Table 1 – Mechanisms of Drug-Induced HTN & Medication Classes Associated With Each1

Mechanism Medication Class Comments

Volume Retention

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

• Decrease PGE2, PGI2, leading to a lack of vasodilation and increased sodium retention
• Extent of BP elevation depends on specific agent
   o Smallest increase in BP (mmHg): aspirin (0.61), diclofenac (1.6), sulindac (2.2)
   o Largest increase in BP (mmHg): ibuprofen (6.5), piroxicam (6.2), naproxen (6.1)
• May require intensification of antihypertensive regimen (especially for diclofenac and piroxicam)
• Risk of BP elevation not significantly lower with COX-2 selective inhibitors

Sex Hormones

• Estrogens, progestins – increase sodium resorption and water retention by increasing production of angiotensin II
   o Case-control study: increase in SBP of 8 mmHg in patients taking oral contraceptives (OC) 
   o Risk factors for developing HTN while taking OC: gestational HTN, family history of HTN, occult renal disease, >35 years old, duration of OC use
• Hormone replacement therapy – no effect on BP or may decrease it
• Testosterone – causes increased sodium and water retention via androgen receptor agonism (more evidence needed)

Corticosteroids

• Mineralocorticoids, glucocorticoids – increase sodium resorption
• BP elevation occurs in dose-dependent fashion
• Prolonged use (>1 month) may not be associated with BP elevation
• High glucocorticoid doses (≥7.5mg of prednisone, or equivalent, daily) associated with higher rate of cardiovascular events

Sympathomimetic Activation

Decongestants

• Cause vasoconstriction via activation of alpha-1 adrenergic receptors
• Considered safe in patients with controlled HTN
• Phenylephrine – 45mg dose associated with increase in SBP by 20 mmHg; bioavailability increases when administered with acetaminophen
• Pseudoephedrine – dose-dependent increase in SBP, DBP, and HR; sustained-release formulation has less of an effect than immediate-release formulation; tolerance may develop

Caffeine

• Increases sympathetic activity and catecholamine release
• Tolerance to BP elevations occurs when intake is consistent

Cocaine

• Causes vasoconstriction through stimulation of adrenergic receptors by excessive NE
• Dose-dependent effect
• BP normally returns to baseline 15 minutes after administration
• Route of administration effects magnitude of BP changes (significant elevation in BP with intranasal administration compared to intrabrachial infusion)

Psychostimulants

• Causes vasoconstriction through stimulation of adrenergic receptors by excessive NE
• Limited information on cardiovascular effects of these medications
• Periodic cardiovascular monitoring is recommended in children taking methylphenidate and dextroamphetamine

Antidepressants

• Tricyclic antidepressants and serotonin norepinephrine reuptake inhibitors (SNRIs) increase NE and sympathetic activity
• Venlafaxine – dose-related effect
• Bupropion – mixed evidence regarding effect on BP (recent studies show a possible decrease in SBP and DBP in patients)
• Monoamine oxidase inhibitors – associated with hypertensive crisis (most likely with tranylcypromine)

Direct Vasoconstriction

Calcineurin Inhibitors

• Increase BP through a variety of mechanisms (inhibition of vasodilation, systemic and renal vasoconstriction, sodium retention)
• Cyclosporine – dose-related effect 
• Incidence of HTN is effected by the transplant type
   o Nearly 100% of heart transplant patients on cyclosporine experience HTN versus 57% of bone marrow transplant patients

VEGF Inhibitors (bevacizumab, lapatinib, sunitinib, sorafenib)

• Cause vasoconstriction through reduction of nitric oxide production and stimulation of endothelin-1 receptors

Abbreviations: BP – blood pressure; DBP – diastolic blood pressure; HR – heart rate; HTN – hypertension; NE – norepinephrine; OC – oral contraceptive; PG – prostaglandin; SBP – systolic blood pressure; VGEF – vascular endothelial growth factor

Figure 1 – Management of Drug-Induced HTN1 (click on figure to see larger version)