Adverse Drug Reactions and Interactions

Adverse Drug Reactions and Interactions

Adverse Drug Reactions and Interactions

On this page

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:

TypeName (📌 Mnemonic)FeaturesExample
AAugmentedDose-dependent, predictable, commonInsulin hypoglycemia
BBizarreNon-dose-dependent, unpredictable, rarePenicillin allergy
CChronicDose & time-related (long-term)Analgesic nephropathy
DDelayed (DoTS)Time-related; Teratogenic, CarcinogenicDES teratogenicity
EEnd-of-useWithdrawal on stoppingOpioid withdrawal
FFailureUnexpected 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:
      EnzymeInteracting Drug 1Interacting Drug 2Outcome
      CYP3A4Grapefruit JuiceSimvastatin↑ Simvastatin, myopathy risk
      CYP2C9RifampicinWarfarin↓ Warfarin, clotting risk
  • Excretion:
    • Renal Secretion: Probenecid + Penicillin → ↑ Penicillin.
    • Urine pH: NaHCO₃ → ↑ salicylate excretion.

⭐ 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 ADrug BOutcome
WarfarinAspirin↑ Bleeding risk
β-blockersVerapamil↑ Bradycardia, Heart Failure (HF)
SildenafilNitratesSevere ↓Blood Pressure (BP)
ACEIK⁺-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_._

Practice Questions: Adverse Drug Reactions and Interactions

Test your understanding with these related questions

Identify the correct match, regarding the drug and its adverse effect.

1 of 5

Flashcards: Adverse Drug Reactions and Interactions

1/4

Hb-F/H/S will lead to a falsely _____ in reading on pulse oximeter

TAP TO REVEAL ANSWER

Hb-F/H/S will lead to a falsely _____ in reading on pulse oximeter

no effect

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial