

Drug reactionsrespiratoryDRUG REACTION CAUSAL AGENTS NOTES

Dry cough ACE inhibitors

Pulmonary fibrosis Bleomycin, Amiodarone, Busulfan, Methotrexate

Breathing Air Badly from Medications

Drug reactionsmultiorganDRUG REACTION CAUSAL AGENTS

Antimuscarinic Atropine, TCAs, H1-blockers, antipsychotics

Disulfiram-like reaction

Metronidazole, certain cephalosporins, griseofulvin, procarbazine, 1st-generation sulfonylureas

Nephrotoxicity/ototoxicity

Aminoglycosides, vancomycin, loop diuretics, cisplatin. Cisplatin toxicity may respond to amifostine.

Cytochrome P-450 interactions (selected)

Inducers (+) Substrates Inhibitors ()

Chronic alcohol use St. Johns wortPhenytoinPhenobarbital NevirapineRifampinGriseofulvinCarbamazepine

Chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs

Anti-epilepticsTheophyllineWarfarinOCPs

Always Think When Outdoors

Acute alcohol abuseRitonavirAmiodaroneCimetidineKetoconazoleSulfonamides Isoniazid (INH)Grapefruit juiceQuinidineMacrolides (except

azithromycin)

AAA RACKS IN GQ Magazine

Sulfa drugs Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonamide antibiotics, Sulfasalazine, Sulfonylureas.

Patients with sulfa allergies may develop fever, urinary tract infection, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives). Symptoms range from mild to life threatening.

Popular FACTSSS


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` P H A R MACO LO G YM I S C E L L A N E O U S

Drug namesENDING CATEGORY EXAMPLE

Antimicrobial-azole Ergosterol synthesis inhibitor Ketoconazole-bendazole Antiparasitic/antihelmintic Mebendazole-cillin Peptidoglycan synthesis inhibitor Ampicillin-cycline Protein synthesis inhibitor Tetracycline-ivir Neuraminidase inhibitor Oseltamivir

-navir Protease inhibitor Ritonavir-ovir DNA polymerase inhibitor Acyclovir-thromycin Macrolide antibiotic AzithromycinCNS-ane Inhalational general anesthetic Halothane-azine Typical antipsychotic Thioridazine-barbital Barbiturate Phenobarbital-caine Local anesthetic Lidocaine-etine SSRI Fluoxetine-ipramine, -triptyline TCA Imipramine, amitriptyline-triptan 5-HT1B/1D agonists Sumatriptan-zepam, -zolam Benzodiazepine Diazepam, alprazolamAutonomic-chol Cholinergic agonist Bethanechol/carbachol-curium, -curonium Nondepolarizing paralytic Atracurium, vecuronium-olol -blocker Propranolol-stigmine AChE inhibitor Neostigmine

-terol 2-agonist Albuterol-zosin 1-antagonist PrazosinCardiovascular-afil PDE-5 inhibitor Sildenafil-dipine Dihydropyridine CCB Amlodipine-pril ACE inhibitor Captopril-sartan Angiotensin-II receptor blocker Losartan-statin HMG-CoA reductase inhibitor AtorvastatinOther-dronate Bisphosphonate Alendronate-glitazone PPAR- activator Rosiglitazone-prazole Proton pump inhibitor Omeprazole-prost Prostaglandin analog Latanoprost-tidine H2-antagonist Cimetidine-tropin Pituitary hormone Somatotropin

-ximab Chimeric monoclonal Ab Basiliximab-zumab Humanized monoclonal Ab Daclizumab


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Autonomic DRUGS