Antihypertensive medications


When to take BP medications? (Encourage patients to consult their Primary Care Provider about dosing schedules to optimize the chronotherapeutic effect)

A prospective, longitudinal term study by Hermida, et al. (2019) of 19,000 participants was carried out to determine the impact of taking blood pressure medication at bedtime or upon awakening. Hermida, et al. (2016), Bowles, et al. (2018), and Zhao, et al. (2011) had previously published short-term studies that demonstrated a reduction in cardiovascular risk and stroke when blood pressure medication was taken at bedtime. This more recent study by Hermida, et al. (2019) is the first longitudinal study. The participants were followed for 6+ years. There were 9,500 participants in each group, bedtime medication and awakening medication. The data was adjusted for characteristics such as age, sex, cholesterol levels and other diseases.

The researchers found the participants who took their blood pressure medication at bedtime, had greater ABP control meaning they had lower BP during sleep while still maintaining BP control when awake. They also had greater sleep-time BP decline and lower prevalence of non-dipping. The prevalence of non-dipping was the best predictor of CVD risk.

The total composite of cardiovascular disease events including cardiovascular disease death, myocardial infarction, coronary revascularization, heart failure, stroke, angina pectoris, peripheral artery disease, and transient ischemic attack were significantly lower in the bedtime medication group. The rate of heart attacks was reduced by an average of 66%, heart failure by 58%, strokes by 51% and death from cardiovascular disease by 44%.

Commonly used medications and their side effects to control hypertension

Diuretics

Diuretics may be ordered for early signs of hypertension. These medications act on the kidneys to increase the elimination of sodium and water thus reducing blood volume. The three types of diuretics are thiazide, loop and potassium-sparing.

Each class of diuretic acts differently on the kidneys and vary in side effects: Low sodium blood levels (hyponatremia) side effects include dizziness, headaches, dehydration, muscle cramps, gout and impotence are also potential side effects (Mayo Clinic Staff, 2016).

Thiazide diuretics result in increased urination and mineral loss. They include:

Possible thiazide side effect

Loop diuretics

Possible loop diuretic side effects ( fewer than thiazide diuretics )

Potassium-sparing diuretics:

Beta blockers

Beta blockers are a class of drugs that antagonize sympathetic stimulation by blocking the binding of catecholamines to beta1 receptors (heart & kidney) and beta2 (lung, peripheral blood vessels and skeletal muscle). The catecholamine norepinephrine, often referred to as a stress hormone, increases blood pressure and heart rate.

Epinephrine, causes smooth muscle relaxation in the airways and is frequently used during asthmatics attacks, it also causes contraction of smooth muscle in arterioles. Blocking these transmitters slows down heart rate and reduces the workload of the heart. They are often used to treat hypertension, arrhythmias and heart failure (Yancy, 2013, p. e182.). Common beta blocker side effects include fatigue, cold extremities and weight gain. They are not recommended for patients with asthma.

Commonly prescribed Beta blockers include:

Generic Drug Name

Drug tradename

Acebutolol

Sectral

Atenolol

Tenormin

Bisoprolol

Zebeta

Carvedilol

Coreg

Esmolol

Brevibloc

Propranolol

Inderal

Labetalol

Normodyne or Trandate

Metoprolol tartrate

Lopressor

Metoprolol succinate 

Toprol XL 

Angiotensin-converting enzyme (ACE inhibitors)

Angiotensin-converting enzyme is a catalytic enzyme in the Renin-Angiotensin-Aldosterone System (RAAS). The RAAS is a hormone system that is involved in the regulation of the plasma sodium concentration and systemic blood pressure.

The plasma protein angiotensinogen is a prohormone produced by the the liver. Under conditions of decreased perfusion, the kidneys produce the catalytic enzyme renin which cleaves angiotensin I from circulating angiotensinogen.

Angiotensin I circulates in the plasma to the lungs where the catalytic enzyme Angiotensin Converting Enzyme (ACE) is highly expressed on the pulmonary capillary endothelium. Endothelium expressed ACE comes in contact with circulating angiotensin I and cleaves it to produce the angiotensin II peptide fragment.  Angiotensin II is a powerful vasoconstrictor that increases blood pressure and also induces insulin resistance and endothelial dysfunction.

Angiotensin II also stimulates the adrenal cortex to produce the hormone aldosterone. Aldosterone causes the distal tubule of the nephron to retain H2O and Na+ which increases the plasma volume, Na+ and blood pressure. Aldosterone has significant pathogenic hypertrophic effects on myocardium.

ACE inhibitors competitively prevent the conversion of the inactive peptide angiotensin I to angiotensin II which is the most potent vasoconstrictor known. Besides vasoconstriction Angiotensin II hormone causes the release of aldosterone from the adrenal glands. Aldosterone causes Na+ and water retention which further increases blood pressure. ACE inhibitors lower blood pressure and reduce the work load of the heart. They also may prevent or reverse the hypertrophy of the heart and vessel walls.

ACE inhibitors have been shown to increase the incidence of birth defects and are contraindicated during pregnancy. They also should be used with caution with other drugs that affect the kidneys like diuretics. Patients using insulin can experience low blood sugar. Increased monitoring is important with diabetics. Some over the counter pain medications, ibuprofen (Advil, Motrin), Naprosyn (Aleve) and similar compounds can make ACE inhibitors less effective. Acetaminophen (Tylenol) has no impact on ACE inhibitors (Sweitzer, 2003).

Examples of ACE inhibitors include:

Angiotensin receptor blockers (ARB)

ARBs have antihypertensive effects similar to angiotensin converting enzyme (ACE) inhibitors, but ARBs act to block the binding of angiotensin II to vascular smooth muscles, while ACE inhibitors prevent the formation of angiotensin II.

Generic ARBs

Calcium channel blockers

Calcium channel blockers work by preventing calcium from entering cells of the heart and blood vessel walls. Blocking calcium affects the muscle cells in the arterial walls leading to relaxed and widened blood vessels.

Grapefruit juice can increase the actions of these medications and should be avoided.


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Kindly select all the medication used to treat hypertension

Diuretics
Statins and PCSK9 Inhibitors
Beta blockers
Calcium channel blockers

ACE inhibitors

Medications that may increase high blood pressure

Antidepressants

People taking selective serotonin reuptake inhibitors (SSRIs) such as Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil, Pexeva) and Sertraline (Zoloft), the most commonly prescribed antidepressants, did not seem to have an increased risk of high blood pressure. Those taking serotonin and norepinephrine reuptake inhibitors (SNRIs) which include Cymbalta, Effexor, Khedezla, Fetzima, and Pristiq had a slightly increased risk of stage 1 hypertension.

But people taking tricyclic antidepressants such as amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Pamelor), and imipramine (Tofranil) were likely to see a rise in blood pressure. Like reuptake inhibitors, tricyclics seem to block the reabsorption of serotonin and epinephrine back into nerve cells after these chemicals are released into a synapse. Patients taking these antidepressants were 20% more likely to develop hypertension (Teply, 2016)

Cold medicines (decongestants)

Decongestants often contain pseudoephedrine or phenylephrine. Sudafed and Neo-Synephrine are common examples. Both these decongestants narrow blood vessels thus increasing blood pressure. Patients with hypertension should check with their physician before using these medications.

Stimulants

Stimulants such as methylphenidate (Ritalin) are generally obtained legally through prescription. They are often used for teens and adults with ADD and ADHD, narcolepsy and occasionally depression. However, they can increase blood pressure. Some stimulants are illegally obtained. These include amphetamines and methamphetamines. These drugs can increase heart rate, damage heart muscle and increase blood pressure. (More information is available on these drugs in the course entitled, Methamphetamine use: What you need to know.)

Other issues

Diabetic therapies

According to Kenny and Abel (2019) certain antihyperglycemic agents may have a negative impact and worsen the HF and risk of HF in patients with diabetes. On the other hand, some classes of agents may reduce HF risk. Studies of these antihyperglycemic agents are being conducted to determine how to best manage the diabetes without increasing the risk of HF and/or worsening that illness state.

Aspirin therapy

Previously patients at risk for most cardiovascular conditions, including HF, were recommended to take low dose aspirin (81 mg) daily. Recent research has challenged that recommendation. There is some disagreement among experts about whether the benefits of aspirin outweigh its potential risk of bleeding.

The 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease (Arnett, 2019) recommend:

There are some situations where bleeding from the aspirin therapy is a greater risk than the cardiovascular benefits that can be provided. Currently, the Food and Drug Administration does not recommend aspirin therapy for patients who have not already had a heart attack, stroke or another cardiovascular condition.

These are some current recommendations for low dose aspirin use to prevent myocardial infarctions and strokes (Mayo Clinic staff, 2019):

Patients for whom daily low dose aspirin therapy might be recommended.

Situations where the use of aspirin is controversial

Research continues to evaluate the benefits and risks of daily low dose aspirin use in adults younger than age 50 and older than age 70 before recommendations can be made for or against aspirin use to prevent cardiovascular diseases, including HF.  Bibbins-Domingo (2016) from the U. S. Preventive Services Task Force, states the current evidence is insufficient to make those recommendations.

Caution

Patients who have been taking aspirin on a daily basis, should not stop abruptly without a discussion with their doctor.  It is possible to have a rebound effect that might trigger a blood clot. Patients who are to undergo surgery need to discuss stopping of aspirin therapy before the surgery to weigh the risks and benefits.

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Loop diuretics generally have fewer side effects than thiazide diuretics.
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References:

Arnett D.K. et al. (2019).  2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019 Mar 17

Bibbins-Domingo, K. (2016). Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 164, 836.

Bowles, N.P., Thosar, S.S., Herzig, M.X. & Shea, S.A. (2018). Chronotherapy for hypertension. Curr Hypertens Rep. 20, 97.

Hermida, R.C., Ayala, D.E., Smolensky, M.H., Fernandez, J.R., Mojon, A. & Portaluppi, F. (2016).

Hermida, R.C., Crespo, J. J., Domınguez-Sardina, M., Otero, A., Moya, A., Rıos, M. T., et al. (2019). Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. European Heart Journal. 0, 1–12.

Kenny, C. & Abel, D. D. (2019). Heart Failure in Type 2 Diabetes Mellitus: Impact of Glucose-Lowering Agents, Heart Failure Therapies, and Novel Therapeutic Strategies. Circulation Research. 124:121–141.

Lemmer B. & Labrecque G. (1987) Chronopharmacology and Chronotherapeutics: Definitions and Concepts, Chronobiology International, 4:3, 319-329

Malha, L., Mann, S.J. (2016). Loop Diuretics in the Treatment of Hypertension. Curr Hypertens Rep. 18(4), 27.

Mayo Clinic staff. (2019). Daily aspirin therapy: Understand the benefits and risks. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/daily-aspirin-therapy/art-20046797.

Mayo Clinic Staff. (2019). High blood pressure (Hypertension). Retrieved from http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ace-inhibitors/art-20047480?pg=2

Mayo Clinic Staff. (2016). Diuretics. Retrieved from http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/diuretics/art-20048129.

Pfeffer, M. A. (2017). Heart Failure and Hypertension: Importance of Prevention. Med Clin North Am.101(1),19-28.
Saito, Y., et al. (2017). Low-dose aspirin for primary prevention of cardiovascular events in patients with Type 2 diabetes mellitus. Circulation. 135, 659.

Zhao, P., Xu, P., Wan, C. & Wang, Z. (2011). Evening versus morning dosing
regimen drug therapy for hypertension. Cochrane Database Syst Rev. CD004184.4.

 


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