Hypertension 1
Definition Hypertension can be defined as a condition where blood pressure is elevated to an extent that clinical benefit is obtained from blood pressure lowering. it is an important risk factor for development of cardiovascular disease. 2
New classification of HT Systolic Diastolic Normal <120 <80 Prehypertension 120---139 80---89 Stage1HT 140---159 90---99 Stage 2 HT >160 or >100 3
Causes of hypertension 1- Primary or Essential hypertension About 90%-95% of cases of HT is essential hypertension, there is no underlying medical illness to cause high blood pressure but may affected by a number of factors including 4
1- Age : BP tends to elevate with increasing age, probably due to decrease compliance of the blood vessels, lead to an alteration in peripheral resistance (PR) & hence to elevate BP. 2-Genetics : Although no single gene appears to be responsible but there is a tendency for HT to run in families, may be due to environmental factors that are acquired from the family (weight, race and high salt or alcohol intake ). 5
2- Secondary hypertension about 5-10 % of cases of HT is secondary hypertension. Common causes of secondary hypertension 1- Renal disease 2- Endocrine disease steroid excess: hyperglucocorticoidism (Cushing s syndrome); hyperaldosteronism (Conn s syndrome) Growth hormone excess: Acromegaly Catecholamine excess: Phaeochromocytoma Others : pre- eclampsia 6
3- Vascular causes renal artery stenosis 4- Drugs Sympathomimetic amines Oestrogens (combined oral contraceptive pills) Cyclosporine Erythropoietin NSAID steroids 7
Regulation of blood pressure The mean blood pressure is the product of cardiac output and total peripheral resistance. In most hypertensive individuals, cardiac output is not increased and high blood pressure arises as a result of increased total peripheral resistance caused by constriction of small arterioles. 8
Blood pressure regulated by Baroreceptor reflex. Renin angiotensin aldosterone system. Nitric oxide, atrial natriuretic peptide, bradykinin and antidiuretic hormone. 9
Clinical presentation of hypertension Hypertension is an incidental finding when subjects present for screening or with unrelated conditions. Severe cases may present with headache, visual disturbances or evidence of target organ damage ( stroke, ischemic heart disease or renal failure). 10
Malignant (accelerated ) hypertension Occur in patient with primary or secondary hypertension & is often associated with renovascular disease. Blood pressure may arise to more than 220\ 120 mmhg. It is characterized by a rapid rise in BP, with associated damage to small blood vessels, seen most markedly in the eye ( hemorrhages ), in kidney (haematuria & proteinurea i.e. impaired renal functions ) & cerebral edema that ends with confusion, headache & coma. 11
This condition usually seen in younger smoker patient. It is a medical emergency that needs hospital admission & rapid control of BP over 12 24 hrs towards normal levels. 12
Diagnosis of hypertension Blood pressure should be measured using a mercury sphygmomanometer. Blood pressure should initially measured in both arms & the arm with the highest value used for the subsequent readings. The subject should be relaxed at least at the first presentation, blood pleasure should be measured in both the sitting and the standing position. 13
Assessment of the hypertensive patient Before initiating any antihypertensive drugs a full history about the patient should obtained including the features & symptoms that might suggest a possible secondary causes. e.g., symptoms of : 14
Patient with renal disease include hematuria & polyuria. Patient with pheochromocytoma may have a history of headaches, sweating, tachycardia, palpitations, and hypertension. In primary aldosteronism, hypokalemic symptoms of muscle cramps and weakness may be present. Patients with hypertension secondary to Cushing s syndrome may complain of weight gain, edema, moon face, buffalo hump, hirsutism, polyuria,, menstrual irregularities, recurrent acne, or muscular weakness. 15
Laboratory tests that should be obtained in all patients prior to initiating drug therapy include urinalysis, urea, creatinine, complete blood cell count, serum chemistries (sodium, potassium, creatinine, fasting glucose, fasting lipid profile). In some patient further investigation may be needed, like the presence of protein, blood cells, and casts in the urine may indicate renovascular disease. plasma and urinary aldosterone levels as well as Renin-angiotensin ratio to investigate a possible hyperaldosteronism. 16
A 24hr or overnight urinary catecholamine for phaeochromocytoma. Also an increase in serum glucose & plasma cortisol to investigate for a possible Cushing syndrome, -----etc. The patient should examine for evidence of end- organ damages from hypertension includes examination of fundus to detect retinal changes, an ECG to detect IHD. Determination of cardiovascular risk is also important for example previous MI or stroke, angina or peripheral vascular disease & D.M. 17
Complication of hypertension: Untreated systemic HT, regardless the cause result in inflammation & necrosis of the arterioles, narrowing blood vessels restricting blood flow to major body organs which may leads to target organ damage including: 1) Brain: A vessel damage within the brain result in - Severe headache with nausea &vomiting - Drowsiness, anxiety & mental impairment. - Stroke or transient ischemic attack. 18
2) Eye: A damage to arterioles that supply the retina result in retinal hemorrhage leads to retinopathy. 3) Heart: Insufficient blood flow to coronary vessels, end with anginal pain. 4) Renal: A renal finding may give rise to polyuria, nocturia, protein & RBC in urine. 5) Peripheral arterial disease: A decreased blood supply to peripheral end with intermittent claudication. 19
Goal of treatment of HT( objective of treatment) 1) To prevent or reverse organ damage. 2) Lower BP below 140/ 85 mmhg with minimum side effect. The overall goal of treating hypertension is to reduce morbidity and mortality. 20
Treatment Non-pharmacological approaches In patients who are overweight, weight loss results in reduction in blood pressure of about 2.5 /1.5 mmhg/kg. Subject should reduce their salt intake (do not add salt to food on the plate) Patient should control their intake of calories &saturated fat, better to take a diet high in fruit, vegetables. 21
Regular exercise on most days for at least 30 minutes is necessary. Alcohol intake should also restricted. Although smoking doesn t affect BP, but it increase cardiovascular risk. 22
Target blood pressures An optimum target blood pressure is less than 140/85mmHg. Goal BP values are <140/85 for most patients, but <130/80 for patients with diabetes mellitus, chronic kidney disease. 23
Choice of therapy Monotherapy starting with one drug to treat HT& a blood pressure goal <140/85mmHg. 24
Stepped care approach A single agent is selected &then increase the dose of the drug first used until BP is controlled, the maximum dose is reached. If goal BP is not achieved substitute another or add a second drug of a different class &if necessary until 3 or 4 drugs are used. 25
Combination therapy: starting therapy with a combination of 2 drugs It is recommended for patient in whom goal BP achievement is difficult like HT patient with D.M. or chronic kidney disease. 26
Antihypertensive drugs Diuretics Thiazide diuretics. Loop diuretics. Potassium sparing diuretics. 27
Thiazide diuretics Chlorothiazide. Hydrochlorothiazide. Benzthiazide. Bendroflumethiazide. Thiazide- like (Chlorthalidone, Indapamide& Xipamide) 28
Thiazide diuretics are both inexpensive & well tolerated by most patients It is used as a step one antihypertensive. Their diuretic action achieved by blockade of distal renal tubular sodium reabsorption. Initially they reduce blood pressure by reducing circulating blood volume but in longer term they reduce total peripheral resistance, suggesting a direct vasodilating action. 29
Thiazide and thiazide- like diuretics may cause hypokalemia, small increases in LDL-Cholesterol & triglyceride, gout associated with impaired urate excretion, hyperglycemia. Erectile dysfunction is also common. Most blood pressure lowering occurs with very low doses of thiazide diuretics. Increasing the dose increases the risk of metabolic disturbances without causing further blood pressure reduction. 30
Loop diuretics Furosemide Torasemide Bumetanide Ethacrynic acid 31
Loop diuretics indicated when the patient is impaired renal function or the patient receiving agents that inhibit the reninangiotensin system. They are also suitable choice if heart failure is present. 32
Side effects of loop diuretics the same as thiazide, hypokalemia, hyperurecimia, hyperglycemia, dehydration. Diuretics should be dosed in the morning if given once daily and in the morning and afternoon if dosed twice daily to minimize the risk of nocturnal diuresis 33
Potassium sparing diuretics Amiloride Triamterene Spironolactone (Aldosteron receptor blocker) (Aldacton) Eplerenone. 34
Spironolactone is not suitable for first line therapy but is important to patient with resistant hypertension, or hyperaldosteronism (it antagonizes aldosterone). It can increase potassium & cause hyperkalemia. This risk is increased in patient with chronic renal failure due to accumulation of potassium & when used in combination with ACE inhibitors or ARBs (should avoided in these patients). 35
Gynecomastia is the most common SE of spironalactone, not occur in Eplerenone. However Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria. 36
β -blockers :( β - adrenoreceptor antagonists) Atenolol Nadolol Pindolol Metoprolol Propranolol Oxprenolol Esmolol Timolol Carvidilol Bisoprolol Labetolol Acebutolol Sotalol Betaxolol 37
Some references indicate that β - blocker along with thiazide are the mainstay of antihypertensive therapy & it can be used as initial therapy for HT. Now a day their use is likely to decline because they seen less effective at preventing stroke & are commonly associated with adverse effects. They remain most suitable for younger hypertensive who have another indication for β - blockade such as coronary heart disease. 38
β -blockers are drugs that block the β - adreno receptor in different organ; in heart, kidney, peripheral vasculature, bronchi. etc There are more than one β - adrenoreceptor, β 1 are found in the heart. Stimulation of β1 causes an increase in heart rate, cardiac output & cardiac contractility. Therefore using β - blocker will decrease cardiac contractility, diminishing cardiac output and decrease blood pressure. 39
There is β-receptor in kidney. A stimulation of such receptor leads to an increase in renin production. That is why using β -blocker will block renin secretion with a decrease in B.P. 40
β 2 adrenoreceptors are wide spread throughout the body ( small blood vessels ) & bronchi. Stimulation of β 2- receptor leads to dilatation of arterioles & veins, also dilatation of bronchioles. Using non selective β -blocker (propranolol ) leads to bronchoconstriction (asthma) & in small vessels,it worsened (intermittent claudication). 41
Side effects from β-blockade in the myocardium include bradycardia, AV conduction abnormalities, and acute heart failure (systolic heart failure). B- blockers contraindicate in patients with heart block and heart failure (except Metoprolol, Bisoprolol,carvidolol safe in CHF). Patient should monitor for sign of reduced cardiac output. ECG should be done routinely. 42
β- blockers cause dyslipidemia, so monitoring lipid profile is necessary. β-blockers increase serum TG levels and decrease HDL cholesterol levels slightly. β-blockers with α-blocking properties (carvedilol and labetalol) do not affect serum lipid concentrations. β -blockers should be used with caution in patients with diabetes mellitus, it can musk hypoglycemia effect such as tachycardia (i.e. mask sign & symptoms of hypoglycemia). 43
The so- called cardioselective β - blockers (β 1- selective) are not free of these adverse effects so no β - blockers is totally safe in patients with bronchospasm because cardioselectively is dose dependent (i.e. even selective β blockers loss its selectivity at high dose ). 44
Blocking β2-receptors in arteriolar smooth muscle may cause cold extremities and aggravate peripheral arterial disease or Raynaud s phenomenon because of decreased peripheral blood flow. Sudden cessation of β - blocker therapy will produce a withdrawal syndrome which includes: Exacerbation of anginal attack, MI & A life threatening rebound of BP to a high level. For these reasons, it always should be tapered gradually over 1 to 2 weeks before discontinuation. 45
Other common SE of β - blockers that should monitored are impotence & increase insulin resistance. 46
Classification of β - blocker 1. Lipophylic β -blocker (lipid soluble): which can enter blood brain barrier (B.B.B.), & have the following central side effect like nightmares, sleep disturbance & hallucination e.g. propranolol. 2. Hydrophilic β - blockers (water soluble): like Atenolol, Nadolol & Sotalol are the most water soluble, less likely to enter the B.B.B,so less sleep disturbance & nightmares. Water soluble β - blockers are excreted by the kidney, so in renal impairment, accumulation will be the result & dosage reduction is necessary. 47
Angiotensin converting enzyme inhibitors: Captopril Enalopril Lisinopril Ramipril Benazepril Fosinopril Moexipril Perindopril Quinapril Trandolapril 48
These drugs act by blocking the conversion of angiotensin I to Angiotensin II & so prevent the vasoconstriction effect of angiotensin II & the sod. retention caused by aldosterone. All ACE inhibitors can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril is reduced by 30% to 40% when given with food. 49
ACEI cause very rapid falls of blood pressure in some patient particularly in those receiving diuretic therapy, in patients who are sodiumor volume-depleted, in heart failure exacerbation, very elderly, or on concurrent vasodilators. Patients with these risk factors should start with half the normal dose followed by slow dose titration (e.g., 6-week intervals). 50
Acute renal failure is a rare but serious side effect of ACE inhibitors; preexisting kidney disease increases the risk. Renal function & electrolytes should be checked before starting ACE inhibitors & monitored during treatment. 51
ACE inhibitors decrease aldosterone and can increase serum potassium concentrations. Hyperkalemia occurs primarily in patients with chronic kidney disease or diabetes and in those also taking ARBs, potassium supplements, or potassium-sparing diuretics. 52
ACE inhibitors causes dry cough, angioedema and renal failure. ACE inhibitors is contraindicated in Reno vascular disease and pregnancy. 53
Angiotensin II receptor blockers : Valsartan Losartan Telmisartan Candesartan Eprosartan Irbesartan Olmesartan 54
ARBs block the action of angiotensin II at the angiotensin II type 2 receptor & so prevent the vasoconstriction effect of angiotensin II & the sod. retention caused by aldosterone. Unlike ACEI, they don t cause dry cough. Like ACE inhibitors, they may cause renal insufficiency, hyperkalemia and orthostatic hypotension. Angioedema is less likely to occur than with ACE inhibitors, but cross reactivity has been reported. ARBs should not be used in pregnancy. 55
Calcium channel blockers CCB: Dihydropyridine CCB Nifedipin Amlodipin Nicardipin Nimodipin Felodipin Isradipine Nisoldipine Non-dihydropyridine CCB Verapamil Diltiazem 56
All these agent block calcium channels in the peripheral blood vessels &/ or the heart. The dihydropyridine group( Nifedipine etc.) work almost exclusively by inhibiting the influx of extra cellular Ca into the cell of smooth muscle of the peripheral arterioles, reducing BP by reducing total peripheral resistance (peripheral vasodilatation). 57
Dihydropyridine group has little direct action on heart but a greater effect on peripheral arterioles, this effect making them more suitable as initial therapy of mild to moderate HT. In contrast, Verapamil & diltiazem work primarily on the heart, reducing heart rate & cardiac output. 58
Verapamil & diltiazem contraindicated in HF and combination with B-blocker, because they may further decrease cardiac function.(diltiazem decrease heart rate but to a lesser extent than verapamil ). Verapamil is an excellent drug for treatment of supraventricular tachycardia. Adverse effects of Dihydropyridine CCB are common, for example Peripheral odema, headache, flushing & postural hypotension. Adverse effects of Non-dihydropyridine CCB include bradycardia and constipation ( only verapamil). 59
α- adrenoreceptor blockers: Drugs of this class antagonise α- adrenoreceptors in the blood vessel wall and, thus, prevent noradrenaline (norepinephrine) induced vasoconstriction. As a result, they reduce total peripheral resistance and blood pressure. Examples of such drugs are :Prazosin, Terazosin and doxazosin. 60
A potentially severe side effect is a first-dose phenomenon characterized by orthostatic hypotension (postural hypotension), so first dose should be given at bedtime. Sodium and water retention can occur with chronic administration. These agents are most effective when given with a diuretic to maintain antihypertensive efficacy and minimize potential edema. 61
Centrally acting drugs: Methyldopa and moxonidine inhibit sympathetic outflow from CNS to the cardiovascular system with a resultant decrease in total peripheral resistance & a decrease in B.P. Methyldopa is not widely used because it has central adverse effects, including tiredness and depression, but safe to use in pregnancy & for patient with resistance HT. 62
It causes orthostatic hypotension so should be used cautiously in elderly patients. It requires the use of diuretic because it causes fluid accumulation. It also causes rebound hypertension upon abrupt withdrawal. Be careful that sedation is common finding at initial therapy & when doses are increased. 63
A liver function test should be followed routinely to monitor hepatic enzymes, (Contraindicated in hepatic dysfunction). It may cause hemolytic anemia which is reversible on discontinuations, so RBCs, HB, blood count should be checked. ( C\I. in hemolytic anemia). 64
Moxonidine appears to have fewer central adverse effect than methyldopa. These agents have anticholenergic SE e.g. sedation,dizziness, dry mouth & sexual dysfunction. 65
Other centrally acting agents such as clonidine and reserpine are never used in modern practice because of their pronounced adverse effects. 66
Vasodilators: These drugs are available for use for people with more resistant HT. They act by direct relaxing peripheral vascular smooth muscle (arterial & venous ) or both. 67
Minoxidil It is a powerful antihypertensive drug but its use associated with sever peripheral edema & reflex tachycardia.it should be restricted to patients with severe hypertension who are also taking diuretics & B-blockers. It cause hirsutism so not a suitable treatment for women. 68
Hydralazine Usually used in moderate to severe HT. It causes direct vasodilatation of arterioles ( relax arterioles ) & reduce PVR. It can be used safely during pregnancy. It is a drug of choice for hypertensive crises, given by i.v. or i.m. route. 69
Useful to combine with diuretic & B- blockers to prevent reflex tachycardia & fluid retention. A liver function test is necessary,since such drug can cause liver damage. It induces systemic lupus erythematosus SLE, which appears after long term therapy with a daily dose over 100mg.Patient needs a complete blood counts with antinuclear antibody titers(ana),that should routinely evaluated.patient should also reports symptoms that are signals for SLE like fatigue, fever, weight loss &joint pain. 70
Sodium Nitroprusside It is a direct acting peripheral dilator. It affects on both arterioles & venous system. It used only in short term emergency treatment of acute hypertensive crises., especially when a rapid onset is required. It also used for acute control of B.P during anesthesia. 71
given by i.v. with continuous B.P. monitoring. To prevent acute hypotension, an initial dose should be very low, followed by slow push until the desired effect is achieved. 72
Diazoxide: It exerts a direct action on arterioles & little effect on venous capacity used by i.v. route in emergency treatment of acute hypertensive crises. It should be administered by slow infusion over a period of 15-30 minutes. 73
It can produce transient hyperglycemia so require caution if administered to diabetic patients. It also require a combination therapy with diuretic to reduce odema SE. 74