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Pharmacology Comprehensive Review – Key Points

First-Pass Effect & Bioavailability

  • First-pass (hepatic) effect: oral drugs absorbed via GI tract enter portal circulation and undergo metabolism in liver before reaching systemic circulation → decreased bioavailability.
  • Route affected: oral (PO) ONLY among common routes tested.
  • Best bioavailability: intravenous (IV) because it bypasses GI tract & liver, \text{F}_{\text{IV}} \approx 100\%.

Antifungal for Steroid-Inhaler Oral Thrush

  • Problem: Fluticasone inhaler → local immunosuppression → candidiasis (oral thrush).
  • Drug of choice: nystatin (topical “swish & swallow” or lozenge).

Vancomycin High-Yield Facts

  • Class: glycopeptide antibiotic (gram+ including MRSA, C. difficile PO).
  • Key adverse effects:
    • “Red-man syndrome”: histamine-mediated flushing, pruritus, hypotension during rapid infusion.
    • Ototoxicity (hearing loss) & nephrotoxicity.
  • Monitoring (see full section below): peaks \& troughs, renal, hearing, infusion reactions.

HIV Antiretrovirals – Classes & Mechanisms

  • Efavirenz → Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) – inhibits reverse transcriptase allosterically.
  • Enfuvirtide → Entry/Fusion inhibitor – binds gp41 preventing viral fusion with CD4 cell membrane.
  • Lopinavir → Protease inhibitor – blocks HIV protease, preventing cleavage of gag-pol polyprotein ⇒ immature virions.

Herbal Supplements & Common Uses

  • Black cohosh → menopausal hot flashes, night sweats.
  • Echinacea → “immune boost” to reduce common-cold duration.
  • Ginger → anti-emetic; decreases nausea (motion sickness, pregnancy).
  • Saw palmetto → benign prostatic hyperplasia (BPH) urinary symptoms.
  • St. John’s wort → mild–moderate depression (CYP-450 inducer → many interactions).

Therapeutic Index (TI)

  • \text{TI}=\frac{\text{TD}{50}}{\text{ED}{50}} or \frac{\text{LD}{50}}{\text{ED}{50}}.
  • High/“wide” TI preferred → greater safety margin.
  • Low/“narrow” TI drugs (e.g., digoxin, lithium, theophylline, warfarin) require close monitoring.

Severe Penicillin Allergy – Drugs to Avoid

  • Cross-reactivity within \beta-lactams (shared ring).
  • Cephalosporins (e.g., cephalexin) contraindicated in severe IgE-mediated PCN allergy (anaphylaxis, angioedema).
  • Alternative agents discussed:
    • Acyclovir (antiviral for HSV, VZV) – safe.
    • Metronidazole (antibiotic/antiprotozoal) – avoid alcohol (disulfiram-like).
    • Tetracycline – photosensitivity → advise protective clothing/≥50 SPF.

Vancomycin – Detailed Monitoring

  • Peaks (30 min after infusion) & troughs (immediately before next dose) maintain 10–20\,\text{\mu g/mL}.
  • Renal function: BUN, serum creatinine (nephrotoxicity risk).
  • Hearing exams (audiometry) for ototoxicity.
  • Infusion site & vitals for Red-man syndrome.
  • Liver tests not routinely required.

Chemotherapy Agents & Signature Toxicities

  • Cyclophosphamide → hemorrhagic cystitis (acrolein metabolite) – give mesna & hydration.
  • Doxorubicin (anthracycline) → cardiomyopathy/heart failure → cumulative lifetime dose limit, baseline \& periodic EKG/echo.
  • Tamoxifen (SERMs) → thromboembolism (DVT, PE); also endometrial cancer risk.
  • Vincristine (vinca alkaloid) → peripheral neuropathy (stocking-glove tingling).

Cyclosporine Essentials

  • Calcineurin inhibitor for transplant rejection prophylaxis, autoimmune (RA, psoriasis).
  • Adverse effects:
    • Bone-marrow suppression → infections, petechiae (tiny red pin-prick hemorrhages), fever.
    • Nephrotoxicity, hypertension, gingival hyperplasia, hirsutism.
    • Lymphoma risk.

NSAIDs & GI Complications

  • Ibuprofen → inhibits COX-1/2 → ↓prostaglandins protecting gastric mucosa → dyspepsia, heartburn, PUD, GI bleed.
  • Comparison adverse-effect pearls:
    • Morphine → nausea, itching, respiratory depression.
    • Levodopa-carbidopa → psychosis (excess dopamine).
    • Clonidine → hypotension, bradycardia; adjunct for alcohol/opioid withdrawal.

Isotretinoin (Accutane) Monitoring

  • Labs: liver function tests (ALT, AST), lipid panel (cholesterol ↑), pregnancy tests (teratogenic: iPLEDGE, 2 forms contraception).

Other Drug–Disease Matches

  • Colchicine → acute gout flares (anti-mitotic; GI upset, \text{N/V/D}).
  • Mupirocin → topical for impetigo (S. aureus).
  • Alendronate (bisphosphonate) → osteoporosis; monitoring: jaw osteonecrosis (dental), esophagitis (upright 30 min).
  • Hydroxychloroquine → rheumatoid arthritis/SLE; monitor ophthalmologic exam q6 months (retinopathy risk).

Rh-Negative Pregnancy & Immunoprophylaxis

  • At 28 weeks gestation + within 72 h postpartum (or after bleeding events) give Rho(D) immune globulin (RhoGAM) to Rh-negative mother carrying Rh-positive fetus → prevents hemolytic disease.
  • Live vaccines (rotavirus, MMR, varicella) contraindicated in pregnancy & immunocompromised.

Succinylcholine & Malignant Hyperthermia

  • Depolarizing neuromuscular blocker; genetics (RYR1) + halogenated anesthetics → malignant hyperthermia: hypercarbia, muscle rigidity, hyperthermia, tachycardia, diaphoresis.
  • Treat with dantrolene, cooling, supportive care.
  • Oxybutynin → anticholinergic for overactive bladder (urge incontinence).
  • Bethanechol → muscarinic agonist for urinary retention; may precipitate bronchospasm in asthma (wheezing).

MAOIs & Tyramine Dietary Warning

  • Phenelzine (MAOI) → avoid aged meats/cheeses, wine, fermented foods (↑tyramine) → hypertensive crisis.
  • Carbamazepine → seizures, bipolar; monitor CBC (aplastic anemia, agranulocytosis).
  • Phenytoin → seizures; narrow TI, monitor serum level 10–20\,\text{\mu g/mL}, signs of toxicity: nystagmus, ataxia, diplopia, gingival hyperplasia, hirsutism.

Smoking Cessation Options

  • Bupropion SR: antidepressant & smoking cessation aid; contraindicated in seizure disorders/eating disorders.
  • Varenicline (Chantix): partial \alpha4\beta2 nicotinic receptor agonist; side effects: vivid dreams, mood change.
  • Other listed options NOT indicated: sumatriptan (migraine), baclofen (muscle relaxant/CNS spasticity).

Atropine Clinical Uses & Contraindications

  • Anticholinergic (muscarinic antagonist) mnemonic DUCT: Dry mouth, Urinary retention, Constipation, Tachycardia.
  • Drug of choice for organophosphate poisoning (symptomatic bradycardia & secretions).
  • In given scenario: chosen to reduce excessive oral secretions during surgery.
  • Contraindicated/worsens: existing tachycardia, urinary retention, uncontrolled hypertension.

Lab/Parameter Monitoring Cheat-Sheet

  • Clozapine (SGA antipsychotic) → absolute neutrophil count (ANC ≥1500/\mu L) weekly ×6 mo ⇒ q2 wks ⇒ monthly.
  • Lithium → TSH (risk of hypothyroidism), serum lithium 0.6–1.2\,\text{mEq/L}, Na^+, renal function (Cr), fluid balance.
  • Methylphenidate (ADHD stimulant) → weight/BMI (appetite suppression), growth velocity, sleep patterns, BP/HR.

Epinephrine Physiologic Effects

  • \alpha_1: vasoconstriction → ↑BP.
  • \beta_1: ↑HR, ↑CO.
  • \beta_2: bronchodilation.
  • Ocular: mydriasis (pupil dilation) – selected answer.

Extrapyramidal Symptoms (EPS) – First-Gen Antipsychotics

  1. Acute dystonia (hours–days) – muscle spasms.
  2. Akathisia – restlessness (selected).
  3. Parkinsonism – stooped posture, shuffling gait (selected).
  4. Tardive dyskinesia – lip smacking, involuntary movements (selected).
  • Weight gain & hyperglycemia are metabolic effects of 2nd-gen agents.

Pharmacokinetic Phases in Order

\boxed{\text{Absorption} \rightarrow \text{Distribution} \rightarrow \text{Metabolism} \rightarrow \text{Excretion}}.

  • Elderly: ↓metabolism (liver mass & CYP450 ↓) & ↓excretion (GFR ↓) → require dose adjustments.

Additional Phenytoin Focus Points (student follow-up)

  • Narrow therapeutic range 10–20\,\text{\mu g/mL}; levels >20 → toxicity.
  • Enzyme inducer (CYP450) – ↓efficacy of OCPs, warfarin, steroids.
  • Gingival hyperplasia → oral hygiene.
  • Folic-acid deficiency & bone demineralization → consider supplementation.
  • Teratogenic: fetal hydantoin syndrome.