HYPERTENSION Hypertension is a risk factor for many coronary cases. However, blood pressure can be lowered through appropriate therapy, thereby reducing the risk of stroke, coronary events, heart and kidney failure. The pathogenesis of hypertension involves many factors. These include increased cardiac output, increased peripheral resistance, vasoconstriction and decreased vasodilation. The kidneys also play a role in blood pressure regulation through the control of sodium and water excretion, and renin secretion, which influences vascular pressure and electrolyte imbalance. Neuronal mechanisms such as the sympathetic nervous system and endocrine system are also involved in blood pressure regulation. Therefore, these systems are targets for drug therapy to lower blood pressure. Target blood pressure. Optimal systolic blood pressure (SBP) is < 140 mmHg and optimal diastolic blood pressure (DBP) is < 85 mmHg. For patients with atherosclerotic cardiovascular disease, diabetes or chronic renal failure the target SBP is 130 mmHg and DBP <80 mmHg. Guidelines for starting pharmacological therapy as recommended in BNF can be seen in Table 1. Regardless of the level of emergency of hypertension, all patients must receive advice/recommendations related to lifestyle management to reduce blood pressure. Includes advice on quitting smoking, losing weight, exercising, reducing alcohol intake and diet. Drug class The classes of antihypertensive drugs that are widely used are thiazide diuretics (eg bendroflumethiazide), beta- ‐blockers, (eg propranolol, atenolol,) angiotensin converting enzymes inhibitors (eg captopril, enalapril), angiotensin II antagonists (eg candesartan, losartan), calcium channel blockers (eg amlodipine, nifedipine) and alphablockers (eg doxasozin). Less frequently used are vasodilators and centrally acting antihypertensives and less commonly, guanethidine, which is indicated in hypertensive crisis situations. Thiazide diuretics Thiazide diuretics are medium-potency diuretics that lower blood pressure by inhibiting sodium reabsorption in the early region of the distal renal tubule, increasing sodium excretion and urine volume. Thiazides also have a direct vasodilating effect on arterioles, thereby maintaining their antihypertensive effect longer. Thiazides are well absorbed upon oral administration, widely distributed and metabolized in the liver. Thiazide diuretic effects occur within 1- ‐2 hours after administration and lasts up to 12- ‐24 hours, so this medicine is enough to be given once a day. The antihypertensive effect occurs at low doses and increasing the dose does not provide benefit on blood pressure, although diuresis increases at high doses. The effect of thiazides on the renal tubules depends on the rate of excretion, therefore thiazides are less useful for patients with impaired renal function. Side effects Increased urine excretion by thiazide diuretics can result in hypokalemia, hyponatriemia, and hypomagnesiemia. Hypercalcemia can occur due to decreased calcium excretion. Interference with uric acid excretion can result in hyperuricemia, so the use of thiazides in gout patients must be careful.- ‐heart. Thiazide diuretics may also interfere Beth Gormer, 2007, trans. Diana Lyrawati, 2008 2 glucose tolerance (insulin resistance) which results in an increased risk of type 2 diabetes mellitus. Another common side effect is hyperlipidemia, causing an increase in LDL and triglycerides and a decrease in HDL. 25% of men receiving thiazide diuretics experience impotence, but this effect disappears if the thiazide is stopped. Beta-blockers Beta blockersblock beta- ‐adrenoceptor. These receptors are classified as beta receptors- ‐1 and beta- ‐2. Beta receptors- ‐1 is mainly found in the heart while beta receptors- ‐2 are mostly found in the lungs- ‐lungs, peripheral blood vessels, and striated muscles. Beta receptors- ‐2 can also be found in the heart, while beta receptors- ‐1 can also be found in the kidneys. Beta receptors can also be found in the brain. Stimulation of beta receptors in the brain and periphery will stimulate the release of neurotransmitters which increase the activity of the sympathetic nervous system. Beta receptor stimulation- ‐1 at the sino node- ‐atrial and myocardial increases heart rate and force of contraction. Stimulation of beta receptors in the kidneys will cause the release of renin, increasing the activity of the reninangiotensin aldosterone system. The net effect is increased cardiac output, increased peripheral resistance and increased aldosterone-mediated sodium and water retention. Therapy using beta‐blockerswill antagonize all these effects resulting in a decrease in blood pressure. Beta- ‐blockersselective (also known as cardioselective beta- ‐blockers), for example bisoprolol, acts on beta receptors- ‐1, but is not specific for beta receptors- ‐1 only therefore its use in patients with a history of asthma and bronchospasm must be careful. Beta- ‐blockerswhich is not- ‐selective (e.g. propranolol) blocks beta receptors- ‐1 and beta- ‐2. Beta- ‐blockerswhich have partial agonist activity (known as intrinsic sympathomimetic activity), for example acebutolol, works as a stimulant‐beta when adrenergic activity is minimal (for example during sleep) but will block beta activity when adrenergic activity increases (for example during exercise). This is beneficial because it reduces bradycardia during the day. Some beta- ‐blockers, for example labetolol, and carvedilol, also block the effects of peripheral adrenoceptoralpha. Other drugs, for example celiprolol, have beta agonist effects- ‐2 or vasodilator. Beta- ‐blockersexcreted via the liver or kidneys depending on the solubility of the drug in water or lipids. Drug- ‐Drugs that are excreted through the liver usually have to be given several times a day, while those that are excreted through the kidneys usually have a longer half-life so they can be given once a day. Beta- ‐blockersshould not be stopped suddenly but should be done gradually, especially in patients with angina, because a rebound phenomenon can occur. Side effects Beta receptor blockade- ‐2 in the bronchi can cause bronchospasm, even if beta is used- ‐cardioselective blocker. Other side effects are bradycardia, myocardial contractile disorders, and hand cramps- ‐the feet feel cold due to vasoconstriction due to beta receptor blockade- ‐2 in peripheral vascular smooth muscle. Awareness of the symptoms of hypoglycemia in some type 1 DM patients may be reduced. This is because of the beta- ‐blockersblocks the sympathetic nervous system which is responsible for “giving warning” if hypoglycemia occurs. Reduced sympathetic blood flow also causes feelings of laziness in patients. Nightmares are sometimes experienced, especially on beta use- ‐blockerslipid soluble ones such as propranolol. Impotence may also occur. Beta- ‐blockersnon‐Selective also causes increases and decreases in serum triglyceride levels. ACE inhibitors Angiotensin converting enzyme inhibitor(ACEi) competitively inhibits the formation of angiotensin II from the inactive precursor angiotensin I, which is found in the blood, blood vessels, kidneys, heart, adrenal glands and brain. Angitensin II is a vaso- ‐A powerful constrictor that stimulates aldosterone release and central and peripheral sympathetic activity. Inhibition of the formation of angiotensin iI will reduce blood pressure. If the angiotensin system- ‐renin- ‐activated aldosterone (for example in conditions of sodium reduction, or in diuretic therapy) the antihypertensive effect of ACEi will be greater. ACE is also responsible for the degradation of quinins, including bradykinin, which has a vasodilatory effect. Inhibition of this degradation will result in a stronger antihypertensive effect. Some differences in the pharmacokinetic parameters of ACEi drugs. Captopril is rapidly absorbed but has a short duration of action, so it is useful for determining whether a patient will respond well to ACEi administration. The first dose of ACEii should be given in the evening because a sudden drop in blood pressure may occur; This effect will increase if the patient has low sodium levels. Angiotensin II antagonist Angiotensin II receptors are found in blood vessels and other targets. Subclassified into AT1 and AT2 receptors. The AT1 receptor mediates pharmacological responses to angiotensin II, such as vasoconstriction and aldosterone release. And therefore becomes a target for drug therapy. The function of the AT2 receptor is still not very clear. Many tissues are able to convert angiotensin I to angiotensin II without ACE. Therefore it blocks the renin system- ‐angiotensin via the AT1 receptor antagonist route with administration of angiotensin II receptor antagonists may be beneficial. Angiotensin II receptor antagonists (AIIRA) have many similarities to ACEi, but AIIRA does not degrade quinine. Because of their effects on the kidneys, ACEi and AIIRA are contraindicated in bilateral renal artery stenosis and in severe stenosis of the arteries supplying only one functioning kidney. Side effects of ACEi and AIIRA Before starting therapy with ACEi or AIIRA the patient's renal function and electrolyte levels should be checked. This monitoring must continue during therapy because these two classes of drugs can interfere with kidney function. Both ACEi and AIIRA can cause hyperkalemia as they decrease- ‐aldosterone production, so potassium supplementation and the use of potassium-sparing diuretics should be avoided if the patient is receiving ACEI or AIIRA therapy. The difference between ACEi and AIIRA is a dry cough which is a side effect found in 15% of patients receiving ACEi therapy. AIIRA does not cause coughing because it does not degrade bradykinin. Calcium channel blockers Calcium channel blockers(CCB) reduces the influx of calcium ions into myocardial cells, cells- ‐cells in the cardiac conduction system, and cells- ‐vascular smooth muscle cells. This effect will reduce heart contractility, suppress the formation and propagation of electrical impulses in the heart and stimulate vasodilation activity, interference with vascular smooth muscle constriction. All of the above are processes that depend on calcium ions. There are three classes of CCBs: dihydropyridines (e.g. nifedipine and amlodipine); phenylalkalamine (verapamil) and benzothiazipine (diltiazem). Dihydropyridine has peripheral vasodilator properties which is its antihypertensive action, while verapamil and diltiazem have cardiac effects and are used to reduce heart rate and prevent angina. All CCBs are metabolized in the liver. Side effects Facial flushing, dizziness and swelling of the ankles are common, due to the vasodilatory effects of dihydropyridine CCBs. Abdominal pain and nausea are also common. The gastrointestinal tract is also often affected by the influx of calcium ions, therefore CCB often results in gastro disorders- ‐intestinal tract, including constipation. Alpha-blockers Alpha- ‐blockers(adreno blocker- ‐alpha septor- ‐1) blocks alpha adrenoceptors- ‐1 peripherally, resulting in a vasodilation effect due to relaxing the smooth muscle of blood vessels. Indicated for resistant hypertension. Side effects Alpha- ‐blockersmay cause postural hypotension, which often occurs with the first dose. Alpha- ‐blockersuseful for male patients- ‐elderly men because it improves symptoms of prostate enlargement. Other groups Vasodilator antihypertensives (eg hydralazine, minoxidil) lower blood pressure by relaxing blood vessel smooth muscle. Centrally acting antihypertensives (e.g. clonidine, methyldopa, monoxidin) act on alpha adrenoceptors- ‐2 or other receptors in the brain stem, reduce sympathetic flow to the heart, blood vessels and kidneys, so that the ultimate effect is to lower blood pressure. Side effects Vasodilator antihypertensives can cause fluid retention. Liver function tests should be monitored during therapy with hydralazine because of its hepatic excretion. Hydralazine is also associated with systemic lupus erythematosus. Minoxidil is associated with hypertrichosis (hirsutism) making it less suitable for female patients. Drug- ‐Central-acting drugs are not specific or selective enough to avoid central nervous system side effects such as sedation, dry mouth and drowsiness, which often occur. Methyldopa has a similar mechanism of action to conidine but can cause side effects on the immune system, including pyrexia, hepatitis and hemolytic anemia. Choice of therapy Updates from NICE can be seen in Table 2. The main change to the NICE guidance is beta- ‐blockers are no longer recommended as first-line therapy in all patients. Beta blockers are less effective at reducing major cardiovascular events, especially stroke, than other antihypertensives. Beta- ‐blockers are also less effective than ACEi or dihydropyridine CCBs for reducing the risk of diabetes, especially in patients receiving thiazide diuretic therapy. If the patient is taking beta- ‐blockersIf other antihypertensives are needed, the preferred choice is ACEi or CCB, rather than thiazides. Special pregnancy considerations Centrally acting drugs have poor CNS profiles. However, methyldopa is used in pregnancy, because of its safety data compared to beta- ‐blockers are used in the third trimester. Intravenous labetolol is only used in hypertensive crisis situations. Sustained-release nifedipine preparations can also be used but are not licensed. Nice special considerations Thiazide diuretics and dihydropyridine CCBs are more effective than beta- ‐blocker for Afro patients- ‐Caribbean. ACEi and AIIRA increase the risk of stroke in patients of this ethnic group so they are not recommended as first-line therapy. Special considerations for seniors The new NICE guidelines suggest that thiazide diuretics or dihydropyridine CCBs are first-line therapy for elderly patients. However, attention must be paid to renal function during therapy with thiazides because elderly patients are more at risk of developing renal impairment. Patients over 80 years old can be given therapy like patients aged > 55 years. Diabetes Diabetes patients require a combination of antihypertensives to achieve optimal blood pressure targets. ACEi is the initial therapy of choice because it can prevent the progression of icroalbumiuria to nephropathy. Patients with diabetic nephropathy should receive ACEi or AIIRA to minimize the risk of further kidney damage, even if their blood pressure is normal. Kidney illness ACEi can reduce or eliminate glomerular filtration and cause severe progressive renal failure. Therefore it is contraindicated in patients with bilateral renal artery stenosis. However, ACEi had no adverse effects on renal function in patients with unilateral renal artery stenosis. Dihydropyridine CCBs may be added if further blood pressure reduction is required, whereas thiazide diuretics are ineffective. Systolic hypertension Systolic hypertension alone (isolated systolic hypertension, ISH) is defined as SBP more than 160 mmHg with DBP less than 90 mmHg. Patients with ISH receive the same therapy as patients with elevated SBP and DBP because ISH is also at risk of the same complications. Dihydropyridine CCBs are used as therapy for ISH in elderly patients, especially if thiazide diuretics are contraindicated. Rapid hypertension (accelerated hypertension) Accelerated hypertensionor very severe hypertension, defined as a DBP of more than 140 mmHg, requiring immediate medical attention. Beta- ‐blockers such as atenolol or labetolol or dihydropyridine CCBs are indicated for this condition. DBP should be reduced to 100- ‐110 mmHg for the first 24 hours. Blood pressure should be lowered again for 2- ‐The next 3 days use a combination of diuretic, vasodilator and ACEi, if necessary. If intravenous therapy is required, sodium nitroprusside or glyceryl trinitrate is recommended. DIABETES MELLITUS Hyperglycemia is a medical condition in which blood glucose levels increase beyond normal limits. Hyperglycemia is one of the typical signs of diabetes mellitus (DM), although it may also occur in several other conditions. Currently, epidemiological research shows a trend of increasing incidence and prevalence of type 2 DM in various parts of the world. The World Health Organization (WHO) predicts an increase in the number of people with DM which is a global health threat. DM disease greatly affects the quality of human resources and has an impact on a significant increase in health costs. Therefore, all parties, both society and government, should actively participate in efforts to overcome DM, especially in prevention efforts. The role of general practitioners as the spearhead in primary health care is very important. Simple DM cases without complications can be managed completely by general practitioners in primary health care. DM sufferers with blood glucose levels that are difficult to control or who have the potential to experience complications from DM need to be periodically consulted by a specialist in internal medicine or a specialist in metabolic endocrine and diabetes consultants at a higher level of health services at a referral hospital. Patients can be sent back to primary care doctors after treatment at the referral hospital is complete. Management of diabetes mellitus In general, there are five principles for managing diabetes mellitus in accordance with the 2006 DM Management Consensus in Indonesia, namely to improve the quality of life of DM patients. The aim of DM management is Short-term: disappearance of complaints and signs of DM, maintaining a sense of comfort and achieving blood glucose control targets. Long-term: preventing and inhibiting the progression of microangiopathy, macroangiopathy and neuropathy complications. The ultimate goal of management is to reduce DM morbidity and mortality. To achieve this goal, it is necessary to control blood glucose, blood pressure, body weight and lipid profile, through holistic patient management by teaching self-care and changing behavior. Diet The principles of eating for people with diabetes are almost the same as the recommendations for eating for the general public, namely food that is balanced and in accordance with the calorie and nutritional needs of each individual. For people with diabetes, it is necessary to emphasize the importance of regular eating in terms of eating schedule, type and amount of food, especially for those who use blood glucose-lowering drugs or insulin. The recommended standard is food with a balanced composition in terms of 60-70% carbohydrates, 20-25% fat and 10-15% protein. To determine nutritional status, it is calculated using BMI (Body Mass Index). Body Mass Index (BMI) is a simple tool or way to monitor the nutritional status of adults, especially those related to underweight and overweight. Exercise It is recommended to exercise regularly (3-4 times a week) for approximately 30 minutes, which is in accordance with Continuous, Rhythmical, Interval, Progressive, Endurance (CRIPE). Training according to the patient's abilities. An example is light exercise, walking for 30 minutes. Avoid sedentary or lazy living habits. Health education Health education is very important in management. Primary prevention health education must be provided to high risk community groups. Secondary health education is provided to the DM patient group. Meanwhile, health education for tertiary prevention is given to patients who already suffer from DM with chronic complications. Drug If the patient has made eating arrangements and physical exercise but is unable to control blood sugar levels, then considering the use of hypoglycemic drugs Diabetes mellitus medications Oral antidiabetic Management of DM patients is carried out by normalizing blood sugar levels and preventing complications. More specifically by eliminating symptoms, optimizing metabolic parameters, and controlling body weight. For type 1 DM patients, insulin use is the main therapy. The indication for oral antidiabetics is mainly intended for the treatment of mild to moderate type 2 DM patients who fail to be controlled by regulating energy and carbohydrate intake and exercise. This class of drug is added if after 4-8 weeks of diet and exercise efforts, blood sugar levels remain above 200 mg% and HbA1c above 8%. So this drug does not replace diet efforts, but rather helps it. Choosing the right oral antidiabetic drug greatly determines the success of diabetes therapy. The choice of therapy using oral antidiabetics can be done with one type of drug or a combination. The selection and determination of the oral antidiabetic regimen used must take into account the severity of DM disease and the patient's general health condition, including other diseases and existing complications. In this case, oral hypoglycemic drugs include sulfonylureas, biguanides, alpha glucosidase inhibitors and insulin sensitizers. Insulin Insulin is a small protein with a molecular weight of 5808 in humans. Insulin contains 51 amino acids arranged in two chains connected by a disulfide bridge, there are differences in the amino acids of the two chains. For patients who are not controlled by diet or oral hypoglycemics, a combination of insulin and other medications can be very effective. Insulin is sometimes used as a temporary option, for example during pregnancy. However, in patients with worsening type 2 DM, total insulin replacement becomes necessary. Insulin is a hormone that affects carbohydrate metabolism as well as protein and fat metabolism. The functions of insulin include increasing the uptake of glucose into the cells of most tissues, increasing the oxidative breakdown of glucose, increasing the formation of glycogen in the liver and muscles and preventing the breakdown of glycogen, stimulating the formation of protein and fat from glucose.