Aiming hypertension

Hypertension is a grave disease and its incidence is on the rise. But there is no dearth of drugs either! Katya Naidu does a status check of the various classes of drugs available for treating this condition.

If incidence is a way to judge the seriousness of a disease, then hypertension ranks very high on the killer list. "About 15 percent of the world's population has hypertension. But a large number of them don't know it because there are no symptoms. One feels fine but it creates damage to organs like heart and kidney. Because one is feeling fine, one thinks there is no necessity for a check up or treatment but there is continuous damage to the vital organs," says Prof Harish Padh, Director of B V Patel, Pharmaceutical Education and Research Development (PERD) Centre in Ahmedabad. Moreover, changing lifestyles are making a number of Indians prone to this disease. And this trend is on the rise.

But if one uses the number of treatments available as a parameter to estimate the disease, hypertension ranks high on the curability list as well. When one talks of the drugs available for hypertension, they are talking of large numbers, be it the classes of drugs or the quantity of drugs in each class. "There are enough classes of types of drugs and several members in each class. There are about seven to eight categories of drugs and in each category there are about six to nine drugs. So there are a lot of drugs available for the treatment," asserts Padh.

The drug classes

There are drug classes that are available in the market and are classified as diuretics, beta-blockers, alpha-blockers, Angiotensin Converting Enzyme (ACE) inhibitors, calcium channel blockers, angiotensin receptors blockers and mineral of corticoid receptor agonists. These categories of drugs differ from each other in their mechanism of action.

Diuretics reduce hypertension by removing excess salt from the system. "Diuretics are the drugs which cause a net loss of sodium by increasing the volume of urine production, thus contributing to the anti-hypertensive effect," says Sakti Chakraborty, President—India Region Formulations, Lupin. When excess salt is retained in the body, the volume of blood will go high and that's why the heart will have to do more work. Once the blood volume is controlled, blood pressure is also controlled. Diuretics are favoured in situations favouring elderly hypertensive patients with sodium retention, obese with volume overload.

Beta-blockers directly inhibit the receptors, which are responsible for heart pumping. If there is a high rate of pumping of the heart, beta-blockers will slow it down a little bit, thus reducing blood pressure. It reduces cardiac output so that the total peripheral resistance decreases and both systolic and diastolic BP falls. It's central action reduces sympathetic outflow by reduced noradrenaline release due to blockade of beta receptor mediated facilitation of the release process. They are suitable for hypertensives with co-existing diseases like angina or post-MI patients, coexisting with anxiety or tachycardia.

Angiotensin-Converting Enzyme (ACE) inhibitors control the function of the kidney and thereby, reduce the blood pressure. They act on renin angiotensin system, it reduces angiotensin II (a substance which increase BP). "They also cause a fall in renin and aldosterone thereby reducing BP by either altering renal functions or cardiovascular structures," says Chakraborty. ACE inhibitors are best suited for those on low salt diet, relatively young patients, diabetics, specially with nephropathy, with left ventricular hypertrophy, post-MI cases. Calcium channel blockers work by dilating the arteries thus reducing the resistance of flow, resulting in fall in blood pressure. They are specially suited for elderly hypertensives, who generally have more arterial wall stiffness, isolated systolic hypertension, physically and or mentally active patients, asthma or COPD patients and peripheral vascular disease patients.

Alpha-blockers are a selective competitive antagonist of the classical alpha1 receptors. It dilates resistance vessels and thus reduces BP.

Combining forces

Dr Abha Doshi Principal MET Institute of Pharmacy

Though there are a number of candidates available for treating hypertension, it is always a challenge to the doctor to treat a hypertension patient. It is because the knowledge behind the cause of hypertension is still obscure. "In most cases, the cause is not precisely determined as to why hypertension is caused, whether it is because of high resistance of the arteries and veins or because of the problem in the lungs or because of the problem in the kidney. It is not possible to determine the etiology of hypertension," says Padh.

K G Rajendran Head-Knowledge Cell USV

Doctors generally adopt a trial and error method to treat hypertension by going in for a combination of drugs. If blood pressure cannot be controlled with a single drug then the combination of two or more agents from different pharmacological classes is given. Since there are quite a few drugs available, it also offers a wide range of choice for combination. "If you have high hypertension, doctors prescribe only one drug. But if your hypertension is severe, then the combination of one or two agents is given with a diuretic. If not controllable, a combination of diuretic and beta-blocker are generally taken. If it is still incurable, a combination of ACE inhibitor or calcium channel blockers are taken into consideration," says Dr Abha Doshi, Principal of MET Institute of Pharmacy. Adds Chakraborty, "Combinations therapies are also used in clinical practice when hypertension is not adequately controlled by monotherapy. It is rational in such cases to combine drugs with different mechanism of action or different pattern in order to achieve hemodynamic effect."

USV has fixed dose combinations (FDCs) for hypertension like Zabesta, a combination of bisoprolol and amlodipine; amlace, which is a combination of amlodipine and lisinopril; polytorva which is a combination of atorvastatin, aspirin and ramipril. "For FDCs, hydrochlorthiazide and beta-blockers are found in most combinations along with an ACE-inhibitor or an angiotensin receptor blocker," says K G Rajendran, Head-Knowledge Cell, USV.

Other effects

Anti-hypertensives are the drugs that need to be taken for a lifetime, once a patient is diagnosed with the condition. Hence, the foremost requirement for any drug is to have the least side-effects. "The side-effects associated with anti-hypertensive drugs are mild and transient. ACE inhibitors cause dry cough, Calcium channel blockers are associated with ankle oedema, diuretics are associated with electrolyte imbalance, beta-blockers result in tiredness, dizziness and gastro-intestinal upset. These can be minimised by regular visit and patient education," says Chakraborty. Agrees Padh, "There are not much of significant side-effects. The hypertensive therapy has to be very safe because people take it life long. The only problem is that these drugs are not equally effective in everybody, leading to right drug and dose by trial and error."

ACE inhibitors are also said to pose other problems. According to a study in New England Journal of Medicine, when pregnant women take ACE inhibitor medication during their first trimester, the risk of the infants having major malformations is more than doubled.

The study authors used data from Tennessee Medicaid records to identify 29,507 infants born between 1985 and 2000, excluding infants born to mothers with diabetes. In the first trimester, 209 infants were exposed to ACE inhibitors and 202 were exposed to other blood pressure drugs. Information regarding major malformations was obtained from linked records and hospitalisation claims during the first year of life. All told, malformations were diagnosed in 856 infants (2.9 percent). Eighteen were in the ACE inhibitor group, four in the other anti-hypertensive medication group, and 834 among the remaining infants.

Though the kitty of drugs for hypertension seems to be full, there are certain issues that are to be addressed like compliance, which are particularly low for hypertension drugs. A lot of naive population also exists for this disease, opening a requirement for intense patient education as well.

editorial@expresspharmaonline.com