Generic Name

Quinine

Mechanism

Quinine is a semi‑synthetic alkaloid that exerts its antimalarial effect by disrupting *Plasmodium*’s intraerythrocytic life cycle.
• Inhibition of heme polymerase – Quinine blocks the detoxification of toxic heme generated during hemoglobin degradation, leading to parasite death.
• Interference with parasite DNA replication – It also binds to *Plasmodium* DNA, impairing nucleic‑acid synthesis.
• Vascular smooth‑muscle relaxation – In addition, it dilates blood vessels, decreasing capillary blood flow, which contributes to its anti‑migraine effects.

Pharmacokinetics

• Absorption: Rapidly absorbed from the gastrointestinal tract; oral bioavailability ~50–70 % (higher with food).
• Distribution: Widely distributes; high volume of distribution (~30 L/kg). Crosses the placenta and blood–brain barrier.
• Metabolism: Hepatic hepatoxylin‑N‑deacetylation → 6‑β‑hydroxy‑quinine. Minor contribution from CYP2D6 and CYP3A4.
• Elimination: Primarily fecal (≈60 %), remainder renal (≈30 %).
• Half‑life: 10–20 h (shorter after repeated dosing due to saturation).
• Drug interactions: Contraindicated with CYP2D6 inhibitors; potentiates QT‑prolonging agents; caution with antitussives (e.g., codeine) due to shared metabolism.

Indications

• P vivax and P ovale malaria – as monotherapy or in combination (e.g., artemisinin‑based combo).
• Recreational antimalarial prophylaxis – in endemic regions (rarely used due to resistance).
• Migraine prophylaxis – intravenous/quasi‑oral forms used in severe cases.
• Hemolytic disease of the newborn – rarely for *P falciparum* prophylaxis in high‑resistance settings.

Contraindications

• Known hypersensitivity to quinine or other alkaloids.
• Q‑wave myocardial infarction or QT‑interval prolongation (≥0.44 s).
• Pregnancy (especially 3rd trimester) – potential fetal toxicity.
• Gout – precipitates hyperuricemia.
• Concurrent use of QT‑prolonging drugs – contraindicated.
• Severe hepatic or renal impairment – caution, dose adjustments needed.

Dosing

• Loading dose may be doubled on day 1 if fever >39.5 °C.
• Maintenance dose—oral 650 mg BID for 7 days post‑parasitemia clearance.
• Pregnancy – use parenteral 5 mg/kg for severe malaria; avoid oral due to QT risk.

Adverse Effects

Common (≤10 %)
• Nausea, vomiting, dyspepsia, abdominal pain
• Headache, dizziness, tinnitus (auditory changes)
• Rash, pruritus, urticaria
• Hypoglycemia, especially in diabetics

Serious (≤1 %)
• Cinchonism – tinnitus, ringing, hearing loss, blurred vision, paresthesia, metallic taste
• Torsades de Pointes – due to QT prolongation, especially with electrolyte imbalance
• Hemolytic anemia in G6PD‑deficient patients
• Allergic reaction – anaphylaxis
• Gastro‑intestinal bleeding – ulceration, gastritis

Monitoring

• Vital signs – HR, BP, temperature each 2 h (first 24 h).
• ECG – baseline and every 6 h if known QT prolongation.
• Hematology – CBC daily; monitor for hemolysis (if G6PD‑deficient).
• Renal & Hepatic panels – baseline, Day 3, and prior to dose escalation.
• Serum electrolytes – K⁺, Mg²⁺, Ca²⁺; correct deficits promptly.
• Audiometry (if prolonged therapy) – screen for auditory toxicity.

Clinical Pearls

• Rapid parasitemia clearance: For severe malaria, give IV quinine 5 mg/kg every 6 h for 24 h; then switch to oral once fever subsides.
• Avoid high doses in late pregnancy; use parenteral hydroxychloroquine or artemisinin‑based combos in endemic regions.
• QT monitoring: baseline at least 48 h before initiating, with repeated checks if electrolyte disturbance develops.
• G6PD deficiency screen before quinine therapy; if positive, avoid quinine outright.
• Contraindicated with codeine: The combination exacerbates QT prolongation and may potentiate serotonin syndrome.
• “Quinine‑related tinnitus” is dose‑related; reduce dose or discontinue if persistent >30 min.
• Use in migraine only for refractory, high‑severity attacks; schedule after non‑pharmacologic measures (e.g., hydration, rest).

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• References:
• WHO Malaria Guidelines 2024
• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 15th ed.
• National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summaries, “Quinine for malaria.”