Pharmacotherapy of hypertension

                     Debashis Kundu
           Bengal school of technology
                (A college of pharmacy)


                              INTRODUCTION:

High blood pressure termed as "hypertension," is a condition that affects more than 207 million persons is the leading cause of illness and death. High blood pressure is much higher than "heart disease" because it affects other parts of the body such as the kidneys, brain, and eyes.

Hypertension is an intermittent or persistent elevation (systolic blood pressure 5 mm Hg or diastolic blood pressure above 90 mm Hg) or (a systolic and diastolic pressure of 20 mm Hg above normal baseline pressure). Hypertension has recently increased the incidence worldwide.  It is believed that with changes in dietary habits and lack of exercise, stresses of daily life lead to increased incidence of hypertension. In the past, hypertension is prevalent only in industrialized and developed countries. However, the number of cases in developing countries has steadily increased from end to end.

It is often asymptomatic, but still, untreated, high blood pressure has led to increased detection rates over the last three decades that can cause organ damage. Thus, physicians have the important responsibility of first finding and then adequate treatment.

Many patients require drug therapy to control hypertension and a variety of agents are available (including new anti-angiotensin II-receptor antagonists). There is considerable debate as  to which class or agent is best for first aid.

Many patients have proven hyperactivity with antihypertensive therapy, especially in the past. Some patients have a secondary cause of hypertension that must be identified and treated, but most, we now realize, is a primary blood pressure that is being treated inadequately.

DEFINITION:

Hypertension is high blood pressure. Blood pressure is the force of blood against the walls of the arteries as it flows through them. The artery is the blood vessel that carries oxygen-rich blood from the heart to the tissues of the body.

DESCRIPTION:

Blood flows through the arteries, pushing it towards the walls of the arteries. Small artery size also affects blood pressure. When the muscle walls of the arteries are relaxed or expanded, the blood pressure flowing through them is less than if the arterial walls are narrower or constrict.

Blood pressure is highest when the heart beats to deliver blood to the arteries of the heart. When the heart is relaxed again, the pressure is at its lowest point. Blood pressure during a heartbeat is called systolic pressure. When the heart is resting, the blood pressure is called diastolic pressure. When blood pressure is measured as systolic, pressure is called the first and diastolic pressure is called the second. Blood pressure is measured in millimeters of mercury (mm Hg).

For example, if a person's systolic pressure is 120 and the diastolic pressure is 80, it is written as 120/80 mm Hg. The American Heart Association considers blood pressure to be over 90 and less than 140 normal for adults.

High blood pressure is a major health problem, especially because it has no symptoms. Many people inadvertently suffer from hypertension, with high blood pressure. High blood pressure is fatal because conditioned people are at higher risk for heart disease and other medical problems than people with normal blood pressure. Serious complications can be avoided through regular blood pressure tests and high blood pressure detection as well as treatment.

If left untreated, hypertension may be a lower treatment condition;

• Arteriosclerosis is also known as atherosclerosis.

• Heart attack

• Stroke

• Heart enlargement

• Kidney damage

Arteriosclerosis is tightening of the arteries. The walls of the arteries have a layer of muscle and elastic tissue that makes them flexible and enables them to flexible to flows the blood between them. High blood pressure can thicken and harden the walls of the arteries.  When the artery  walls become thick, the inner part of the artery shrinks. Cholesterol and fat are likely to grow on the walls of damaged arteries, making them even more narrow. A blood clot can get stuck in a narrow artery, blocking the flow of blood.

Arteries narrowed by arteriosclerosis cannot supply adequate blood to organs and other tissues. Reduced or blocked blood flow to the heart can cause a heart attack. A stroke can result if an artery in the brain is blocked.

High blood pressure makes it harder for the heart to pump blood through the body. Excessive workload can make the heart muscle thicker and wider. When the heart becomes too large it cannot pump enough blood. If high blood pressure is left untreated, the heart can fail.

Kidney removes body waste from the blood. High blood pressure makes the arteries thick in the kidneys, filtering less waste from the blood. As the condition worsens, the kidney fails and blood is wasted. When the kidney fails, dialysis or kidney transplant is required. About 25% of people with kidney dialysis acquire kidney failure due to high blood pressure.

CLASSIFICTION:

CLASSIFICATION:

1. Essential hypertension

2. Secondary hypertension

A) Systolic hypertension with wide pulse pressure:

• Aortic regurgitation

• Thyrotoxicosis

• Patent ductus arterious

B) Systolic and diastolic hypertension with increased PVR

1. Renal

• Glomerulonephritis (acute or chronic)

• Pyelonephritis

• Polycystic kidneys

• Renal artery stenosis

2. Endocrine

• Cushing's syndrome (excessive glucocorticoids)

• Congential adrenal hyperplasia

• Conn's syndrome (primary hyperaldosteronism)

• Phaeochromocytoma

• Hypothyroidism

• Acromegaly

3. Neurogenic

• Raised intracranial pressure

• Psychological ("white coat hypertension")

• Acute porphyria

• Lead poisoning

4. Miscellaneous

• Coarctation of the aorta

• Polyarteritis Nodosa

• Hypercalcaemia

• Increased intravascular volume (PRV)

EPIDEMIOLOGY:

In India, 2.5 million people died of heart disease in the year 1; This is expected to double by 2020. Hypertension is directly responsible for 57% of stroke-related deaths and 24% of coronary heart disease deaths in India. In the mid-1950s an Indian urban population study (WH> OR +  160 and / or 95 mmHg) used the old WHO guidelines to diagnose and reported an prevalence of 1.2-2.0% of hypertension. Subsequent studies have shown uninterrupted growth from 5% in the 1960s to 12-15% in the 1990s. The prevalence of hypertension is low in the rural Indian population, although it has increased slowly over time. Recent studies using modified criteria(BP> OR = 140 and / or 90 mmHg) have shown a higher incidence of hypertension among urban adults: male 30% female 44% Jaipur (1995), male Mumbai 44% (1999), male 31%, Thiruvananthapuram is 36% (2000). According to the rural population, the prevalence of hypertension is 20% in men, 5% in Rajasthan women (1). In many tests, hypertension has been detected in Mumbai, with 2% male and 25% female officer (Haryana) and 1.5% rural subject (1999). There is a strong correlation between lifestyle changes and increased hypertension in India. Further studies on the nature of genetic contribution and environmental interaction of  genes are needed to accelerate the high blood pressure epidemic in India. A pool of epidemiological studies suggests that 25% of urban and 10% of rural subjects present hypertension in India. At an early age, there are 31.5 million in the rural population and 34 million in the urban population. About 70% of these will be stage I hypertension (systolic BP 140–159 and / or diastolic BP 90–99 mmHg). Recent reports indicate that borderline hypertension * systolic BP 130–139 and / or diastolic BP 85–89 mmHg) and stage I hypertension carries a significant cardiovascular risk and should lower blood pressure. Population-based cost- effective hypertension control strategies should be developed.

Epidemiology of hypertension, both as a risk factor for cardiovascular and other diseases, and in the case of its own etiology, is a major area of inquiry with a huge peer-reviewed literature every year. As Paul Eliot said in the opening sentence of this book, "Ranking with tobacco because of the burden of worldwide death today is one of the most important risk factors for morbidity and mortality in the world" "

An interest in circulation pressure levels began in 1733, when Harvey placed a glass tube in a horse's artery for almost 100 years after demonstrating blood circulation. Such direct measurement of arterial pressure was clearly unreasonable in clinical practice, and efforts to develop instruments for indirect measurement ended in Rava-Rossi's 1896 description of the 19th century. The pulse was swollen by a cuff to stop it. The diffusion pressure was recorded by the parsonometer. In 1901, it was praised that the Rev-Cocosci Café, which was 5 centimeters wide, mistakenly suppressed high tendency, and a larger cuff was introduced. In 1905, Korotkief published his paper, outlining the use of a stethoscope to overcome diastolic and systolic blood pressure. This technique became widely accepted within a few years and opened the way for regular collection of blood pressure data for a large number of people, including relatively affordable sphygmomanometers. The source of measurement styles in addition to the size of the cuff and the need to standardize measurement methods to reduce these patterns was appreciated before World War I. Soon hypertension distribution increased mortality in practical studies increased The emergence of chronic disease epidemics and especially cardiac epidemiology following World War II followed the development of effective pharmacological therapies in the 1950s and their trials in randomized trials beginning in the 1960s. The areas of high blood pressure epidemiology, treatment and population control are beginning to take their modern form.

The Hypertension Handbook is a multi-volume series covering these fields as well as experimental, pathophysiologic and genetic aspects. The current volume is an updated version of the 1985 version of the epidemiology of hypertension, and contains 41 chapters by various authors covering various aspects of the epidemiology of hypertension. The very high quality supervision of these chapters is evidence of a strong editorial hand in both the selection and writing of the authors. There are categories of hypertension in the population; Blood pressure measurement; Blood pressure and environment; Blood pressure and nutrition;  Secondary forms of hypertension; A bunch of genetics and risk factors; Blood pressure, hormone replacement and oral contraceptives; Community control of hypertension; Problems with community control of hypertension and community control in different countries. This final section has two chapters, both exemplary, the first number of clinical labeling (to inform people that they are suffering from hypertension) and the second, about the broader role of the pharmaceutical industry in influencing decision making. One of the strengths of this book is the authors' directness in  writing the boundaries of data, unresolved conflicts and conflicting views of experts in the field. Another strength for the American reader is the original European author's list and a coherent quote from European publications. The literature is high international and usually up in 1998. Some of the chapters I thought were particularly great were the Chapter on Safarol and Smullen on diastolic blood pressure, the Paragraph section on blood pressure for children and adolescents, Saver and Poulter's chapter on Blood Pressure and Migration, Sodium Acquisition's Simpson's Chapter, Renin's system for Robertson-Angioten and Angiotensin. One of the blood pressure treatment programs In the chapter on governance in the comprehensive review. Many more can be added to this list.

ETIOLOGY OF ESSSENTIAL HYPERTENSION:

Environment: 

Many environmental factors are involved in the development of hypertension, including salt intake, obesity, occupation, alcohol intake, family size, excessive noise performance, and congestion.

Salt sensitivity: 

Sodium is the environmental factor that has attracted the most attention. It may be noted that essential hypertension accounts for approximately 60% of the population's sodium intake.

Role of rennin: 

Renin is an enzyme that is stored by the juxtaglomerular cells of the kidney and binds to aldosterone in a negative feedback loop. Plasma renin activity is seen more widely  in hypertensive subjects tan in conventional ones. As a result, some hypertensive patients are defined as requiring low hrenin and high renin due to other hypertension.

Insulin resistance: 

The main purpose of the polypeptide hormone stored by the insulin pancreas is to regulate glucose levels in the body along with some other effects. Insulin  resistance and / or hyperinsulinemia have been suggested to be responsible for increasing arterial pressure in some patients with hypertension. The feature is now widely recognized as part of Syndrome X, or metabolic syndrome.

Insomnia: 

Sleep apnea is a common cause of recognized hypertension. It is well treated with weight loss and nocturnal positive airway pressure.

Genetics: 

Hypertension is one of the most common complex genetic disorders, with an average of 30% genetic heredity d. The data supporting this approach originate from animal studies and population studies in humans. Most of these studies support the notion that inheritance is probably polyandrous or that each of the many genetic defects has hypertension as their phenotypic expression. In association studies with hypertension, more than 50 genes have been tested and the number is steadily increasing.

Other Etiologies: 

There are some subtle or transient causes of high blood pressure. They do not need to be confused with a disease called hypertension where there is an internal physiological system described above.

Etiology of secondary hypertension:

Only a minority of patients with elevated arterial pressure can identify a specific cause. These individuals will likely have an endocrine or renal failure, which, if corrected, returns the blood pressure to normal values.

Renal hypertension:

A simple explanation of renal vascular hypertension produced by kidney disease is that perfusion of renal tissue due to stenosis of the root or branch renal artery activates the renin – angiotensin system.

Adrenal hypertension: 

Hypertension is a symptom of adrenal cortical abnormality. There is a clear correlation between aldosterone-induced sodium retention and hypertension in primary aldosteronism.In patients with pheochromocytoma, the tumor increases the secretion of catecholamine such as epinephrine and norepinephrine (most often located in the adrenal marrow) (adrenergic receptor), resulting in peripheral vasoconstriction and cardiac stimulation. The diagnosis was confirmed by determining urinary urinary incontinence and / or their metabolism (vanillomandalic acid) of epinephrine and norepinephrine.

Coarctation of the Aorta:

Diet:

Some medications, particularly NSAIDS (Motrin / Ibuprofen) and steroids can cause high blood pressure. Eating imported licorice (Glycyrrhiza glabra) can lead to secondary hypoaldosterism, which in itself causes hypertension.

Age:

Over time, the number of collagen fibers in the arteries and artery walls increases, making blood vessels stronger. With dense elasticity, a small cross-sectional area falls into systole and therefore arising means arterial blood pressure.

Pathophysiology

• Abrupt increases in systemic vascular resistance likely related to humoral vasoconstrictors.

• Endothelial injury

• Fibrinoid recrosis of the arterioles

• Deposition of platelets and fibrin 

• Breakdown of the normal autoregulatory function

• The resulting ischemia prompts further release of vasoactive substances completing a vicious cycle.

There is still a lot of uncertainty about the pathophysiology of hypertension. A small number of patients (between 2% and 5%) have stomach or adrenal disease, which increases their blood pressure. Of the rest, however, no clear single identifiable cause was found, and their status was identified as "essential hypertension." Many physiological processes are involved in normal blood pressure maintenance, and their derivation may play a role in the development of essential hypertension.

It is likely that many interrelated factors contribute to elevated blood pressure in hypertensive patients, and their respective roles may vary among individuals. Things that have been closely studied are salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. Over the years, genetics, endothelial dysfunction (such as changes in endothelia and nitric oxide), low birth weight and endogenous nutrition and other factors such as neurovascular impairment are evaluated.

Signs and symptoms:

Most people with high blood pressure have dangerous blood pressure readers, but have no symptoms.Although some people with hypertension may have an existential headache or a digestive tract or some bleeding above normal, these symptoms and symptoms may not be seen until hypertension develops - possibly life-threateningly - periodically.

What are the signs and symptoms of pulmonary artery hypertension?

Breathing or shortness of breath(Dyspnea) is a major symptom of pulmonary arterial hypertension (PH). If you have PAH, you may find that it is hard to get enough air.

Other Common Signs and Symptoms

• Fatique

• Dizziness

• Fainting spells (syncope)

• Swelling in the ankles or legs (edema)

• Bluish lips and skin (cyanosis)

• Chest pain

• Racing pulse

• Palpitations (a strong feeling of a fast heartbeat)

As the disease advances

• The pumping action of your heart grows weaker.

• Your energy decreases

In the more advanced stages, you:

• Are able to perform very little activity

• Have symptoms even when resting

• May become completely bedridden.

Risk factors:

There are several risk factors for hypertension. Some you cannot control.

Age:

The risk of high blood pressure increases with high middle age, hypertension is more common in men Omen women are more likely to have high blood pressure after menopause.

Race: 

Hypertension is particularly prevalent among blacks, and it often develops at a younger age than whites. Serious complications, such as stroke and heart attack, are more common in blacks.

Family history:

Hypertension persists in families.

Excess weight:

The higher your body mass, the more blood you will need to provide oxygen and nutrients to your tissues. As the blood flow through your arteries increases, the pressure on the walls of your arteries increases.

Inactivity:

people have a high heart rate. The higher your heart rate, the harder you have to work with each beat - and the greater the strength in your arteries. Lack of physical activity also increases the risk of being overweight.

Tobacco use:

 Tobacco chemicals can damage the lining of your artery walls, which encourages narrowing of the arteries.

Sodium intake: 

Too much sodium in your diet - especially if you have sodium sensitivity - increases fluid retention and blood pressure.

Low potassium intake:

 Potassium helps to balance the amount of sodium  in  your cells. If you do not take or keep enough potassium, too much sodium can accumulate in your blood.

Excessive alcohol:

 Over time, heavy alcohol can damage your heart.

Stress: 

High levels of pressure are temporary but increase dramatically. If you try to relax by eating too much, drinking tobacco or alcohol, you can only exacerbate the problem of high blood pressure.

Some chronic conditions may increase the risk of hypertension, including high cholesterol, diabetes, kidney disease, and sleep apnea. Sometimes pregnancy contributes to high blood pressure.

A 2006 study found that adults who work more than six hours a week - especially clerical and non-skilled workers - are more likely to have high blood pressure than those who spend 5 hours a week or Used to work less than that. Researchers linked employees to higher exposure to healthy food, less exercise, more stress, and less sleep.

Although hypertension is commonly seen in older adults, children may also be at risk. Hypertension in some children is caused by kidney or heart problems, but increasing numbers of children, due to poor lifestyle - such as unhealthy diet and lack of exercise - contribute to high blood pressure.

Methods for measuring hypertension:

• Palpatory method

• auscutatory

Clinical manifestations:

The manifestations of hypertensive crises are end-stage dysfunction:

• Hypertensive encephalopathy

• Acute aortic dissection

• Acute myocardial infarction

• Acute cerebral vascular accident

• Acute hypertensive kidney injury

• Acute Congestive Heart Failure.

It is important to recognize that the absolute level of BP may not be as significant as the rate of increase. Patients with chronic hypertension can tolerate up to 200 mm Hg or diastolic BP up to 150 mm Hg without the development of hypertensive encephalopathy, whereas encephalopathy with diastolic BP 100 mm Hg may develop in infants or pregnant women.

ACE INHIBITORS:

Example

• benazepril
• captopril
• enalapril
• fosinopril
• lisinopril
• moexipril
• quinapril
• ramipril

Mechanism of action

ACE inhibitors produce vasodilation by inhibiting the formation of angiotensin II. This vasoconstrictor is formed by the proteolytic action of renin (released by the kidneys) acting on circulating angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme.
ACE also breaks down bradykinin (a vasodilator substance). Therefore, ACE inhibitors, by blocking the breakdown of bradykinin, increase bradykinin levels, which can contribute to the vasodilator action of ACE inhibitors. The increase in bradykinin is also believed to be responsible for a troublesome side effect of ACE inhibitors, namely, a dry cough.
Angiotensin II constricts arteries and veins by binding to AT₁ receptors located on the smooth muscle, which are coupled to a Gq-protein and the the IP₃ signal transduction pathway. Angiotensin II also facilitates the release of norepinephrine from sympathetic adrenergic nerves and inhibits norepinephrine reuptake by these nerves. This effect of angiotensin II augments sympathetic activity on the heart and blood vessels.

Vasodilators:

Arteriolar: Hydralazine, Diazoxide & minoxidil Arteriolar + venous: Sodium nitroprusside

Mode of action:

Hydralazine acts primarily in the artery by an unknown mechanism (distinct from nitric oxide). Minoxidil (or its sulfate metabolite) relaxes vascular smooth muscle by opening ATP-dependent K-channels. Sodium nitroprusside is a nitro-dilator that directly activates the gannet cyclone.

Use:

Special indications are pregnancy-induced hypertension (hydrazine) and severe obstructive hypertension (minoxidil).

Causes of both hydrangeen and minoxidil: (1) a reflex tachycardia - which often requires beta- blocking (2) rebound or no retention - is contrary to their hypothetical action and requires aggressive use of loop dietetics. , Especially in the case of minoxidil.

Acting centrally on anti-hypertensive agents:

These agents have historically enjoyed greater use outside the UK (especially in the US) as they cannot be considered as first-line / alternative first / line agents:

EXAMPLE: Clonidine,Methyldopa

• Poor side effect profile

• Conspicuous lack of outcome data.

NB: Non-methyl-dopa is still widely prescribed for pregnancy-induced hypertension.

Mechanism:

Work centrally to reduce sympathetic flow. The target receptors (probably not A2 and 11) reside in the vasomotor nucleus of the lake brain that projects to the body of sympathetic granule cells  in the spinal cord. All of which, at one point, led to rebellion and many disappointments.

Adverse reaction:

• Rebound hypertension - missed dose followed

• Rebound hypertension - greatest risk with CLONIDINE and least with MOXONIDINE

• Dry Mouth - CLONIDINE >> MOXONIDINE

• In 20% of patients with hemolytic anemia methyl DOPA tested positive comb with only 1% of hemolysis.

Alpha blockers:

Examples: doxazosin, Terazosin,Doxazosin,Phentolamine,Phenoxybenzamide

Mechanism of action:

Anti-competitive 1-receptor antagonists, resulting in anterior vasodilatation.

Adverse effect:

• Postural hypotension

• Nasal stuffiness – similar side effect to a –methyl-DOPA.

• Ejaculatory failure

• Detrusor relaxation – may alleviate outflow obstruction in men (with BPH) or precipitate urinary incontinence in women

NB: Phenoxybenzamine differs from other alpha blockers in acting as irreversible (and relatively obsolete) receptor antagonists. It is used only in patients with PHAEOCHROMOCYTOMA, where competitive blockade may exceed catecholamine levels.

Beta blockers:

With respect to:

• Relative selection for B1 compared to B2 receptors

• Lipid solubility

• Understanding sympathetic activity

• Membrane stabilizing activity Example:Propanolol,Metoprolol,Atenolol

These features are not important except the following:

• Selective agent is less likely to have worsening of peripheral vascular disease or reduced awareness of hypoglycemia in diabetes.

• Lipid-soluble beta-blockers enter the CNS and are commonly associated with sleep disturbances / nightmares.

• ISA deficient agents may be more effective in preventing angina and preventing migraine attacks.

Mechanism of action (chronic dose):

• Inhibition of beta-receptor-mediated renin release

• Increased Barceptor Sensitivity

• Reducing noradrenaline release by blockade of presynaptic B-receptors

•

Adverse effect:

• Worsening bronchoconstriction – even with 1 selective agents

• Worsening of heart failure

• Cardiac conduction defects

• Worsening peripheral vascular disease

• Loss of awareness of hypoglycaemia

• Exercise related fatigue

Thiazide diuretic:

Thiazides are the cheapest agent and contain long-term death data for the prevention of heart and cerebrovascular disease.

Example:Hydrochlorothiazide,chlorthalidone.

Mechanism of action:

• The loop is however neuronetic compared to diuretics. Most patients show little or no decrease in conventional doses when given for a long time.

• Reduce resistance vessels in intravenous vasoconstriction

for example.  Noradrenaline.  This may be neither due to intracellular (and therefore CA) or the effects of unknown membrane ion channels.

Adverse effect:

• Impairment of glucose tolerance

• Adverse effect on lipid profile

• Raised blood urate and risk of gout

• Tendency to hypokalaemia

• Impotence

• Photosensitive rashes.

Angiotensin converting enzyme inhibitors (ACEI)

For example lisinopril and captopril with long and short duration sequences. Process of action

1. Actively inhibiting the enzyme responsible for converting angiotensin I biologically ingested into angiotensin II (ATII)

2. ACII also inhibits the degradation of kinase (kinase II = ACE). Bradkin is a powerful vasodilator.

Adverse effect:

• Dry cough - affects 20% of patients; Improvement in BK levels is common in women  and surrounding airway C fibers.

• Angioporotic inflammation - rare but fatal when laryngeal involvement occurs (common in Afro-Caribbean).

• Changed flavors - older agents only - SH groups such as captopril.

• Risk of hypercalcemia

• Impairment of renal function in patients with renal artery stenosis - AIII-dependent glomerular perfusion.

• First dose hypotension - only if plasma renin is elevated (eg DS follow loop diuretics), then hypertension is usually not a problem with CCF.

NB: Angiotensin receptor antagonists (such as Larsartan, IRBisartan) also act on the renin- angiotensin axis but block 1 receptors. They can alter ACII in both hypertension and heart  failure.

• For any indication, no outcome data exist with these AT1 receptor antagonists

• He is currently licensed to be used for hypertension and for heart failure.

• They tolerate better than ACEI - they do not cough.

• They may be superior to ACI due to the regression of LVH due to stimulation of antiproliferative AT2 receptors.

•

Calcium channel blockers: Example:Verapamil,diltiazem,Nifidipine,Felodipine,Amlodipine. Classification:

• Dehydropyridines (DHP) - Nifedipine, Amlodipine

• Non-dehydropyrimidines (non-DHP) - daltizem, verapamil.

Mechanism of action:

The voltage gated L-type (for large / chronic current) of vascular smooth muscle cells and cardiac myocytes inhibits the passage of calcium through the calcium channel, reducing the availability of calcium for muscle contraction. Note that the inhibitor of the T-type (transient current) cardiac calcium channel, MIBFRDIL, has recently been abolished due to unacceptable drug interactions. The ion channel describes the blockade monitoring.

• Peripheral vasodilation

• Negative inotropic and negative chronotropic effects.

Adverse effects:

• Flushing

• Headache

• Palpitations - reflecting the reflex tachycardia in response to vasodilatation.

• Pedal oedema – dilatation of the precapillary 'sphincters' NOT generally a reflection of worsening heart failure.

• May worsen heart failure due to their negative inotropic effect.

These effects are most commonly known when absorption causes rapid process vasomotor reactions; Especially with Nifedipine's early 'instant' release formulas. These problems clearly reduce the onset of recession (eg. AMLODIPINE) or correction agents in preparation for 'sustained' release.

Most agents are negatively inotropic - D-DHP CCB more than DHP amlodipine is exceptional in having a 'neutral' inotropic effect and is well tolerated in heart failure (value studies).

NB: Non-DHP also has AV nodal blocking properties (verapami> diltizem) that cause any reflex tachycardia. They may also interact with other agents affecting conduction: beta-blockers should be cautiously combined with verapamil.

SOME ANTIHYPERTENSIVE COMBINATION:

1. Amlodipine 5 mg + Lisinopril 5 mg

2. Amlodipine 5 mg + Atenolol 50 mg

3. Amlodipine 5 mg Enalapril 5 mg

4. Atenolol 25 mg or 50 mg + chlorthalidone 12.5 mg

5. Enalapril 10 mg + Hydrochlorothiazide 25 mg

6. Ramipril 2.5 mg + Hydrochlorothiazide 12.5 mg

7. Losartan 50 mg + Hydrochlorothiazide 12.5 mg

8. Lisinopril 5 mg +Hydrochlorothiazide 12.5 mg

9. Losartan 50 mg + Ramipril 2.5 mg or 5 mg

10. Losartan 50 mg + Amlodipine 5 mg

11. Losartan 50 mg +Ramipril 2.5 mg +ydrochlorothiazide 12.5 mg

12. Irbesartan 150 mg + Hydrochlorothiazide 12.5 mg

Why should pharmacists be involved in hypertension management?

Advantage:

More than 200 million people visit the pharmacy every day in Europe. A community pharmacist is a highly trained professional who is seen in an informal setting without an appointment that is often considered part of the daily experience. Therefore pharmacists are the most accessible members of the primary health team. Pharmacists in the community are visited by sick people and people in good health. Community pharmacies therefore have the potential to promote health and prevent disease. Regular visits of a person suffering from hypertension to prescribed drug therapy place the patient in regular contact with the pharmacist and allow him to intervene. Pharmacists can supplement GPs in hypertension management in a number of ways (7-10).Below are examples of opportunities where pharmacists participate in community-based health promotion and disease prevention and management programs with other health care professionals.

• Pharmacists have extensive knowledge of drug therapy, drug use and prevention policies.

• The pharmacy can validate and improve patients' knowledge about lifestyle changes and drug use and improve adherence to therapy.

• Pharmacists can identify problems related to drug therapy and suggest possible solutions, including referral to GPs.

• Pharmacists may monitor treatment outcomes for hypertension management.

Adherence long-term treatment:

Pharmaceutical care is an effective way to improve adherence to long-term treatment Counselling, information, and referral by community pharmacists have been shown to significantly improve adherence to antihypertensive therapy and improve coagulation pressure.

Pharmacists are also involved in providing information and services to patients with hypertension. It has been found that after providing appropriate health education and monitoring services to patients with hypertension, primary care pharmacists have enabled patients to use less expensive antihypertensive drugs. Hypertensive parents seek medication care from community pharmacies for advice and recommendations to consult GPs on drug therapy. In several studies, the intervention group showed a significant decrease in mean blood pressure.

Pharmacist involvement in the management of hypertension is consistent with good pharmacy practice documents created and adopted by the Pharmaceutical Group (PGU) of the European Union in 1994. It is the first set of standards for pharmacy practice developed by professionals and with international standards for good pharmacy practice (GPP) in a community and hospital pharmacy setting developed by WHO. The first component of good pharmacy practice is to promote health and prevent ill health and according to the document many national standards are to be interpreted in this area. Currently, new programs involving community pharmacies in Good Pharmacy Practice programs or Pharmaceutical Care programs are being developed and launched.  Some medium-term results from Portugal, Spain, and the United Kingdom suggest  that community pharmacists are able to optimize drug treatment and provide pharmaceutical care for optimal outcomes to achieve more cost-effective output.

Many patients with diabetes mellitus and hypertension did not receive a definition of hypertension in 2003, according to the guidelines, with 47% not being treated with antihypertensive drugs. Reducing the cut point to define hypertension has increased the proportion of sufferers substantially. Specific risk factors may help identify patients at high risk for inadequate treatment. Resolving these issues requires patient and provider education, public health approaches, and changes in the health system. Further work needs to be done to determine the reasons for the 2003 Guidelines for Lack of Control, Improvement of Control and Long Term Patient Outcomes and to determine the effectiveness and cost effectiveness of budgets.

Hypertension is an additional risk factor for people with diabetes mellitus in macrovascular and microvascular complications. The health and budget implications of addressing treatment gaps need to be further explored.

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