Indications of special treatment needed
Specialists assume that in cases of steady rise of diastolic pressure (higher than 90 mmHg) and after 65 years even an increase of systolic blood pressure (higher than 160 mmHg) the cause of the disease should be found and some treatment actions taken. It must be considered that men have a higher risk of complications than women having the same pressure level and young people higher than elder. Furthermore, the treatment itself is attended by a risk of hypotensive drugs side effects, for instance, 35% of men that are treated for hypertensive disease, suffer from different degree potency disorders and some clinicians assume this as an unjustified risk. For example, for women after 70 years with asymptomatic diastolic pressure elevation up to 90 mmHg and men after 30 years with diastolic pressure elevation higher than 90 mmHg antihypertensive therapy is essential. Great deal of choice of hypotensive drugs is a factor that helps to select an ideal treatment schedule with minimum side effects in 95% of cases. Patients suffering from hypertension that do not get any antihypertensive treatment have to pass a check-up every 3 months. Patients with cardiac angina or diabetes mellitus in confirmed ischemic heart disease or in presence of atherosclerosis threats have to undergo an antihypertensive treatment even in a slightly increased ABP. In such a situation it is prescribed even at 85-90 mmHg of diastolic ABP.
Drug-free treatment in presence of hypertension is obligatory to every patient.
It consists of:
- 1. Limitation of emotional stress
- 2. Appropriate diet (reduction of salt intake)
- 3. Exercise therapy
- 4. Fat loss (special fat-loss diet)
- 5. Atherosclerosis risk factor reduction
Although emotional stress is quite impossible to be excluded completely, it is recommended to reduce it. Sometimes people have to change their job or lifestyle. It is proved that salt-free diet drops the ABP level, that’s why patients need to cut down their salt consumption. Some recent investigations have shown that reduction of sodium intake on 4,0 g/day reduce systolic pressure on 5 mmHg and diastolic on 2,6 mmHg. However, low-salt diet does not effect on pressure, but it potentiates all the hypotensive drugs what helps to cut down the doses and reduce the side effects risk. Sometimes though, low-salt diet directly reduces ABP. As far as it is harmless, patients are suggested to pare down consumption of sodium chlorate to 5 g/day what is only about to add no salt in your foods while eating.
Some researches published in professional literature performed that pressure is reduced in high intake of calcium and potassium. The other researches have shown potassium added to ration (50-120 mmol/day) leads to systolic pressure reduction on 6 mmHg and diastolic on 3,4 mmHg – the results are similar to low-salt diet. Moreover, heavy potassium consumption (1,5 g/day) assists in senile osteoporosis. Against presentation of obesity in patients with hypertension, it is recommended to keep the low-fat diet, as far as sometimes it is enough to get rid of excessive weight to have the pressure level decreased. In clinical research of TAIM (Trial of Antihypertensive Interventions and Management) fat loss (4,4 kg at 6 months on the average) has shown to reduce the pressure on 2,5 mmHg.
Cholesterol and saturated fatty acids consumption limitation also leads to reduction of a atherogenesis onset risk. On top of this, it is necessary to limit alcohol consumption as it produces a rise of pressure, especially in cases of abusive drinking. Exercise therapy schedule should be chosen by taking into account patient’s possibilities. That helps to loose weight and reduce the pressure due to accelerated tissue oxygenation. Those patients are recommended to do some isotonic exercises (jogging, swimming) and never non-isometric (weight-lifting) that boosts pressure. The diet should be matched by other risk factors elimination. One of the most significant steps is being off smoking.
It is necessary to understand action mechanisms of antihypertensive drugs to use them in the most effective way. Nowadays hypotension treatment includes 6 basic drug groups:
- Medicines that decrease the activity of sympathoadrenal system,
- Direct vasodilator,
- Calcium antagonist,
- ACE blockers,
- Angiotensin receptors antagonist.
Thiazide diuretics are the most studied drugs and there is enough clinical experience accumulated. They decrease pressure within a short space of time, usually it takes 3-4 days by means of sodium excretion and hypovolemia. At current observations, diuretics decrease total peripheral vascular resistance. According to long-term clinical trials, thiazide diuretics significantly decrease fatality and hypertensive disease hazards (in Israel it is “Disothiazid”). Over the last years their popularity has dropped principally due to the negative impact on electrolyte exchange as prolonged usage can lead to hypokalemia (potassium excretion), hyperuricemia (uric acid retention) and hyperlipoproteinemia. Strong drugs – loop diuretics “furosemide” and “bumetanide” – are also good at decreasing arterial pressure but their usage is limited due to the short duration. Competitive antagonist of aldosterone – spironolactone – in Israel is sold under the name of “Aldactone” – Russian annona “Verospiron” increases sodium excretion and has a great effect on hyperaldosteronism (primary and secondary). Two other potassium-sparing diuretics – “Triamterene” and “Amiloride” – effect on the same nephron units, prevent from sodium reabsorption but their action is not connected with aldosterone. The indications of “Triamterene” and “Amiloride” prescription are similar to “spironolactone”, by the way, triamterene has hypotensive action. The main drawback of potassium-sparing diuretics is a hyperkalemia hazard, especially in chronic renal insufficiency, although they can be combined with thiazide diuretics to potassium loss reduction.
II. Medications that reduce sympathoadrenal system activity
The points of use of these medications are vasomotor center of medulla, sympathetic postganglionic neurons and peripheral adrenoreceptors. Usually they have the same effect – cardiac output and heart rate reduction but baroreflex does not change and that’s why they do not lead to orthostatic hypotony. In recent decade ganglionic blockers are rarely used – just in cases of emergency to decrease pressure quickly – because of the hazard of side effects. Risk of complications makes it hard to use sympatholytics. “Guanetidin” and its short-range analog “guanadrel” block norepinephrine output from sympathetic nerve terminals. As a result, cardiac output reduces and systolic blood pressure drops lower than diastolic pressure. Orthostatic hypotony arises more frequently and it is extremely intensive than in case of another sympatholic use – reserpine. As well as α-blockers, β-blockers also have an effect on peripheral adrenoreceptors.
Alpha and Beta - adrenoblockers. In Israel those are:
- Cadex – selective alpha-1-blocker.
- Cardiloc – selective β-blocker.
- Neobloc – selective α-blocker.
- Normiten – α-blocker.
- Slouderolin – α-blocker.
- Lopresor – selective β-blocker.
Those drugs block catecholamine influence on heart and that helps them significantly to cut down cardiac output and decrease pressure when sympathetic tone is risen. They also inhibit renin rush from juxtaglomerular cells stimulated by catecholamine what leads to drop in pressure. Beta-adrenoblockers are better combined with direct vasodilators that reflexively increase heart rate and with diuretics that activate renin plasma. Generally, beta-adrenoblockers help even in cases of healthy sympathetic tone, approximately in 50% of patients with hypertension arterial pressure goes down. Clinical trials have shown that beta-adrenoblockers as well as diuretics cut down lethality and complications risk. The main side effects are bronchospasm and cardiac failure aggravation, so, it is recommended to use beta-adrenoblockers carefully against the background of sugar-lowering therapy as far as they level up hypoglycemia manifestation. Beta1-arenoblockers (cardioselective) “metoprolol” and “atenolol” are probably less dangerous in chronic obstructive pulmonary disease than unselective agents (for instance, propranolol and timolol). Unselective agents pindolol and acebutolol have a low β2-adrenoceptor agonists activity and do not lead to bradycardia at rest. Hypotensive effect of “labetalol” is determined by peripheral vascular resistance lowering due to its qualities of α- and β- adrenoblockers. It acts more promptly than the other β-adrenoblockers but also oftener leads to orthostatic hypotony and invirility.
III. Direct vasodilators
The most popular one is “hydralazine”. It is prescribed parenterally and its action is focused on arterioles and do not lead to orthostatic hypotony. Total peripheral vascular resistance lowering levels out by sympathetic tone growth that speeds up heart rate and cardiac output what limits hydralazine usage, especially in cases of severe atherosclerotic cardiovascular disease. Hydralazine is better to be combined with β-adrenoblockers, methyldopa and “clonidine” to cut down the sympathetic tone rise. “Minoxidil” reduces pressure in a better way than “hydralazine” but it can cause water retention so it is used only in cases of severe hypertension and chronic renal insufficiency. In Israel it is called “Nipruss”. “Diazoxide” due to its formation is close to thiazide diuretics but it has no diuretic action and also retains sodium. As well as thiazide diuretics, diazoxide reduces glucose tolerance. For the last decade direct dilators are not in demand.
IV. ACE Blockers (angiotensin-converting enzyme blockers)
Angiotensin II synthesis can be reduced on different levels: some hypotensive drugs (clonidine, reserpine, methyldopa, β-adrenoblockers) cut down renin excretion, the others – ACE blockers – prevent angiotensin I from transformation into angiotensin II. Moreover, ACE blockers interrupt the powerful vasodilator’s bradykinin destruction process, have an impact on prostaglandin synthesis (especially it is expressed in captopril) and on sympathetic tone. ACE blockers are drugs of choice in presence of renovascular hypertension, hypertension accompanied by kidney disease, evolving and cacoethic hypertension. However, in cases of both-sided renal artery stenosis their intake can lead to rapid onset of renal dysfunction. At mild intact arterial hypertension ACE blockers work even better than β-adrenoblockers and thiazide diuretics causing less side effects that cast a blight on patient’s life. In Israel it is called “Benzepril” and “Cilaril”.
V. Angiotensin receptors blockers
Due to their effect these drugs stand close to ACE blockers. They do not compete with angiotensin I receptors having no influence on angiotensin II formation. The effectivity and side effects are similar to ACE blockers but there never occurs any cough. In Israel these are called CO – Diovan in varying dosage as far as the ingredients of the medicines contain diuretics.
VI. Calcium Channel blockers
This product group has 3 subgroups:
- 1. Phenylalkilamin (verapamil),
- 2. Benzothiazepine (diltiazem),
- 3. Dihydropyridines.
The last subgroup can be divided into first generation (nifedipine) and second generation drugs. Every calcium antagonist has an influence on cells’ calcium flow connected with some exact parts of voltage-dependent calcium channel α1-subunit of L-type. Due to the T- and N-types calcium channels calcium antagonists have just a little effect on a calcium transport in cells. Some drugs’ act habits are determined by the facts that every calcium antagonist subgroup has it’s individual connecting parts on α1-subunit and their quantity is different in every tissue. All the calcium antagonists have vasodilatory action but the reflex tachycardia can be caused only by dihydropyridines. Whereas, diltiazem and verapamil slow down AV-conduction. In Israel they are better known as: “Vasodip”, “Norvasc”, “Lercapress”, “Lercanidirine”. Some negative inotropic effect of calcium antagonist makes them right for angina treatment, in adverse, they can be rarely used in cases of arterial hypotension with cardiac failure.
Drug treatment general outline
The aim of the treatment is to regulate arterial pressure with the help of one of the listed drugs or their combination, so that the side effects are minimal. It is considered that the ideal pressure in drug administration period should be 120/80 ml/Hg. The treatment should be pathogenic to the fullest extent. If the pathogenesis of increased pressure is unknown, therapy is prescribed speculatively considering patient’s readiness, therapy’s effectivity, safety, convenience and an impact on working ability. Monotherapy is prescribed in case, when diastolic pressure is lower than 130 mmHg. Combined therapy is more effective when drugs with different action mechanisms are used. There are loads of hypotensive medication kinds as well as dosing regimens but there are no general ones. 10 years ago the therapy was started from diuretics or β-adrenoblockers intake: many clinical researches have proved that they are the most effective drugs of the therapy onset period. Anyway, ACE blockers and calcium antagonists are not less effective than diuretics or β-adrenoblockers.
Usually, one of these medications is prescribed speculatively but we prefer to start the treatment with ACE blockers or calcium antagonists due to less side effects of their impact on human body and, moreover, ACE blockers are remarkably better at long-term action and convenient administration. It is also preferred to start with angiotensin receptor blockers. The need of additional potassium drugs or potassium-sparing diuretics increases treatment cost by 8-10 times. Great sympathetic tonicity (tachycardia is used as a sign) makes it clear, that β-adrenoblockers are the best solution, in all the other cases – ACE blockers or calcium antagonists.
Drug administration should be started from low doses: for instance, atenolol is prescribed in doses of 25 mg/day, captopril – 25 mg/day, enalapril – 5 mg/day, diltiazem – 120 mg/day, the doses should be divided. If the pressure is lower than 140/90, then the dosage stays unchanged. When the tension is kept on the same level for 1-3 months, the dosage is doubled. Hydrochlorothiazide is added in cases, when nothing helps at doses of 25 mg/day per os or some other thiazide diuretic. Thiazide diuretics potentiate ACE blockers and β-adrenoblockers, moreover, coupled with calcium antagonists their hypotensive effect is summarized. Combination of thiazide diuretics and ACE blockers seems to be the best one, as far as ACE blockers level out diuretics adverse effects on metabolism. β-adrenoblockers and calcium antagonists have no of such qualities, some β-adrenoblockers can also enhance side effects of thiazide diuretics (hypokalemia and hypercholesterolemia).
If on the course of the treatment by two kinds of drugs, hypertension does not stabilize, then the daily dosage of the first main medication is maximized.
It is not restricted to intake even bigger doses than the recommended ones, but it is thought that the change of the main drug can bring better results. If the hypotension does not drop, it would be better to exclude symptomatic hypertension. If there is no hypertension found, then patient's diet should be checked. Those cases demand for salt intake limitation (less than 5 mg/day) to reduce the hypotension level. If nothing changes, then the main drug is changed and diuretic left. It should be considered that patient who has never taken ACE blockers previously, can have a great improvement in his hypotension using them in combination with diuretics. The medication change can bring no results, so then calcium antagonists with ACE blockers or combination of 3 drugs (diuretics, ACE blockers and hydralazine) should be prescribed. When hypotension goes down, it is recommended to cut down the doses or cancel the administration at all, so that the hypotention is lower than 140/90 mmHg. Nevertheless, almost 5% of hypotension patients have high pressure. When this occurs, it is important to eliminate everything that cuts down the therapy's effectivity and add some direct vasodilators (for example, hydralazin, prazosin and clonidine). When the minimal pressure is reached, previously used drugs are gradually cancelled but it is essential to keep an eye to its level.
Presented treatment plan works as often as not, but it is not multi purpose: every patient has an individual drug and drug-combination response. If the final configuration consists from several types of drugs, it is possible to use some ready-made coformulated drugs – they are better for intake. It is essential to do the utmost to make patients keep the plan and continue their usual daily activities. The treatment is lifelong, so if patients feel that they have no problems at all, persuading them that loads of drugs should be administered turns out to be a great problem, especially in cases of adverse events occurrence. Particular approach should be used in following situations:
Ordinary after the treatment course when pressure drops in renal dysfunction patients creatinine blood level rises. Usually it is not connected with future kidney injuries so there is no point in treatment cancelling: over some time, creatinine level will be normalized. Creatinine level rise following the ACE blockers intake demands for some extra attention. It would be better, if both renal arteries stenosis is rejected as far as those patients could have breakdown of renal function during the treatment course. Due to that fact in cases of renal dysfunctions ACE blockers are used carefully and it is necessary to have renal check-up every 4-5 days for the first 3 weeks. ACE blockers are contraindicative to both-sided renal artery stenosis, but it is a great option in unilateral stenosis when the second kidney functions properly and in chronical renal insufficiency (including diabetes patients).
Coronary artery disease
In cases of CAD, especially against the background of cardiac glycoside administration (when CAD is accompanied with cardiac insufficiency), thiazide diuretics are used carefully paying close attention to potassium blood level. Beta-adrenoblockers in CAD are not cancelled or are cancelled gradually. Calcium antagonists and ACE blockers can be recommended thankfully to their action that suppresses other drugs side effects, especially this is true about vasodilators.
Hypertension treatment can be complicated in diabetes mellitus presence as far as many hypotensive drugs violate glucose exchange. The best choice is ACE blockers: they have no influence on the glucose and lipoproteins exchange but they slow down diabetic nephropathy development as they decrease renal vascular tone and renal perfusion pressure.
Hypertension and pregnancy hypertension (preeclampsia and eclampsia) are hard to treat during pregnancy. It is unknown whether self-regulation of uterine blood flow occurs at the background of hypotensive therapy and that’s why pressure loss can lead to placental and fetal ischemia. Drug-free treatment is the most preferred one. Hypotensive drugs are never prescribed at the 2 and 3 pregnancy trimesters if diastolic blood pressure level is not higher than 95 mmHg. Salt-free diet and diuretics can expose to unnecessary risk of premature delivery and generally are never used. Beta-adrenoblockers usage is restricted for the same reasons. Usually prescribed medications are “Methyldopa” and “hydralazine”, scarcer – calcium antagonists, they have no negative effect on fetus. Little is known about the other drugs safety levels. ACE blockers can injure fetus and that why – contraindicated during pregnancy.
Clinical tests performed that generally healthy elderly people subjected to arterial hypertension of both sexes, who administer moderate doses of hypotensive drugs, can be rarely related to cerebral crisis and mortality risk groups. This is mostly referable to isolated systolic hypertension.