Lectures 4 to 8 (ophthalmic, ear-nose-throat, antihypertensive, lipid-lowering and myocardial ischemia drugs), Adam Wood Pharm.D. DABAT. Each lecture opens with what he says is NOT on the exam. ★ = professor emphasized (Lectures 6, 7 and 8 from the recording; Lecture 5 has no stars yet).
| Term | What you need to know |
|---|---|
| Dosing | “Not for memorization sake necessarily, because you can always look up the dosing for a medication if you know which drug you actually want to use in the first place.” The deck is full of regimens. Learn none of them. |
| Formulations | “I don’t care that you memorize that necessarily, with some exceptions.” Percent strengths, solution against ointment: not the question. |
| That ONE indications table | “Don’t worry so much about indications for use… a lot of them have a lot of crossover.” He means the slide listing ten antibiotics against overlapping indications — orientation, not content. What each agent is FOR is still asked. |
| Which agent irritates | “Don’t memorize which ones cause eye irritation or hypersensitivity. Any of these can do that.” That is about the GENERIC irritation. The effects that name one drug are fair game — ciprofloxacin’s white precipitate, the bitter taste of the carbonic anhydrase inhibitors, iris color change with the prostaglandins. |
| Combination products | “The specific combinations, I don’t care that you memorize, BUT just know if I was to say, hey, patient’s on this drug right now, what would be a helpful second line agent to add on?” Products out, reasoning in. |
| ★ What IS promised | “I will tell you, I will ask this question… there’s rebound hyperemia.” It is in the allergy block below. |
| Term | What you need to know |
|---|---|
| ONE variable | Time in contact with the eye. Gels, ointments and solid inserts exist to prolong contact in the cul-de-sac. So does blocking the tear ducts with silicone plugs or cautery. |
| Two routes, two effects | TRANSCORNEAL → local effect. Has a lag time; rate depends on the CONCENTRATION GRADIENT, governed by Fick’s law. NASOLACRIMAL → systemic effect, and it AVOIDS FIRST-PASS METABOLISM — which is why a topical beta blocker can drop a heart rate. |
| Four absorption determinants | Time in cul-de-sac and tear film · nasolacrimal drainage · protein binding · diffusion across cornea and conjunctiva. |
| Prodrugs activated IN the eye | Dipivefrin → epinephrine. Latanoprost → prostaglandin F2-alpha. Some drugs instead ACCUMULATE — chloroquine’s bull’s eye lesion. |
| Route trade-offs | TOPICAL: convenient, economical, safe; costs compliance, surface toxicity, systemic absorption. PERIOCULAR (subconjunctival, sub-Tenon’s, retrobulbar): reaches posterior uveitis and cystoid macular edema; risks globe perforation, optic nerve trauma, retinal vessel occlusion. INTRACAMERAL: prompt, anterior segment, short-lived. |
| Term | What you need to know |
|---|---|
| ★ THE MECHANISM PAIR | Macrolides → 50S (block transpeptidation). Aminoglycosides → 30S. Same endpoint, different subunit. |
| The other mechanisms | Fluoroquinolones → DNA gyrase + topoisomerase IV, double-stranded breakage. Bacitracin → blocks mucopeptide transfer into the CELL WALL. Polymyxin B → binds membrane phospholipids, contents leak. Sulfacetamide → antagonizes PABA. Trimethoprim → blocks reduction to tetrahydrofolate. (The last two are the same pathway, one step apart.) |
| ★ DRUG CHOICE | Erythromycin = commonest, SOOTHING, usable before a bacterial cause is confirmed; also ophthalmia neonatorum prophylaxis. Fluoroquinolone = corneal ulcers, suspected Pseudomonas, and therefore CONTACT LENS wearers once keratitis is excluded. Azithromycin = twice daily instead of 4+, but expensive and used less. |
| The only two adverse effects that name a drug | Ciprofloxacin → white precipitate in ~17%. Aminoglycoside over several days → corneal ulceration and reactive keratoconjunctivitis. Everything else irritates. |
| The only hard contraindication | Sulfacetamide in sulfonamide allergy. |
| Conjunctivitis context | Most is NOT bacterial: viruses, allergy, irritants, contact lenses. Bacteria: Neisseria, Haemophilus, Strep pneumoniae, Staph aureus, Moraxella. Treat empirically, broad spectrum, no cultures unless an unusual organism is expected. |
| Term | What you need to know |
|---|---|
| ★ NO antiviral for adenoviral conjunctivitis | Self-limited; symptomatic relief only. Antivirals exist for keratitis, herpes zoster ophthalmicus, retinitis. |
| Topical antivirals | Trifluridine → inhibits thymidylate synthetase AND substitutes for thymidine in viral DNA. Ganciclovir → competitively inhibits dGTP binding to DNA polymerase; intravitreal for CMV retinitis. |
| Systemic antivirals | Acyclovir, valacyclovir, famciclovir oral — zoster ophthalmicus, simplex keratitis. Foscarnet intravenous — CMV retinitis. |
| ★ Natamycin | The ONLY commercially available ophthalmic antifungal. Polyene — binds sterol, increases membrane permeability. Covers Aspergillus, Candida, Cephalosporium, Fusarium, Penicillium. Amphotericin B is the one with every route (topical, subconjunctival, intravitreal, intravenous). |
| ★ Fungal risk factors | Trauma · chronic ocular surface disease · contact lens wear · immunosuppression — including topical steroid use. The only one a prescription creates. |
| Term | What you need to know |
|---|---|
| ★★ REBOUND HYPEREMIA | The promised question. OTC redness drops are alpha-1 agonists → vasoconstriction. Constant activation DOWNREGULATES the receptors → on stopping, fewer receptors for endogenous catecholamines → vessels blow open. Use <2 weeks; no improvement in 72 hours → stop and be seen. |
| ★ Imidazoline ingestion | LOCALLY alpha-1. SYSTEMICALLY alpha-2. That is why a toddler who swallows the bottle gets CNS depression and apnea, not hypertension. Same receptor logic as the brimonidine age limit. |
| H1 agents | Not antagonists — INVERSE AGONISTS that inactivate the receptor, still competitive with histamine. Onset minutes; allow 2 weeks for full efficacy. Typically preferred over mast cell stabilizers. Can worsen dryness. |
| Mast cell stabilizers | Cromolyn, lodoxamide, nedocromil. Inhibit degranulation (histamine, tryptase, PGD2). 5–14 days to full effect — NOT for acute symptoms. Often 4× daily. For predictable seasonal allergy in someone intolerant of alternatives. |
| The cascade | IgE binds Fc receptors on mast cells and basophils; tyrosine kinases in 5–15 seconds; histamine, PAF, leukotrienes → vasodilation, swelling, redness, itch. |
| Term | What you need to know |
|---|---|
| ★ One step apart | STEROIDS inhibit phospholipase A2 — arachidonic acid never liberated, whole cascade fails. NSAIDs block cyclooxygenase — only the prostaglandin/thromboxane arm. |
| NSAIDs | Bromfenac, diclofenac, flurbiprofen, ketorolac, nepafenac. For postoperative inflammation and pain and allergic conjunctivitis; NOT routinely for conjunctivitis. Adverse: lacrimation, keratitis, raised IOP. |
| ★ Steroid risks → <2 week pulse | Cataract · raised IOP and glaucoma (more with family history) · infection · delayed wound healing · corneal ulcers. Also inhibit fibrin/collagen deposition → less scarring. |
| ★ “Soft steroids” | Fluorometholone, loteprednol, rimexolone — lower IOP risk. Triamcinolone = intravitreal. |
| Dry eye order | TREAT THE DISEASE FIRST (Sjogren, rheumatoid, vitamin A deficiency, Stevens-Johnson). Then punctal plugs or surgical occlusion, then tear substitutes (electrolytes + surfactants + thickeners to prolong cul-de-sac time). |
| Cyclosporine | Inhibits interleukin-2 → less T cell activation → less lacrimal gland inflammation → more tears. For chronic dry eye WITH inflammation. Warn: burning in ~17%. |
| Term | What you need to know |
|---|---|
| ★ Sort every drug by side | INCREASE OUTFLOW: prostaglandins, alpha agonists, cholinergics. DECREASE PRODUCTION: alpha agonists, beta blockers, carbonic anhydrase inhibitors. Alpha agonists are on BOTH — that is where the errors come from. |
| The three definitions | Ocular hypertension = high pressure, NO nerve damage, NO field loss. Open angle = increased production or decreased drainage; may have damage. Angle closure = blocked canal, often normal nerve, usually acute PAIN. Normal IOP 10–21 mmHg. Drugs target OPEN angle. |
| ★ Prostaglandins | FIRST LINE, most commonly used. Increase outflow. ONCE DAILY — exceeding it INHIBITS the effect. Warn: eyelash length and IRIS COLOR change, hyperemia. Latanoprost, travoprost, bimatoprost, tafluprost. |
| ★ Beta blockers | Block beta receptors in ciliary epithelium → less cAMP → less production. Betaxolol = beta-1 SELECTIVE (safer in asthma). Carteolol, timolol, levobunolol = non-selective, more efficacious, more risk. Systemic: heart failure, bradycardia, heart block, airway resistance. |
| ★ Alpha-2 agonists | Apraclonidine, brimonidine. Reduce production AND increase outflow. CONTRAINDICATED UNDER 2 YEARS — CNS depression and apnea. Apraclonidine ionized → less blood-brain penetration; brimonidine lipophilic but less allergic conjunctivitis. |
| Carbonic anhydrase inhibitors | Dorzolamide, brinzolamide. Less bicarbonate → less fluid. Tolerability is the issue: bitter taste ~25%, stinging ~33%. |
| Cholinergics | Pilocarpine, carbachol, acetylcholine. Muscarinic → ciliary muscle contracts → outflow opens. Fixed small pupils, myopia, blurring — young patients cannot tolerate it. |
| ★ Treat / target | Treat those with risk factors; monitor those without. Start with a prostaglandin or beta blocker, optionally one eye as its own control. Goal: 20–30% reduction. Combinations are synergistic across DIFFERENT routes. |
| Term | What you need to know |
|---|---|
| ★ Anesthetics | Tetracaine, proparacaine. Inhibit sodium influx. For tonometry, foreign body removal, superficial corneal surgery. Numb 10–20 min with NO BLINK REFLEX. DO NOT PRESCRIBE — repeated use is epithelial-toxic and delays healing. |
| Cycloplegics — two routes | ANTIMUSCARINICS (atropine, cyclopentolate, tropicamide) block muscarinic receptors → mydriasis. SYMPATHOMIMETIC (phenylephrine) stimulates the dilator → pupil stays more light-reactive. Uses: fundoscopy; uveitis to prevent synechiae and relieve ciliary spasm. |
| Fluorescein | Reveals epithelial defects of cornea and conjunctiva. Anterior segment staining; discloses corneal injury. |
| ★ BEFORE any drop | MEASURE VISUAL ACUITY. Document allergies and last eye exam. Repeat acuity every visit — if it worsens, immediate ophthalmology consult. |
| Instillation | Wash hands (most important) → dropper touches nothing → head back, lower lid pocket → one drop → close eyes, tilt forward, finger over lacrimal duct → hold 2–3 minutes → wipe, wash again. |
| Ointments & lenses | Ointment suits children and poor compliers (works even from the lashes); ribbon into the pocket, no duct occlusion needed; blurs vision ~20 min. Contact lenses: stop; resume after 24 h free of inflammation and discharge; discard or disinfect the lens; bin the eye makeup. |
| Term | What you need to know |
|---|---|
| Same 3 bugs | Otitis media and sinusitis: S. pneumoniae, H. influenzae, M. catarrhalis (sinusitis adds S. pyogenes, S. aureus, gram-negative bacilli). Pharyngitis: mostly viral; group A strep in 15–30%. |
| Otitis media | High-dose amoxicillin (overcomes pneumococcal resistance). Severe/resistant or antibiotics in the last month → amoxicillin-clavulanate. Penicillin allergy → cefdinir or azithromycin (up to 50% of pneumococci macrolide-resistant). No improvement in 3 days = failure → amoxicillin-clavulanate or cefdinir → ceftriaxone intramuscular/intravenous. |
| Sinusitis | Bacterial only if >10 days or worsening. Amoxicillin-clavulanate (beta-lactamase H. influenzae). Allergy → clindamycin + cefixime, or levofloxacin. Saline irrigation helps. |
| Pharyngitis | Goal: prevent rheumatic fever and suppurative complications. Rapid strep test first. Amoxicillin 10 days or benzathine penicillin G once. Allergy: cephalexin, clindamycin, azithromycin. |
| Otic drops | Antibiotic + steroid (growth ↓ + cytokines ↓). Polymyxin B: NOT with ruptured eardrum or tubes — cochlear damage, hearing loss. Neomycin → hypersensitivity. Ciprofloxacin/dexamethasone = expensive → ofloxacin + dexamethasone ophthalmic. |
| Antifungals | Nystatin: NOT absorbed; binds membrane sterols; oral thrush (inhaled steroids, HIV/AIDS (human immunodeficiency virus and acquired immunodeficiency syndrome), chemotherapy); only GI (gastrointestinal) effects. Ketoconazole: systemic fungal infection; CYP3A4 (cytochrome P450 3A4) inhibitor; QTc (corrected QT interval) prolongation; hepatitis → hepatic failure; hyperlipidemia, orthostatic hypotension. |
| Term | What you need to know |
|---|---|
| Aspirin | IRREVERSIBLE, noncompetitive platelet inhibitor; non-selective COX-1/COX-2 (cyclooxygenase-1 and -2) (cyclooxygenase). Oral → hepatic conjugation → renal excretion. |
| The ladder (no grams) | Antiplatelet → analgesic/antipyretic → anti-inflammatory (TINNITUS) → salicylism: hyperventilation + alkalosis → fever, dehydration, metabolic acidosis → shock, coma, death. |
| Aspirin contraindications | Bleeding disorders · pregnancy (very low dose may help pre-eclampsia) · child with viral fever (chickenpox, influenza) → REYE SYNDROME. |
| Reye syndrome | Under 15; 50% mortality; vomiting, progressive CNS (central nervous system) damage, hepatic injury, hypoglycemia; fatty liver, cerebral edema; 5 stages ending in seizures and death. |
| Ibuprofen | REVERSIBLE COX-1/2 (cyclooxygenase-1 and -2) inhibitor. Ulcers/bleeding, edema, acute renal failure. Interactions: ↓ ACE-inhibitor effect; diuretics → renal failure; ↑ lithium and methotrexate (toxic); anticoagulants → GI (gastrointestinal) bleeds. Avoid: asthma, under 6 months, ulcer history, renal dysfunction. Naproxen = longer half-life. |
| Acetaminophen | Analgesic + antipyretic, NOT anti-inflammatory; mechanism unclear; well tolerated. Chronic alcohol → liver damage. |
| Term | What you need to know |
|---|---|
| Triple response | Redness (direct vasodilation) · wheal (post-capillary permeability) · flare (axon-reflex vasodilation). H1: permeability, bronchoconstriction, itch. H2: gastric acid, cardiac contractility. |
| 1st vs 2nd generation | 1st generation enters the CNS (central nervous system) + hits muscarinic/serotonin receptors → SEDATION (additive with alcohol; doxylamine sleep aid), antiemetic, dry mouth, urinary retention, blurred vision; excitation in children/overdose. 2nd generation (cetirizine, fexofenadine, loratadine) → little sedation. |
| Named agents | Promethazine = strongest antimuscarinic, motion sickness. Meclizine, hydroxyzine = high antiemetic. Azelastine = nasal H1 blocker; bitter taste, epistaxis. |
| H1 uses | Allergic rhinitis, urticaria, insect bites, drug reactions; motion sickness and vestibular upset; sleep aids; adjuvant in anaphylaxis. |
| Nasal steroids | Beclomethasone, budesonide, flunisolide, fluticasone (Flonase, not Flovent), mometasone, triamcinolone. Allergic/vasomotor rhinitis. Epistaxis, septal perforation, bad taste. |
| Systemic steroids | Dexamethasone, prednisone/prednisolone. Fluid/sodium retention, potassium loss, hyperglycemia, tendon rupture, cataract/glaucoma, infection. Contraindicated in systemic fungal infection. Dexamethasone + diuretic → hypokalemia (→ arrhythmia with digoxin); macrolides ↓ its clearance. Do not stop abruptly; avoid live vaccines on prednisone. |
| Term | What you need to know |
|---|---|
| Decongestants | All alpha agonists. Oxymetazoline spray: 3–5 days max → rebound rhinitis (rhinitis medicamentosa); MAOI (monoamine oxidase inhibitor) interaction. Pseudoephedrine oral: tachycardia, hypertension, headache; ↓ antihypertensive effect; eustachian tube dysfunction. Phenylephrine = pseudoephedrine-free (Sudafed PE). |
| Spray technique | Head down, aim away from the septum, right hand → left nostril, don’t tilt back, no other sprays; nosebleed → stop and follow up. |
| Antitussives | Benzonatate: numbs lung stretch receptors; non-productive cough; swallow whole (chewing numbs mouth); tetracaine allergy. Dextromethorphan: medullary cough center, sigma receptor; serotonin syndrome; no MAOI within 2 weeks. |
| Mucus | Guaifenesin: expectorant, ↓ viscosity; fluids; expect more drainage. Dornase alfa: cleaves neutrophil DNA in cystic fibrosis sputum. Hypertonic saline. N-acetylcysteine: splits disulfide bonds; rotten-egg smell, bronchospasm; also the acetaminophen antidote. |
| Term | What you need to know |
|---|---|
| NOT on it | Diuretics/heart-failure drugs (Lecture 9, Exam 3) · which ACE (angiotensin-converting enzyme) inhibitors are prodrugs · elimination routes · plus counts in the CCB (calcium channel blocker) table · MSA/ISA columns · carteolol, betaxolol, terazosin/doxazosin detail · AT2 (angiotensin II type 2 receptor) · doses. |
| Suffixes | -pril ACE inhibitor · -sartan ARB (angiotensin receptor blocker) · -dipine DHP (dihydropyridine) CCB · -olol beta blocker (N–Z non-selective, A–M beta-1 selective; carvedilol, labetalol exceptions) · -zosin alpha-1 blocker. |
| ★★ HYPERKALEMIA | ACE inhibitors AND ARBs (angiotensin receptor blockers): renal disease, potassium-sparing diuretics, K+ (potassium) supplements, salt substitutes. His strongest cue: “very easy test question.” |
| ★ ACE inhibitor uses | Preferred in diabetics (kidney protective); all with LV (left ventricular) dysfunction unless contraindicated; post-MI; diabetic nephropathy. Enalaprilat = intravenous. |
| ★ ACE inhibitor harms | Dry cough (bradykinin, substance P; 1 week–6 months). Angioedema (bradykinin, first week). First-dose hypotension (sodium-depleted, heart failure, multiple drugs). GFR (glomerular filtration rate) drops dramatically if angiotensin-dependent → start low, go slow. 2nd/3rd trimester contraindicated. NSAIDs ↓ effect. |
| ★ ARB vs ACE inhibitor | ARBs block AT1 (angiotensin II type 1 receptor); don’t touch bradykinin → NO cough, less angioedema → the switch. Same hyperkalemia and pregnancy rules. For LV dysfunction when an ACE inhibitor is not tolerated. Add a diuretic for more effect. |
| Term | What you need to know |
|---|---|
| ★ THE SPLIT | Non-DHP (diltiazem, verapamil) = HEART: slow AV (atrioventricular) conduction, ↓ rate and contractility (verapamil most). DHP (dihydropyridine) (-dipine) = VESSELS: no AV effect. Arteries 3–10× more sensitive; afterload ↓, preload unchanged. |
| ★ Non-DHP | Angina, hypertension, SVT (supraventricular tachycardia) (atrial fibrillation/flutter, PSVT (paroxysmal supraventricular tachycardia)). 1st-degree AV block, bradycardia, worse heart failure, constipation, gingival hyperplasia. Contraindicated: advanced heart block, hypotension (relative: heart failure, liver disease, GERD (gastroesophageal reflux disease)). |
| ★ CYP3A4 (cytochrome P450 3A4) + P-gp (P-glycoprotein) | Non-DHPs inhibit CYP3A4 (↑ atorvastatin, lovastatin, simvastatin, carbamazepine, propranolol, tacrolimus, cyclosporine) and P-glycoprotein (↑ digoxin). DHPs (dihydropyridines) are substrates only. |
| ★ DHP | Rebound (reflex) tachycardia, peripheral edema, gingival hyperplasia. Nimodipine = subarachnoid hemorrhage. Nicardipine = the intravenous one. Contraindicated: severe aortic stenosis; unstable angina/recent MI (myocardial infarction) with immediate release. |
| Beta blocker + non-DHP | Synergistic ↓ BP (blood pressure), rate, contractility → lower doses of each (the slide allows it). |
| Term | What you need to know |
|---|---|
| Generations | 1st non-selective (nadolol, pindolol, propranolol, sotalol, timolol) · 2nd beta-1 selective (acebutolol, atenolol, bisoprolol, esmolol IV (intravenous), metoprolol) · 3rd vasodilating: ★ carvedilol, labetalol = alpha-1 block too. |
| ★ Hypertension | Not first line. Work best in young (tachycardia, high renin); fatigue, less exercise tolerance. First after MI (myocardial infarction). |
| ★ Heart failure trio | Carvedilol, metoprolol succinate, bisoprolol — start very low, increase slowly (worsen at first). |
| Other uses | Glaucoma (timolol), migraine prophylaxis (propranolol, timolol), hyperthyroidism (↓ T4→T3), angina, acute MI (avoid ISA (intrinsic sympathomimetic activity)), SVT (supraventricular tachycardia), panic, essential tremor. |
| ★ Harms | Bronchospasm (less with beta-1 selective; contraindicated in COPD (chronic obstructive pulmonary disease) with bronchospasm) · bradycardia, heart block · masked, prolonged hypoglycemia · cold extremities, claudication · sudden withdrawal → angina, MI, high BP (blood pressure): taper · propranolol (lipid soluble) → depression, nightmares · ↑ triglycerides. |
| Term | What you need to know |
|---|---|
| Alpha-1 blockers | Prazosin: orthostatic hypotension, mild reflex tachycardia, sodium retention, impotence; lipids improve; NSAIDs blunt, beta blockers worsen postural drop. Terazosin/doxazosin: once daily, BPH (benign prostatic hyperplasia) too. Tamsulosin = alpha-1A → BPH, little vascular effect. |
| Central alpha-2 agonists | ↓ sympathetic outflow (brainstem). Sedation, dry mouth, narrow therapeutic range, ★ abrupt-withdrawal hypertension; lipid-neutral. Clonidine: sodium retention (+ diuretic), ↑ glucose, blunts opiate withdrawal. Guanfacine: most alpha-2 selective, less sedation. (Slide 75’s “blocker” is a slip — AGONIST.) |
| ★ Hydralazine | N-acetylated → fast/slow acetylators; lupus syndrome (high dose, long term, women, slow acetylators, Caucasians); contraindicated in CAD (coronary artery disease), elderly, ischemia; stools may turn black. |
| Minoxidil / nitroprusside | Minoxidil: K+ (potassium) channel opener; severe reflexes, ischemia, arrhythmia, hypertrichosis; triple therapy for refractory HTN (hypertension). Nitroprusside IV (intravenous) for hypertensive crisis; veins + arterioles; cyanide → sodium thiosulfate; thiocyanate with long infusion/renal failure. |
| ★ Algorithm | >20/10 above goal → ACE (angiotensin-converting enzyme) inhibitor (OR ARB (angiotensin receptor blocker)) + DHP (dihydropyridine). Albuminuria (ACR (urine albumin-to-creatinine ratio) ≥300) → ACE inhibitor or ARB. Otherwise one of them → combine → + thiazide-like diuretic. Reassess at ~4 weeks. Failure: nonadherence, white coat, bad measurement. |
| Term | What you need to know |
|---|---|
| NOT on it | Picking an intensity for a scenario · calculating 10-year risk · statin PK (pharmacokinetics) table except the CYP row · IDL (intermediate-density lipoprotein) · ezetimibe + cyclosporine · doses. |
| Memory aid (not fact) | Liver = depot; LDL (low-density lipoprotein) = delivery truck (ApoB-100 (apolipoprotein B-100) badge); LDL receptor = receiving gate; HDL (high-density lipoprotein) = garbage truck; VLDL (very-low-density lipoprotein) = fuel tanker; PCSK9 (proprotein convertase subtilisin/kexin type 9) = demolition crew; bile = sewer. |
| The drugs in the story | Statins cut the depot’s own output + add gates · ezetimibe narrows the port’s import gate · resins block the sewer’s recycling (more gates, but more tankers → TG (triglycerides) ↑) · fibrates fewer tankers, more garbage trucks · niacin cuts the fuel line from fat stores · PCSK9 inhibitors stop the demolition crew. |
| ★ Key point | Statins, ezetimibe, resins, PCSK9 inhibitors all end in more hepatic LDL receptors. |
| Term | What you need to know |
|---|---|
| ★ Mechanism | HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase ↓ → less liver cholesterol → ↑ LDL (low-density lipoprotein) receptors → ↓ LDL. Pleiotropic: plaque stabilization, endothelium, antithrombotic. |
| ★ First line | Most efficacious, best tolerated; first line whenever LDL lowering is indicated. “10 times out of 10.” |
| ★ CYP3A4 (cytochrome P450 3A4) | Atorvastatin, lovastatin, simvastatin; rosuvastatin minimal CYP; pravastatin non-CYP. Interactions: verapamil, amiodarone, niacin, fibrates, GRAPEFRUIT JUICE. |
| ★ Harms | Liver enzymes ↑ 0.5–2.5%, serious liver problems exceedingly rare → reduce/hold. Myalgia → myopathy → rare rhabdomyolysis; combine with fibrates cautiously; muscle toxicity → STOP. |
| ★ Contraindications | Hepatic disease, pregnancy. Relative: cyclosporine, gemfibrozil, niacin, erythromycin. |
| ★ AHA/ACC (American Heart Association and American College of Cardiology) | Moderate/high intensity for the 4 groups; no LDL target; recheck lipids for adherence. Groups: clinical ASCVD (atherosclerotic cardiovascular disease) · LDL >190 · diabetes 40–75 with LDL 70–189 · 10-year risk >7.5% with LDL 70–189. |
| ★ Intensity | High ≥50% LDL fall = atorvastatin, rosuvastatin only; moderate 30–49%; low <30%. Not tolerated → maximum tolerated dose. Recheck LDL at 6 weeks (expect 30–50%). |
| Term | What you need to know |
|---|---|
| Ezetimibe | ↓ intestinal cholesterol absorption → ↑ LDL (low-density lipoprotein) receptors; add-on to a statin; enterohepatic (glucuronide); transaminases ↑ with statin; antacids and resins ↓ levels; fibrates → gallstones. |
| ★ Resins | Cholestyramine, colestipol, colesevelam. Bind bile acids → ↑ LDL receptors. Not absorbed → children, adolescents, PREGNANCY; poorly tolerated; constipation; ADEK (vitamins A, D, E and K) + folate malabsorption; ↑ VLDL (very-low-density lipoprotein) → TG (triglycerides) ↑. |
| ★ Resin contraindication | Absolute: TG >400, familial dysbetalipoproteinemia. Relative: TG >200. TG 600 → the resin is the wrong answer. |
| ★ Resin administration | Mix powder in water/pulpy juice; within 1 h of a meal; other drugs (digoxin, warfarin, thyroxine, beta blockers, thiazides) 1 h before or 4 h after. |
| ★ Fibrates | PPAR-alpha (peroxisome proliferator-activated receptor alpha) → ↓ VLDL/TG, ↑ ApoA-1/HDL. TG >1000 or low HDL (high-density lipoprotein). Gallstones, myopathy. Contraindicated: pregnancy, severe hepatic/renal disease, gallbladder disease. ↑ warfarin effect. |
| ★ Niacin | ↓ FFA (free fatty acids) from fat → ↓ VLDL, LDL; biggest HDL rise. Flushing = prostaglandins → aspirin first. ↑ LFTs (liver function tests), glucose, uric acid. Absolute: chronic liver disease; relative: peptic ulcer, gout, hyperuricemia, diabetes. Alcohol interacts. Niacinamide is NOT an antilipemic. |
| PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors | Alirocumab, evolocumab: monoclonal antibodies, injectable only, expensive; keep LDL receptors active; hypersensitivity is the most serious reaction. |
| ★ Which lipid | LDL → statins. TG ↓ + HDL ↑ → niacin, fibrates. Resins are the only class bad for TG. |
| Term | What you need to know |
|---|---|
| Last lecture | “The end of the testable material for the exam for Monday ends with this PowerPoint.” The diuretics and heart failure deck after it is the next exam. |
| Cell lines | “I don’t care that you know the difference between which one’s made with E. coli versus hamster cells.” Skip the Chinese hamster ovary cells against Escherichia coli detail. |
| Streptokinase the drug | “I don’t want you to worry so much about that, but I do want to focus on this picture.” Learn the PICTURE: plasminogen → plasmin, by a streptokinase complex or by tissue plasminogen activator. |
| Dosing | This site leaves milligram amounts out (doses are not tested in this course, per the earlier lectures); he quoted the aspirin loading amount without saying whether it is examined. Timings and routes (12 hours on and off, under the tongue) are fair. |
| ★ What he stressed | Prevention against quick relief (“I will reiterate and reiterate and reiterate”); what to add next and what to switch to; and the comorbidity table (“a cornucopia of test questions”). |
| Term | What you need to know |
|---|---|
| Definitions | Ischemic heart disease = imbalance between myocardial oxygen supply and demand. Coronary heart disease = atherosclerotic narrowing of coronary arteries. Angina pectoris = chest pain, the clinical manifestation of ischemia. Acute coronary syndrome = unstable angina, acute myocardial infarction, sudden cardiac death. |
| Demand | Heart rate, contractility, systolic wall tension. Wall tension = preload (initial stretch, ventricular volume) plus afterload (pressure ejected against, systemic vascular resistance). |
| Supply | Arterial oxygen pressure and hemoglobin; coronary flow and its distribution; oxygen extraction and microcirculation. |
| Stenosis | Clinically significant: 50% of the left main or 75% of another major coronary artery. Above 90% = virtually no flow. |
| ★ Variant (Prinzmetal) angina | Vasospasm; younger, fewer risk factors; often night or early morning; ST elevation may or may not show. Treat with calcium channel blockers and nitrates; AVOID beta blockers (worse symptoms). |
| Risk factors | Non-modifiable: family history of premature cardiovascular event; age above 45 (men), 55 (women). Modifiable: sedentary life, diabetes, tobacco, overweight, hypertension, dyslipidemia. |
| Goals and strategy | More quantity of life (prevent acute coronary syndrome) and quality (relieve and prevent symptoms). Lower demand (rate, contractility, wall tension) and raise supply (coronary flow); stabilize plaque; fix risk factors. |
| ★ Prevention vs quick relief | PREVENT (beta blockers, calcium channel blockers, long-acting nitrates) vs QUICK RELIEF (short-acting sublingual nitroglycerin). A stem asks for one and offers the other. |
| Three treatment arms | Revascularization (percutaneous coronary intervention, bypass grafting) · antianginals (beta blockers, calcium channel blockers, nitrates) · vasculoprotective (antiplatelets, statins, angiotensin-converting enzyme inhibitors) · lifestyle. |
| ★ Grades of angina | Graded by how much activity he can do; exercise capacity also shows whether therapy works. I no limitation · II slight, symptoms with more than ordinary activity · III marked, symptoms with ordinary activity · IV any activity; may have symptoms at rest. Comfortable at rest in I to III. |
| Memory aid (not fact) | Oxygen BUDGET: supply = income, demand = spending, angina = overdraft warning. Beta blockers cut spending only; calcium channel blockers and nitrates cut spending AND lift income. |
| FLAG: slide 13 | Slide lists aspirin and clopidogrel as raising coronary flow. Truth: they prevent clots; they do not dilate. Learn them as vasculoprotective. |
| Term | What you need to know |
|---|---|
| ★ Beta blockers: role | First line for angina if no contraindication. Helpful with hypertension, anxiety, supraventricular arrhythmias, heart failure, prior myocardial infarction. Act on DEMAND only: lower rate, contractility, systolic pressure; no effect on supply; left ventricular volume goes UP. |
| ★ Agents (alphabet rule) | Beta-1 selective A–M: metoprolol, atenolol. Non-selective N–Z: propranolol, nadolol. Third generation, the exception: carvedilol, labetalol. |
| Beta blocker contraindications | Heart rate below 60; systolic pressure below 100 mmHg; atrioventricular block; acute decompensated heart failure. Precautions: reactive airway disease, systolic heart failure, diabetes, peripheral vascular disease. |
| ★ Beta blocker harms and teaching | Hypotension, bradycardia, hyperglycemia, dyslipidemia; fatigue, sexual dysfunction, nightmares, worse claudication. Monitor heart rate, blood sugar, lipids. Teach: do not stop suddenly; dizziness, fatigue. |
| ★ Calcium channel blockers: supply AND demand | Mild dilation where stenosis is fixed; relief of vasospasm. Non-dihydropyridine (diltiazem, verapamil) = HEART: rate, contractility, atrioventricular conduction all down (verapamil most). Dihydropyridine (nifedipine, amlodipine, felodipine) = VESSELS: most vasodilation, no atrioventricular effect; rate up with nifedipine and felodipine, unchanged with amlodipine. |
| ★ Place in therapy | Non-dihydropyridine first when beta blockers are contraindicated or not tolerated. Dihydropyridine ADDED to a beta blocker when it fails. Also with long-acting nitrates. AVOID short-acting agents (nifedipine). Good for vasospastic angina, severe peripheral vascular disease, asthma, uncontrolled diabetes, left ventricular dysfunction (dihydropyridine only). |
| ★ Calcium channel blocker contraindications | Systolic pressure below 100 mmHg. Non-dihydropyridine only: heart rate below 60, acute heart failure, ejection fraction below 40%. Atrioventricular block (FLAG: means the non-dihydropyridines; dihydropyridines do not slow conduction). Precautions: beta blocker with a non-dihydropyridine; CYP3A4 (cytochrome P450 3A4) interactions. |
| ★ Calcium channel blocker harms and teaching | Hypotension; dihydropyridines: headache, flushing, peripheral edema. Monitor symptom relief and heart rate (non-dihydropyridine). Teach: dizziness, constipation (straining strains the heart; ask about bowel habits). |
| ★ Combinations and the switch | Nifedipine and felodipine ALONE raise the heart rate (amlodipine leaves it unchanged) → add a dihydropyridine to a beta blocker. Beta blocker + non-dihydropyridine = avoid (more bradycardia, heart block). Nightmares on a beta blocker → switch to a non-dihydropyridine. Left ventricular dysfunction → dihydropyridine only. |
| ★ CYP3A4 (cytochrome P450 3A4) | The one enzyme to know. Non-dihydropyridines (verapamil, diltiazem) inhibit it AND are substrates; dihydropyridines (amlodipine) are only substrates. Verapamil + simvastatin → simvastatin levels rise (sections 3.4, 4.2). |
| Demand table | Beta blockers: rate DOWN, left ventricular volume UP. Dihydropyridine: rate UP, pressure down hard. Non-dihydropyridine: rate DOWN. Nitrates: rate UP, left ventricular volume DOWN hard. |
| Term | What you need to know |
|---|---|
| Mechanism | Nitric oxide → guanosine triphosphate to cyclic guanosine monophosphate → protein kinase G → lower cytosolic calcium → smooth muscle relaxation, vasodilation, lower blood pressure. Phosphodiesterase type 5 breaks cyclic guanosine monophosphate down. |
| Effects | Demand: pressure down, left ventricular volume down hard, rate up. Supply: dilate coronary arteries, relieve vasospasm, antithrombotic and antiplatelet effects. |
| ★ Short-acting | Sublingual tablet or spray = the QUICK-RELIEF answer. Goals: relieve acute ischemia AND prevent effort angina. Teach: orthostatic hypotension; original packaging, cool dry place; replace tablets 3 to 6 months after opening (the course rule; FLAG: current labeling ties expiry to the printed date in the original closed bottle); under the tongue. |
| ★★ Five-minute rule | No relief 5 minutes after the first dose → call emergency medical services. (The slide says dose every 5 minutes until relief or help arrives; standard practice caps it at three doses; his words: keep dosing while waiting.) The action is the answer, not the number. |
| ★ Long-acting | Usually the third add-on; usually an adjunct; not recommended as monotherapy. Allowed as initial therapy only when beta blockers AND calcium channel blockers are both contraindicated or not tolerated; otherwise added to them when they are not successful. Isosorbide mononitrate: lasts 12 hours, once daily. Isosorbide dinitrate: 3 to 6 hours, three times daily. Forms: ointment, transdermal patch. |
| Ointment and patch | 12 hours on, 12 hours off. Ointment: measure on applicator paper, thin layer on chest, keep covered, wipe off the old dose first. |
| ★ Nitrate-free interval (tachyphylaxis) | All you need to know: 12 hours on, 12 hours off, off when the patient is least likely to have symptoms (asleep). Tolerance with continued use; cause not fully understood (cofactor depletion, renin-angiotensin and sympathetic counter-regulation, plasma volume expansion, less enzyme activity). Fix: nitrate-free interval when symptoms are least frequent. |
| Adverse reactions | Headache, flushing, postural hypotension, reflex tachycardia. |
| ★ Contraindications | Phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil) are absolute → hypotension, myocardial infarction or stroke. FLAG: the slide lists aortic valve stenosis and obstructive cardiomyopathy as contraindications; current labeling says avoid in severe aortic stenosis and obstructive cardiomyopathy. |
| Term | What you need to know |
|---|---|
| ★ Order of use | Add-on: beta blocker, then a dihydropyridine, then a long-acting nitrate. Switch: beta blocker not tolerated → non-dihydropyridine. Third agent → further workup. Beta blocker + non-dihydropyridine: “begging for trouble.” |
| Combination | Consider when angina persists on one drug. Beta blocker plus calcium channel blocker if tolerated (may lengthen exercise). A third agent means further workup (angiography). |
| ★ Comorbid table: solid rows | Prior myocardial infarction, hypertension, reduced left ventricular function → beta blocker first (reduced function: amlodipine is the calcium channel blocker alternative; avoid the others). Bradycardia or atrioventricular block → dihydropyridine first; avoid non-dihydropyridines AND beta blockers. Asthma → avoid non-cardioselective beta blockers. |
| ★ Comorbid table: two course cells | Prior myocardial infarction → beta blocker first; AVOID calcium channel blockers. Diabetes → non-dihydropyridine first; alternatives long-acting nitrate and cardioselective beta blocker; avoid non-cardioselective beta blockers (beta blockers can raise blood sugar and mask hypoglycemia). These are the course answers. FLAG: current practice is less absolute (a non-dihydropyridine can substitute after infarction when a beta blocker cannot be used; a cardioselective beta blocker is still sound in diabetes). |
| ★ Angiotensin-converting enzyme inhibitors | For coronary disease with diabetes and/or left ventricular systolic dysfunction. Do NOT change oxygen use and do NOT relieve angina; may slow disease progression. Continue indefinitely after myocardial infarction, left ventricular dysfunction, or diabetes; consider in all vascular disease. |
| ★ Antiplatelets | Aspirin for all ischemic heart disease without contraindication (prevents acute coronary syndrome). Clopidogrel = as good as aspirin in secondary prevention; for aspirin allergy. |
| ★ One-slide strategy (the standing list) | Everyone (unless contraindicated): aspirin, lipid-lowering, sublingual nitroglycerin; beta blocker if prior infarction; angiotensin-converting enzyme inhibitor with diabetes or left ventricular dysfunction. Daily symptoms: beta blocker, calcium channel blocker, long-acting nitrate. |
| Term | What you need to know |
|---|---|
| Classification | ST-elevation myocardial infarction. Non-ST-elevation acute coronary syndrome = unstable angina + non-ST-elevation myocardial infarction; a biochemical marker separates angina from infarction. |
| Clot, step by step | Plaque under a fibrous cap → spontaneous or procedural (balloon) injury leaves injured endothelium → platelet adhesion, activation, aggregation → fibrin strands → occlusive thrombus. |
| ★ Thrombin is the link | The two factors to know: X and II (thrombin). Collagen exposure → adenosine diphosphate and thromboxane A2 activate platelets. Tissue factor starts the cascade: prothrombin → thrombin → fibrinogen to fibrin. |
| Three phases | Initiation: tissue factor with factor VIIa activates X and IX, a little thrombin. Amplification: thrombin activates platelets and factors V and VIII; complexes assemble on platelets. Propagation: more thrombin, fibrin, clot stabilization. |
| Goals | Restore coronary flow · relieve chest pain · prevent infarction · prevent heart failure · prevent death. |
| ★ Aspirin | Give at first signs of chest pain, chew and swallow. Lowers mortality and reinfarction. Contraindicated: allergy, recent gastrointestinal bleed, recent intracranial hemorrhage. |
| ★ Nitrates | Sublingual, then intravenous infusion in hospital. Relieve pain ONLY: no mortality benefit. Hypotension, headache, reflex tachycardia. Avoid with hypotension or phosphodiesterase inhibitors. |
| ★ Beta blockers | Intravenous first, then oral. Reduce early and late mortality, infarct size, heart failure and sudden cardiac death (course answer). Caution: bradycardia or hypotension, heart block, severe reactive airway disease. (FLAG: current guidelines favor oral in the first 24 hours, avoid the intravenous route with heart failure or shock risk, and rest the benefit mainly on long-term use after infarction.) |
| ★ Morphine | Opioid for chest pain not relieved by nitrates; used in ST-elevation myocardial infarction; may raise mortality in unstable angina and non-ST-elevation myocardial infarction; controversial. Hypotension, allergy. |
| Term | What you need to know |
|---|---|
| System | Plasminogen → plasmin (by tissue plasminogen activator) → plasmin lyses fibrin (and fibrinogen). Brakes: plasminogen activator inhibitor-1 and -2, alpha-2 antiplasmin, thrombin-activatable fibrinolysis inhibitor. |
| ★ Mechanisms (learn the picture) | Streptokinase (the drug is low priority; the picture is not) forms a stable 1:1 complex with plasminogen that converts more plasminogen to plasmin. Alteplase (tissue plasminogen activator) acts on fibrin-bound plasminogen. Reteplase and tenecteplase behave like it. |
| ★ Agents | The three main ones are very similar (provider preference, formulary; all costly, all allergy and bleeding), and all three favor clot-bound plasminogen (reteplase less than alteplase, see the flag). Alteplase (Activase) is very expensive. Tenecteplase (TNKase) has substituted amino acids. Reteplase and tenecteplase: longer half-life than alteplase. The slide says both resist plasminogen activator inhibitor-1, but that is established for tenecteplase only. |
| FLAG: three slide errors | Fibrin affinity: true for tenecteplase, FALSE for reteplase (less than alteplase). Factor list (II, V, VII) for plasmin: do not learn. Fever, chills, rash “with streptokinase and urokinase”: only streptokinase is antigenic. |
| ★ Adverse effects | Bleeding is the big one (including intracranial hemorrhage), allergic reactions, anaphylaxis, ventricular arrhythmias. Fever, chills, rash = streptokinase. |
| ★ Nine contraindications (the checklist) | Recent surgery or trauma · serious gastrointestinal bleeding · severe hypertension · active bleeding or bleeding disorder · prior stroke (firm for hemorrhagic or recent ischemic stroke) or intracranial tumor · aortic dissection · acute pericarditis · prior streptokinase exposure or allergy · pregnancy (a relative contraindication in current guidance). Mostly anything that could bleed; the exception is prior streptokinase exposure or allergy, which bars streptokinase only. |
| ★ Indication | ST-elevation myocardial infarction within 12 hours of symptom onset (the slide adds an age limit, an older cut-off). NOT recommended in non-ST-elevation acute coronary syndrome. Few patients receive them; main risk bleeding. |
| ★ Other antithrombotics | Glycoprotein IIb/IIIa inhibitors: not routine before percutaneous coronary intervention. P2Y12 receptor antagonists: before intervention and with stents. Heparins: with fibrinolysis or antiplatelets. |
| ★ Non-ST-elevation acute coronary syndrome | Early care like ST-elevation myocardial infarction, BUT fibrinolytics NOT recommended (bleeding outweighs benefit); enoxaparin preferred over unfractionated heparin (older studies; either is accepted today); glycoprotein IIb/IIIa inhibitors more common. |