How can I slow the metabolism of dextroamphetamine (Dexedrine)?

Methods to Slow the Metabolism of Dextroamphetamine

The most effective way to slow dextroamphetamine metabolism is through urinary alkalinizing agents like sodium bicarbonate, which increase blood levels by decreasing urinary excretion of the drug. 1

Pharmacological Mechanisms for Slowing Dextroamphetamine Metabolism

Alkalinizing Agents

• Gastrointestinal alkalinizing agents (sodium bicarbonate) increase absorption of amphetamines 1
• Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion 1
• Both groups of agents increase blood levels and therefore potentiate the actions of dextroamphetamine 1

CYP2D6 Inhibitors

• CYP2D6 inhibitors may increase the exposure of dextroamphetamine compared to the drug alone 1
• Examples include:
  • Paroxetine
  • Fluoxetine
  • Quinidine
  • Ritonavir

Agents to Avoid When Trying to Slow Metabolism

Acidifying Agents

• Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices) lower absorption of amphetamines 1
• Urinary acidifying agents (ammonium chloride, sodium acid phosphate) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion 1
• Both groups of agents lower blood levels and efficacy of amphetamines 1

Important Safety Considerations

Serotonin Syndrome Risk

• When combining dextroamphetamine with CYP2D6 inhibitors, there is an increased risk of serotonin syndrome 1
• Monitor for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine initiation or dosage increase 1
• If serotonin syndrome occurs, discontinue dextroamphetamine and the CYP2D6 inhibitor 1

Cardiovascular Considerations

• Slowing metabolism increases drug exposure and may exacerbate cardiovascular side effects 1
• Be particularly cautious in patients with:
  • History of cardiovascular disease
  • Hypertension
  • Peripheral vasculopathy, including Raynaud's phenomenon 1

Drug Interactions

• MAO Inhibitors: Slow amphetamine metabolism, potentiating effects and increasing risk of hypertensive crisis 1
• Tricyclic antidepressants: Can cause striking and sustained increases in the concentration of dextroamphetamine in the brain 1
• Antihypertensives: Amphetamines may antagonize the hypotensive effects of these medications 1

Clinical Application

When attempting to slow dextroamphetamine metabolism:

1. First-line approach: Consider urinary alkalinizing agents like sodium bicarbonate
2. Alternative approach: Consider CYP2D6 inhibitors with careful monitoring for serotonin syndrome
3. Avoid: Acidifying agents (both gastrointestinal and urinary)
4. Monitor: Blood pressure, heart rate, peripheral circulation, and signs of serotonin syndrome

Cautions and Contraindications

• This approach should be used with extreme caution in patients with:
  • History of substance abuse (dextroamphetamine is a Schedule II controlled substance) 2
  • Cardiovascular disease
  • Hypertension
  • History of serotonin syndrome
  • Pregnancy (dextroamphetamine may cause fetal harm) 2

Remember that slowing the metabolism of dextroamphetamine increases exposure to the drug, which may increase both therapeutic effects and adverse effects. Careful monitoring is essential when implementing any strategy to alter the metabolism of this medication.