Download - Autonomic DRUGS
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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
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!decreases the predominant tone in each system
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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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Page 91 of K
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BARORECEPTOR REFLEX OCCURS THROUGH AUTONOMIC
GANGLION (NICOTINIC RECEPTORS)
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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
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG S SECTION II 245
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)
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG SSECTION II246
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
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG S SECTION II 247
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
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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.
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG SSECTION II248
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
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG S SECTION II 249
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
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG SSECTION II250
-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
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PHARMACOLOGY `P HAR MACOLOGYAUTONOM IC DR UG S SECTION II 251
-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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PHA RMACOLOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TSPH AR MACOLOG Y `PHARMACOLOGYAUTONOMIC DRUGS SEC TION II 257
` P H A R MACO LO G YTOX I C I T I E S A N D S I D E E F F E C TS
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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PH ARMACOLOGY `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TSP HARMACO LOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TSS E C TIO N II258
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
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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
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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 HAR MACOLOG Y `PHARMACOLOGYMISCELLANEOUSPH AR MACOLOG Y `PHARMACOLOGYTOXICITIES AND SIDE EFFEC TS SEC TION II 261
` 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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