School of Pharmaceutical Sciences

FAR 453/3
Case Report 1: Hypertension
Group : 7 :
95316 95317 95318 95319 95320 95321 95322 95323 95324 95325

Group members

MUHAMMAD AZZIM BIN IZUDDIN MUHAMMAD HAMDI BIN ISMAIL MURSHIDA BT IBRAHIM MUSLIHAH BT RAFFLI NABILAH BINTI JAMALUDIN NG KAI YEONG NGU CHIEW PIN NIK NUR NASEELA FATHIN BINTI NIK MOHD SABRI NOOR AQIDAH BINTI ROSLI NOOR FARAHIN BINTI HANIZA (L)

Date
OBJECTIVE

15 July 2010

To describe the definition and classification of hypertension based on current guidelines

To

explain

the

general

approach

to

the

management

of

hypertension

To evaluate the factors that affect management of hypertension, including presence of target organ damage, other cardiovascular risk factors or concomitant disorders

To evaluate the factors that affect management of hypertension, including presence of target organ damage, other cardiovascular risk factors or concomitant disorders

To suggest appropriate pharmacological and non-pharmacological management for hypertension

To provide counselling information for pharmacological agents involved in the management of hypertension

CASE 1
Mrs. Minoh is a 52 year-old housewife whose blood pressure (BP) has been found to be sustained around 138/88 mmHg. She lives with her husband and has five grown children. Shes slightly overweight (height= 55 weight = 76kg) but does not drink alcohol or smokes cigarettes. She has no other cardiovascular risk factors.
1. What is the classification of Mrs. Minohs blood pressure?

Mrs.

Minoh

blood

pressure

(138/88

mmHg)

is

classified

as

Prehypertension. The classification of blood pressure based on the Clinical Practice Guidelines Management of Hypertension 3rd edition, February 2008 is as follow:

The risk

stratification

based on cardiovascular risks

factors,

presence of target organ damage and others is as follow, which is taken from Clinical Practice Guidelines Management of Hypertension 3rd edition, February 2008:

The major cardiovascular risk factors include:

i) ii) iii) iv) v) vi) vii) viii) ix)

Physical inactivity Hypertension Cigarette smoking Central obesity Dyslipidemia Diabetes mellitus Kidney disease (microalbuminuria / estimated GFR less than 60ml/min) Age more than 55 years (men) / 65 years (women) Family history of premature cardiovascular disease (men < 55 years old/ women < 65 years old)

The target organ damage may involved:

i) ii) iii) iv)

Kidney (chronic kidney disease) Brain (stroke or transient ischemic attack) Eyes (retinopathy) Heart failure) (left ventricular hypertrophy (LVH), angina, prior myocardial infarction, prior coronary revascularization, heart

v)

Peripheral vasculature (peripheral arterial disease)

Based on the above, Mrs. Minoh is classified as having low risk of cardiovascular events.
2. What would you suggest to manage Mrs. Minoh?

Since Mrs. Minoh is in prehypertension stage without any risk factors or target organ damage, according to JNC VII, the ideal management of her condition would be non-pharmacological approach through lifestyle modifications. The classification of

hypertension and their management according to JNC VII is as follow:

The suitable lifestyle modifications for Mrs. Minoh would be weight reduction, reduction of dietary sodium intake, regular exercise and DASH eating plan. It would be good for her to achieve BP < 120/80mmHg (normal range). The non-pharmacological approach management of hypertension

according to JNC VII are as follow:

For Mrs. Minoh weight reduction plan, the current BMI of Mrs. Minoh is calculated as follow: BMI = weight (kg) Height2 (m2) = 76/1.652 =27.91 kg/m2 Ideal BMI = at max 25 Target weight = 25 X Height2 (m2) = 25 X 1.652 = 68 kg or lower

CASE 2
After a few months, Mrs. Minoh BP was found to be around 160/100 mmHg on several occasions. Her weight now is 80kg. She was started on two antihypertensive agents by her physician: T. Chlorothiazide 500mg qd T. Metoprolol 100mg bd

1. What are the possible reasons for her elevated BP? The possible reasons for her elevated BP include non adherence to non-pharmacological management. This can be seen from the increasing body weight from 76 kg to 80kg. The failure of nonpharmacological management may include unsuccessful weight reduction, sedentary lifestyle, poor diet control and stress. Poor diet control and sedentary lifestyle may leads to increased body weight and eventually increase in BP. Mrs. Minoh might have taken too much food rich in sodium, a lot of fatty and oily food in her diet. The other possible factor is due to compensatory mechanism leading to increased blood pressure. Since she is in prehypertension stage, constant higher blood pressure may damage kidney and leads to secretion of renin due to low GFR. Renin secretion will activates angiotensin converting enzyme which in turn converts angiotensin I to angiotensin II. Angiotensin II have vasoconstriction activity on renal efferent tubule causing increased GFR. However at the same time, angiotensin II also have vasoconstriction activity in other peripheral blood vessels resulting in increased total peripheral resistance and hence blood pressure. The other compensatory mechanism is secretion of renin may leads to release of aldosterone from the adrenal gland. Aldosterone will cause sodium and water retention, leading to increased blood volume. Increased blood volume results in increased preload, hence increases the stroke

volume and increases cardiac output. Due to increased cardiac output, blood pressure increases. BP = CO X TPR, CO = SV X HR

2. Why did the prescriber choose the two antihypertensive agents for

Mrs. Minoh? The reason why 2 antihypertensive agents are used is because Mrs. Minohs current blood pressure is 160/100 mmHg, which is stage 2 hypertension, which requires 2 agents according to the algorithm for managing the condition. Since there is no compelling indication, usually a thiazide diuretic combined with one of either ACEI, BB, ARB or CCB is used. Here, thiazide diuretic chlorothiazide is used because it is the most effective diuretic to be used. It is cheap and effective. Pharmacologically, thiazides act at the proximal renal tubule and block sodium reabsorption, leading to increased volume of water loss in urine. This will reduce the fluid volume hence reduce preload and subsequently cardiac output and blood pressure. Besides, thiazides is also clinically proven to be the most efficacious the elderly patient and also less expensive than other antihypertensive drugs. A beta blocker is used here, which is metoprolol. Metoprolol is a cardioselective beta blocker, which exerts its effect mainly in the heart on the beta 1 receptor. By antagonising action of catecholamine on the heart, the heart rate is lowered, as well as reduced contractility of the heart. Hence, cardiac output will decrease, and blood pressure can be lowered. The combination of beta blocker and thiazide diuretic here also can increase the BP lowering effects as they work synergistically. At the same time, the combination of beta blocker and thiazide diuretic also reduces the side effects of the drugs.

The compelling indications of each class of antihypertensives are as follow:

The algorithm for the treatment of hypertension according to the Malaysian Clinical Practice Guideline is as follow:

The algorithm for management of hypertension according to JNC VII is as follow:

3. What counselling information would you provide to Mrs. Minoh regarding her antihypertensive agents. The counselling information needed for Mrs. Minoh includes the purpose of the drugs prescribed is to lower her blood pressure. Then it is important also to explain to her the importance of taking the medication despite not having any symptoms of hypertension. We need to emphasis more on the implication of uncontrolled hypertension which can results in target organ damages such as stroke, heart failure, retinopathy, renal failure and so one. This will increase her compliance to the drug regimen Besides, we also need to explain the possible side effects of the drugs taken. We need to tell patient that she may experience

frequent urination due to taking of chlorothiazide. Besides, we also need to advice that metoprolol may cause weakness, dizziness (due to hypotension) and bradycardia. Other than that, we need to tell the patient to take the medications on time. For chlorothiazide, it is best to be taken daily in the morning everyday, while metoprolol should be taken twice a day, together with food since metoprolol absorption is increased by food.

CASE 3
Today Mrs. Minoh was admitted to the hospital since her BP was found to be 220/126 mmHg. She previously complained of headache, weakness and dizziness for the past week. The attending physician found evidence of retinal changes (grade III) but no overt organ failure.
1. What are the recommended antihypertensive agents for Mrs.

Minoh? Acute hypertensive disorders are divided into two general

categories: hypertensive emergencies and hypertensive urgencies. Signs and symptoms for these disorders are nonspecific and may overlap. factor. Hypertensive emergencies Hypertensive urgencies Noncompliance and rebound hypertension following withdrawal of therapy should always be considered as an etiologic

Similarity: Severely elevated blood pressure (diastolic >120mmHg) Differences: Potentially life threatening Not life threatening

End-organ damage present or Minimal end-organ damage with high risk: no pending complications CNS (dizziness, nausea/vomiting, Accelerated encephalopathy, confusion, hypertension weakness, intracranial or subarachnoid hemorrhage, Optic disc edema stroke) malignant

Eyes (ocular hemorrhage or Coronary artery disease fundoscopic changes, blurred Postor perioperative vision, loss of sight) hypertension Heart (left ventricular failure, pulmonary edema, MI, angina, Pre- or postkidney transplant aortic dissection) Renal failure/insufficiency Phaeochromocytoma Drug-induced crisis: hypertensive

MAOI-tyramine interactions Overdose with PCP, cocaine or LSD Drug interaction-induced hypertension Clonidine withdrawal Eclampsia (complicated pregnancy) Requires reduction immediate pressure Treated over several hours to day Oral therapy or slower-acting parenteral drugs preferred

Requires IV therapy

From the table above, we can tell that Mrs Minoh is suffering from hypertensive emergency since she is having symptoms of weakness and dizziness. Besides, she also has retinal changes.

The available agents to treat her condition include the following: Table 20-2 Parenteral Drugs Commonly Used in the Treatment of Hypertensive Emergencies
Onset of Duration Drug (Brand Name) Dose/Route Action of Action Nitroprussidea (Nitropress) 50 IV infusiona Sec 35 min mg/2 mL (most commonly Start: 0.5 mcg/kg/min after D/C used) Usual: 25 mcg/kg/min infusion Max: 8 mcg/kg/min Diazoxide (Hyperstat IV) 300 50150 mg IV Q 5 min or as infusion 15 min 412 hr mg/20 mL of 7.530 mg/mind Enalaprilate (Vasotec IV) 1.25 0.6251.25 mg IV Q 6 hr 15 min 612 hr mg/mL 2.5 mg/2 mL (max, 14 hr) Esmololf (Brevibloc) 100 250500 mcg/kg over 1 minute then 12 min 1020 min mg/10 mL 2,500 mg/10 mL 50300 mcg/kg/min concentrate Fenoldopam (Corlopam) 10 0.10.3 mcg/kg/min <5 min 30 min mg/mL 20 mg/2 mL 50 mg/5 mL Hydralazineg (generic) 20 1020 mg IV 520 min 26 hr mg/mL Labetalolh (Normodyne) 20 2 mg/min IV or 2080 mg Q 10 min 25 min 36 hr mg/4 mL 40 mg/8 mL 100 up to 300 mg total dose mg/20 mL 200 mg/20 mL Nicardipinei (Cardene IV) 25 IV loading dose 5 mg/hr increased 210 min 4060 min mg/10 mL by 2.5 mg/hr Q 5 min to desired BP (max, 812 after D/C or a max of 15 mg/hr Q 15 min, hr) infusion followed by maintenance infusion of 3 mg/hr Nitroglycerinj (Tridil, Nitro-Bid IV infusion pump 5100 mcg/min 25 min 510 min IV, Nitro-Stat IV) 5 mg/mL 5 after D/C mg/10 mL25 mg/5 mL 50 infusion mg/10 mL 100 mg/20 mL Trimethaphan (Arfonad) 500 IV infusion pump 0.55 mg/min 15 min 10 min mg/10 mL after D/C infusion Phentolamine (Regitine) 15 mg IV initially, repeat as needed Immediate 1015 min

Nitroprusside is the drug of choice for acute hypertensive emergencies. It is supplied as 50 mg of lyophilized powder that is reconstituted with 23 mL of 5% dextrose in water (D5W), yielding a red-brown solution. The contents of the vial are added to 250, 500, or 1,000 mL of D5W to produce a solution for IV administration at a concentration of 200, 100, or 50

mcg/mL, respectively. The container should be wrapped with metal foil to prevent light-induced decompensation. Under these conditions, the solution is stable for 4 to 24 hr. A rising BP may indicate loss of potency. A change in color to yellow does not indicate effectiveness. The appearance of a dark brown, green, or blue color indicates loss in activity. The drug is more effective if the head of the bed is slightly raised. When changing to a new
b

bag,

the

administration

rate

may

require

adjustment.

Thiocyanate levels rise gradually in proportion to the dose and duration of

administration. The t1/2 of thiocyanate is 2.7 days with normal renal function and 9 days in patients with renal failure. Toxicity occurs after 7 14 days in patients with normal renal function and 36 days in renal failure patients. Thiocyanate serum levels should be measured after 34 days of therapy, and the drug should be discontinued if levels exceed 1012 mg/dL. Thiocyanate toxicity causes a neurotoxic syndrome of toxic psychosis, hyperreflexia, confusion, weakness, tinnitus, seizures, and coma.
c

Signs of cyanide toxicity include lactic acidosis, hypoxemia, tachycardia,

altered consciousness, seizures, and the smell of almonds on the breath. Concurrent administration of sodium thiosulfate or hydroxocobalamin may reduce
d

the

risk

of

cyanide

toxicity

in

high-risk

patients.

Diazoxide is administered as a bolus dose (13 mg/kg Q 5 min to a max of

150 mg/injection) or as a slow infusion (1520 mg/min) until a diastolic pressure of 100 mmHg is reached. Significant fluid retention following diazoxide can cause HF and pulmonary edema. Concurrent loop diuretics are recommended (e.g., furosemide 40 mg IV) if diazoxide is given by rapid IV bolus. Reflex in heart rate and stroke volume are potentially dangerous in patients with angina or MI. Concurrent -blockers may be protective.
e

Not approved by the U.S. Food and Drug Administration for treatment of hypertension.

acute
f g

Approved for intraoperative and postoperative treatment of hypertension. Parenteral hydralazine is an intermediate treatment between oral agents

and more aggressive therapies such as nitroprusside or diazoxide. It can be given IV or intramuscularly, but there is no appreciable difference in onset of action (2040 min) between the two routes. This slow onset minimizes hypotension.

Labetalol is contraindicated in acute decompensated HF due to its -

blocking properties. A solution for continuous infusion is prepared by adding two 100-mg ampules to 160 mL of IV fluid to give a final concentration of 1 mg/mL. Infusions start at 2 mg/min and are titrated until a satisfactory response or a cumulative dose of 300 mg is achieved.
i

Indicated for short-term treatment of hypertension when the oral route is feasible or desirable. Requires special delivery system due to drug binding to PVC tubing. Also

not
j

see Chapters 16 and 17 for further information regarding nitroglycerin. ACE, angiotensin-converting enzyme; BP, blood pressure; Ca, calcium; D/C, discontinued; HF, heart failure; IV, intravenous; MI, myocardial infarction; Na, sodium; Q, every.

2. How would you improve long-term hypertension control in Mrs. Minoh? To improve long-term hypertension control in Mrs. Minoh, it important for us to encourage Mrs. Minoh to self-monitor her blood pressure and record the reading according. The target blood pressure for her is below 140/100 mmHg. Also, it is also important to ensure the compliance of Mrs. Minoh towards her medication. It is also encourage that Mrs. Minoh continues her lifestyle modifications management of hypertension that is discussed earlier.

REFERENCE
1. Lloyd Y. Young, Koda-Kimble, Applied Therapeutic: The Clinical Use

of Drugs (9th edition), San Francisco, Applied Therapeutic Inc. 2. Joseph T. Dipiro et al. Pharmacotherapy. A pathophysiologic Approach, (latest edition), Elsevier, London 3. Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII). Arch Intern Med 1997;157;2413-1446. JAMA 2003;289

4. Clinical Practice Guidelines on the management of Hypertension 2002. Ministry of Health, Malaysia