Usmle Step 1 High Yield Pharmacology

This deck gathers the most frequently tested pharmacology concepts for USMLE Step 1 into one focused review set. The cards walk through key drug mechanisms, clinical effects, toxicity patterns, and antidotes across major classes including analgesics, antihypertensives, lipid-lowering agents, and anticoagulants. Because pharmacology questions on Step 1 often hinge on recognizing a drug's mechanism or its hallmark side effect, this collection emphasizes exactly those high-yield associations the exam rewards.

The material is best suited for medical students in their dedicated study period or final review weeks before the exam, though it can also serve as a refresher during second-year systems coursework. If you are earlier in your training, the cards work well as a way to anchor classroom learning with board-relevant details. Students should ideally have already covered the corresponding physiology and pathology, since the questions assume familiarity with the disease context in which each drug is used.

To get the most out of these cards, try active recall first by attempting each question before flipping to the answer, and then verbally explain the mechanism or reasoning out loud as if teaching a peer. Spacing your review across several days rather than cramming will help move these associations into long-term memory, which matters on a long exam like Step 1. Pay special attention to classic antidotes and reversal agents, since these are quick points that are easy to lock in and frequently appear on test day.

Acetaminophen produces analgesia and antipyresis but overdose is dangerous because hepatic CYP2E1 converts it to the toxic metabolite NAPQI, which is normally detoxified by glutathione. In overdose glutathione is depleted and centrilobular hepatic necrosis ensues, so the antidote N-acetylcysteine replenishes glutathione stores and is most effective when given early. Aspirin irreversibly inhibits COX-1 and COX-2, blocking thromboxane A2 in platelets (antithrombotic) and reducing prostaglandin synthesis (analgesic, antipyretic, anti-inflammatory). Aspirin overdose creates a characteristic mixed acid-base disturbance: early respiratory alkalosis from direct medullary stimulation followed by anion-gap metabolic acidosis from uncoupled oxidative phosphorylation. Aspirin should be avoided in children with viral illness because of Reye syndrome, an acute hepatic encephalopathy with mitochondrial dysfunction.

NSAIDs share COX inhibition but have distinct safety profiles. Nonselective NSAIDs cause GI bleeding because COX-1 inhibition depletes protective gastric prostaglandins (PGE2, PGI2) that maintain mucus, bicarbonate, and mucosal blood flow. Renal prostaglandin inhibition reduces afferent arteriolar dilation, lowering GFR and predisposing to acute interstitial nephritis and papillary necrosis in volume-depleted, elderly, or CKD patients. Celecoxib selectively inhibits COX-2, sparing antiplatelet activity but raising cardiovascular and thrombotic risk.

Gout therapy uses NSAIDs (indomethacin, naproxen) as first-line for acute flares, with colchicine as an alternative within the first 24 hours; colchicine binds tubulin to impair microtubule polymerization and neutrophil chemotaxis, with diarrhea as its main toxicity and myelosuppression with chronic use. Allopurinol and febuxostat inhibit xanthine oxidase to lower uric acid synthesis, with a critical drug interaction warning for azathioprine (also metabolized by xanthine oxidase). Febuxostat is a non-purine alternative used in allopurinol intolerance but carries a higher cardiovascular death warning. Probenecid is a uricosuric that blocks proximal tubular reabsorption of uric acid but is ineffective when GFR is reduced and can precipitate urate stones. Rasburicase, a recombinant urate oxidase that converts uric acid to soluble allantoin, is reserved for tumor lysis syndrome and is contraindicated in G6PD deficiency.

Warfarin inhibits vitamin K epoxide reductase, depleting active vitamin K and reducing synthesis of the vitamin K-dependent clotting factors II, VII, IX, and X (mnemonic "1972") along with the anticoagulant proteins C and S. Because proteins C and S have shorter half-lives than the clotting factors, an initial prothrombotic state can occur at warfarin initiation. Reversal of warfarin uses vitamin K for slow correction or fresh frozen plasma or 4-factor prothrombin complex concentrate for urgent reversal.

Heparin binds antithrombin III and accelerates its inactivation of thrombin (factor IIa) and factor Xa, with monitoring via aPTT. Low-molecular-weight heparins such as enoxaparin have more predictable pharmacokinetics, longer half-life, subcutaneous administration, and preferential anti-Xa activity; routine monitoring is unnecessary except in renal failure or obesity. Heparin-induced thrombocytopenia (HIT) type II is an immune-mediated reaction in which antibodies against the heparin-PF4 complex paradoxically cause thrombosis along with platelet decline about 5 to 10 days after starting heparin. Management requires stopping all heparin and switching to a non-heparin anticoagulant such as argatroban or bivalirudin; protamine sulfate reverses unfractionated heparin and partially reverses LMWH.

The direct oral anticoagulants include the anti-Xa agents apixaban and rivaroxaban and the direct thrombin inhibitor dabigatran, all of which eliminate the need for INR monitoring. Targeted reversal agents are available: idarucizumab for dabigatran and andexanet alfa for the anti-Xa DOACs, providing rapid reversal in life-threatening bleeding.

ACE inhibitors reduce blood pressure and provide mortality benefit in heart failure and proteinuric kidney disease but produce a recognizable cluster of side effects: dry cough, angioedema (more common in black patients), hyperkalemia, a small creatinine rise, and teratogenicity. The cough and angioedema stem from bradykinin accumulation, since ACE normally degrades bradykinin. In bilateral renal artery stenosis, ACE inhibitors can cause an acute GFR drop because the kidneys depend on angiotensin II to maintain efferent arteriolar tone. ARBs block the AT1 receptor instead, avoiding bradykinin-related effects while retaining the same potassium and creatinine risks. Aliskiren directly inhibits renin, and sacubitril/valsartan combines a neprilysin inhibitor (raising natriuretic peptides) with an ARB for HFrEF but requires a 36-hour washout from ACE inhibitors to prevent angioedema. Statins inhibit HMG-CoA reductase to lower cholesterol synthesis, with major adverse effects of myopathy and rhabdomyolysis (especially combined with fibrates) and hepatotoxicity.

Beta-blockers are stratified by selectivity: metoprolol, atenolol, esmolol, and bisoprolol are β1-selective (preferred in asthma/COPD and diabetes, although selectivity is lost at high doses), while propranolol is non-selective and also blocks β2 receptors. They are contraindicated in severe bradycardia, AV block, decompensated heart failure, and severe asthma. Carvedilol, metoprolol succinate, and bisoprolol specifically reduce mortality in HFrEF by blunting sympathetic-driven remodeling. Non-selective beta-blockers tend to increase triglycerides and decrease HDL. Prazosin is a selective α1 antagonist used for hypertension and PTSD-related nightmares, with a first-dose orthostatic hypotension warning. Phenoxybenzamine is an irreversible non-selective alpha antagonist used preoperatively for pheochromocytoma (a beta-blocker is added only after adequate alpha blockade to avoid unopposed alpha vasoconstriction), and phentolamine is a reversible non-selective alpha antagonist for MAOI-tyramine crisis and norepinephrine extravasation. Central α2 agonists clonidine and methyldopa reduce sympathetic outflow; clonidine is used for ADHD and opioid withdrawal with rebound hypertension on abrupt discontinuation, while methyldopa is a mainstay for hypertension in pregnancy despite risk of Coombs-positive hemolytic anemia.

Direct vasodilators include hydralazine, an arteriolar vasodilator that can cause a lupus-like syndrome and reflex tachycardia and is often combined with a beta-blocker and diuretic; it is safe in pregnancy. Nitroprusside is an NO donor metabolized to cyanide, with toxicity risk during prolonged high-dose infusion or in renal failure, treated with hydroxocobalamin or sodium thiosulfate. Nitrates also release NO, primarily causing venodilation at low doses and reducing preload, with reflex tachycardia and headache; tolerance develops with continuous exposure and is prevented by a daily nitrate-free interval. Isosorbide dinitrate requires hepatic first-pass activation and is shorter acting with more tolerance issues, while isosorbide mononitrate is the active metabolite with longer duration. Calcium channel blockers split into dihydropyridines (amlodipine, nifedipine) that are vascular-selective and cause reflex tachycardia, and non-dihydropyridines (verapamil, diltiazem) with cardiac effects; verapamil causes more constipation and cardiac depression while diltiazem is intermediate and often used for rate control in atrial fibrillation. Diuretics include loop agents (furosemide blocks Na-K-2Cl in the thick ascending limb, causing hypokalemia, hypocalcemia, ototoxicity at high IV doses, and hyperuricemia), thiazides (hyperGLUC: hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, plus hyponatremia, hypokalemia, hypomagnesemia), and potassium-sparing aldosterone antagonists (spironolactone causes gynecomastia via anti-androgen effect while eplerenone does not).

Class IA antiarrhythmics (quinidine, procainamide) slow phase 0 and prolong the action potential. Class IB agents like lidocaine have a fast off-rate and shorten the action potential, useful for ventricular arrhythmias but with CNS toxicity at high plasma levels. Class IC (flecainide) is the strongest sodium blocker and is avoided post-MI. Amiodarone is a Class III agent with properties of all four classes and characteristic toxicities including pulmonary fibrosis, hypo- and hyperthyroidism (it contains iodine and inhibits 5'-deiodinase), corneal microdeposits, blue-gray skin discoloration, and hepatotoxicity; it inhibits CYP3A4 and P-glycoprotein, raising warfarin and digoxin levels and displacing digoxin from tissues. Sotalol combines Class III activity with non-selective beta-blockade, predisposing to torsades. Ibutilide is a Class III agent used for pharmacologic cardioversion of atrial flutter and fibrillation with the same torsades risk. Cardiac inotropes include digoxin, which inhibits Na/K-ATPase to increase intracellular Na and via the Na/Ca exchanger raise intracellular Ca and inotropy, producing scooped ST depression on ECG, with toxicity including yellow-green vision (xanthopsia), AV block, and arrhythmias worsened by hypokalemia, treated with digoxin immune Fab for severe toxicity; loop and thiazide diuretics worsen digoxin toxicity through hypokalemia, so potassium supplementation or potassium-sparing diuretics are often co-administered. Milrinone is a PDE3 inhibitor producing inotropy and vasodilation but increasing mortality with long-term use; dobutamine is a β1 agonist useful in acute decompensated heart failure and stress testing but causing tachyarrhythmias; and nesiritide is recombinant BNP causing vasodilation and natriuresis with limited mortality benefit. Adenosine activates A1 receptors to hyperpolarize the AV node for transient block in SVT, with effects lasting only about 10 seconds, but is contraindicated in WPW with atrial fibrillation because blocking the AV node can drive conduction down the accessory pathway and precipitate ventricular fibrillation.

Insulin preparations are categorized by onset and duration: rapid-acting lispro, aspart, and glulisine; short-acting regular insulin; intermediate-acting NPH; and long-acting glargine, detemir, and degludec. Metformin works primarily by reducing hepatic gluconeogenesis through AMPK activation and, importantly, does not cause hypoglycemia as monotherapy. It is contraindicated when eGFR falls below 30 because of lactic acidosis risk, which is the most feared adverse effect.

SGLT2 inhibitors such as empagliflozin, dapagliflozin, and canagliflozin block glucose reabsorption in the proximal convoluted tubule, producing glucosuria, modest glycemic control, weight loss, and meaningful cardiovascular and renal protection. Their side effects include genitourinary infections, euglycemic diabetic ketoacidosis, and volume depletion. GLP-1 receptor agonists (semaglutide, liraglutide) augment glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and produce substantial weight loss, with gastrointestinal side effects and a small pancreatitis risk being the main drawbacks.

Thyroid storm is a hypermetabolic crisis managed with a multi-pronged approach: a beta-blocker (typically propranolol) to control adrenergic symptoms, a thionamide such as PTU or methimazole to block new thyroid hormone synthesis, iodine (Lugol's solution) given after the thionamide to block thyroid hormone release via the Wolff-Chaikoff effect, and corticosteroids to impair peripheral T4-to-T3 conversion and address relative adrenal insufficiency, alongside fever control and supportive care.

Aminoglycosides such as gentamicin act via concentration-dependent killing and are limited by nephrotoxicity and ototoxicity, both of which can be reduced by once-daily dosing. Vancomycin infusion reactions, termed red man syndrome, result from histamine release during rapid infusion, producing flushing and pruritus rather than a true IgE-mediated allergy; slowing the infusion prevents the reaction. The cross-reactivity risk between penicillins and cephalosporins has historically been quoted as around 10%, but modern estimates place the actual rate closer to 1-2%, particularly with first-generation cephalosporins sharing a similar R1 side chain, and even lower with third- and fourth-generation agents.

Antivirals for herpesviruses center on acyclovir, which is activated by viral thymidine kinase to its triphosphate form and acts as a DNA chain terminator, primarily against HSV and VZV, with nephrotoxicity if patients are not adequately hydrated. Ganciclovir is the CMV-specific counterpart, much more potent against CMV but considerably more myelosuppressive. The four first-line anti-tuberculosis drugs each carry distinct toxicities: isoniazid causes hepatotoxicity and peripheral neuropathy from vitamin B6 depletion, so B6 (pyridoxine) supplementation is given prophylactically; rifampin is a potent CYP450 inducer (reducing levels of many drugs including oral contraceptives and warfarin) and produces benign orange discoloration of body fluids; ethambutol's signature toxicity is optic neuritis with red-green color blindness; and pyrazinamide causes both hepatotoxicity and hyperuricemia that can precipitate gout.

Antidepressants include SSRIs (fluoxetine, sertraline, escitalopram), SNRIs (venlafaxine, duloxetine), TCAs (amitriptyline, nortriptyline, imipramine, clomipramine, doxepin), MAOIs (phenelzine, tranylcypromine), and atypicals such as bupropion and mirtazapine. SSRIs and SNRIs can cause serotonin syndrome when combined with other serotonergic agents, producing the classic triad of autonomic instability, neuromuscular hyperactivity (clonus, hyperreflexia), and altered mental status, with cyproheptadine used for severe cases; triptans should also be avoided with serotonergic agents for the same reason. MAOIs require dietary restriction of tyramine-rich foods such as aged cheese, cured meats, and wine to prevent hypertensive crisis. TCA overdose produces the anticholinergic-cardiac-CNS triad of mydriasis and dry skin, wide QRS with ventricular tachycardia, and seizures or coma, with QRS widening treated by sodium bicarbonate. Bupropion lowers the seizure threshold and is contraindicated in seizure and eating disorders but is useful for smoking cessation. Mirtazapine causes sedation and weight gain via H1 and 5-HT2C antagonism but has fewer sexual side effects. Lithium toxicity manifests as tremor, confusion, ataxia, and seizures, with hemodialysis for severe cases. Anxiolytics and sedatives include benzodiazepines, which are positive allosteric modulators at the GABA-A receptor increasing the frequency of chloride channel opening and reversed by flumazenil (which can precipitate seizures in chronic users). Benzodiazepine withdrawal requires a slow taper with a long-acting agent such as diazepam or chlordiazepoxide to avoid seizures, delirium, and death; flumazenil is contraindicated. Barbiturates (phenobarbital, thiopental) are GABA-A agonists and CYP450 inducers with overdose treated supportively. Buspirone is a 5-HT1A partial agonist for generalized anxiety disorder that lacks sedation, dependence, and respiratory depression but takes 1-2 weeks for effect. Zolpidem is a non-benzodiazepine selective for the BZ-1 subtype, with minimal muscle relaxation and less dependence, though overdose is still reversed by flumazenil.

Neurodegenerative and related CNS therapy centers on neurotransmitter modulation. In Parkinson disease, levodopa is combined with carbidopa, a peripheral DOPA decarboxylase inhibitor that reduces peripheral conversion to dopamine, increasing CNS availability and decreasing peripheral side effects. Selegiline selectively inhibits MAO-B at low doses for early disease. Benztropine is a muscarinic antagonist for tremor and rigidity, while amantadine increases dopamine release and blocks NMDA receptors, particularly useful for levodopa-induced dyskinesias. For Alzheimer disease, donepezil is an acetylcholinesterase inhibitor (causing bradycardia, syncope, GI upset, and vivid dreams) and memantine is an uncompetitive NMDA antagonist for moderate-to-severe disease. Riluzole modestly prolongs survival in ALS by inhibiting glutamate release and NMDA effects. Sumatriptan is a 5-HT1B/1D agonist producing cranial vasoconstriction, contraindicated in CAD, Prinzmetal angina, and uncontrolled hypertension. Spasticity can be reduced with dantrolene (a direct ryanodine receptor blocker acting on muscle), baclofen (a GABA-B receptor agonist acting in the spinal cord), or tizanidine (a central α2 agonist used especially in multiple sclerosis and spinal cord injury with LFT monitoring). Other CNS agents include ondansetron, a 5-HT3 antagonist for chemotherapy-induced and postoperative nausea, now carrying an FDA warning for QT prolongation, and metoclopramide, a D2 antagonist prokinetic with risk of extrapyramidal symptoms and tardive dyskinesia, with acute dystonia responsive to diphenhydramine or benztropine.

The autonomic nervous system drugs span muscarinic agents. Atropine is a muscarinic antagonist used for symptomatic bradycardia and preoperatively to dry secretions, with classic anticholinergic effects (mydriasis, hyperthermia, dry mouth, urinary retention). Bethanechol is a direct muscarinic agonist for postoperative urinary retention and neurogenic ileus, contraindicated in mechanical obstruction. Pilocarpine is a direct muscarinic agonist used in open-angle glaucoma and acute angle-closure glaucoma (after laser peripheral iridotomy) to produce miosis and open the trabecular meshwork. Organophosphates irreversibly inhibit acetylcholinesterase, producing the DUMBBBELS syndrome of diarrhea, urination, miosis, bronchospasm, bradycardia, emesis, lacrimation, salivation, and sweating, treated with atropine plus pralidoxime, which regenerates acetylcholinesterase before aging occurs but does not reverse CNS effects.

Neuromuscular pharmacology centers on junctional agents. Succinylcholine is a depolarizing NMJ blocker with Phase I block that releases potassium and is contraindicated in hyperkalemia, denervation injuries, burn patients, malignant hyperthermia history, and muscular dystrophy. Malignant hyperthermia is triggered by succinylcholine or volatile anesthetics in patients with RyR1 mutations, producing sustained calcium release and hyperthermia and rigidity, treated with dantrolene. Non-depolarizing agents such as vecuronium, rocuronium, and cisatracurium are reversed by sugammadex (a cyclodextrin that binds rocuronium) or by neostigmine combined with glycopyrrolate to prevent muscarinic effects. Myasthenia gravis is diagnosed with the short-acting AChE inhibitor edrophonium and treated chronically with pyridostigmine, immunosuppressants, and thymectomy. Lambert-Eaton syndrome features antibodies to presynaptic voltage-gated calcium channels with strength improving on repeated stimulation (opposite of myasthenia), often associated with small cell lung cancer and treated with 3,4-diaminopyridine. Botulinum toxin cleaves SNARE proteins to block acetylcholine release at the NMJ, used for spasticity, blepharospasm, strabismus, migraine prophylaxis, and cosmetic indications, but is also responsible for foodborne botulism. Tetrodotoxin blocks voltage-gated sodium channels on nerves (classically from puffer fish), producing ascending paralysis and respiratory failure with no specific antidote, requiring supportive care only.

Inhaled anesthetic potency is inversely related to the minimum alveolar concentration (MAC), while speed of onset is governed by the blood:gas partition coefficient, with lower values yielding faster onset and nitrous oxide being the prototypical fast agent. Methoxyflurane is rarely used because of fluoride-induced nephrotoxicity. Propofol potentiates GABA-A receptors for rapid induction and emergence but can cause propofol infusion syndrome (acidosis, rhabdomyolysis, cardiac failure) with prolonged high-dose use, plus hypotension on induction. Etomidate is hemodynamically stable but suppresses the adrenal axis via 11β-hydroxylase inhibition, which is associated with increased mortality in sepsis. Ketamine is an NMDA antagonist producing dissociative anesthesia with bronchodilation, sympathomimetic effects (increased blood pressure and heart rate), and minimal respiratory depression, useful in pediatrics and trauma, though emergence reactions and hallucinations can occur.

Local anesthetics block voltage-gated sodium channels on nerve axons. Amides (lidocaine, bupivacaine) are metabolized in the liver, while esters (procaine, tetracaine) are metabolized by plasma cholinesterase and can cross-react with PABA allergy. Lidocaine also serves as a Class IB antiarrhythmic, with CNS toxicity (perioral numbness, tinnitus, seizures, coma) at high plasma levels and cardiac depression at very high levels. Bupivacaine is more cardiotoxic than lidocaine if delivered intravascularly, producing difficult-to-treat ventricular arrhythmias. Epinephrine is added to local anesthetics for vasoconstriction, which prolongs anesthesia, reduces systemic absorption, and decreases bleeding, but is avoided in end-arterial sites (fingers, toes, nose, penis) due to ischemia risk.

Opioids act on mu-opioid receptors and share key adverse effects: respiratory depression, miosis, constipation, tolerance, and dependence. Morphine additionally releases histamine, which can cause hypotension and bronchospasm. Naloxone is a competitive antagonist for acute overdose reversal, but its short half-life means re-dosing may be needed, particularly with methadone. Naltrexone is a long-acting antagonist for alcohol use disorder and opioid dependence maintenance. Methadone is a long-acting mu agonist and NMDA antagonist with a long, variable half-life that can lead to accumulation, used for opioid maintenance and chronic pain and notable for QT prolongation. Buprenorphine is a partial mu agonist and kappa antagonist with a ceiling effect on respiratory depression; the sublingual combination with naloxone (Suboxone) deters intravenous misuse. Tramadol is a weak mu agonist plus serotonin and norepinephrine reuptake inhibitor that lowers the seizure threshold and can cause serotonin syndrome when combined with SSRIs or MAOIs. Fentanyl is approximately 100 times more potent than morphine, with rapid onset and short duration by intravenous routes but available transdermally for chronic pain. Diphenoxylate combined with atropine (Lomotil) is used for diarrhea, with the atropine component producing anticholinergic effects at supratherapeutic doses to discourage abuse.

Cytotoxic chemotherapy spans several mechanistic classes. Cyclophosphamide is an alkylating agent that crosslinks DNA, with signature toxicities of hemorrhagic cystitis (prevented with MESNA), SIADH, myelosuppression, and secondary malignancies including bladder cancer and leukemia. Methotrexate inhibits dihydrofolate reductase, reducing purine and thymidylate synthesis; leucovorin (folinic acid) rescue protects normal cells, with toxicities including hepatotoxicity, pulmonary fibrosis, mucositis, myelosuppression, and nephrotoxicity. 5-Fluorouracil is a pyrimidine analog that blocks thymidylate synthase to decrease dTMP, causing myelosuppression, mucositis, hand-foot syndrome, and photosensitivity. 6-Mercaptopurine and its prodrug azathioprine are purine analogs metabolized by xanthine oxidase, so concurrent allopurinol causes severe toxicity. Bleomycin generates free radicals to produce DNA strand breaks, with dose-limiting pulmonary fibrosis worsened by supplemental oxygen, used in Hodgkin lymphoma (ABVD) and testicular cancer. Doxorubicin inhibits topoisomerase II, causing dose-dependent dilated cardiomyopathy preventable with dexrazoxane, an iron chelator. Cisplatin crosslinks DNA but is severely nephrotoxic (requiring aggressive hydration or amifostine), ototoxic, emetogenic, and causes peripheral neuropathy; carboplatin shares the mechanism but is more myelosuppressive (especially thrombocytopenia) and less nephro- and ototoxic, dosed by the Calvert formula using GFR. Paclitaxel stabilizes microtubules against depolymerization, producing mitotic arrest with dose-limiting peripheral neuropathy and myelosuppression, plus hypersensitivity requiring premedication. Vincristine and vinblastine bind beta-tubulin to prevent microtubule polymerization; vincristine causes peripheral neuropathy as its dose-limiting toxicity while vinblastine is more myelosuppressive. Etoposide inhibits topoisomerase II with myelosuppression and risk of secondary AML.

Targeted therapies include imatinib, a BCR-ABL tyrosine kinase inhibitor for chronic myeloid leukemia and c-KIT-positive GIST. Rituximab is an anti-CD20 monoclonal antibody for B-cell lymphomas and CLL with risk of progressive multifocal leukoencephalopathy (PML) and HBV reactivation. Bevacizumab is an anti-VEGF antibody causing hypertension, proteinuria, poor wound healing, bleeding, thrombosis, and GI perforation. Trastuzumab is an anti-HER2 antibody for HER2-positive breast cancer that causes reversible (not dose-dependent) cardiomyopathy, requiring LVEF monitoring. Immunosuppressants cyclosporine and tacrolimus are calcineurin inhibitors that block IL-2 transcription in T cells, with shared toxicities of nephrotoxicity, hypertension, and neurotoxicity; cyclosporine additionally causes gum hyperplasia.

Hormonal therapies include leuprolide, a continuous GnRH analog that downregulates pituitary GnRH receptors and lowers LH/FSH for prostate cancer, endometriosis, precocious puberty, and fibroids. Finasteride is a 5α-reductase inhibitor that blocks conversion of testosterone to DHT, used for BPH and male-pattern baldness; pregnant women should not handle crushed tablets due to teratogenicity. Tamoxifen is a SERM that is an antagonist in breast tissue but an agonist in endometrium and bone, raising risks of endometrial cancer and thromboembolism. Raloxifene is a SERM that is an agonist in bone (osteoporosis) and antagonist in breast (chemoprevention) without endometrial stimulation, though DVT risk persists. Aromatase inhibitors (anastrozole, letrozole, exemestane) block peripheral conversion of androgens to estrogens as first-line therapy for postmenopausal ER-positive breast cancer, with osteoporosis and arthralgias as major adverse effects.

Specialty drugs include sildenafil, a PDE5 inhibitor that increases cGMP for smooth muscle relaxation in the corpus cavernosum, contraindicated with nitrates due to severe hypotension, with additional risks of blue-tinted vision and hearing loss. Latanoprost is a prostaglandin F2α analog that increases uveoscleral outflow in glaucoma with cosmetic side effects of iris hyperpigmentation, eyelash growth, and periorbital fat atrophy. Hydroxychloroquine, used in SLE and RA, has toxicities of retinopathy (bull's-eye maculopathy), QT prolongation, hemolysis in G6PD deficiency, and neuromyopathy. Many drugs across classes prolong the QT interval and risk torsades de pointes, including macrolides, fluoroquinolones, methadone, antipsychotics, ondansetron, and several antiarrhythmics, so avoiding stacking and obtaining a baseline ECG is prudent.