Hypertension

HYPERTESION; THE MOST COMMON “HEART-BREAKER”  AMONGST ASIAN COMMUNITIES IN THE WORLD

By Dr Gayathri Delanerolle

Hypertension [HT] or high blood pressure [HBP] results from the forceful nature of blood being pushed against artery walls as it flows through them and is known as the silent killer. As blood increases the pressure exerted on the walls of the arteries, blood pressure [BP] increases resulting in hypertension. Systolic pressure or the maximum pressure during the beating of the heart, results in an elevated BP to push blood out of the arteries, while diastolic pressure which is the minimum pressure within the arteries in between heart beats at the resting position, results in a reduced BP. The measurement of BP is a measure of these two systolic and diastolic pressures in units’ mmHg. First systolic pressure is noted followed by the diastolic pressure. Although, the standard reading for BP is 120 mmHg/ 80 mmHg, normal BP may be defined with a range of values depending upon the condition of the subject at the time of the measurement such as stress or anxiety resulting in elevations of BP which are temporary. Therefore several reading of BP is important to rule out any discrepancies. In elderly subjects systolic HT is diagnosed when the diastolic pressure is either normal or low with an elevation of systolic pressure [about 170 mmHg /70 mmHg]. BP measurements are classified as pre-hypertension and hypertension stage 1[primary] and 2 [secondary] with  readings of 120-129 mmHg/ 80-89 mmHg,  140-159 mmHg/ 90-99 mmHg and 160-179 mmHg/ 100-109 mmHg respectively. 

HT may lack initial symptoms, although with the increase in the condition may result in headaches, sleepiness, confusion or coma. HT can be caused due to unknown reasons which are known as primary HT or essential HT and accounts for 90% of all HT patients. HT may be caused by conditions such as Cushing’s syndrome, renal failure, chronic alcohol abuse, endocrine tumours and hormonal disturbances. This type of HT is known as secondary HT as it’s a complication of an existing medical condition and mounts to 10% of HT subjects. HT may result in complications such as atherosclerosis [narrowing of the arteries], stroke [haemorrhage in the brain], cardiac failure [reduced output of the cardiac cycle], renal failure and persistent damage of eyes. Factors such as obesity, smoking, diabetes mellitus type 1 and 2, increased salt intake, lack of exercise, use of oral contraceptives, increased alcohol consumption and drugs such as steroids may increase the risk of HT. However, the prevalence of HT is common amongst South Asian communities such as Indians and Sri Lankans due to their dietary indiscretions such as high salt intake. 

Diagnosis of HT is based upon several measurements of BP, physical examination and haematological tests ranging from chest X rays, electrocardiographs [ECG], medical and family history, opthalmoscopy, blood and urine tests respectively. The family and medical history is used to determine complications or disorders which may lead to HT as family history of HT may suggest genetic predisposition of the condition. Ophthalmoscope is used to determine blood vessel damage in eyes as HT may cause haemorrhages or abnormalities of small vessels. A chest x ray is vital to detect any abnormalities in arteries or the heart such as thickening or enlargement while ECG measures the electrical activity of the heart and is useful in determining damaged or blocked arteries. Urine and blood tests help evaluate conditions which may cause HT.

The control of BP is important in the prevention and treatment of HT. In order to reduce BP the systolic pressure must be reduced to less than 140mmHg alongside a diastolic pressure of 85mmHg. However, this target is considerably different to diabetics where the systolic pressure must be reduced to 130mmHg with a diastolic pressure of 80mmHg. Medication such as ACE- inhibitors, Angiotensin II receptor antagonists, β blockers, α blockers, calcium channel blockers and diuretics are used in the treatment of HT. 

The mechanism of ACE inhibitors (Fig. 1) involves the Renin- angiotensin-aldosterone-system [RAAS], which plays an important role in BP regulation. ACE plays an important role within RAAS by producing angiotensin II via the conversion of the inactive angiotensin I. Angiotensin II is a vasoconstrictive substance which increases BP and promotes the retention of sodium and water through the production of aldosterone. ACE inhibitors are used to reduce the production of angiotensin II and promote the excretion of water and sodium and reduce BP through vasodilatation of blood vessels. However, non-ACE pathways (Fig. 1) produce angiotensin II; therefore, ACE inhibitory substances cannot halt the production of angiotensin II completely. ACE also inactivates bradykinin which is a vasodilator via stimulating the production of prostaglandins and nitric oxide, thus inhibition of ACE reduces BP via the inhibition of metabolism of bradykinine and the increase production of vasodilators. ACE inhibitors are the primary therapeutic method used for uncomplicated HT but not complex HT. Complicated HT is primarily treated through the use if thiazide diuretics and β blockers. ACE inhibitors are also the first line of defence against HT in Diabetes Mellitus type 1 patients with complications such as proteinuria and heart failure. ACE inhibitors can also be used to treat hypertrophy of the left ventricle [which is a clinical marker of HT subjects], patients with heart failure, post MI, renal disease, metabolic side effects such as dyslipidemia, hyperinsulinemia and glucose intolerance. It also provides the best results when used on African Americans in combination with diuretics. ACE inhibitors lack adverse effects but can cause dose dependent hypotension in patients with reduced serum sodium which may be a result of reduced dietary intake of sodium or usage of diuretics. Figure 2 is a table of ACE inhibitors and their description. 

DRUG	INFORMATION FOR USE	GENERAL INFOMATION ON DRUG	ADVERSE EFFECTS	PRECAUTIONARY  MEASURES
Captopril	Available in tablet form, taken 2-3 times daily. Initial dosage is from 12.5-25mg with a gradual increase to 50-150mg.	Used to treat HT and heart failure via the dilation of blood vessel walls thus rapid reduction of BP but may require several weeks for complete effects.	Minor effects such as loss of taste, persistent dry cough and rash may be present in certain individuals.	Driving and alcohol consumption must be avoided while reduced dosage is given to patients above the age of 60 and breast feeding mothers.
Cilazapril	Available in tablet form. The treatment of this drug is lifelong and is taken once a day.	Used to treat HT and heart failure via blood vessel relaxation thus reducing BP.	Common side effects include headaches, constipation, dry cough, tiredness and joint pain.	Patients with cardiomyopathy, atherosclerosis, renal or liver disease and pregnant mothers must avoid the use of this drug.
Enalapril	Available in tablet form, taken 2-3 times a day with an initial dose of 2.5-5mg and a maintenance dose of 10-40mg.	Used to treat HT, heart attacks and heart failure. Often given with a diuretic.	Common effects include dizziness and headaches which is diminished with long term treatment of the drug.	Driving, hazardous work and consumption of alcohol must be avoided. It is not recommended for infants, children or pregnant mothers. Reduced doses are prescribed to patients above the age of 60 and breast feeding mothers.
Fosinopril	Available in tablet form, taken 2-3 times a day.	Used to treat HT and heart attack.	Common effects include light headedness, blurred vision and dizziness.	Sudden swelling of the tongue, face and eyelids may be caused by the drug in which case A&E must be contacted. Must be avoided if pregnant, breast feeding or is a sufferer of renal disease.
Lisinopril [CONTINUED]	Available in tablet form, taken once daily. The dosage for HT sufferers range from 2.5-10mg, heart failure/diabetics (neuropathy) up to 20mg and 2.5-5mg to prevent further heart attacks.	Used to treat HT caused by diabetes with renal complications, heart failure and heart attack. This drug relaxes the muscles of the blood vessel reducing BP.	Common side effects are nausea, vomiting, dry cough, dizziness and diarrhoea. Jaundice and sore throat can also be observed in rare cases.	Driving, hazardous work and alcohol consumption must be avoided and is not prescribed for infants, children, breast feeding and pregnant mothers.
Perindopril	Available in tablet form, taken once daily 30 minutes prior to breakfast. Initial dose of 2mg is followed by an increase 4-8mg. The duration of effect is 24 hours.	Used to treat HT and heart failure. It’s also given to patients with heart conditions to prevent heart attacks. The drug relaxes the walls of blood vessels allowing free movement of blood reducing BP.	This may cause kidney impairment and large reductions in BP. Common side effects include loss of taste, nausea abdominal pain, rash and fatigue.	Driving, hazardous work and alcohol consumption must be avoided. The drug is not prescribed to infant, children and pregnant and breast feeding mothers. Elderly patients above the age of 60 are more sensitive to the drug therefore reduced doses are provided.
Quinapril	Available in tablet form with an initial dose of 5-10mg followed by an increase to 20-40mg once daily.	Used to treat HT and heart failure.  Each of these tablets contains candillia wax, crospovidone, gelatine, lactose, magnesium carbonate, magnesium stearate, synthetic red iron oxide and titanium dioxide.	This may cause kidney impairment. Common effects are dizziness, dry cough, fatigue, nausea and vomiting.	Patients above the age of 60 are prescribed 10mg dosage daily. Consumption of alcohol must be avoided. Pregnant mothers in their second or third trimester and breast feeding mothers are not prescribed with quinapril.
Ramipril	Available in tablet and capsule form. HT patients are given 1.25-10mg once daily while patients with heart failure or history with a heart attack are given 5-10mg 1-2 daily. The duration of the drug effect is 24 hours.	Used to treat HT and to reduce strain in the heart in patients with a history of heart attacks. The first dose may cause a sudden drop in BP and therefore bed rest is advised.	Common side effects include dizziness, nausea, headaches, dry mouth and cough. This may also cause an elevation in serum potassium and in rare occasions cause a decline in kidney function or GI tract disturbances.	Not prescribed for infants, children, pregnant and breast feeding mothers. Driving, hazardous work and consumption of alcohol must be avoided. Reduced doses are given to patients above 60 years of age.
Trandopril	Available in tablet form.	Used to treat HT and heart failure.	Adverse effects include, increase lithium levels, hyperkalemia and hypotension. Common side effects include nausea and cough.	Not prescribed to infants, children, pregnant mother in the second or third trimester and breast feeding mothers.

β- blockers or β- adrenergic blockers interrupt stimuli via binding to β-adrenoreceptors blocking the binding of norepinepherine and epinephrine throughout the body. According to the classification of β- blockers there is cardio-selective and non selective. Sympathetic effects are inhibited through this action and therefore these are known as sympatholytic drugs. Some β-blockers are partial agonists providing some activity of the sympathetic effects and therefore consist of an intrinsic sympathomimetic activity [ISA]. Some β- blockers consist of membrane stabilising activity [MSA]. Drugs in this category may be prescribed for heart disorders and other conditions. Cardio-selective β- blockers are used in the latter stages of HT treatment and not in the initial stages. Cardio-selective β- blockers are selective of the β-1 adrenoreceptor but at an elevated dose of drugs may result in the selectivity being compromised. β- blockers bind to the adrenoreceptors of the cardiac nodal tissue, conducting system and myocytes. The heart consists of β-1 and β-2 adrenoreceptors but β-1 adrenoreceptors are greater in number and function and bind to norepinepherine which are released from the sympathetic adrenergic nerves. β- Adrenoreceptors are coupled with Gs- proteins which form cAMP from ATP from activated adenylyl cyclise and increase the heart rate (Fig.3). When cAMP is elevated PK-A [protein kinase A] is activated which phophorylates L-type calcium channels thus increasing the movement of calcium into cells which in turn enhances the release of calcium from sarcoplasmic reticulum located in the heart (Fig.4). The sympathetic tone produced by β- blockers results in the reduction of electrical conduction [negative dromotrophy], contractility [negative introphy], heart rate [negative chronotrophy] and relaxation [negative lusitrophy] therefore therapeutic uses for β- blockers are HT, angina, myocardial infarction, arrhythmias and cardiac failure. As the sympathetic effect enhances the effect of β- blocker drugs increase. Figure 5 is a table with common types of cardio-selective drugs used for HT.

 

                             

DRUG	INFORMATION FOR USE	GENERAL INFORMATION OF THE DRUG	ADVERSE EFFECTS	PRECAUTIONARY MEASURES
Acebutolol	Available in tablet  and intravenous [for clinical monitoring in hospitals] form, given twice daily with an initial dose of 12.5- 25 mg with a gradual increase to 75-100mg. Initial treatment is administered in low doses and is dependent on the response for each patient.	Used to treat HT in patients with high or normal rennin concentrations and is administered with diuretics. This is a lipophilic drug and therefore crosses the blood-brain barrier.	10-30% of patients develop anti-antibodies and in about 1% hepatotoxicity with elevated liver enzymes. 5-6% of patients discontinue the drug due to intolerable effects.	Cardio selective properties of the drug are destroyed when the dose increases 800mg and therefore must be administered carefully.
Atenolol	Available in tablets, liquid and injection. Administered 1-2 times daily with 25-100mg doses. The duration of the effect of the drug is 20-30 hours.	Used to treat angina, HT and arrhythmias. Atenolol is not used as the initial form of treatment in HT.	Common side effects are muscle aches, fatigue and dry eyes which are temporary.	Driving, hazardous work and consumption of alcohol must be avoided. Not prescribed for infants, children, breast feeding and pregnant mothers. Reduced doses are required for adults over the age of 60.
Betaxolol	Available in tablet form and administered once daily in10-20mg doses.	Used to treat HT and angina pectoris. Betaxolol is administered with a combination of HT drugs.	The drug is usually will tolerated and the side effects are mild. Rare side effects include diarrhoea, constipation, fatigue, depression and nausea.	Driving, hazardous work and consumption must be avoided.
Bisoprolol [CONTINUED]	Available in tablet form and administered once daily. Patients with heart failure are opted for 1.25mg initial doses increasing up to 10mg. HT and angina patients are administered with 5-20mg doses. The duration of action for the drug is 24 hours.	Used to treat angina pectoris, HT [not initial treatment] and cardiac failure. Bisprolol is used in combination with ACE inhibitors and diuretics.	Common side effects include lethargy, fatigue, cold hands and feet and muscular pains. These are temporary effects of the drug.	Driving, hazardous work and consumption of alcohol must be avoided. Patients over the age of 60 are not prescribed this drug due to the adverse side effects.  Infants, children, pregnant and breast feeding mothers are also not prescribed bioprolol.
Celiprolol	Available in tablet form 1-2 daily half an hour before breakfast.	Used to treat HT. The active substance of the drug is celiprolol hydrochloride, sodium carboxymethylcellulose, microcrystalline cellulose 102, and sodium lauryl sulphate and magnesium stearate.	Common side effects are dizziness, headaches, tremor and sleeping difficulties. It also has rare side effects such as mental illness, hallucinations and diarrhoea.	Driving, hazardous work and consumption of alcohol must be avoided. Patients of renal disease, liver disease, diabetes mellitus and overactive thyroids should avoid this drug. Infants, children, pregnant and breast feeding women are also not prescribed this drug.
Esmolol	Available in intravenous form.	Used to treat HT and	Common side effects include blurred vision, confusion, dizziness, tiredness and lightneadedness.	Inadequate information is indicated for paediatric patients and pregnant and breast feeding mothers and therefore the precautions are unknown.
Metoprolol [CONTINUED]	Available in tablet, SR or slow release-tablet and intravenous form. HT patients are administered with 1-2 times a day while angina and arrhythmias subjects require 2-3 times a day. Patients with history heart attacks are given 4 times daily for 2 days and 2 times daily thereafter for prevention of further heart attacks. The daily dose is 100-400mg with duration of action of 3-7 hours.	Used to treat HT, angina, arrhythmias, migraine attacks and patients with a history of heart attacks. However, metoprolol is not the initial form of treatment for HT.	Common side effects include cold hands and feet, nightmares, drowsiness, fatigue, headaches and dizziness.	Not prescribed for children, infant, patient with respiratory diseases, pregnant and breast feeding mothers. Driving, hazardous work and consumption of alcohol must be avoided. Elderly patients above the age of 60 are prescribed reduced doses due to the increase risk of adverse effects.
Nebivolol	Available in tablet form taken in 5mg doses daily.	Used to treat HT. This drug is used with a combination of anti hypertension drugs in patients with renal and hepatic insufficiency and the elderly. Nebivolol consists of vasodilatation properties due to the release of nitric oxide from endothelial cells. It is a replacement drug amongst patients who are unable to tolerate atenolol.	Common side effects include headaches, dizziness, tiredness and paraesthesia.	Infants, children, pregnant and breast feeding mothers must not be prescribed.

Angiotensin II receptor antagonists [AIIRA] are another class of drugs used to provide therapeutic effects for HT. It is also used in the management of diabetic nephropathy, and heart failure. AIIRA blocks the angiotensin II AT¹ receptor and consists of vasopressor effects and regulate aldosterone and do not inhibit metabolism of bradykinin synthesis of prostaglandins as ACE inhibitors. The use of AIIRA is considered safe and effective treatment for HT according to the clinical trials conducted (American Family Physician).

DRUG	INFORMATION FOR USE	GENERAL INFORMATION OF THE DRUG	ADVERSE EFFECTS	PRECATIONARY MEASURES
Candesartan	Available in tablet form, administered once daily with 4mg dose initially and is increased to 32mg[maximum]	Used to treat HT and cardiac failure. The drug works by blocking angiotensin II resulting in the relaxation of blood vessel walls reducing BP.	Common side effects include dizziness, headaches and cold and flu like symptoms.	Not prescribed for infants, children and pregnant mothers. Breast feeding mothers and elderly patient above the age of 60 may be administered in low doses.
Losartan	Available in tablet form, administered once daily with a range of doses ranging from 25-50-100mg depending upon the severity of the disease.	Used to treat HT, diabetes type 2 renal insufficiencies and hypertrophy of the left side of the heart.	Common side effects include diarrhoea, dizziness, tiredness and cough.	Prescribed cautiously for breast feeding and pregnant mothers and patients with liver or kidney problems.
Valsartan	Available in tablet form, administered in range of doses from 40-80-160-320mg depending on the severity of the condition.	Used to treat HT, post myocardial infarction and cardiac failure.	Common side effects are dizziness, hypotension, diarrhoea, fatigue, and hyperkalemia and back pain.	Children and Infants and pregnant mothers are not prescribed with valsartan.
Telmisartan			Common side effects include headaches, dizziness and pain.
Irbesartan	Available in tablet form.	Used to treat HT. Alterations of the dosage is not required for the elderly or patients with renal or hepatic failure.	Common side effects include dizziness and headaches.

α- blockers or α- adrenergic blockers, block the α- 1receptors in vascular smooth muscles preventing the binding of catecholamines resulting in vasodilatation and the movement of blood more freely thus reducing BP.  Vascular muscle consist of two classes of α- adrenoreceptors; α-1 and α- 2. α-1 adrenorecoptors are in vascular smooth muscle while α- 2 is in vascular smooth muscle as well as sympathetic nerve terminals.  Gq- proteins activate smooth muscle contraction via IP3- signal transduction pathway and both α- 1 and 2 receptors are linked to them (Fig.8). Vasodilatation is a result of  α- 1 adrenoreceptor antagonists preventing the binding of norepinepherine to smooth muscle receptors. Non- selective α- 1 and α- 2 receptors block post- junctional α- 1and 2 receptors resulting in vasodilatation while pre- jucntional α- 2 blocking results in an elevation of norepinepgerine which in turn effect the post- junctional α- 1 and 2 adrenorecetor blockage. α-  blockers dilate both blood vessels and veins with a pronounced vasodilatation effect in arterial resistance of blood vessels. α- blockers use the sympathetic tone of blood vessels under basal conditions, and sympathetic activity is increased or during increased pathological conditions the effects of these drugs increase. α- blockers are primary antihypersensitive drugs and water retention may be observed if administered with diuretics. Figure 9 consists of drugs which are cardio-selective α- blockers.

DRUG	INFORMATION FOR USE	GENERAL INFORMATION OF THE DRUG	ADVERSE EFFECTS	PRECAUTIONARY MEASURES
Doxazosin	Available in MR or modified release- tablet form and is administered once daily. The drug must be used at the same time daily; HT patients are given doses of 1mg initially with a gradual increase up to 16mg. The duration of the drug action is 24 hours.	Used to treat HT. This is a vasodilator and may be administered with other anti-HT drugs such as beta blockers as the effects of the drug is increased when used in conjugated form.	During the initial phase of treatment of the drug patients may experience dizziness, fainting and nausea as BP is reduced considerably and therefore should be taken in the night.	Not recommended for infants, children, pregnant and breast feeding mothers. Reduced doses are given to elderly patients above the age of 60. Driving, hazardous work and consumption of alcohol must be avoided.
Indoramine	Available in tablet form and is administered twice daily with initial doses of 25mg and a gradual increase up to 200mg.	Used to treat HT.	Common side effects include dry mouth, dizziness, depression and ejaculation problems.	Caution is required for patients with liver, kidney dysfunction or Parkinson’s disease using this drug.
Prazosin	Available in tablet form and dosage is dependent on the severity of the condition.	Used to treat HT, cardiac failure and Reynaud’s syndrome.	Common side effects include feeling sick, diarrhoea, headache, drowsiness and blurred vision.	Not recommended for pregnant and breast feeding mother or patients with renal failure
Terazosin	Available in tablet form and dosage is recommended according to the type and nature of the medical condition.	Used to treat HT and enlarged prostate glands. This drug work in two different organs of the body. In HT patients the drug bind to the α receptors on blood vessel walls reducing BP and in enlarged prostate patients the α receptor of the prostate gland.	Common side effects include dizziness, drowsiness, lack of energy, fainting and depression.	Consumption of alcohol, driving, pregnant and breast feeding mothers and hazardous work must be avoided.  Must be used with caution with elderly patients.

 

Calcium channel blockers [CCB] are another group of drugs used in the treatment of HT and may be conjugated with β- blockers. CCB bind to L- type calcium channels which are located in smooth muscle, cardiac myocytes and nodal tissue in the sino-arterial and atrioventricular nodes. L-type calcium channels regulate calcium influx in smooth muscle which stimulates the contractions of smooth muscle and cardiac myocytes (Fig.10). L-type calcium channels also play a role in the nodal tissue for pacemaker currents. CCB’s cause vasodilatation, negative introphy, negative chronotrophy and negative dromotrophy by preventing the entry of calcium into cells. CCB’s reduce the systemic vascular resistance resulting in the reductions in arterial blood pressure thus lowering BP in HT patients.  CCB’s are classified as dihydropyridines and non- dihydropyridines which consists of phenylalkylamine and benzothiazepine class. Most CCB’s are dihypropyridines due to their high vascular selectivity as they reduce arterial pressure and systemic vascular resistance and thereby excellent in the treatment of HT. Some of these drugs are described in figure 11.

 

DRUG	IFORMATION FOR USE	GENERAL INFORMATION OF THE DRUG	ADVERSE EFFECTS	PRECAUTIONARY MEASURES
Amlodipine	Available in tablet form and is administered once daily with doses of 5-10mg. The drug has 24 hours of action.	Used to treat HT, angina and prevent heart attacks. The drug can be used safely with asthmatic and non-insulin dependent diabetes patients.	Common side effects include headaches, dizziness, flushing, abdominal pain, palpations and swelling of legs and ankles.	Not recommended for infant, children, pregnant and breast feeding mothers.
Isradipine	Available in tablet form and is administered in 25mg doses.	Used to treat HT by reducing the movement of calcium resulting in reduced rate of heart beat and widening of blood vessels.	Common side effects include dizziness, palpitations, headaches and swollen legs or ankles.	Not recommended for infants, children, pregnant and breast feeding mother. Sufferers of liver or kidney complications, diabetes and any other heart problems must be cautious when using the drug.
Felodipine	Available in MR- tablet form.	Used in the treatment of HT and preventing angina.	Common side effects include dizziness and headaches.	Food containing grapefruit must be avoided. Not recommended for children, infants, pregnant and breast feeding mothers.
Nifedipine	Available in tablet and capsule form.	Used in the treatment of HT, angina and Raynaud’s disorder.	Common side effects include dizziness, headaches, constipation, palpitations and water retention.	Not recommended for children, infants, pregnant and breast feeding mothers. Sufferers of diabetes, porphyria, cardiac failure, liver problems and unstable angina must be cautious when using the drug.

Diuretics are a class of drugs which removes excess salts and water from the body and often referred to as water pills. These are used in conjugation with β- blockers and ACE inhibitors to enhance drug effects to reduce BP in the treatment of HT. Classification of diuretics include thiazide, loop and potassium sparing. Thiazide diuretics are used to treat HT as it is the most effective in reducing BP and moderately increasing the excretion of sodium. Thiazide diuretics the most commonly used which inhibits the sodium – chloride transporter in the distal tubule of the kidneys (Fig.12). Sodium is released into the distal tubule in the presence of thiazide diuretics resulting in hypokalemia due to the stimulation of aldosterone – sensitive sodium pump which increases sodium reabsorption in exchange for potassium and hydrogen ions which in turn is excreted via urine. Loss of hydrogen through loop and thiazide diuretics is a result of the activation of RAAS which in turn leads to metabolic alkalosis. Thiazide dirutics reduce venous pressure and blood volume resulting in reduced cardiac pre-load, ventricular stroke volume and cardiac output. Reduced venous pressure results in the reduction of capillary hydrostatic pressure causing reductions in capillary fluid filtration promoting capillary fluid reabsorption.  Thiazide is used mainly amongst primary HT patients while potassium sparing and aldoseterone blocking diuretics are used amongst secondary HT patients. Figure 13 is a table with drugs which are thiazide diuretics.

DRUG	INFORMATION FOR USE	GENERAL INFORMATION OF THE DRUG	ADVERSE EFFECTS	PRECAUTIONARY MEASURES
Chlorothiazide	Available in tablet form and is used in small doses of 0.5-1.0g, 1-2 times a day.	Used to treat HT as the main therapeutic drug. This can also be used to enhance the effects of other ants-HT drugs.	Common side effects are hypokalemia, metabolic acidosis, dehydration, hypovolemia, hyponatremia, azotemia and hyperuricemia.	Not recommended for pregnant and breast feeding mothers. Hyperglycaemia may occur amongst diabetics and therefore may/may not be recommended.
Chorlthalidone	Available in tablet form which has low toxicity and has prolonged effects between 48-72 hours. 50-100mg initial doses followed by 25-100mg maintenance doses and 50-200mg doses every other day.	Used to treat HT, oedema, congestive heart failure and cirrhosis of the liver.	Common side effects are dry mouth, nausea, hypovelemia, muscle pain and easy bruising or bleeding.	Consumption of alcohol must be avoided as it increases the side effects. The drug shouldn’t be consumed during over heated or dehydrated conditions
Hydrochlorothiazide	Available in capsule, tablet and oral liquid form.	Used to treat HT, oedema and cirrhosis of the liver.	Common side effects are hypovolemia, nausea, dry mouth, headaches, dizziness and muscle pain.	Not recommended for patients with allergies to hydrochlorothiazide. Consumption of alcohol must be avoided.
Hydroflumethiazide	Available in tablet form, administered in 25-200mg per day.	Used to treat HT. The drug may be used as the main therapeutic drug or to enhance the effects of another anti- HT drug.	Common side effects include	Must be avoided by pregnant and breast feeding mothers.
Indapamide	Available in tablet and MR- tablet form.	Used to treat HT.	Common side effects include headache, rash, impotence, dizziness, fatigue and muscle cramps.	Not recommended for patients with liver failure and poor kidney function. Elderly patients and diabetics must use the drug with caution.
Methyclothiazide	Available in tablet form.	Used to treat HT and cirrhosis of the liver.	Common side effects include dizziness, headaches and hypovelimea.	Not recommended for patients with liver problems. Consumption of alcohol must be avoided.
Metolazone	Available in tablet form.	Used to treat HT and oedema.	Common side effects include dizziness, headaches and muscular pains.	Not recommended for patients with liver and kidney disorders and pregnant and breast feeding mothers.
Polythiazide	Available in tablet, capsule and injection form. For oral tablets adult dosage may be 1-4mg once a day. Children dosage is dependent on body weight and is recommended by the doctor.	Used to treat HT.	Common side effects include dizziness, muscular pains, headaches and sensitive skin.	Not recommended for diabetics, liver and kidney disease patients. Caution must be taken if the patient is pregnant, breast feeding, infant or a child.