Which of the following is classified as a Type E adverse reaction?

Rebound effect due to drug withdrawal

Which of the following statements represents the most clinically significant aspect of drug metabolism?

Most common enzyme involved is CYP 3A4/5

Glucuronidation is a phase II reaction

Reduction is a phase I reaction

Cytochrome P450 is involved in phase I reactions

Which one of the following is true for competitive antagonism?

Agonist and competitive antagonist bind to the same receptor

Agonist cannot displace an antagonist from the receptor

Antagonism cannot be completely reversed by an increased dose of an agonist

Maximum response (Emax) is reduced in the presence of a competitive antagonist

A 42-year-old man was seen in the clinic because of pain and redness in his finger. Last week he had injured the finger while working in his garage. On physical examination, there is erythema, swelling, and tenderness of the second digit in the right hand. Flexion and extension of the finger were normal. A clinical diagnosis of cellulitis is made and he is prescribed cephalexin. A few days later he presents to the emergency room complaining of difficulty breathing. He has angioedema due to a drug reaction to the cephalexin. Which of the following physical findings is characteristic of this syndrome?

Involvement of lips, tongue, eyelids, genitalia, and dorsum of hands or feet

Fluid extravasation from subcutaneous and intradermal postcapillary venules

Adverse Drug Reactions and Interactions for FMGE: High-Yield Internal Medicine Lessons

ADR Basics - Defining Dangers

ADR (Adverse Drug Reaction): Harmful, unintended response to normal drug doses.
ADE (Adverse Drug Event): Injury from drug-related medical intervention (includes errors).
Side Effect: Known, unavoidable pharmacological effect at therapeutic doses.

Rawlins & Thompson Classification:

Type	Name (📌 Mnemonic)	Features	Example
A	Augmented	Dose-dependent, predictable, common	Insulin hypoglycemia
B	Bizarre	Non-dose-dependent, unpredictable, rare	Penicillin allergy
C	Chronic	Dose & time-related (long-term)	Analgesic nephropathy
D	Delayed (DoTS)	Time-related; Teratogenic, Carcinogenic	DES teratogenicity
E	End-of-use	Withdrawal on stopping	Opioid withdrawal
F	Failure	Unexpected therapy failure (e.g., resistance)	OC failure (inducers)

PK Puzzles - Drug Journey Jams

PK interactions alter ADME (Absorption, Distribution, Metabolism, Excretion), changing drug levels & effects.

Absorption:
- Chelation: Tetracycline + Antacids (Ca²⁺) → ↓ absorption.
- pH: Ketoconazole + PPIs → ↓ absorption.
Distribution:
- Protein displacement: Warfarin + NSAIDs → ↑ free warfarin, ↑ bleeding.
Metabolism (CYP450):
- Inducers (↓ drug effect): 📌 CRAP GPS (Carbamazepine, Rifampicin, Phenytoin, etc.)
- Inhibitors (↑ drug effect/toxicity): 📌 SICKFACES.COM (Valproate, Isoniazid, Cimetidine, Ketoconazole, Erythromycin, etc.), Grapefruit juice.
- Example Interactions:
  Enzyme Interacting Drug 1 Interacting Drug 2 Outcome
  CYP3A4 Grapefruit Juice Simvastatin ↑ Simvastatin, myopathy risk
  CYP2C9 Rifampicin Warfarin ↓ Warfarin, clotting risk
Excretion:
- Renal Secretion: Probenecid + Penicillin → ↑ Penicillin.
- Urine pH: NaHCO₃ → ↑ salicylate excretion.

Enzyme	Interacting Drug 1	Interacting Drug 2	Outcome
CYP3A4	Grapefruit Juice	Simvastatin	↑ Simvastatin, myopathy risk
CYP2C9	Rifampicin	Warfarin	↓ Warfarin, clotting risk

⭐ Grapefruit juice (CYP3A4 inhibitor) significantly ↑ levels of statins, CCBs.

PD Predicaments - Receptor Reactions

Pharmacodynamic (PD) interactions: Drugs modify effects of one another directly at receptor or physiological target sites.

Synergism: Combined effect $1+1 > 2$.
- e.g., TMP-SMX (enhanced antimicrobial effect).
Antagonism: Combined effect $1+1 < 2$.
- Receptor: Naloxone + Morphine (opioid reversal).
- Physiological: Adrenaline + Histamine (opposing actions).
Additive: Combined effect $1+1 = 2$.
- e.g., Aspirin + Paracetamol (analgesia).

Agonist and Antagonist Ligand Actions at the Receptor

Key PD Interactions:

Drug A	Drug B	Outcome
Warfarin	Aspirin	↑ Bleeding risk
β-blockers	Verapamil	↑ Bradycardia, Heart Failure (HF)
Sildenafil	Nitrates	Severe ↓Blood Pressure (BP)
ACEI	K⁺-sparing diuretic	↑ Serum K⁺ (Hyperkalemia)

Risk & Rescue - ADR Avoidance

Patient Risk Factors:
- Extremes of age (elderly, neonates)
- Renal or hepatic dysfunction
- Genetic factors (e.g., G6PD deficiency)
- Prior allergy history
Drug Risk Factors:
- Polypharmacy: ≥5 drugs
- Narrow Therapeutic Index (NTI) drugs (e.g., warfarin, digoxin)
- Newly marketed drugs
- Complex dosing schedules

📌 ADR Management (ABCDE): Assess, Blame drug, Cease drug, Diminish effects, Exchange drug.

⭐ The Beers Criteria is crucial for identifying potentially inappropriate medications in the elderly, reducing ADR risk.

High‑Yield Points - ⚡ Biggest Takeaways

Type A ADRs: Dose-dependent, predictable, from known pharmacology (e.g., bleeding with anticoagulants).

Type B ADRs: Idiosyncratic, unpredictable, often immune-mediated, not dose-related (e.g., anaphylaxis).

CYP450 enzymes: Inducers (rifampicin) ↓ drug effect; inhibitors (ketoconazole) ↑ drug toxicity.

PK interactions alter drug ADME; PD interactions affect drug action at target sites.

Critical interactions: Serotonin syndrome (SSRIs + MAOIs), Malignant hyperthermia (halothane + succinylcholine).

Grapefruit juice: Potent CYP3A4 inhibitor, increases oral drug bioavailability and toxicity_._

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play