Hypertension

 

Hypertension is the medical term for elevated blood pressure. This is a higher than normal pressure within the blood vessels as blood travels through it. High blood pressure in the short term does not cause any significant damage in the body and may even go unnoticed. However, prolonged elevation of the blood pressure can lead to a host of diseases affecting primarily the cardiovascular system and having secondary effects on almost every organ and system in the  body.




Normal and High Blood Pressure
The accurate definition of hypertension is the elevation of arterial blood pressure – pressure against the arterial walls. Pressure within the arteries ensures that there is sufficient force to propel oxygen-rich blood to all the tissues in the body. It also ensures that this force is transmitted through to the veins so that the oxygen-deficient blood can return back to the heart for re-oxygenation at the lungs.
The pressure at which the blood has to be maintained without causing damage to the blood vessels or body is commonly referred to as the normal blood pressure. A systolic pressure of 120 mm Hg and diastolic pressure of 80 mm Hg is considered as a normal blood pressure in adults (120/80 mm Hg). It can be slightly higher or lower and still remain within a normal range.
If it rises significantly above this then it is defined as hypertension according to the criteria below. If the blood pressure is significantly lower than the normal value then it is defined as hypotension (low blood pressure).
With regards to the actual pressure and values, the following criteria need to be present for a diagnosis of hypertension to be established.
▪ a systolic pressure, which is the pressure in the blood vessels during contraction of the heart, exceeding 139 mm Hg.
▪ a diastolic pressure, which is the pressure in the blood vessels while the heart is relaxing and the ventricles filling with blood, exceeding 89 mm Hg.
Ideally, three readings showing an elevated blood pressure of 140/90 mm Hg should be recorded in order for hypertension to be diagnosed.

Types of Hypertension

Hypertension can be broadly divided into benign and malignant.
▪ Benign hypertension includes primary (essential) hypertension and secondary hypertension.
▪ Primary hypertension is also known as essential hypertension or idiopathic hypertension. The exact cause is unknown although the disease mechanism has been established to a large degree and a variety of hypotheses exists as to why it occurs.
▪ Secondary hypertension is a consequence of certain diseases.
▪ Benign hypertension, primary or secondary, can lead to a host of complications over several years or even decades.
▪ Malignant hypertension is also known as accelerated hypertension and accounts for  a minority of hypertension cases. It is a sudden and severe form of hypertension which if left untreated can lead to death within one or two years.
Pathophysiology
Although the cause of primary hypertension is not fully understood, its close link to obesity and often improvement after weight loss may suggest one or more of the following mechanisms :
1. Cardiac output increased as blood needs to be distributed to a larger body mass.
2. Vascular resistance caused by constriction of the arteries (vasoconstriction) as a result of sympathetic activity and possibly further contributed to by hormonal influence associated with increased fat stores.
3. Salt and water retention is due to greater reabsorption from the renal tubules (kidney) and normal mechanisms for water-electrolyte balance may be disrupted in obesity.

Primary hypertension may therefore be due to a combination of one of more of the factors above. A related concept that is important to understand is the renin-angiotensin system which may lead to vasoconstriction as well as salt and water reabsorption. This system exists to help the body stabilize the blood pressure in the event of a drop in pressure. However, in patients with primary hypertension, this system appears to be overactive. The effects of the renin-angiotensin system is to cause vascular resistance and increase salt and water resistance.

Explaining High Blood Pressure
The simplest way to explain the concept of hypertension is to consider the analogy of the garden hose or hose pipe. The water needs to exit the hose at a certain pressure which will allow it to reach its destination.  The force of the water spraying out at the end is proportional to the pressure within the pipe.
▪ The more a faucet is opened, the higher the pressure of the water and faster the speed of the spraying water. This is related to the cardiac output component of blood pressure explained above.
▪ If the pipe is wider, the pressure is reduced and the water exits at a slower speed. If the pipe is narrower, the pressure within the pipe is greater. This aspect is related to the increased vascular resistance (vasoconstriction).
▪ If a larger than normal volume of water is pushed through a pipe, then the pressure increases just as is the case with water retention.
Benign hypertension, primary or secondary, can lead to a host of complications over several years or eve decades.




Medications For Hypertension


There are several types of drugs to treat hypertension and the use of each is dependent on the severity, duration and type of hypertension. Other underlying diseases also have to be taken into account when prescribing the most appropriate antihypertensive drug, even if the condition is not directly contributing to the raised blood pressure. Antihypertensive drugs work by either reducing the peripheral vascular resistance, cardiac output and/or fluid volume in the body.

The four main groups of antihypertensives based on different mechanisms of action. Hypertension medication may have different names depending on the class of drugs but fall into one or more of these categories  :
▪ Angiotensin II modulators
▪ Angiotensin-converting enzyme (ACE) inhibitors
▪ Angiotensin II receptor blockers
▪ Renin inhibitors
▪ Sympathetic (adrenergic) blockers
▪ Centrally acting sympathetic blockers
▪ Autonomic ganglion blockers
▪ Sympathetic nerve terminal blockers
▪ Adrenergic receptor blockers
▪ Alpha blockers
▪ Beta blockers
▪ Diuretics
▪ Thiazides and thiazide-like diuretics
▪ Potassium-sparing diuretics
▪ Loop diuretics
▪ Vasodilators
▪ Calcium channel blockers (CCBs)
▪ Vaso-selective blockers
▪ Cardio-selective blockers
▪ Nitrates
▪ Potassium channel openers
▪ Other antihypertensives

Angiotensin Converting Enzyme (ACE) Inhibitors
ACE inhibitors  inhibit formation of angiotensin II from angiotensin I. This includes drugs like captopril, enalapril, lisinopril, benazepril, quinapril, ramipril and perindopril.
ACE inhibitors reduce the constricting actions of angiotensin II on blood vessels and reduces the release of aldosterone. These two effects of reduced angiotensin II levels is primarily responsible for the blood pressure lowering action of ACE inhibitors. Bradykinin is a powerful dilator of blood vessels and it reduces peripheral vascular resistance. ACE inhibitors also inhibits break down of bradykinin and increases the levels of bradykinin. This also assists with lowering the the blood pressure.

ACE inhibitors are most useful in hypertensive patients with concomitant heart failure, diabetes mellitus, diabetic renal diseases (diabetic nephropathy), or hyperlipidemia and following a myocardial infarction (heart attack).
ACE inhibitors are not indicated in hypertensive patients with hypovolemia (low blood volume) as it can cause very low blood pressure (hypo. Use of ACE inhibitors in patients with narrowed renal arteries (renal stenosis) is not recommended as it can further damage the kidney. It is also contraindicated in pregnant women. Most common side effects of ACE inhibitors are a dry cough (due to increased levels of bradykinin) and hyperkalemia (increased levels of potassium of in blood).

Angiotensin II receptor blockers (ARBs)
Angiotensin II receptor blockers reduce blood pressure by blocking the actions of angiotensin II. This includes drugs like  losartan, valsartan, irbesartan, candesartan, telmisartan and olmesartan.
The efficacy, beneficial effects and side effect profile of angiotensin II receptor blockers are similar to that of ACE inhibitors. Unlike ACE inhibitors, the angiotensin II receptor blockers do not have any effect on bradykinin levels. This has resulted in minimal incidence of dry cough associated with angiotensin II receptor blockers.

Renin inhibitors
Renin inhibitor aliskiren decreases the conversion of angiotensin I to angiotensin II and is therefore useful in the treatment of hypertension. The side effects of rennin inhibitor are similar to that of ACE inhibitors.

Centrally Acting Sympathetic Blockers
Centrally acting sympathetic blockers reduce central sympathetic outflow and reduce norepinephrine release from adrenergic nerve endings. This includes drugs like clonidine and methyldopa.
These drugs are useful in treatment of hypertension. Clonidine is also öuse for treating symptoms of withdrawal from abused drugs and a prominent side effect of its use is sedation. Methyldopa is safe for use in pregnant women with hypertension.

Autonomic Ganglion Blockers
Autonomic ganglion blockers block the ganglionic nicotinic receptors of acetylcholine. These includes drugs like trimethaphan which causes a fall in blood pressure. It is also associated with a wide spread action not limited to cardiovascular system. These drugs are not regularly used for treatment of hypertension.

Sympathetic Nerve Terminal Blockers
Sympathetic nerve terminal blockers reduce sympathetic flow at the sympathetic nerve terminals by interfering with storage and release of noradrenaline. This includes drugs like reserpine and guanethedine.
It is effective in reducing blood pressure but is rarely used at present because of side effects. Reserpine is associated with toxicities like severe depression with suicidal thoughts and drug–induced Parkinsonism.

Adrenergic Receptor Blockers
Alpha blockers
Alpha blockers are effective in treatment of hypertension. This includes drugs like prazosin and terazosin. Alpha blockers are considered to be third-line agents in hypertension.
Alpha blockers reduce the blood pressure by preventing the normal alpha receptor (sympathetic) mediated blood vessel constriction. Alpha blockers also relieve the difficulty in passing urine in patients with prostate enlargement. Alpha blockers are thus ideal for older men with hypertension and prostate enlargement. The most prominent drawback of alpha blockers is the postural hypotension.

Beta blockers
Beta blockers are one of the most important groups of antihypertensive drugs. The group includes drugs like propranolol, atenolol, metoprolol, pindolol, bisoprolol and carvediolol.
Beta blockers reduce blood pressure by reducing the heart rate and its force of contraction. Some of the drugs among them (like atenolol and metoprolol) are very selective in its action on heart. Drugs like propranolol are not selective for heart and have some additional constricting action on bronchi. Beta blockers are useful in treatment of hypertension, cardiac arrhythmias and in controlling symptoms of hyperthyroidism. It is also useful in long term prophylaxis against ischemic heart disease (IHD).

Carvediolol has additional alpha blocking action and is also useful in conditions like heart failure. Use of other beta blockers in heart failure can worsen it. Beta blockers are generally not recommended in patients with concomitant bronchial asthma. It can interfere with awareness and recovery from hypoglycemia (low blood sugar levels) resulting from use of anti-diabetic medicines. Hence, its use in diabetic patients has to be done very cautiously. Beta blockers can also dangerously reduce heart rate in patients with heart block and when combined with other cardiac depressant drugs (like verapamil).

Thiazides and Thiazide-like Diuretics
Thiazide diuretics (like hydrochlorothiazide) are the most important antihypertensive diuretic group. Thiazide diuretics are usually used in combination with potassium-sparing diuretics like spironolactone.
Thiazides are known to cause hypokalemia (low potassium levels), which is countered or prevented with the use of potassium-sparing diuretics. Glucose intolerance and lipid level abnormalities are other common adverse effects of thiazides. It is used in mild to moderate primary hypertension. It is also of use in patients with concomitant mild heart failure.

Potassium-sparing Diuretics
Potassium-sparing diuretics (like spironolactone, eplerenone, amiloride etc) are used along with thiazides or loop diuretics. These drugs combinations act synergistically in lowering blood pressure and in reducing or preventing hypokalemia.

Loop Diuretics
Loop diuretics are less commonly used in long term management of hypertension and includes drugs like furosemide. It may be used along with potassium-sparing diuretics in management of severe hypertension along with other antihypertensive drugs. It may be also be used in patients with concomitant heart failure.

Calcium channel blockers (CCBs)
Calcium channel blockers are important group antihypertensive drugs. Some of the calcium channel blockers block the entry of calcium into vascular smooth muscle cells. This causes vasodilation due to relaxation of the vascular smooth muscle cells. These drugs are called vaso-selective calcium channel blockers.
Some of the CCBs inhibit the calcium channels in the cardiac muscle cells. This results in depression of cardiac functions and subsequent fall in blood pressure.

These are called cardio-selective calcium channel blockers.

Vasoselective calcium channel blockers
Vaso-selective CCBs include amlodipine, felodipine, isradipine, nicardipine, nimodipine and nifedipine. These drugs primarily reduce blood pressure by dilating the blood vessels. This group of drug is used in treatment of hypertension. Hypertensive patients with concomitant peripheral vascular diseases also benefit from vaso-selective CCBs.
Postural hypotension is a common side effect for these drugs. It can also cause increase in heart rate, flushing, edema, and sometimes precipitate cardiac pain (ischemic attack). This group of CCBs can be safely combined with other cardiac suppressant drugs like beta blockers and other drugs like diuretics.

Cardio-Selective Calcium Channel Blockers
Cardio-selective CCBs include verapamil and diltiazem. These drugs reduce blood pressure by suppressing the cardiac function. Heart rate and force of contraction of the heart is therefore also reduced.
This group of drug is used in treatment of hypertension, cardiac arrhythmias and angina pectoris. Heart rate can be dangerously reduced by these drugs occasionally as a side effect. Combining with other cardiac depressants like beta blockers is contraindicated. The group is also contraindicated in heart failure patients.

Nitrates
Nitrates have very potent dilating action on blood vessels but are not used for regular management of hypertension. Nitrates lower blood pressure very quickly and are preferred drugs in hypertensive emergencies (acute development of very high blood pressure). It can be administered intravenously for hypertensive emergencies. Important antihypertensive nitrates include sodium nitroprusside and nitroglycerine. Use of nitrates is associated with severe headache, sweating, palpitation and postural hypotension.

Potassium channel openers
Potassium channel openers like minoxidil produce blood pressure lowering effects by dilation of the blood vessels resulting from relaxation of the vascular smooth muscles. Potassium channel openers are less commonly used as antihypertensive drugs.
Minoxidil is more commonly used for treatment of male-pattern baldness. The use of these drugs as antihypertensive drugs is associated with hirsutism (abnormal facial hair growth in women), sweating, palpitations, and postural hypotension.

Others Antihypertensives
Several other drugs are known to have antihypertensive actions. Hydralazine, diazoxide, and fenoldapam are some of these other types of hypertensives. Hydralazine is available as tablets and for intravenous use. Hydralazine tablets are now rarely used for regular treatment of hypertension. The intravenous preparation is useful in hypertensive emergencies. Diazoxide and fenoldapam are also available as intravenous preparations for use in hypertensive emergencies.