Drug-induced hypertension, also known as iatrogenic hypertension, is mainly caused by adverse drug reactions and improper interaction methods of combination drugs.
The mechanism of vasopressor growth of drug-induced hypertension is complex, but most of the conditions are mild, reversible after discontinuation, and rarely have serious complications. Clinically, a high degree of awareness and active prevention are required.
This article collates the drugs that may cause blood pressure to rise or affect the efficacy of antihypertensive efficacy and the corresponding treatment strategies.
1
Hormonal drugs
Oral contraceptives
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Oral contraceptives are a combination of estrogen and progesterone, and the main component of their hypertension is estrogen.
Estrogen has a mineralocorticoid effect, which can promote water and sodium retention, transfer the fluid in the blood vessels to the interstitial space, reduce the amount of circulating blood, excite the sympathetic nerves, and lead to an increase in blood pressure.
Estrogen can also increase plasma hepatic and renal angiotensin concentrations, increase the activity of the anti-renin angiotensin aldosterone system (RAAS), and further raise hypertension.
Recombinant human erythropoietin (r-HuEPO)
r-HuEPO is used to treat refractory anemia such as renal anemia and malignant tumor-associated anemia.
30% of patients treated with r-HuEPO develop hypertension, and even hypertensive encephalopathy and cerebrovascular accidents occur. In addition to the pathological mechanisms of the disease itself (eg, sodium and water retention in renal failure) can cause increased blood pressure, the pharmacological effects of r-HuEPO itself can also cause hypertension.
Mineralocorticoids
Mineralocorticoids promote the reabsorption of sodium and the excretion of potassium by the distal tubules, leading to hypokalmic hypertension.
Mineralocorticoids such as fludrocortisone, whose mechanism of hypertension is to promote the reabsorption of sodium water by the distal curved tubules of the kidneys, resulting in increased blood volume, and are often used to treat orthostatic hypotension caused by primary adrenal hypocoidism and autonomic neuropathy.
Glucocorticoids
Glucocorticoids have a mineralocorticoid-like effect, which can cause water and sodium retention, activate the sympathetic nervous system, promote the synthesis of proanginogen in the liver, and increase RAAS activity.
Although glucocorticoids such as hydrocortisone, prednisone, and methylprednisolone have low mineralocorticoid receptor activity, when applied in high doses, they can still induce mineralocorticoid receptor activation and promote sodium water reabsorption, resulting in increased blood pressure.
Draw the point
It is recommended that the clinical use of steroid hormones (salt corticosteroids, glucocorticoids) should be used with the minimum effective dose and the shortest maintenance time to reduce adverse reactions such as increased blood pressure.
Hypertension caused by steroid hormones is usually reversible, and blood pressure can basically return to normal after discontinuation, and some patients need medication.
Pharmacotherapy can achieve good blood pressure control mainly by reducing water and sodium retention to counteract its effects on the kidneys, preferring diuretics, combined with angiotensin-converting enzyme inhibitors (ACE Inhibitors) or angiotensin II receptor antagonists (ARBs).
2
Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit cyclooxygenase synthesis, reducing the synthesis and release of prostaglandinSO2 and prostaglandin E2, leading to vasoconstriction and sodium retention.
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In addition, NSAIDs can reduce the hypotensive effect of antihypertensive drugs such as β receptor blockers, diuretics, and angiotensin-converting enzyme inhibitors, but have no significant effect on the antihypertensive effects of calcium antagonists.
The significant increase in blood pressure caused by NSAIDs is mainly seen in hypertensive patients taking NSAIDs, which have little effect on normal blood pressure and are common in the elderly, diabetes, and renal insufficiency.
The effects of different types of NSAIDs on blood pressure vary widely.
The selective NSAID boosting effect is stronger than that of non-selective NSAIDs, with the most pronounced effect of rofecoxib in raising blood pressure. Nonselective NSAIDs have the largest increase in blood pressure in patients with naproxen, indomethacin, and piroxicam causing hypertension.
3
Antidepressant drugs
Monoamine oxidase inhibitors, tricyclic antidepressants, and venlafaxine in antidepressants can cause drug-induced hypertension.
Monoamine oxidase inhibitors inhibit monoamine oxidase activity, causing catecholamines and serotonin to accumulate, causing an increase in blood pressure.
Patients with depression may reduce the dose of venlafaxine if there is a mild increase in blood pressure, and if the dose is less effective for depression, try the usual dose in combination with antihypertensive drugs or switch to other antidepressants.
4
Sympathomimetic active agent
In clinical practice, sympathomimetic active drugs are often used as decongestants to treat cold nasal congestion and catarrhal symptoms, and the commonly used drugs are pseudoephedrine.
Pseudoephedrine can activate the sympathetic nervous system by stimulating α1 adrenergic receptors on vascular smooth muscle, thereby causing vasoconstriction, resulting in increased blood pressure, and there is a gender difference in its effect on blood pressure, compared with men, pseudoephedrine has less effect on women's blood pressure and heart rate.
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The Expert Consensus on the Standardized Diagnosis and Treatment of the Common Cold states:
Pseudoephedrine is one of the main drugs that effectively relieve cold symptoms, but in addition to relieving the nasal symptoms of colds, pseudoephedrine still has effects such as increasing blood pressure and increasing the body's metabolic rate.
People with high blood pressure, heart disease, glaucoma, diabetes, hyperthyroidism, and prostate enlargement should use drugs containing pseudoephedrine with caution, and athletes should also use caution before competition.
5
Vascular endothelial growth factor inhibitors
Vascular endothelial growth factor and its receptors play an important role in normal angiogenesis and also play an important role in promoting tumor growth and metastasis spread.
Therefore, vascular endothelial growth factor inhibitors (VEGI) can be used in antitumor therapy. Common VEGI include bevacizumab and sorafenib, both of which are common adverse effects of hypertension.
Angiogenesis inhibitors cause vasoconstriction, which raises blood pressure by:
Blockade of vascular endothelial growth factor signaling pathway mediated reduction in endothelial cell synthesis of nitric oxide;
Leads to thinning of microvascular and a decrease in the number of capillaries that make up microcirculation;
Increases the activity of endothelin 1.
Patients with vegetative tumors receiving VEGI should be noted for cardiovascular complications and associated risk factors to prevent the development of malignant hypertension.
Discontinuation or tapering of hypertensive drugs should be considered when hypertensive emergencies or antihypertensive drugs are insufficient to control blood pressure.
Since the hypertensive effect of the drug depends mainly on an increase in peripheral vascular resistance, dihydropyridine calcium antagonists and RAAS inhibitors may be the most suitable antihypertensive agents.
06
Licorice and its active ingredients
Licorice and its active ingredient, glycyrrhizic acid, are widely used as flavoring additives for beverages, candy and other foods or cigarettes and chewable tobacco. Licorice root is also widely used as an herb.
Licorice causes an increase in blood pressure mainly through the active ingredient glycyrrhizic acid, which inhibits the dehydrogenase of 11-β-hydroxysteroids, which converts cortisol into corticosterone, and after inhibition, cortisol increases, acting on mineralocorticoid receptors to produce mineralocorticoid activity, resulting in a "pseudoaldosterone increase effect".
Meta-analyses have shown that continuous intake of products containing more than 100 mg of glycyrrhizic acid can result in an increase in mean systolic blood pressure of 5 mmHg and an increase in mean diastolic blood pressure by 3 mmHg, while serum potassium, renin, and aldosterone levels will be suppressed.
In 2019, the American Heart Association (AHA) also issued a reminder that "natural" drugs are not necessarily safe, some herbs such as licorice can cause blood pressure to rise, and certain foods can also interact with drugs, resulting in negative effects.
Elevated blood pressure due to licorice preparations generally recovers spontaneously after discontinuation, requires close monitoring of blood pressure during use, and can be treated with aldosterone receptor antagonists if necessary.
07
immunosuppressant
Immunosuppressants are widely used in clinical practice for the treatment of post-transplant rejection and autoimmune diseases, such as graft-versus-host disease, rheumatic diseases, nephrotic syndrome, etc. Commonly used drugs include cyclosporine and tacrolimus, which are closely related to the occurrence of hypertension.
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Among them, the immunosuppressants that can cause a significant increase in blood pressure are mainly cyclosporine A, while rapamycin and mycophenolate mate matate have less effect on blood pressure.
The mechanisms by which cyclosporine causes hypertension include activation of the RAAS and endothelin systems, an increase in sympathetic nervous system activity, and drugs that simultaneously inhibit the synthesis of NO, increasing the formation of free radicals, which leads to endothelial dysfunction.
All antihypertensive drug therapy is effective in reducing post-transplant hypertension, although the risk of graft failure and patient death is significantly increased with ACEI or β receptor blockers, not with ARB or CCB. Therefore, ARB or CCB is a safe and effective drug for the treatment of cyclosporine-associated hypertension.
08
Anti-tuberculosis drugs
The anti-TB drug rifampicin is a classic anti-TB drug that has a killing effect on both intracellular and extracellular TB bacteria. Rifampicin has liver enzyme-inducing properties that determine its interaction with a variety of drugs.
In the cytochrome P450 superfamily, rifampicin induces cytochrome P450 3A4 to be the most prominent, which can significantly reduce the blood concentration of transchrome PC3A4 metabolism drugs.
Among the commonly used antihypertensive drugs in the clinic, sulfonamide diuretics (indapamide), CCB (nifedipine, verapamil) and ARB (losartan) are all metabolized by cytochrome P450 3A4, affected by rifampicin, the antihypertensive effect of these drugs is weakened, and other antihypertensive drugs are less affected by rifampicin.
Therefore, in the treatment of rifampicin anti-tuberculosis, antihypertensive drugs should be selected ACEI, β receptor blockers, and non-sulfaditic diuretics.
9
antibiotic
There are many antimicrobials that can cause hypertension, mainly penicillins, cephalosporins, quinolones, etc., and the mechanism of hypertension caused by different antibacterial drugs may also be different.
10
other
Carmazepine. Hypertension caused by this drug is very rare and occurs in patients who have overdose and who require high-dose maintenance therapy.
Scopolamine, naloxone, alkylating agents, bromocriptine, and amphotericin B may also increase blood pressure in patients.
In addition to the above types of drugs, there are the following factors that can easily lead to increased blood pressure, which are often overlooked!
alcohol
Alcohol can directly enhance sympathetic excitability, causing positive cardiac changes, force changes and variable conduction, thereby accelerating heart rate, enhancing myocardial contractility, and increasing myocardial oxygen consumption.
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After sympathetic excitement, it will increase the secretion of epinephrine and norepinephrine, contract the surrounding blood vessels, and raise blood pressure; after drinking ethanol, it will circulate to the liver, convert it to acetaldehyde through the action of ethanol dehydrogenase system, and convert it to acetic acid through the action of acetaldehyde dehydrogenase system, ethanol and acetaldehyde can cause vasodilation, thereby causing blood pressure to decrease.
Patients who drink a lot of alcohol often vomit frequently due to gastrointestinal stimulation by ethanol, which reduces the blood volume of the effective circulation, reduces the blood pressure again, reduces the amount of coronary perfusion, reduces the perfusion pressure, reduces the effective circulating blood volume, the blood is relatively concentrated, and the blood lipids are relatively high; it will also cause water electrolyte disorders, especially hypokalemia.
caffeine
The mechanisms of caffeine-induced increase in blood pressure mainly include increased sympathetic activity and catecholamine release, and as endogenous adenosine antagonists.
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Studies have shown that ingestion of 200 to 300 mg of caffeine in one hour can increase systolic and diastolic blood pressure by 8.1 mmHg and 5.7 mmHg. Acute blood pressure elevation due to caffeine usually disappears after 2 weeks, and caffeine, the main component in coffee, may affect blood pressure levels in the acute phase.
Patients with hypertension who are unstable should avoid caffeinated beverages.
China Medical Tribune Small Circle Finishing
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