Probably one of the most feared issues in modern society, hypertension has taken over the lifestyles of several thousands of people today. Doctors generally attribute hypertension to unhealthy diets, smoking and genetic mutations. Over the years, cardiovascular medicine in particular has seen vast transformations. Initially, one had to keep count of the pills, but with the newly developed vaccines one may keep hypertension at bay for several weeks. This report serves to explain the pharmacodynamics of antihypertensive drugs and also give an overview of the possibilities of the commercialization of vaccines for the same purpose.
The tiny protein with a big effect-Angiotensin:
When blood pressure is low, the kidneys release renin, which converts angiotensinogen to angiotensin I. Angiotension converting enzyme (ACE) then transform that into angiotensin II. This peptide causes narrowing of blood vessels leading to increased blood pressure. Angiotensin II also stimulates the release of aldosterone from the adrenal cortex, which helps in reabsorption of water and sodium from the distal convoluted tubule of the kidneys. The increased volume of fluids in the circulatory system also causes an increase in blood pressure.
Pharmacodynamics of antihypertensive drugs:
The simplest of the antihypertensives are the diuretics, which increases the rate of urination in the subject by acting on different sections of the kidney. This assists in lowering the water and sodium content in blood, which causes a decrease in blood pressure. Calcium channel blockers are another set of drugs that lower the intracellular concentration of calcium in muscle cells, thus reducing muscular contractions.
However, the most specific drugs available in today's market would be the ones that alter the functioning of the renin-angiotensin-aldosterone system. As the name suggests, angiotensin-converting enzyme (ACE) inhibitors stymie the production of angiotensin II by binding to the angiotensin-converting enzyme. As a result, aldosterone levels fall and bradykinin levels increase. Bradykinin is a peptide that promotes vasodilation causing a decrease in blood pressure. Commonly used ACE inhibitors are ramipril, captopril and fosinopril.
Angiotensin II receptor blockers (ARBs) are another group of antihypertensive drugs. They prevent angiotensin II from binding to AT1 receptors. This in turn prevents aldosterone synthesis causing decrease in the fluid volume of blood and consequently a decrease in blood pressure. According to the United States Food and Drug Administration, Valsartan is the most potent ARB as it has the greatest affinity for AT1 receptors, while Losartan has the least affinity for these receptors. ARBs have been linked to an increased risk of myocardial infarction, but the issue remains debatable till date.
Issues with pills:
With an increase in the number of possible drugs for patients with hypertension, doctors are using combination therapies of ACE inhibitors and ARBs to control their patients' blood pressure levels in the best possible manner. For most patients, the issue does not deal with any adverse effects of the drugs. Rather, they face a dilemma of keeping track of which pills to take and how many of each pill they are supposed to take.
An innovative approach:
Cytos, a Swiss biotechnology company, identified this weakness in the market for antihypertensive drugs. If the majority of hypertension victims have an issue with popping pills regularly, why not create a drug that has a more prolonged effect. Scientists at Cytos came up with a proposal to create an antihypertensive vaccine named CYT006-AngQb.
Generally, vaccines are created from killed or attenuated microorganisms or specific components of the microorganism that would generate an immune response. Similarly, the antihypertensive vaccine consists of a laboratory generated version of angiotensin II, which behaves like a virus. When this replica of angiotensin II is injected into the bloodstream, the immune system will enlist it as an antigen. Consequently, the naturally produced angiotensin II will also be attacked by antibodies thus preventing it from functioning normally.
The question is: Is it practical for people to use an antihypertensive vaccine? The major drawback is that if there is an overinhibition of angiotensin II due to the vaccine, the effects may not be reversible. Doctors can control a patient's intake of pills, but cannot control the action of the vaccine in the bloodstream. The plus point is that patients will no longer be required to take medication on a daily basis once this vaccine is approved. Weekly shots of CYT006-AngQb should keep blood pressure levels under control. The vaccine is currently undergoing phase II clinical trials and several positive results have been observed.
Once antihypertensive vaccines are approved by the Food & Drug Administration, they may create a major milestone in the history of medicine. The ability to create a drug that can keep hypertension under control for weeks is an attractive opportunity for pharmaceutical companies to capitalize on. From the customer's point of view, the vaccine would help them save time and money for controlling and monitoring their blood pressure. It is in the hands of researchers to minimize the risks associated with the vaccine and simultaneously make it beneficial to the end user.
About Author / Additional Info:
An undergraduate biotechnology student interested in specializing in Pharmaceutical Regulatory Affairs.