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Drug-Induced Hypertension
1
What are the four main mechanisms by which drug-induced hypertension may occur?
See Fig. 13.1 :
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Sympathomimetic activation
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Volume retention via mineralocorticoid activation
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Direct vasoconstriction via increased vasoconstrictors, decreased vasodilators, or upregulation of the angiotensin II receptor type 1 (AT 1 )
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Drug withdrawal
2
What drug classes cause hypertension by sympathomimetic activation?
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See Fig. 13.1
3
What drug classes cause hypertension by mineralocorticoid activation?
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See Fig. 13.1
4
What drug classes cause hypertension by direct vasoconstriction?
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See Fig. 13.1
5
What drug classes cause hypertension as a withdrawal syndrome?
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See Fig. 13.1
6
What hypertension-producing drugs do patients routinely omit from their medication list?
Patients unintentionally omit over-the-counter medications (e.g., nonsteroidal antiinflammatory drugs [NSAIDs], nasal decongestants), herbal medications, and nutritional supplements from their medication list ( Table 13.1 ). Alcohol or recreational drug use may be withheld due to social stigma or for legal reasons. Unless specifically asked, patients may not report recent cessation or intermittent use of a drug that may cause withdrawal or rebound effects.
Table 13.1
Hypertension-Inducing Drugs to Consider in Association with Specific Patient Populations
| IF UNEXPLAINED HYPERTENSION OCCURS IN: | RULE OUT DRUG-INDUCED HYPERTENSION FROM: |
|---|---|
| Patient currently using recreational substances | Amphetamine, MDMA, cocaine |
| Patient recently using recreational substances | Withdrawal from opioids, benzodiazepines, or ethanol |
| Patient being treated for pain | NSAIDs (ibuprofen, naproxen), TCAs (amitriptyline, nortriptyline) |
| Patient being treated for muscle spasms | Withdrawal from alpha-2 agonists (tizanidine) |
| Patient being treated for a cold | Alpha-1 agonists for nasal congestion (pseudoephedrine, oxymetazoline), SNRIs for cough suppression (dextromethorphan) |
| Patient being treated for cancer | VEGF inhibitors (bevacizumab), calcineurin inhibitors (tacrolimus, cyclosporine), receptor tyrosine kinase inhibitors (sunitinib, sorafenib), CYP17 inhibitors (abiraterone) |
| Patient being treated for anemia | Exogenous erythropoietin |
| Patient being treated for fungal infection | CYP11B1 inhibitors (posaconazole, fluconazole), HSD11B2 inhibitors (itraconazole, posaconazole) |
| Reproductive-aged woman | Estrogen-containing oral contraceptives |
| Patient attempting to build muscle mass | Anabolic steroids (stanozolol, nandrolone decanoate) |
| Patient being treated for depression or anxiety | SNRIs (venlafaxine, sibutramine, duloxetine) |
| Patient being treated for ADHD | Stimulants (methylphenidate, dextroamphetamine) |
| Patient being treated for trouble staying awake | Stimulants (modafinil, adrafinil, armodafinil) |
| Patient attempting to lose weight | Weight loss supplements (sibutramine, ephedra) |
| Patient using eye drops | Alpha-1 agonists (phenylephrine) |
| Patient being treated for vasculitis or other systemic inflammatory disorder | Glucocorticoids (prednisone, methylprednisolone) |
| Patient being treated for opioid overdose | Opioid antagonists (naloxone) |
| Patient who drinks caffeine | Caffeine |
| Patient who smokes | Tobacco |
| Patient who eats licorice | Glycyrrhizzic acid |
| Patient recently taken off an antihypertensive | Withdrawal from clonidine, methyldopa, or atenolol |
HSD11B2, 11-β-H-hydroxysteroid dehydrogenase type 2; ADHD, attention deficit/hyperactivity disorder; CYP17, cytochrome P450 17α-hydroxy/17,20-lyase; CYP11B1, cytochrome P450 11β-hydroxylase; MDMA, 3,4-methylenedioxymethamphetamine (ecstasy, molly); NSAIDs, nonsteroidal antiinflammatory drugs; SNRI, serotonin-norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant; VEGF, vascular endothelial growth factor.
7
Which drugs of abuse cause or worsen hypertension and how?
3,4-Methylenedioxy methamphetamine (MDMA), also known as ecstasy or molly, acts at the vesicular monoamine transporter 2 and trace amine-associated receptor 1 (TAAR1) to stimulate release of serotonin, norepinephrine, and dopamine, resulting in increased sympathetic activation.
Phencyclidine (PCP), or angel dust, is an N -methyl- d -aspartate (NMDA) receptor antagonist that also inhibits synaptic uptake of dopamine and norepinephrine, resulting in increased sympathetic activation.
Cocaine blocks the dopamine transporter protein, causing synaptic accumulation of dopamine and norepinephrine, which results in increased sympathetic activation. Dopamine stimulation of the ventral tegmental area increases blood pressure. Moreover, cocaine’s primary vasoactive metabolite, benzoylmethylecgonine, blocks sodium channels, resulting in enhanced sympathetic activity. Finally, chronic cocaine use increases levels of vascular cell adhesion molecules and intracellular adhesion molecules, increasing arterial wall stiffness and peripheral vascular resistance.
8
How do stimulants cause or worsen hypertension?
Agents used to stimulate wakefulness, such as modafanil, adrafanil, and armodafinil, block the dopamine transporter and prevent dopamine reuptake, potentiating noradrenergic neurotransmission and increasing sympathetic activation. Similarly, agents used to treat attention deficit/hyperactivity disorder, such as dextroamphetamine and methylphenidate, are norepinephrine-dopamine reuptake inhibitors and thus potentiate noradrenergic neurotransmission and increase sympathetic activation.
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