Dexamphetamine and Orthostatic Hypotension
No, dexamphetamine does not cause orthostatic hypotension; in fact, it typically causes hypertension due to its sympathomimetic effects. 1
Mechanism of Action and Cardiovascular Effects
- Dexamphetamine (dextroamphetamine) is a sympathomimetic drug that stimulates adrenergic receptors directly as an agonist and indirectly causes the release of dopamine and norepinephrine from presynaptic terminals 1
- The 2018 ACC/AHA guideline specifically lists dexamphetamine among medications that may cause elevated blood pressure rather than hypotension 1
- Cardiovascular effects of dexamphetamine typically include hypertension and tachycardia due to its sympathomimetic properties 1
Evidence Against Orthostatic Hypotension
- In overdose situations, dexamphetamine is associated with hypertension or hypotension, but hypertension is the more common presentation 2
- Studies examining cardiovascular effects of dextroamphetamine in children with ADHD found no significant blood pressure changes, and in adults, it was associated with hypertension rather than hypotension 3
- A study evaluating drug effects on orthostatic intolerance actually used dextroamphetamine (5 mg) as a countermeasure to prevent orthostatic hypotension by enhancing norepinephrine release 4
Medications That Do Cause Orthostatic Hypotension
- Dexmedetomidine (an alpha-2 adrenoreceptor agonist) has a biphasic cardiovascular effect with an initial increase in blood pressure followed by a 10-20% decrease in blood pressure due to inhibition of central sympathetic outflow 1
- Antipsychotics, phenothiazines, tricyclic antidepressants, and monoamine oxidase inhibitors are more commonly associated with orthostatic hypotension 5, 6
- Diphenhydramine can cause hypotension as an adverse effect 1
Management of Orthostatic Hypotension
- For patients with orthostatic hypotension, non-pharmacological measures are first-line: increasing fluid and salt intake, physical counter-maneuvers (leg-crossing, stooping), and gradual staged movements 7
- Pharmacological options for orthostatic hypotension include midodrine, fludrocortisone, or droxidopa, which are used when non-pharmacological measures fail 7
- Interestingly, sympathomimetic medications like dextroamphetamine have actually been used experimentally to treat orthostatic hypotension by enhancing norepinephrine release 4, 8
Clinical Implications
- When prescribing dexamphetamine, clinicians should monitor for hypertension rather than hypotension 1, 3
- Dexamphetamine should be avoided in patients with uncontrolled hypertension, underlying coronary artery disease, and tachyarrhythmias 1
- The typical starting dose of dextroamphetamine is 2.5-5 mg daily or twice daily, with a usual dose range of 5-30 mg/day 1
In summary, dexamphetamine is not associated with causing orthostatic hypotension. Due to its sympathomimetic properties, it more commonly causes hypertension and tachycardia. When monitoring patients on dexamphetamine therapy, clinicians should be vigilant for elevated blood pressure rather than orthostatic hypotension.