Common Medications and Substances that May Induce Hypertension

Cassandra Pardini, PharmD

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June 13, 2017

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

Mechanism					Medication Class					Comments
Volume Retention					Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Related Content					• 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
Direct Vasoconstriction					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)