Questions

Outline the objectives to be achieved at the end of the discussion of this case
❖ Identify medication related problems.
❖ Describe the clinical presentation of hypertension.
❖ Assess and evaluate the causative factors of hypertension.
❖ Discuss the diagnostic features of hypertension..
❖ Discuss and implement the pharmacological and non-pharmacological approach to managing hypertension.
❖ Develop a treatment plan including monitoring for both the positive and negative outcomes.

2 Create a list of health and medicines therapy problems for this patient.
 Pseudoephedrine HCl 30mg tablets
 Food condition interactions
 owever, NSAIDs can make your body retain fluid and decrease the function of your kidneys. This may cause your blood pressure to
rise even higher, putting greater stress on your heart and kidneys. NSAIDs can also raise your risk for heart attack or stroke,
especially in higher doses. The mechanism of action of ibuprofen involves inhibition of the enzyme cyclooxygenase, thereby
inhibiting the synthesis of inflammatory prostaglandins and vasodilatory prostaglandins that increase renal blood flow and thus favor
the excretion of water and sodium
 She reports that she used to smoke a packet of cigarettes per month but quit 10 years ago. She drinks 2 glasses of alcohol during the
weekend.
 Decongestants (pseudoephedrine, phenylephrine)
 Nonsteroidal anti-inflammatory drugs—cyclooxygenase-2 selective (celecoxib) and nonselective (aspirin [at higher doses], choline
magnesium trisalicylate, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac,
meclofenamate, efenamic acid, meloxicam, nabumetone, naproxen sodium, oxaprozin, piroxicam, salsalate, sulindac, tolmetin)
 If you were to collect additional information from the patients, what would it be?
Duration – minutes / hours / days / weeks / months / year

 Chest pain – SOCRATES

 Dyspnoea – exertional / orthopnea / paroxysmal nocturnal dyspnoea
 Palpitations – ask patient to tap out the rhythm 
 Syncope / dizziness – postural / exertional / random
 Oedema – peripheral oedema (e.g. lower limbs) / sacral oedema
 Intermittent claudication – e.g. leg pain worsened on exertion / improved at rest
 Systemic symptoms – fatigue / fever / weight loss / weight gain

Hyperlipidaemia, Drug history, Herbal remedies , Family history, Cardiovascular disease at a young age 

Living situation:

House/bungalow? – adaptations / stairs 

 Who lives with the patient? – is the patient supported at home?
 Any carer input? – what level of care do they receive?

Activities of daily living:

 Is the patient independent and able to fully care for themselves?

 Can they manage self hygiene / housework / food shopping?

Occupation – sedentary jobs –  ↑ cardiovascular risk  – e.g. lorry driver

Stress levels - occupational and others.

 Occupation: establish whether this is sedentary or active and, if the latter, how active.

4 a) How is HTN classified and how would you classify this patient’s HTN?

TABLE 13-3 Classification of Blood Pressure in Adults (Age ≥18 Years)a

Classification Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg)

Normal <120 and <80

Prehypertensionb 120-139 or 80-89

Stage 1 hypertension 140-159 or 90-99

Stage 2 hypertension ≥160 or ≥100

Stage 2vhypertension

Adapted AHA/ACC Hypertension Guidelines, 2017

4b. What are the features of target organ damage in hypertension and which ones is this patient presenting with?

The classic manifestations of hypertensive end organ damage include the following: vascular and hemorrhagic stroke, retinopathy, coronary
heart disease/myocardial infarction and heart failure, proteinuria and renal failure and in the vasculature, atherosclerotic change including the
development of stenosis

Hypertension-related complications: The patient may have a previous medical history or diagnostic findings that indicate the presence of
hypertension-associated complications: Brain (stroke, transient ischemic attack, dementia)

Eyes (retinopathy)
Heart (left ventricular hypertrophy [LVH], angina, prior MI, prior coronary revascularization, heart failure)

Kidney (chronic kidney disease [CKD])

Peripheral vasculature (peripheral arterial disease [PAD])

Urinalysis: proteinuria, She dies chest pains, decreased urine output, blurred vision , Arteriovenous nicking

ECG: Normal sinus rhythm, left atrial enlargement, LVH

What factors contribute to uncontrolled HTN and which ones is this patient presenting with? i.e. what are the risk factors for HTN?
Age (greater than or equal to 55 years for men, greater than or equal to 65 years for women)
Diabetes (type 1 or type 2)
Dyslipidemia
Albuminuria
Family history of premature CV disease
Overweight (body mass index [BMI] 27-29.9 kg/m2) or Obesity (BMI greater than or equal to 30 kg/m2)
Physical inactivity
Tobacco use

Results showed that elderly, living in rural and suburban areas, low education level, family history of hypertension, smoking, excessive salt
consumption, lack of physical activity, overweight, obese and diabetes were associated with uncontrolled hypertension

.Discuss the etiology and pathophysiology of HTN?

ETIOLOGY

In most patients, hypertension results from unknown pathophysiologic etiology (essential or primary hypertension).

This form of hypertension cannot be cured, but it can be controlled. A small percentage of patients have a specific

cause of their hypertension (secondary hypertension). There are many potential secondary causes that either are
concurrent medical conditions or are endogenously induced. If the cause can be identified, hypertension in these

patients can be mitigated or potentially be cured

Essential Hypertension
Genetic factors may play a role in the development of essential hypertension by

affecting sodium balance, or other BP regulating pathways. In the future, genetic testing for these traits could lead

to alternative approaches to preventing or treating hypertension. However, this is not currently recommended

Secondary Hypertension

a comorbid disease or a drug (or other

product) is responsible for elevating BP (Table 13-1).1,6 In most of these cases, renal dysfunction resulting from

severe chronic kidney disease (CKD) or renovascular disease is the most common secondary cause. Certain drugs

(or other products), either directly or indirectly, can cause hypertension or exacerbate hypertension by increasing

BP. The most common agents are listed in Table 13-1. When a secondary cause is identified, removing the

offending agent (when feasible) or treating/correcting the underlying comorbid condition should be the first step

TABLE 13-1 Secondary Causes of Hypertension

Disease Drugs and Other Products Associated with Hypertensiona

Chronic kidney disease Cushing’s syndrome Coarctation of the aorta Prescription drugs Amphetamines (amphetamine, dexmethylphenidate,
dextroamphetamine, lisdexamfetamine, methylphenidate, phendimetrazine, phentermine) Antivascular endothelin growth factor agents
 (bevacizumab, sorafenib, sunitinib) Corticosteroids (cortisone, dexamethasone, fludrocortisone, hydrocortisone, Disease Drugs and Other
Products Associated with Hypertensiona Obstructive sleep apnea Parathyroid disease Pheochromocytoma Primary aldosteronism Renovascular
disease Thyroid disease methylprednisolone, prednisolone, prednisone, triamcinolone) Calcineurin inhibitors (cyclosporine, tacrolimus)
Decongestants (pseudoephedrine, phenylephrine) Ergot alkaloids (bromocriptine, dihydroergotamine, methysergide) Erythropoiesis-stimulating
agents (erythropoietin, darbepoetin) Estrogen-containing oral contraceptives Nonsteroidal anti-inflammatory drugs—cyclooxygenase-2 selective
(celecoxib) and nonselective (aspirin [at higher doses], choline magnesium trisalicylate, diclofenac,diflunisal, etodolac, fenoprofen, flurbiprofen,
ibuprofen, indomethacin, ketoprofen,ketorolac, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen,naproxen sodium,
oxaprozin, piroxicam, salsalate, sulindac, tolmetin)Others: desvenlafaxine, venlafaxine, bupropionSituations: β-blocker or centrally acting α-
agonists (when abruptly discontinued);β-blocker without α-blocker first when treating pheochromocytoma; use of amonoamine oxidase inhibitor
(isocarboxazid, phenelzine, tranylcypromine) withtryamine-containing foods or certain drugsStreet drugs and other products Cocaine and
cocaine withdrawal Ephedra alkaloids (eg, Ma huang), “herbal ecstasy,” other analoguesNicotine and withdrawal, anabolic steroids, narcotic
withdrawal, ergot-containing herbal products, St. John’s wort Food substances Sodium Ethanol Licoricea Agents of most clinical importance.

PATHOPHYSIOLOGY

Multiple factors that control BP are potential contributing components in the development of essential hypertension. These include malfunctions
in either humoral (ie, the renin–angiotensin–aldosterone system [RAAS]) or vasodepressor mechanisms, abnormal neuronal mechanisms, defects
in peripheral autoregulation, and disturbances in sodium, calcium, and natriuretic hormones. Many of these factors are cumulatively affected by
the multifaceted RAAS, which ultimately regulates arterial BP. It is probable that no one factor is solely responsible for essential hypertension

Arterial BP is the pressure in the arterial wall measured in millimeters of mercury (mm Hg). The two identified arterial BP values are systolic BP
(SBP) and diastolic BP (DBP). SBP represents the peak value, which is achieved during cardiac contraction. DBP is achieved after contraction
when the cardiac chambers are filling, and represents the nadir value. The difference between SBP and DBP is called the pulse pressure and is a
measure of arterial wall tension. Mean arterial pressure (MAP) is the average pressure throughout the cardiac cycle of contraction. It is sometimes
used clinically to represent overall arterial BP, especially in hypertensive emergency. During a cardiac cycle, two-thirds of the time is spent in
diastole and one third in systole. Therefore, the MAP is calculated by using the following equation:

Pathogenesis of Essential Hypertension

The pathogenesis of essential hypertension is multifactorial and highly complex. The kidney is both the contributing and the target organ of the
hypertensive processes, [1] and the disease involves the interaction of multiple organ systems and numerous mechanisms of independent or
interdependent pathways. Factors that play an important role in the pathogenesis of hypertension include genetics, activation of neurohormonal
systems such as the sympathetic nervous system and renin-angiotensin-aldosterone system, obesity, and increased dietary salt intake.
Arterial hypertension is the condition of persistent elevation of systemic blood pressure (BP). BP is the product of cardiac output and total
peripheral vascular resistance. Multiple factors are involved in short-term and long-term regulation of BP for adequate tissue perfusion; these
include the following:
 Cardiac output and circulatory blood volume
 Vascular caliber, elasticity, and reactivity
 Humoral mediators
 Neural stimulation
Over the course of its natural history, essential hypertension progresses from occasional to established hypertension. After a long, invariable,
asymptomatic period, persistent hypertension develops into complicated hypertension, in which target organ damage to the aorta and small
arteries, heart, kidneys, retina, and central nervous system is evident.
How is HTN diagnosed?

Measuring BP

The measurement of BP is a common routine medical screening tool that should be conducted at every healthcare

encounter.1

Cuff Measurement

The most common procedure to measure BP in clinical practice is the indirect measurement of BP using an oscillometric device or
sphygmomanometry

 Blood pressure is measured using a blood pressure cuff, which is a non-invasive device that can detect the pressure inside your arteries,
conveying numerical values using a sphygmomanometer or an electronic device

Blood Tests:Blood tests may be needed to determine if you have secondary hypertension due to a serious or treatable health condition.5 Blood
tests that may be ordered to assist in the diagnosis of hypertension include:

 Electrolyte levels
 Blood glucose 
 Thyroid function tests
 Kidney function tests: blood urea nitrogen (BUN) and creatinine levels
Urine Tests Urine tests can help determine if diabetes, kidney failure, or illegal drugs are causing or contributing to high blood pressure

Electrocardiogram (EKG)

An EKG is a fairly simple and rapid test that assesses your heart rhythm. Heart rhythm abnormalities can cause high blood pressure.
Likewise, hypertension can produce long-term changes that result in heart rhythm abnormalities. 

Echocardiogram

Your heart function can be examined using an imaging test that visualizes your heart as it moves. Excessively high blood pressure may produce
changes that can be identified using echocardiography, and some heart function abnormalities can produce high blood pressure. 

Ultrasound

A test that is useful for evaluating the kidneys and the blood vessels, an ultrasound may be needed if your doctor is concerned about certain
aspects of your blood flow. For example, if your doctor believes that you may have excessive narrowing in one or more of your blood vessels,
this can be evaluated using an ultrasound. 

What is the general approach to management of HTN? i.e.

Develop the goals of management of HTN

The overall goal of treating hypertension is to reduce associated morbidity and mortality from CV events (eg, coronary events, cerebrovascular
events, heart failure, kidney disease). Therefore, the specific selection of antihypertensive drug therapy should be based on evidence
demonstrating CV event reduction
The overall goal of treatment in hypertensive patients is to reduce the risk of cardiovascular morbidity and mortality by lowering BP and treating
other modifiable risk factors. In general, the goal is to lower BP to below 140/90 mm Hg. In patients with heart failure, diabetes, or renal disease,
the goal is to lower BP to below 130/85 mm Hg (Table II). In older patients with isolated systolic hypertension (ISH), the goal is to lower
systolic BP to below 140 mm Hg.

CLINICAL PRESENTATION Desired Outcomes: Goal BP Values Most patients, including diabetes and/or CKD and the elderly less than
140/90 mm Hg Frail elderly at high risk for serious adverse effects less than 150/90 mm Hg Certain Patients with lower goals as a therapeutic
option (not a standard of care) Some patients with diabetes (eg, younger patients), less than 130/80 mm Hg may be an option if achieved without
undue treatment burden Some patients with CKD (nondialysis) who have persistent urine albumin excretion of greater than 30 mg per 24 hours
(or equivalent), less than 130/80 mm Hg may be an option if achieved without undue treatment burden Some patients greater than 50 years at
increased risk of CV disease (one or more risk factors including clinical or subclinical CVD other than stroke, CKD with eGFR 20-60
mL/min/1.73m2, 10-year risk of CVD greater than or equal to 15%, greater than or equal to 75 years) but without diabetes, may consider SBP
goal less than 120 mm Hg

Explain the non-pharmacological approach to management of HTN.

The Dietary Approaches to Stop Hypertension (DASH) eating plan is a diet that is rich in fruits, vegetables, and low-fat dairy products with a
reduced content of saturated and total fat. It is recommended as a reasonable and feasible diet that has proven to lower BP. Intake of sodium
should be minimized as much as possible, ideally to 1.5 g/day, although an interim goal of less than 2.3 g/day may be reasonable considering the
difficulty in achieving these low intakes. Patients should be aware of the multiple sources of dietary sodium (eg, processed foods, soups, and
table salt) so that they may follow these recommendations. Potassium intake should be encouraged through fruits and vegetables with high
content (ideally 4.7 g/day) in those with normal kidney function or without impaired potassium excretion. Excessive alcohol use can either cause
or worsen hypertension. Patients with hypertension who drink alcoholic beverages should restrict their daily intake.

Aerobic physical activity consisting of 3 to 4 sessions per week, lasting on average 40 minutes per session, and involving moderate- to vigorous-
intensity physical activity should be encouraged when possible. Studies have shown that aerobic physical activity can reduce BP, even in the
absence of weight loss. Patients should consult their physicians before starting an exercise program, especially those with hypertension-
associated complications.

Cigarette smoking is not a secondary cause of essential hypertension. Therefore, smoking cessation is not a recommended strategy to control BP.
Smoking is a major, independent, modifiable risk factor for CV disease. Patients with hypertension who smoke should be counseled regarding
the additional health risks that result from smoking. Moreover, the potential benefits that cessation can provide should be explained to encourage
cessation.

Reduced salt intake

Evidence from animal studies, epidemiological studies, clinical trials, and meta-analyses suggests that with increase in dietary salt (sodium
chloride) intake, BP also rises. The most persuasive evidence about the effects of salt on BP comes from rigorously controlled, dose response
trials Each of these trials tested sodium levels and documented significant relationships. The largest of the dose response trials, the DASH-
Sodium trial, tested the effects of 3 different doses of sodium intakes separately in two distinct diets: the DASH diet and a control diet (more
typical of what Americans eat). BP reduction was the highest in the group with the lowest sodium levels. In addition, clinical trials have
documented that a reduced sodium intake can prevent hypertension (relative risk reduction of about 20% with or without concomitant weight
loss), can lower BP in the setting of antihypertensive medication, and can facilitate hypertension control In observational studies, reduced
sodium intake is associated with a blunted age-related rise in systolic BP. In other observational studies, reduced salt intake is associated with a
reduced risk of atherosclerotic cardiovascular events and congestive heart failure.

The BP response to differences and changes in intake of dietary sodium intake is heterogeneous (as is the BP response to other dietary changes).
Despite use of the terms “salt sensitive” and “salt resistant” to classify individuals in research studies, the change in BP in response to a change
in salt intake is not binary. Rather, the reduction in BP from a reduced sodium intake has a continuous distribution, with individuals having
greater or lesser degrees of BP reduction In general, the effects of sodium reduction on BP tend to be greater in blacks; middle-aged and older
persons; and individuals with hypertension, diabetes, or chronic kidney disease. In Indian arm of the international INTERSALT study, response
of Indian subjects to dietary sodium was no different from other groups

The Indian Council of Medical Research (ICMR) recommends 1.5 g/d (65 mmol/d) sodium as an adequate intake level, primarily to ensure
nutrient adequacy. Although a sodium intake below this level is associated with lower BP, little information is available about the nutrient
content of diets that provide <1.5 g/d of sodium. From the DASH-Sodium trial, it is apparent that western-type diets can provide this level of
sodium intake and that such a diet can also provide adequate levels of other nutrients. Because the relationship between sodium intake and BP is
direct and progressive without an apparent threshold, it is difficult to set an upper level of sodium intake, which could be 65 mmol/day (4 g salt).
However, in view of the available food supply and the currently high levels of sodium consumption, a reduction in sodium intake to 65 mmol
daily is not easily achievable. In the interim, a reasonable recommendation is an upper limit of 100 mmol of sodium equivalent to 6 g common
salt/day. In aggregate, available data strongly support current, population-wide recommendations to lower salt intake. To reduce salt intake,
people should choose foods low in salt and limit the amount of salt added to food. However, because >75 per cent of consumed salt in India
comes from home cooked foods, any meaningful strategy to reduce salt intake must involve public education to change consumption In view of
the escalating influence of food industry in India focus should also be on the food manufacturers and restaurants, which should progressively
reduce the salt added to foods by 50 per cent.

Increased potassium intake

High potassium intake is associated with reduced BP. Although data from individual trials have been inconsistent, three meta-analyses of these
trials have documented a significant inverse relationship between potassium intake and BP in non-hypertensive and hypertensive individuals21. In
the meta-analysis by Whelton et al30 average systolic and diastolic BP reductions associated with increase in urinary potassium excretion of 2 g/d
(50 mmol/d) were 4.4 and 2.5 mm Hg in hypertensive and 1.8 and 1.0 mm Hg in non-hypertensive individuals. Available data suggest that
increased potassium has beneficial effects on BP in the setting of salt intake that is low. Potassium reduces BP to a greater extent in blacks than
in whites. A study from India reports similar BP reduction with potassium supplementation as observed in the Caucasian whites31.
Because a high potassium intake can be achieved through diet rather than pills and because potassium derived from foods is also accompanied
by a variety of other nutrients, the preferred strategy to increase potassium intake is to consume foods such as fruits and vegetables rich in
potassium, rather than supplements. In the DASH trial, the two groups that increased fruit and vegetable consumption both lowered BP.22 In the
generally healthy population with normal kidney function, a potassium intake from foods >4.7 g/d (120 mmol/d) poses no risk because excess
potassium is readily excreted in the urine. However, in individuals whose urinary potassium excretion is impaired, a potassium intake <4.7 g/d
(120 mmol/d) is appropriate because of adverse cardiac effects from hyperkalaemia. Common drugs that can impair potassium excretion are
ACE inhibitors, ARBs, nonsteroidal antiinflammatory agents, and potassium-sparing diuretics. Medical conditions associated with impaired
potassium excretion include diabetes, chronic renal insufficiency, end-stage renal disease, severe heart failure, and adrenal insufficiency. Elderly
individuals are at increased risk of hyperkalaemia because they often have one or more of these conditions or take one or more medications that
impair potassium excretion.

Moderation of alcohol intake

Observational studies and clinical trials have documented a direct, dose-dependent relationship between alcohol intake and BP, particularly
when the intake of alcohol increases above 2 drinks per day32. Importantly, this relationship has been shown to be independent of potential
confounders such as age, obesity, and salt intake. A recent meta-analysis of 15 randomized controlled trials reported that decreased consumption
of alcohol reduced systolic and diastolic BP by 3.3 and 2.0 mm Hg, respectively33. BP reductions were similar in non-hypertensive and
hypertensive individuals. Available evidence supports moderation of alcohol intake (among those who drink) as an effective approach to lower
BP. Alcohol consumption should be limited to ≤ 2 alcoholic drinks per day in most men and ≤1 alcoholic drink per day in women and lighter-
weight persons. Note that one drink is defined as 360 ml of regular beer, 150 ml of wine (12% alcohol), and 45 ml of 80-proof distilled spirits.

Increase in fibre, fruits and vegetables

Dietary fibre consists of the indigestible components of food from plants. Evidence from observational studies and several clinical trials suggests
that increased fibre intake may reduce BP13. More than 40 randomized trials of dietary fibre supplementation have been conducted21. Still, most
did not have BP as their primary outcome, and many had a multicomponent intervention. A meta-analysis of these trials, restricted to the 20
trials that increased just fibre intake, documented that supplemental fibre (average increase, 14 g/d) was associated with net systolic and diastolic
BP reductions of 1.6 and 2.0 mm Hg, respectively34. Overall data are insufficient to recommend an increased intake of fibre alone as a means to
lower BP. Similarly, high fruit and vegetable intake have been reported to lower BP in small trials but no large study has demonstrated BP
lowering effects independent to overall dietary changes16,21.
Dietary factors of limited or uncertain effects
Many dietary factors have been evaluated for influence on hypertension control. These include dietary fish oil supplementation, fats other than
omega-3 fatty acids, calcium, magnesium, carbohydrates and proteins. Although there are studies supporting their role in BP control, robust
scientific evidence from randomized trials is lacking21. These factors should, therefore, be considered as of limited or no major importance.

Comprehensive diet management

Multiple dietary factors are involved in hypertension and it is reasonable that a comprehensive dietary management would be the best approach
to manage hypertension and to reduce overall cardiovascular risk.

DASH and related dietary patterns

Dietary Approaches to Stop Hypertension (DASH) was a program by the National Institutes of Health, USA16,22,35. This series of three large
controlled trials tested the effects of dietary patterns on BP. The first trial was a randomized feeding study that compared 3 dietary patterns16. Of
the 3 diets studied, the most effective diet, now called the DASH diet, emphasized fruits, vegetables, and low-fat dairy products; included whole
grains, poultry, fish and nuts; and was low in fats, red meat, sweets, and sugar-containing beverages. Accordingly, it was rich in potassium,
magnesium, calcium, and fiber and was low in total fat, saturated fat, and cholesterol; it also was slightly high in protein. It is likely that several
aspects of the diet, rather than just one nutrient or food, reduced BP. Among all participants, the DASH diet significantly lowered mean systolic
BP by 5.5 mm Hg and mean diastolic BP by 3.0 mm Hg. A second diet, which emphasized just fruits and vegetables also significantly reduced
BP but to about half of the effect of the DASH diet22. The effects of DASH diet were significantly greater in the black participants (systolic and
diastolic BP reductions of 6.9 and 3.7 mm Hg) than in whites (3.3 and 2.4 mm Hg)35. The effects in hypertensive individuals (systolic and
diastolic BP reductions of 11.6 and 5.3 mm Hg) were striking and were significantly greater than the corresponding effects in non-hypertensive
individuals (3.5 and 2.2 mm Hg).
The OmniHeart trial36 compared the effects of 3 healthy dietary patterns: a diet rich in carbohydrate (58% of total calories), a second diet rich in
protein (about half from plant sources), and a third diet rich in unsaturated fat (predominantly monounsaturated fat). Similar to the DASH diet,
each of the OmniHeart diets was low in saturated fat and cholesterol and rich in fruit, vegetables, fiber, potassium, and other minerals.
Substituting some of the carbohydrate (10% of total calories) with either protein (about half from plant sources) or unsaturated fat (mostly
monounsaturated fat) further lowered BP. The DASH diet and the diets studied in the OmniHeart trial are safe and broadly applicable to the
general population. However, because of their relatively high potassium and phosphorus content (in all diets) and high protein content (in the
DASH diet and the protein-rich diet in OmniHeart), these diets are not recommended in persons with chronic kidney disease.
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The Indian vegetarian diet
Vegetarian diets have been associated with low BP. In industrialized countries individuals who consume a vegetarian diet have markedly lower
BP than do nonvegetarians37.Vegetarians also experience a lower age-related rise in BP. Some of the lowest BP observed in developed countries
are documented in strict vegetarians. Several aspects of a vegetarian lifestyle might lower BP, including nondietary factors (e.g., physical
activity), established dietary risk factors (e.g., low weight, high potassium, and low-to-moderate alcohol intake), and other aspects of vegetarian
diets (e.g., high fibre, no meat). Limited trial evidence, indicates that non-dietary factors and established dietary risk factors are not fully
responsible for the BP-lowering effects of vegetarian diets and that some other aspects of vegetarian diets lower BP.
In India, diets in many rural and urban populations are predominantly vegetarian38,39. BP levels are also lower in these subjects15. Large studies
that have evaluated comprehensive dietary patterns with BP levels are not available from India. Chhajer et al40 have modified the Ornish
diet41 into low-fat Indian vegetarian diet and reported significant reductions in multiple cardiovascular risk factors including BP42. Importance of
comprehensive dietary change in prevention and management of high BP among Indians has been highlighted28,29,43. Larger controlled
interventional studies are needed to confirm superiority of a particular type of Indian vegetarian diet over other similar diets as in India many
“healthy” diets are prevalent38.
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Weight management
A substantial and consistent body of evidence from observational studies and clinical trials shows that weight is directly associated with BP13.
The importance of this relationship is reinforced by the high and increasing prevalence of overweight and obesity throughout the world as well
as India44. Approximately 30-35 per cent or urban Indian adults have a body mass index (BMI) ≥ 25 kg/m2 and, therefore, are classified as either
overweight or obese45 and there is a significant correlation of increasing body weight with hypertension46.
With rare exception, clinical trials have documented that weight loss lowers BP. Importantly, reductions in BP occur before, and without,
attainment of a desirable body weight. In one meta-analysis that aggregated results across 25 trials, mean systolic and diastolic BP reductions
from an average weight loss of 5.1 kg were 4.4 and 3.6 mm Hg, respectively47. Additional trials have documented that modest weight loss, with
or without sodium reduction, can prevent hypertension by about 20 per cent among overweight, prehypertensive individuals and can facilitate
medication step-down and drug withdrawal18–21. Thus, available evidence strongly supports weight reduction- attainment of a BMI <25 kg/m2 or
even <23 kg/m2 in Indians- as effective approach to prevent and treat hypertension. More importantly, in view of the well-recognized difficulties
of sustaining weight loss, efforts to prevent weight gain among those who have normal body weight are critically important. Central or truncal
obesity is also a major hypertension risk factor in Indians48. Maintaining a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2,
preferably < 23.0 kg/m2) and waist circumference (<90 cm in men and < 80 cm in women) is therefore recommended.
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Smoking and tobacco intake

Smoking as a hypertension risk factor is not well defined. In western countries epidemiological studies have reported that smokers tend to have
lower BP than non-smokers49. This is partly accounted for by the fact that smokers tend to be less obese, effect of white coat hypertension is less
pronounced in these subjects and usually BP is recorded after abstaining. Ambulatory BP measurements, however, show that the BP of smokers
tends to be greater than non-smokers. The effect of smoking on hypertension in less obese subjects of developing countries has not been well
studied50. In a predominantly bidi smoking population in India we reported that mean systolic BP was significantly greater among men who
smoked (rural 127.4 ± 14 vs 125.9 ± 14 mm Hg; urban 126.9 ± 16 vs 123.7 ± 16 mm Hg, P<0.01)51. The relative risk of hypertension (95% CI)
in rural males among mild smokers (1.30, CI 1.00-1.69), moderate smokers (1.39, CI 1.16-1.66) and heavy smokers (1.55, CI 1.03-2.33) was
significant. Similar trends were observed in urban men51. Many other epidemiological studies from India have reported significant association of
smoking and hypertension50. Multiple pathophysiological mechanisms explaining smoking with high BP have been postulated49. Smoking is one
of the more important cardiovascular risk factor in India52 and smoking cessation and tobacco control must be an important initial strategy to
reduce hypertension as well as overall cardiovascular risk.
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Physical activity
Several large epidemiological studies have reported an inverse relationship between BP and physical activity13. Longitudinal intervention studies
are more appropriate for assessing the effects of physical activity. In a meta-analysis of randomized controlled trials it was reported that aerobic
exercise was associated with a significant reduction in mean systolic (-3.84 mm Hg) as well as diastolic BP (-2.58 mm Hg)53. This reduction was
observed in hypertensive as well as normotensive individuals and in normal weight as well as overweight participants. On the other hand in
another meta-analysis involving 72 trials with 105 study groups, significant reduction in daytime and ambulatory BP was observed, more in
hypertensive groups (-6.9/-4.9 mm Hg) than in other groups (-1.9/-1.6, P<0.01)54. The reduction was associated with decrease in systemic
vascular resistance, plasma norepinephrine, plasma rennin activity, body weight, waist size, per cent body fat and insulin resistance. Usefulness
of dynamic and static resistance training in BP management is controversial. Regular moderate physical activity is recommended by all the
guidelines for BP management13 and at least 30 min of moderate physical activity on all days of the week is suggested.
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Yoga and stress management
The role of yogic practices in BP management is controversial. Yogic practices have been reported to reduce BP and multiple cardiovascular risk
factors in many studies from India55. From UK, Patel et al56 reported long-term benefit of yoga in reducing coronary risk but a randomized trial of
relaxation therapy and meditation in the Netherlands failed to show any benefit on ambulatory BP57. In a meta-analysis of lifestyle interventions
to reduce raised BP data from 105 trials were included58. Robust statistically significant benefits were observed for improved diet, aerobic
exercise, alcohol and sodium restriction and fish oil supplements with BP reductions of 5.0/4.6 mm Hg. Relaxation significantly reduced BP
only when compared with non-intervention controls and the authors did not recommend this form of therapy for BP control. The American
Seventh Joint National Committee (JNC-7) report or the European Society of Hypertension guidelines do not recommend stress management
and yoga for hypertension control due to lack of evidence13,59.

A) Discuss the pharmacological approach (Use the aid of table where possible)

a. Various classes of medicines and commonly used generic medicines and their common brand names.

b. Mechanisms of action of the medicines used in management of HTN.

c. Dosing for the medicines used in the management of HTN.

d. Common side effects, adverse drugs reactions, toxicities and medicine interactions for antihypertensive medicines.
 Class: ACEi MOA : The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance.  Block the ACE that cleaves
angiotensin I to form the potent vasoconstrictor angiotensin II.  ACE inhibitors decrease angiotensin II and increase bradykinin levels.  ACE
inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention

DRUGS DOSING & frequency Side effects Adr and toxities medicine interaction

Captopril 12.5-50mg twice daily A persistent brassy cough caused by numbness, tingling, or Potassium-sparing diurectics e.g
inhibition of bradykinin/substance P burning pain in your spironolactoneor potassium
Enalapril 10-20mg once/twice daily breakdown in the lungs of susceptible
individuals. Angioedema also due to hands or feet Dizziness, supplements should be used with
Lisinopril 5-20mg once daily
increased levels of bradykinin . Rash headache, drowsiness are caution serious hyperkalaemia may
Ramipril 2.5-10mg once/twice daily because captopril has sulfhydryl moiety
some of the adverse drug occur (ACE inhibitors are potassium
Hyperkalemia due to decrease in sparing agents)
reaction experienced
aldosterone, Digoxin,lithium:Serum concentration of
with the use of ACE
thse agants may be increased by ACE
inhibitors .Toxicity with
inhibitors
ACEI include
High dose asprin and other
Hypotension and
NSAIDS:Reduce antihypertensive
Hyperkalemia . Toxicities
effect of ACE inhibitors
symptoms include
Angioedema
 Neutropenia

Class :Angiotensin II receptor blockers (ARBs) are medications that block the action of angiotensin II by preventing angiotensin II from binding
to angiotensin II receptors on the muscles surrounding blood vessels. As a result, blood vessels enlarge (dilate) and blood pressure is reduced.

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

Candesartan Starting dose 16 mg then 8-32mg Hyperkalaemia due to potassium cough,elevated potassiu Digoxin - telmisartan has been shown to
once daily (maintanace) retention mediated by reduction m levels,low blood press increase digoxin levels
Potassium supplements (K-Dur®, etc.) -
Telmisartan Starting dose 40mg once daily then of aldosterone. uremuscle or bone pain,
ARBs can elevate potassium levels.
40mg -80mg maintaince dose and rash.
Increase serum creatinine: ARB Potassium levels should be monitored
Losartan Starting dose 50mg once daily causes the level of angiotensin II Toxicities: Heart failure, frequently in patients taking potassium
then increased to 100mg once to reduce or blocked from supplements and ARBs
daily if necessary binding. This results in efferent Aliskiren (Tekturna®) - Aliskiren should

Valsartan Starting dose 80mg once daily arteriolar dilatation and not be prescribed with ARBs in patients
with diabetes or decreased kidney function
then increased if necessary to 80- decreased effective GFR
(GFR<60ml/min)
160mg once daily
Lithium - ARBs can increase lithium
levels. This combination should be avoided,
or lithium levels should be checked
frequently if they are taken together.
 Calcium channel blocker:  reduce electrical conduction within the heart, decrease the force of contraction (work) of the muscle cells, and dilate arteries.
Dilation of the arteries reduces blood pressure and thereby the effort the heart must exert to pump blood

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

Dihydropyridine: Amlodipine Initially 5mg once daily, Frequent side effects are Gynecomastia,palpitati Theophylline - ↑ plasma conc of
Acts increased after 10-14 days palpitation, ons,depression,insomni theophylline
predominately to a maximum of 10mg a,impotence,GI
flushing, ankle edema, Ciclosporin – plasma conc ↑
on peripheral once daily discomfort,bradycardia
hypotension due to a
vasculature Nidefipine Extended release: Initially decrease . Digoxin – plasma conc ↑
in arteriolar
30mg once daily increased resistance that goes
Hypotension and Antifungals - ↑ plasma conc of
if necessary up to
a unmatched in the venous
bradycardia are the dihydropyridines
maximum of 90mg daily circulation
primary features seen in
retard release :Oral,10- Grapefruit Juice - ↑ plasma conc
headache, drowsiness and calcium channel
20mg twice daily of dihydropyridines (though not
nausea. These are antagonist poisoning.
maximum 60mg/day as significant an interaction as
These findings are due
related to peaks of drug to with simvastatin)
peripheral
level in blood. vasodilatation and
reduced cardiac
contractility.

Non Diltiazem Short acting formulation Headache,dizziness,fluid Palpitations,Diaphore Carbamazipine:Metabolisimis

Dihydropyridine: :Initially 90mg /day in retention,facial flushing, sis, Flushing, inhibited by verapamil to an
divided doses, gradually Peripheral edema extent which may lead to toxicity
Less selective- both gingival growth due to
increased according to Dabigatran:Increased
cardiac & blockage aldosterone  Toxicity
peripheral response; maximum concentration of dabigatran
synthesis in zona glomerulosa :lightheadedness, fatigue,
vasculature 360mg/day of the adrenal cortex    Simvastatin:Concomitant use
change in mentation,
Long acting Elevated levels of testosterone asscoicated with
syncope, coma
formulation(swallow may act on the gingival cells myopathy/rhabdomyololyisis
and matrix to produce gingival
intact),180CR,180mg once
hyperplasia
or twice daily,242
CR,240mg once daily

Verapamil 240mg-480mg daily in 2-3

divided doses. Slow release
tablet, 240mg once daily:
maximum 240mg 12 hourly

In overdose, receptor selectivity is lostDistinction between these agents may not be clinically evident

Diuretic drugs increase urine output by the kidney (i.e., promote diuresis). This is accomplished by altering how the kidney handles sodium. If the
kidney excretes more sodium, then water excretion will also increase. Most diuretics produce diuresis by inhibiting the reabsorption of sodium at
different segments of the renal tubular system. Sometimes a combination of two diuretics is given because this can be significantly more effective than
either compound alone (synergistic effect). The reason for this is that one nephron segment can compensate for altered sodium reabsorption at
another nephron segment; therefore, blocking multiple nephron sites significantly enhances efficacy
Low-ceiling diuretics(Thiazides);
Mode of action : control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules
in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter
Drugs Dosing and Side effects ADR & toxicities Medicine interactions
frequency

Hydrochlorothiazid 12.5 mg/day as  Elevation of ADH as a result of hypovolemia. chills Beta blockers:Contamitant use
e a single dose in Hyperuricemia: Decreasing the amount of acid increases the risk of diabetes
clay-colored stools
the morning. excreted by the organic acid secretory system.  Potassium-depleting agents:e,g
cloudy urine cold
Generally, avoid Volume depletion: Orthostatic hypotension. corticosteroid and amphotericin
sweats,confusion
doses >25mg Hypercalcemia: Inhibit the secretion of Ca2+. B:Increased risk of
daily Hyperglycemia: Glucose intolerance 10 Overdose hypokalaemia(and
hypokalemia, hypomagnesaemia)
hyponatremia. Lithium:Excretion of lithium may be
Dehydration. substantially reduced
Chlortalidone 12.5-25mg once hypokalemia may cholestyramine:Absorption of
daily accentuate cardiac thiazides is inhibited
arrhythmias. Antidiabetic agents:Thiasides may
alter alter the requirements of these
agents
 Loop diuretics act on the Na+-K+-2Cl− symporter (NKCC2) in the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium
reabsorption. This is achieved by competing for the Cl − binding site. Loop diuretics also inhibits NKCC2 at macula densa, reducing sodium transported into
macula densa cells. This stimulates the release of renin, which through renin–angiotensin system, increases fluid retention in the body, increases the
perfusion of glomerulus, thus increasing glomerular filtration rate (GFR). At the same time, loop diuretics inhibits the tubuloglomerular
feedback mechanism so that increase in salts at the lumen near macula densa does not trigger a response that reduces the GFR

Drugs Dosingand Side effects ADR & Medicine interactions

frequency toxicities

High ceiling Furosemide Lower doses,20- Hyperuricemia: Furosemide and gout, Aminoglycosides:Nephrotoxicity and
(LOOP) diuretics 40mg twice daily ethacrynic acid compete with uric acid dizziness, ototxicity potentiated
MOA Indapamide Oral, 2.5mg daily in for the renal secretory systems, thus postural Potassium-depleteng agents,such as

the morning blocking its secretion and, in turn, hypotension, corticosteroid or amphotericin

Slow release causing or exacerbating gouty attacks. syncope. B:Increased risk of hypokalaemia and

preparation: 1.5mg hypomanesaemia

Potassium depletion: The heavy load  Electrolyte
daily in the morning. NSAIDs:May reduce the furosemide
of Na+ presented to the imbalance
antihypertensive efficacy of furosemide
may lead to
collecting tubule results in increased
cardiac
exchange of tubular Na+
arrhythmias
for K+, leading to the possibility of and may
hypokalemia. Oedema of stria enhance
vascularis loss of endocochlear digitalis
 potential destruction of hair cells. toxicity

Potassium sparing diuretics: The potassium-sparing diuretics are competitive antagonists that either compete with aldosterone for intracellular
cytoplasmic receptor sites, or directly block sodium channels (specifically epithelial sodium channels (ENaC) by amiloride). The former prevents the
production of proteins that are normally synthesized in reaction to aldosterone. These mediator proteins are not produced, and so stimulation of
sodium-potassium exchange sites in the collection tubule does not occur. This prevents sodium re-absorption and potassium and hydrogen ion
secretion in the late distal tubule and collecting duct of a nephron in the kidneys. [3]

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

Potassium Spirinolact 25-50mg once daily Spinolactone chemically resembles drowsiness,confus Given together with K+ supplements
sparing agents one some of the sex steroids, ion, abdominal dangerous hyperkalaemia can occur.

Amiloride Initial dose: 5 mg spironolactone may induce upset, hirsutism,

2. Aspirin blocks spironolactone action
orally once a day. gynecomastia in male patients and
toxicities by inhibiting tubular secretion of
Maintenance dose: 5- menstrual irregularities in female
canrenone.
10 mg once a day. patients. Hyperkalemia, nausea, hyperkalaemia
lethargy, and mental confusion can that may occur 3. More pronounced hyperkalaemia can

occur.Impotence . cardiac occur in patients receiving ACE

arrhythmias due an increase
in serum potassium
Especially if renal
inhibitors/angiotensin receptor blockers
function is
(ARBs).
inadequate.
Spironolactone increases plasma
Acidosis is a risk, digoxin concentration.

My#mom1234

β-Blocker

MOA: Beta blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline. Beta blockers cause your heart to
beat more slowly and with less force, which lowers blood pressure. Beta blockers also help open up your veins and arteries to improve blood
flow

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

Bisoprolol 5mg daily, increased to 10mg Central nervous dry mouth and eyes, dry Digoxin,verapamil and
Cardioselective penetration skin, diarrhea, nausea diltiazem:Risk of additive

Atenolol(Tenopr 25-100mg daily as a single (insomnia,depression) and vomiting, and depressant effect on AV

ess) dose hyperglycemia by feelings of coldness in nodal conduction and

impairing the release of the hands and feet. increased risk of heart block
insulin from the and extreme sinus
pancreatic β-cell Toxicities: Bradycardia
Nonselective Propranolol 5mg daily, increased to 10mg bradycardia
and hypotension
Timolol 10 mg of oral timolol twice Alterations in serum lipid
patterns: Noncardioselective Insulin and antidiabetic
daily. If the patient’s response β-blockers may disturb lipid
metabolism, decreasing high- agents:Increased risk of
is inadequate, then the dose can density hyperglycaemia and
lipoprotein cholesterol and
be increased incrementally to a
increasing triglycerides. masking of hypoglycaemia
maximum of 60 mg per day.

Mixed α- and β-blockers

Drugs Dosing and frequency Side effects ADR & Medicine interactions
toxicities

Cardioselective Carvedilol(carl Initially 12.5mg once daily increased Fatigue,Isomia Oedema of Same to those for beta blockers
oc) after 2 days to 25mg once daily: may be drowsiness,orth the legs
increased at intervals of at least 2 weeks ostatic
 up to a maximum of 50mg/day in single hypotenstion
or divided doses

Labetalol(Tran 100 mg PO q12hr initially; increased by

date) 100 mg q12hr every 2-3 days

Usual dosage range: 200-400 mg PO

q12hr; not to exceed 2400 mg/day

α1-Blocker

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

α1-Blocker: Doxazosin Controlled-release tablets, usually 4mg First dose Nause,nervousnes Alcohol,verapamil,Beta blocker and
Terazosin,
daily: may be increased to 8mg daily if hypotension s,restlessness or cimetidine may increase the effects of
doxazosin and (Cardura)
tamsulosin are the necessary ,dizziness,v irritabilry alpha adrenergic blockers
peferred α1 Terazosin Initially 1mg at night (to avoid first dose- ertigo,heada Toxicity
blockers because hypotenstion), increased at weekly che and symptoms are
of once daily
(Hytrin)
intervals up to 20 mg.Usual maintenance fatigue charatterised by
dosing
1-5mg once daily. aerrthymeia,dispo
nea,orthostatichyp
otension

Central

α2-agonist

Drugs Dosing and frequency Side effects ADR & toxicities Medicine interactions

Cardioselective Clonidine An initial oral dose of 0.1 to Sedation, lethargy and Toxicity:  coma, Tricyclic antidepressants reverse its
 0.2 mg of clonidine reduced mental, hypothermia, action by blocking its active transport
hydrochloride followed by Postural hypotension is hypotension, into the adrenergic neurones
hourly doses of 0.05 or 0.1 generally mild but more bradycardia
hen methyldopa and lithium are given
mg until goal blood pressure common
concomitantly the patient should be
Methyldopa Initially 250mg twice
than with clonidine; carefully monitored for symptoms of
daily,increasing
lithium toxicity.
gradually(with at least 2 –day
intervals)until the desired
response is obtained,usually
not more than 15-2g daily in
divided doses

Direct arterial

Vasodilator

Drugs Dosing and frequency Side effects ADR & Medicine interactions
toxicities
Cardioselective Minoxidil Initial: 5mg in single or Facial flushing,conjunctival injection, Head Nitrates:Hydralizine may
divided doses,increased throbbing,headache, dizziness, tachycardia, lessen nitrate tolerance by
Loniten®
slowly by 5-10mg/day palpitation, nasal stuffiness, nausea, the attenuation of
intervals, according to fluidretention, edema, CHF due to sweating, superoxide formation
respose:maximum vasodilation Minoxidil causes arrhythmia,
Ciproflaxacin given together
100mg/day. Usual range/day hypertrichosis growth by increasing blood and
with Hydralaizne might
Hydralazine Initially 20-25mg twice daily, flow to the hair follicle by dilating the precipitation of
increase the risk of bleeding
Hyperphen® increased according to blood vessels.This means that more angina

response:usualy 25-100mg nutrients get hair the hair follicle thus

ache, Nausea
twice daily promoting hair growth

a. Compare and contrast the various classes of medicines used in the management of HTN and indicate when to use each class of medicines.

Diuretics
They are effective in lowering blood pressure in the great majority of patients, especially those over 60, African
Americans, and those with diabetes. Diuretics increase the effectiveness of all other categories of antihypertensives.
That is why they are an essential part of almost any multidrug regimen for hypertension. Diuretics are more effective in
reducing blood pressure when given with dietary salt restrictions.
Diuretics also increase the effectiveness or all other classes of antihypertensive agents
If monotherapy is appropriate in a patient with hypertension and osteoporosis, thiazide-like diuretics may have advantages over ACE inhibitors,
ARBs, and calcium channel blockers. These drugs stimulate distal tubular reabsorption of calcium, leading to a decrease in urinary calcium
excretion. As a result, thiazide diuretics may have a beneficial effect on bone mineral density
Thiazide diuretics reduce calcium excretion and have beneficial effects in preventing bone loss and fractures, especially
in elderly subjects.
Loop diuretics has a longer duration and is preferred in patients with heart failure. Loop diuretics are not as effective as
thiazides in lowering blood pressure in patients with hypertension. They are used especially to treat edema (swelling of
the ankles) or heart failure. However, unlike thiazides, they effective in patients with poor kidney function in lowering
blood pressure or treating edema.
a mineralocorticoid receptor antagonist (spironolactone or eplerenone) is indicated in patients with HF who have relatively preserved kidney
function and for the prevention or treatment of hypokalemia.

Distal, potassium retaining diuretics include such as amiloride (Midamor) and spironolactone (Aldactone) and
eplerenone (Inspra). All these agents can raise serum potassium. This is usually beneficial in patients receiving thiazide
or loop diuretics who have increased loss of potassium in the urine. Thus these drugs are often prescribed together.
However an increase in serum potassium predisposes to cardiac arrhythmias and can be especially dangerous in patients
with a thickened heart (left ventricular hypertrophy) or coronary artery disease.
ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs)

Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy in all patients who have HF or asymptomatic LV dysfunction, in all
patients who have had an ST elevation MI, in patients with a non-ST elevation MI who have had an anterior infarction, diabetes, or systolic
dysfunction, and in patients with proteinuric chronic kidney disease
It has been suggested that ACE inhibitors and ARBs have a cardioprotective effect independent of blood pressure lowering in patients at high
risk for a cardiovascular event. However, as mentioned above and described in detail elsewhere, the available evidence suggests that the
attained blood pressure, not the drug used, is of primary importance in such patients. (See 'Importance of attained blood pressure' above.)
ACEIs are widely used to treat hypertension because they are effective, have relatively few side effects and in reduce
the complications of hypertension such as heart attacks and strokes.

They have a special use in patients with diabetes mellitus who have protein the urine (“diabetic nephropathy”) and in
patients with chronic kidney disease (CKD) in whom they appeared to have beneficial actions in slowing the loss of
kidney function above that achieved by other agents.
These drugs target important hypertensive mechanisms. Younger and white subjects are particularly likely to have an
activated RAS whereas elderly and African American subjects are less likely. Therefore, ACEIs are especially effective
in the Younger and white subjects. They interact very well with diuretics. Diuretics enhance the action of ACEIs,
whereas ACEIs themselves act on the kidney to retain some potassium, thereby reducing the adverse effect of low
blood potassium that can occur during diuretic therapy. There are a number of combination drugs in which an ACEI
and a diuretic are included in the same medication eg ena-co The quality of life of patients receiving ACE inhibitors is
not impaired in comparison to those taking spironolactone . They do not affect concentration, sleep, exercise abilities,
sexual performance or wellbeing. ACEI treatment has been shown in some, but not all studies do delay the onset of end
stage renal disease (ESRD). ESRD is the requirements for dialysis or renal transplant in patients with progressive
kidney disease. Generally, ACEIs improve blood glucose and maybe beneficial in patients at risk for developing
diabetes mellitus. These drugs can reduce the thickness of the heart (left ventricular hypertrophy), which occur after
prolonged hypertension and predisposes to congestive heart failure (CHF). ACEIs are strongly indicated in patients who
have congestive heart failure since numerous studies have shown that cardiac performance and life expectancy is
improved in patients who receive these drugs even if they are not hypertensive.
ANGIOTENSIN RECEPTOR BLOCKERS (ARBs):
 

An ARB is particularly indicated in patients who do not tolerate ACE inhibitors (primarily because of cough)
ARBs also block the renin angiotensin system (RAS), similar to ACEIs, but have a different mechanism of action by
blocking the actions of angiotensin II in the tissues rather than the generation of angiotensin II, which is the action of
ACEIs. These drugs also have an excellent acceptability and preservation of quality of life. Moreover, they do not cause
an irritant cough or the rare danger of swelling of the lips, tongue and throat, that can occur with ACEIs. In general, the
indications for their use, their effectiveness and beneficial interactions with thiazides and loop diuretics are similar to
ACEIs. Some studies have suggested they are particularly effective in preventing stroke and that they may have an
additional action to diminish the progression of Alzheimer’s disease in those with early dementia, but this requires
conformation.

BETA BLOCKERS, ALPHA BLOCKERS AND SYMPATHOLYTIC DRUGS

A beta blocker without intrinsic sympathomimetic activity should be given after an acute myocardial infarction and to stable patients
with heart failure or asymptomatic left ventricular dysfunction (beginning with very low doses to minimize the risk and degree of
initial worsening of myocardial function). The use of beta blockers in these settings is in addition to the recommendations for ACE
inhibitors in these disorders. (See "Acute myocardial infarction: Role of beta blocker therapy" and "Initial pharmacologic therapy of
heart failure with reduced ejection fraction in adults", section on 'Beta blocker'.)

Beta blockers are also given for rate control in patients with atrial fibrillation, for control of angina, and for symptom control in a
number of other disorders (table 2).

They act on a part of the nervous system that controls blood pressure, known as the sympathetic nervous system.
Blockade of the sympathetic nervous system reduces blood pressure by relaxing blood vessels, and decreasing the rate
and force of contraction of the heart. Therefore, beta blockers and sympatholytics typically slow the heart rate which
can occasionally cause problems in subjects with a slow heart rate.
The actions of these agents are enhanced in patients taking diuretic drugs and therefore are a good second or third line
selection in those patients who are not controlled with a diuretic and an ACEI or ARB. Unfortunately, alpha blockers
have been shown to be less affective than other groups of blood pressure lowering agents in preventing the
complications of heart failure and heart attacks in hypertensive subjects.  Therefore, they are not routinely used and so
will not be discussed further. he ALLHAT trial cited above included a doxazosin arm that was terminated prematurely because of a
significantly increased risk of heart failure compared to chlorthalidone (relative risk 2 after adjusting for a 3 mmHg higher in-trial systolic
pressure with doxazosin) noted during an interim analysis [85] and a higher rate of cardiovascular events [86]. Thus, an alpha blocker
is not recommended for initial monotherapy, with the possible exception of older men with symptoms of prostatism and if they are not at high
cardiovascular risk. (See "Medical treatment of benign prostatic hyperplasia".)

Beta blockers are affective in lower blood pressure and reducing its complications. However, their popularity has
diminished because of a large range of annoying adverse effects. Although these are rarely serious, they do adversely
impact the quality of life of some patients, and this limits their popularity. Nevertheless, beta blockers have been shown
in many trials to prevent the probability of a recurrence in patients who have had a heart attack. Therefore, they are
strongly indicated in these patients even if they cause some side effects or the patient does not have high blood pressure.

Sympatholytic agents act in the brain to decrease the drive to the sympathetic nerves. In this sense, the effects are
somewhat similar to beta blockers, but because of their action in the brain, they have a different, and often rather worse,
spectrum of adverse effects.

There are significant differences between many of the drugs in this class. Some such as atenolol abd metoprolol work
on a selective part of the sympathetic nervous system and do not have so many adverse effects regarding precipitating
asthma. Others such as carvedilol and labetalol act on additional parts of the sympathetic nervous system and are
therefore more potent. The physician may change therapy from one to another beta blocker if it is insufficient or
producing adverse effects.
Adverse Effects: The most frequent adverse effects of beta blockers are: slow heart rate, depression and irritability,
impaired sleep, decreased exercise capacity, wheezing and precipitation of asthma, sexual dysfunction, and an increase
in serum potassium (hyperkalemia). These effects are mostly dose dependent and, if encountered, may be amendable to
reduction in dosage.
Special Indications: Beta blockers have some additional effects that make them attractive therapy for certain of
patients. Thus, they are effective in reducing the frequency of migraine attacks, their slowing of the heart can be
beneficial in people who have fast and irregular heart rates or atrial fibrillation, they reduce the symptoms and bad
outcome in patients who have angina (chest pain on exertion due to narrowed coronary arteries), they reduce tremor of
the hands in patients with essential tremor and they are protective in patients who have had a prior heart attack. They
are used increasingly in patients with congestive heart failure.
Central Sympatholytic Agent: These agents include the following: clonidine (Catapres), and alpha methyldopa
(Aldomet). Catapres is available as a patch similar to a band-aid which provides slow release of the drug over the
course of a week. This is especially beneficial in patients who have difficulty in remembering to take the medication,
but often leads to allergic skin troubles after some months.
CALCIUM CHANNEL BLOCKERS (CCBs)
Calcium channel blockers — There are no absolute indications for calcium channel blockers in patients with hypertension. Long-acting
dihydropyridines are most commonly used. Like beta blockers, the nondihydropyridine calcium channel blockers (verapamil, diltiazem) can be
given for rate control in patients with atrial fibrillation or for control of angina in patients with coronary disease and normal left ventricular systolic
function [73]. Calcium channel blockers also may be preferred in patients with obstructive airways disease. (See "Treatment of hypertension in
asthma and COPD".)
The management of hypertension in a patient with asthma or chronic obstructive pulmonary disease (COPD) is a common problem owing to
the high prevalence of each condition in the adult population. It may be made difficult by the asthma-exacerbating effect of some
antihypertensives. As an example, beta blockers should be used with great caution or not at all in patients with chronic asthma (but not COPD)
or acute allergic or exercise-induced bronchospasm. The angiotensin-converting enzyme (ACE) inhibitors, among the most widely used
antihypertensive drugs, can induce a bothersome cough that, although not damaging to the lungs, often can be confused with cough due to
such underlying pulmonary diseases such as asthma and COPD.
These are very effective in lowering blood pressure. They act directly on the blood vessels to cause relaxation. They are
used sometimes as first line therapy but more often with diuretics or ACEIs or ARBs as second or third line therapy.
They are especially effective in lowering blood pressure in elderly, black, obese, and diabetic patients. They are
excellent in preventing stroke but rather less effective than diuretics, ACEIs, and ARBs in preventing heart failure.

Individual drugs: They fall into two categories. The first are called dihydropyridine CCBs and include amlodipine
(Norvasc), felodipine (Plendil), nifedipine (Procardia), and nicardipine (Cardene). The second, termed
nondihydropyridine CCBs include two drugs, diltiazem (Dilacor, Cardizem, Cartia, and Tiazac), and verapamil (Calan,
Covera, Isoptin, Verelan). Both groups are effective in lowering the blood pressure but have different effects on the
heart and rather different adverse effects. Dihydropyridine drugs generally do not impair the function of the heart and
do not cause much cardiac slowing but can cause swelling of the ankles. Nondihydropyridine drugs, especially
verapamil, slow the heart, similar to beta blockers and cause constipation, especially in elderly subjects.
Non-dihydropyridine CCBs cause cardiac slowing. This typically reduces the heart rate by about 10%. It can be
beneficial in some patients with a fast heart rate or who have irregular heartbeat (atrial fibrillation), but in those with a
slow initial heart rate, it can cause symptoms of decreased cardiac output (tiredness, lethargy, and dizziness on
exertion). This group of drugs also can cause constipation, especially in the elderly but rarely cause edema.

Within each class, compare and contrast the various medicines and indicate when
particular medicines will be used.
When considering factors such as increased ejection fraction, stroke volume, and decreasing mean arterial pressure, our results suggest that enalapril was
the most effective ACE inhibitor. However, enalapril was also associated with the highest incidence of cough, as well as renal function deterioration and
gastrointestinal discomfort. An increase in all-cause mortality combined with a limited effect on reducing systolic and diastolic blood pressure made
lisinopril the worest choice among the ACE inhibitors evaluated. Ramipril was associated with the lowest incidence of all-cause mortality. Trandolapril
ranked first in reducing systolic and diastolic blood pressure. More high quality, randomized controlled trials of longer duration and with a larger sample
size should be performed to confirm these results and explore the impact of different ACE inhibitors on other important outcomes such as rehospitalization
and cardiac death.

ll ACE inhibitors share the same basic structure; however, they can be separated on the basis of their functional (binding) group: carboxyl, sulfhydryl,
or phosphinyl. These functional groups are, in part, responsible for differences in the pharmacokinetic and safety profiles of these agents. Captopril
and lisinopril are the only ACE inhibitors that are not prodrugs requiring activation through hepatic biotransformation. Differences among the ACE
inhibitors in lipophilicity are described; fosinopril has the greatest lipophilicity and lisinopril the least. ACE is found in numerous tissues, and there is
increasing evidence of differences among ACE inhibitors in their ability to inhibit tissue ACE. Most ACE inhibitors are eliminated mainly by the kidneys
and to a lesser extent through the liver. Lisinopril is the only ACE inhibitor that does not require hepatic metabolism. In the selection of an ACE
inhibitor for once-daily use to treat hypertension, differences in trough-peak ratios are clinically relevant. Fosinopril, ramipril, and trandolapril have
minimum trough-peak ratios of 50% or greater. ACE inhibitors are generally well tolerated, with hypotension, cough, and hyperkalemia being the
most frequently reported adverse effects for the entire class. Drug interactions across the ACE inhibitor class as well as agent-specific interactions are
described.

According to a meta-analysis of eight trials, telmisartan was superior to other ARBs in reducing fasting plasma glucose and increasing adiponectin levels.
Using an 80-mg dose, telmisartan may also reduce fasting plasma insulin levels as well as homeostasis model assessment of insulin resistance
The long-lasting antihypertensive effects of telmisartan compared with other ARBs are likely due to this agent having
the longest plasma elimination half-life of approximately 24 hours (Table 3), as well as the highest affinity for the
AT1 receptor [70–72]. As the most lipophilic of the ARBs, telmisartan also has the highest volume of distribution,
which facilitates tissue/organ penetration (Table 3) [70–73]. Moreover, as a partial agonist of peroxisome
proliferator-activated receptor-gamma, telmisartan may offer advantages in patients with insulin resistance and
glucose intolerance, as well as hypertension

These unique characteristics of telmisartan manifest in a number of clinical advantages, such as long-lasting BP
control and CV protection - consequently telmisartan has been identified as a gold-standard treatment and has been
recommended as a preferred ARB treatment option [76, 77]. Furthermore, telmisartan has been recognised as an
important therapeutic option for type 2 diabetes patients in the optimisation of CV and renal prevention [78]. These
endorsements nominate telmisartan as the preferred ARB choice in combination therapy.

tmax(h) Bioavailability (%) T1/2 Vd Interaction with food

(h) (L)

inCandesartan 3.0-5.0 42 9-13 0.13 (L/kg) 67

Eprosartan 2.0-6.0 13 5-7 308 90

Irbesartan 1.0-2.0 60-80 12-20 53-93 80

Losartan 1.0 (3.0-4.0) 1

33 2 (4-6) 1
34 (12) 1
60

Olmesartan 1.4-2.8 26 2
11.8-14.7 15-20 51-66 3

Telmisartan 1 43 24 500 > 98 4

Valsartan 2 23 7 17 83
 tmax(h) Bioavailability (%) T1/2 Vd Interaction with food
(h) (L)

Azilsartan 1.5-3.0 60 11 16 55

 CTLD has longer elimination half-life than HCTZ 40–60 h compared with 6–15 h. Apart from the longer duration of action,
CTLD is approximately twice as potent as HCTZ. This shows that these two compounds are quite dissimilar
pharmacokinetically despite their similar structure [19, 20]. Due to BP-lowering efficacy throughout the nighttime hours half the
dose of CTLD is more effective in lowering SBP than HCTZ.
urthermore, a retrospective comparative analysis demonstrated that CTLD reduces CVEs more than HCTZ [7]. Therefore, a
recent guideline recommended the use of CTLD or INDAP in preference to HCTZ [21, 24].

Loop diuretics
Furosemide has a wide variability in the bioavailability in patients with HF, between 10% and 100%, suggesting altered absorption.
Torsemide and bumetanide have greater bioavailability (80% to 100%) and a more consistent rate of absorption in HF patients.

Torsemide has a longer half-life in patients with HF, approximately 6 hours, compared to furosemide or bumetanide, which have a half-
life of approximately 2 hours. Hence, one should consider switching to torsemide or bumetanide if increasing the dose and frequency of
furosemide does not overcome the diuretic resistance.

Furosemide, torsemide, and bumetanide are the most commonly used loop diuretics in the management of HF. The rate of absorption
and metabolism among loop diuretics are different.

Torsemide and bumetanide have a greater bioavailability (80% to 100%) and a more consistent rate of absorption in patients with heart
failure than furosemide. Furosemide has a wider variability in the bioavailability in patients with HF, between 10% to 100%, suggesting
altered absorption.
Furthermore, torsemide has a longer half-life in patients with HF, approximately 6 hours as compared to furosemide or bumetanide,
which have a half-life of approximately 2 hours.

Mechanistically, the aldosterone antagonists, spironolactone, and eplerenone are different from amiloride and triamterene in that they
work as mineralocorticoid receptor blockers, whereas amiloride and triamterene block the epithelial sodium channel. The onset of the
diuretic actions of spironolactone is slow, with a peak response at ≥ 48 hour after the first dose, which is related to the time needed for
the active metabolites of spironolactone to reach steady-state levels in plasma and/or tissue. Eplerenone, a highly selective
mineralocorticoid receptor blocker with reduced affinity for androgen and progesterone receptors, has fewer endocrine side effects than
with spironolactone.

Spironolactone can trigger a natriuretic response when it is given to patients with heart failure, particularly if it is given in combination with
a loop and/or a thiazide-type diuretic. In contrast, eplerenone has a mild diuretic effect, which may relate to its having a short half-life and
no active metabolites.

These studies indicate that timolol significantly and safely reduced arterial pressure in mild to moderately severe essential hypertensive patients.
The reduction in mean arterial pressure with timolol was equivalent to the pressure reduction with propranolol when the doses of 30 and 120
mg. per day, respectively, were used.

Propranolol is the prototypical b-blocker. It lacks selectivity and effectively blocks both b1 and b2. Clinically, b-blockers are used in a variety of settings.
First and foremost, they are used to treat hypertension. They are also effective in angina (by reducing workload and the concomitant oxygen demand)
and in the treatment of atrial fibrillation, where they reduce atrioventricular nodal conduction and protect the

Finally, certain b-blockers, such as carvedilol and metoprolol, are effective in the treatment of congestive heart failure, where few classes of drugs have
been shown to reduce mortality rates. Acebutolol (as well as pindolol) represents a novel antagonist that has weak intrinsic agonist activity—also called
partial agonist activity, or in the case of the cardiovascular system, intrinsic sympathomimetic activity.
Labetalol is another drug with a unique mechanism of action: it is a nonselective a1 and b1/b2 blocker. Based on this spectrum of activity, labetalol decreases cardiac output and total
peripheral resistance (see Fig. 6-9). Similarly, carvedilol has both a1- and b1-selective blocking properties. Orthostatic hypotension is a significant side effect of these agents. Nebivolol
is the newest b-blocker and displays a preference for the b1-receptor (cardioselective b-blocker). As a result, it has some value in treating hypertension. However, nebivolol is much
more restricted in its use; unlike carvedilol, it is not approved for heart failure or left ventricular dysfunction after myocardial infarctio

Clinical indication
Labetalol is approved for treatmeant of hypertensive emergencies such as eclampsia during pregnancy.Acebutolo ,atenolol,labetalol ,metoprolol,nodalol,pindolo,propranolol and
timolol can also be used as anti-anginal
Receptor selectivity pindolol,propranol,sotalol and timolol are non-selective means that the drugs block beta1(cardiac and beta2 maily somooth muscle in the bronchi and blood
vessels .blockade of beta2 receptors is associated with adverse effects such as bronchoconstriction ,peripheral vasoconstriction ,and interference with gylocgenolysis
.Acebutolol,atenolol,betaxolo,bisoprolo esmolo and metoprolol are cardioselctive agents meaning that they have more effect on beta 1 receptors than on beta 2 receptors .as a results
they may cause less bronchospasm,kess impairment glucose metabolism and less peripheral vascular insufficiency .These drugs are preffered when beta blockers are needed by
patients with diabetes mellitus ,peripheral vascular disorders,or asthma or other bronchospastic pulmonary disorders however cardioselectivity is lost at higher doses because most
organis have both beta1 and beta2 receprtors rather thn one or the other exclusively .Labetalo and carvediolo block alpha 1 receptors to cause vasoldiation and beta1 anf beta2
receptors to cause all the effecys of nonselctive agents.Both alpha and beta adrenergic blocking actions contribute to antihypertensive effects ,bt is u
dRugs with intrinsic activity (acebutalol,carvedilol and pindolol have a chemical structure similar to that of catecholamines.As a result thy can block some beta receptors and stimulate
others.It was once thought.

Poatssium channel blockade

Unique among beta blockers ,sotallol exert anti-dysrthymic effect by blocking potassium channels iin cell membrane thereby prolong repolarization and refractory period of the
heart .At low doses ,beta blocking effects predominate and high doses anti-dysrthymic effect predominate .Sotalol is used to treat life-threating ventricular dysrhymias and maintain
normal sinus rhythm in patiet who frequently reconvert to atrial fibrillation/flutter

Routes of elimination
Most beta-blocking drugs are metabolized in the liver.Acebutolo,atenolol,nadolol,sotalol and an active metabolite of acebutolo are excreted by the kidneys:dosage must be reduced in
the presence of renal failure .Bisoprolol is eliminated equally by both remal and non renal pathways :thus dosage must be reduces and titrated carefully in the presence of renal failure

Routes of administration
Most beta blockers can be given orally .Esmolol ,labetalol ,metoprolol and propranolol can be goven intravenously

Duration of action
Acebutolo ,atenolol,bisoprolol and nodalol have long serum half lives and can usually be given once daily.Carvedilol,labetalol,metoprolol,pindolol,sotalol and timolol are usually
given twice daily .Propranolol

Pharmacokinetics Alpha-blockers are well absorbed after oral administration and undergo extensive hepatic metabolism. The main difference between
agents is in elimination half-life: short with indoramin and prazosin and much longer with doxazosin and terazosin
All alpha-blockers reduce blood pressure. However, doxazosin is the preferred option because its longer duration of action allows once-daily administration.
With the sustainedrelease formulation (Cardura XL) the onset of action of doxazosin is gradual, making first-dose hypotension less common. Alpha-blockers
are usually used with other agents in the treatment of resistant hypertension
Doxazosin, a potent antihypertensive agent, selectively inhibits α 1 adrenoceptors. Its pharmacokinetic profile,
including gradual onset of action, long plasma elimination half-life and long duration of action, permits once-daily
dosing. Terazosin, a structural analog of prazosin, also inhibits α 1 adrenoceptors and is recommended as once or
twice-daily therapy.
Terazosin It is chemically and pharmacologically
similar to prazosin; differences are higher
bioavailability (90%) and longer plasma t½ (~12
hr); a single daily dose lowers BP over 24 hrs.
Terazosin is more popular for use in BHP due to
single daily dose and a probable apoptosis
promoting effect on prostate.
HYTRIN, TERALFA, OLYSTER 1, 2, 5 mg tab; usual
maintenance dose 2–10 mg OD.
Doxazosin Another long acting (t½ 18 hr) congener
of prazosin with similar pharmacological
profile, used in hypertension and BHP.
Dose: 1 mg OD initially, increase upto 8 mg BD;

methlydpa
Though methyldopa is transported actively by intestinal amino acid carrier, less than 1/3 of an oral dose is absorbed. It is partly metabolized and partly excreted unchanged in urine.
Antihypertensive effect develops over 4–6 hours and lasts for 12–24 hours.

Clonidine is well absorbed orally; peak occurs in 2–4 hours; 1/2 to 2/3 of an oral dose is excreted unchanged in urine, the rest as metabolites. Plasma t½ is 8–12 hours. Effect of a
single dose lasts for 6–24 hours.

Antihypertensive appearing in Botswana essential list

Amiloride+Hydrochlorothiazide (5+50) mg tablet

Amlodipine

Atenolol

Dihydralazine

Doxazocin
Enalapril maleate

Hydralazine

Methyldopa

Minoxidil

Nifedipine SR

Nifedipine XL 30 mg tablet

Propranolol 40 mg tablet

Sodium nitroprusside 10 mg/mL pwd infusion

Telmisartan 40 mg tablet

Telmisartan 80 mg tablet

Telmisartan + Hydrochlorthiazide (40+12.5) mg

tablet

Telmisartan + Hydrochlorothiazide (80+12.5) mg

tablet

Verapamil 240 mg SR tablet

Indapamide

Labetalol Ideal choice in eclampsia or preeclampsia

Spironolactone is better studied in resistant hypertension; consider eplerenone for spironolactone intolerance because of antitestosterone effects
Does not require hepatic activation; enalaprilat is the active form of enalapril and is 10–20 times as potent as captopril Avoid in acute coronary syndrome

If starting or changing diuretic treatment for hypertension, offer a 18 thiazide-like diuretic, such as indapamide or chlorthalidone in preference 19 to a
conventional thiazide diuretic such as bendroflumethiazide or 20 hydrochlorothiazide.
Bumetanide 0.5–4 2 For patients with symptomatic heart failure, loop diuretics are preferred.

Furosemide 20–80 1–2 For patients with CKD stage 3–4, loop diuretics are preferred.

Aldosterone Eplerenon 50–100 1–2 Spironolactone increases the risk of breast hyperplasia and ED in men
antagonists e compared with eplerenone.

α1-receptor Doxazosin 1–16 1 Those drugs may cause postural hypotension, particularly in the elderly patients.
antagonism α1-receptor antagonism can be used as second-line drug for the patients with benign prostatic hyperplasia.

Hydralazine 25–100 2