Requip
Requip
Generic Name
Requip
Mechanism
- Selectively stimulates dopamine D₃ receptors > D₂ receptors; weakly activates D₁.
- Mimics endogenous dopamine in the basal ganglia, replenishing central dopaminergic tone compromised in Parkinson’s disease.
- Increases phasic firing of nigrostriatal neurons and enhances motor circuit output without requiring L‑dopa metabolism.
Pharmacokinetics
- Oral bioavailability: ~75 % after a single dose, decreases slightly with food.
- Peak serum concentration (Tmax): 2–4 h.
- Half‑life (t½): 8–13 h; dose‑dependent due to saturation of hepatic glucuronidation.
- Metabolism: Phase‑II glucuronidation (UGT1A) → inactive metabolites (pramipexole‑N‑glucuronide).
- Excretion: Primarily renal (≈70 % unchanged); 20‑30 % via biliary‑fecal route.
- Population PK: No clinically significant interactions with CYP450 enzymes; minimal protein binding (~3 %).
Indications
- Parkinson’s Disease (PD): adjunct or monotherapy in early, moderate, or advanced stages.
- Restless Legs Syndrome (RLS)/Will‑Sensing Syndrome: first‑line oral therapy for moderate‑to‑severe disease.
- Off‑period reduction in PD patients on L‑dopa (as add‑on).
Contraindications
| Contraindication / Warning | Key Points |
| Hypoglycemia (history or risk) | Pramipexole can lower blood glucose; monitor fasting glucose. |
| Impulse‑control disorders | Emerging data on compulsive behaviors (gambling, sexual urges, eating). |
| Severe renal impairment (CrCl <30 mL/min) | Dose adjustment or avoidance; excretion largely renal. |
| Severe hepatic dysfunction | Minimal hepatic metabolism; still caution if advanced liver disease. |
| Pregnancy / Lactation | Category B; use only if benefits outweigh potential risks. |
| Concurrent serotonergic drugs | Rare reports of serotonin syndrome; monitor. |
Warnings
• Potential for orthostatic hypotension at dose titration.
• Can precipitate or worsen parkinsonian hallucinations at higher doses.
Adverse Effects
| Category | Examples |
| Common (≥10 %) | Nausea, dizziness, somnolence, edema, weight gain, dyskinesia, dry mouth, orthostatic hypotension |
| Serious (≤5 %) | Impulse‑control disorders (gambling, binge eating), acute dystonia, hypoglycemia, hypersensitivity reactions, severe orthostatic hypotension, serotonin syndrome (rare) |
Monitoring
- Baseline and Periodic Labs: CBC, CMP, fasting glucose, serum amylase (rare pancreatitis).
- Renal Function: CrCl ≥30 mL/min to use standard dose.
- Weight/BMI: Expect modest increase; reassess annually.
- Blood Pressure: Monitor at each titration step; watch for orthostatic changes.
- Psychiatric Screening: At baseline and during therapy, screen for impulse‑control behaviors.
- Motor Function: UPDRS in PD; International Restless Legs Rating Scale (IRLS) in RLS.
Clinical Pearls
- Early titration is KEY: 0.125 mg BID in PD minimizes nausea and dizziness; increase only after 3–5 days tolerance.
- RLS dosing differs: QID is usually needed to control nighttime symptoms; a single morning dose can be inadequate.
- Avoid high‑fat meals: Though bioavailability is modestly affected, absorption is best with low‑fat intake.
- Renal dose reduction: For CrCl<30 mL/min, use 0.0625 mg QID and titrate over longer intervals.
- Serious impulse control: A 12‑week screening questionnaire (e.g., Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s Disease) can catch early symptoms.
- Drug‑drug interactions: Though minimal CYP interactions, avoid excessive use of serotonergic medications to mitigate serotonin syndrome risk.
- Long‑term use: Consider rotational therapy or “cheat” days if dose escalation stalls due to tolerance or side effects.
--
• This concise, SEO‑friendly card delivers high‑yield information for students and clinicians, ensuring quick reference and rapid recall of Requip pharmacology.