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Blood Pressure

Hypertension – Antihypertensive Medications

junio 9, 2018

[VidSitePro id=39 ]Hello everyone today I will be discussing anti hypertensive medications the learning objectives are first to list the major classes of antihypertensives and describe their mechanisms of action and second to choose an initial anti hypertensive regimen based upon a patient’s demographics and medical comorbidities to introduce the classes of antihypertensives I’m going to bring back some diagrams from the introductory video on hypertension in that video I discussed that the two major physiologic systems which were indisputably involved in the development of hypertension or the rena in angiotensin aldosterone system and the sympathetic nervous system so here is a diagram of the first of those two this displays how a series of pro hormones are converted through a series of steps catalyzed by the enzyme renin and angiotensin converting enzyme the net consequence of which is the production of the active hormones angiotensin ii and aldosterone which collectively work to cause systemic vasoconstriction and increased reabsorption of sodium in the renal tubules there are five distinct classes of antihypertensive medications which interfere with one of the steps shown here starting with the two most important angiotensin converting enzyme inhibitors commonly called ACE inhibitors block the conversion of the inactive angiotensin one to the active angiotensin 2 diuretic medications which are a particularly diverse class including thiazide loop and so called potassium sparing diuretics directly interfere with renal sodium reabsorption in the kidneys there are also angiotensin ii receptor blockers also called AR bezoar ARBs which block the action of angiotensin ii and are clinically almost identical to ace inhibitors likewise there are also aldosterone antagonists finally the newest class of medications which interfere with this system are called direct meaning inhibitors then there are drugs that inhibit the sympathetic nervous system coincidentally there are also five general categories here these include beta blockers which inhibit epinephrine and norepinephrine activities at beta adrenergic receptors which are normally responsible for increasing the heart rates and myocardial contractility and there are alpha blockers which inhibit those hormones activity on alpha adrenergic receptors which are normally responsible for inducing systemic vasoconstriction there are two different subtypes of calcium channel blockers they include dihydropyridine s which act to block systemic vasoconstriction and there are non dihydropyridine s which primarily act to reduce heart rates and contractility although clinically it isn’t typically grouped with the dihydropyridine i think on purely physiologic grounds the medication hydralazine belongs here as it is a pure arterial vasodilator with similar effect finally the last category here are the centrally active alpha-2 agonist s’ clonidine and methyl dopa which inhibit the sympathetic nervous system within the brainstem although it would seem that these two drugs would be the best as they act very approximately and can thus inhibit both the cardiac and Vascular end effects of sympathetic stimulation unfortunately they have not been nearly as helpful as the other classes of drugs method opa is used almost solely in pregnancy when many other drugs are held due to concern for risk to the fetus and clonidine is reserved for a third or even fourth line medication pretty much to be used only when all else fails there is one final class of medications which does not clearly map to one of these two diagrams that class is nitrates for example Isis or bide mononitrate and Isis or bind dye nitrate these two drugs work primarily by inducing Vino dilation we know dilation reduces blood returned to the heart which in patients with normal or near-normal intracardiac blood volume results in a reduction in cardiac output nitrates also lead to arterial and arteriolar dilation but this effect is usually less pronounced if you count the three subclasses of diuretics separately that gives us 13 different classes of medications to remember which can be difficult when first starting out to medicine luckily there are some naming conventions that can help identifying drug class ACE inhibitors always end in PR IL or prill common examples include lisinopril banaz ‘april vas in Aprill and enalapril important side effects of the ACE inhibitors is a dry cough and renal dysfunction thiazide diuretics have no common suffix but there are only a couple to remember all with similar sounding names hydrochlorothiazide chloro thiazide and chlorella Doane side effects include hypokalemia hyponatremia renal dysfunction and a modest increase in insulin resistance that means it can make type-2 diabetes just a little bit worse loop diuretics have no common suffix but there are also very few a number in the US they are essentially just furosemide bumetanide and taurus amide side effects are similar to the thighs IDEs except for the insulin resistance which is not present from the loop diuretics dihydropyridine calcium channel blockers all end in typing such as amlodipine Philippine micarta pain and nifedipine common side effects are constipation and lower extremity edema the non dihydropyridine s have no common suffix and essentially just include Delta ism and verapamil as you might expect they can lead to low cardiac output and bradycardia the ARB Zanden Sartain such as losartan valsartan and airbus arjun they can cause renal dysfunction beta blockers and in all law such as metoprolol carvedilol labetalol propranolol and esmolol in an acute timeframe they can lower myocardial contractility even if they can improve it in the long term other side effects include bradycardia fatigue sexual dysfunction and depression my personal experience is that beta blockers are the antihypertensive drug class that when used in relatively healthy people for the treatment of hypertension have the greatest risk of some side effect developing finally alpha blockers and in Osen to reduce in processing and oxytocin the major side effect of alpha blockers is orthostatic hypotension with so many choices once the decision has been made to start an anti hypertensive how does one choose one the first general principle of drug selection is that the primary benefit from antihypertensive therapy is more associated with a degree of improvement in the blood pressure and not associated with the use of any one specific drug therefore selection of initial mono therapy is largely driven by side-effect profile and patient preference if the systolic blood pressure is more than 20 points above target or diastolic blood pressure is more than 10 points above target once you consider that mono therapy will not be sufficient and that dual therapy might be best even to start off with at the beginning so what are my specific recommendations for initial mono therapy assuming there are no compelling secondary indications or specific contraindications which we’ll talk about in a few minutes for non-elderly non-black patients I recommend starting either an ACE inhibitor I personally prefer twice-daily lisinopril or a thiazide diuretic in which place chlorella Doane might be preferred over the much more common hydrochlorothiazide for non elderly black patients I recommend either cloth alone or a dihydropyridine calcium channel blocker such as I’m low doping the difference in recommendations for black and non black patients stemming from data suggesting that black patients tend to be less responsive to inhibition of the reading angiotensin aldosterone system in elderly patients because of increased risk of side effects and increased risk from side effects I recommend avoiding meds that can be leading to renal dysfunction or electrolyte abnormalities thus dihydropyridine calcium channel blockers are the best option so why do I focus on these three medication classes instead of the other ten it’s a combination of best general side effect profiles most frequently studied medications most recommended meds by professional guidelines and personal experience with choosing antihypertensives there are sometimes compelling secondary indications for one or another drug which might overrule the typical recommendations here let me run through them diuretics particularly loop diuretics are also helpful in heart failure ACE inhibitors and ARVs are helpful in patients post mi those with heart failure those with chronic kidney disease and those with diabetes the non de hydro pyridine can help rate control patients with atrial fibrillation beta blockers are also indicated in stable angina post mi heart failure and can control afib nitrates are indicated in angina and heart failure both hydralazine and aldosterone antagonists are frequently used in heart failure and finally the primary indication for alpha is actually not hypertension but rather treatment of urinary difficulties associated with benign prostatic hypertrophy the blood pressure lowering effect is oftentimes just a secondary benefit in addition to compelling secondary indications there are also compelling contraindications to specific anti hypertensive classes for example thiazide diuretics are relatively contraindicated in diabetes since they can contribute to insulin resistance in effect which is probably quite small the non de hydro pyridine are contraindicated in heart failure as they have negative inotropic properties some beta blockers are believed to worsen insulin resistance though it’s not clear how significant this effect is and it’s not believed to be effective seen with carvedilol beta blockers are also relatively contraindicated in COPD hydralazine is associated or is at least rumored to be associated with a reflex tachycardia and thus is generally considered contraindicated in patients with angina aldosterone antagonists can lead to hyperkalemia and are thus to be avoided in chronic kidney disease and the last some studies show worse outcomes when alpha blockers are used in patients with heart failure inevitably all clinicians will be faced with the question of what to do if initial therapy is insufficient in general either switching to a different mono therapy or adding a second drug is more effective in controlling hypertension than escalating doses of the first drug the risk of side effects may be increased by either adding a second drug or by escalating doses of the first depending upon the patient and specific situation and of course adding a second drug may result in decreased compliance unless a combination pill is used so the bottom line is it’s not really clear what the best strategy is if the initial dose of the initial drug is insufficient if the decision is made to start combination therapy the first line combination therapy is generally considered by experts to be either an ACE inhibitor or ARB plus a dihydropyridine calcium channel blocker for example the combination of banaz Aprill and M lo de peen why is this combination thought to be the best it’s largely based on a study published in the New England Journal of Medicine in 2008 called the accomplished trial in which 11,000 patients with hypertension and other cardiovascular risk factors were randomized to receive either a combination of banaz Aprill and amlodipine or benazzo krill and hydrochlorothiazide the trial was terminated after three years when she became clear that the banaz Aprilia plus an low doping group were having fewer heart attacks fewer strokes and less hospitalizations unfortunately the accomplished trial was not perfect for example some clinicians believe that chlorella Doane may be a superior thiazide diuretic to hydrochlorothiazide and would therefore have been a better drug to have included in the study the trial also had no calcium channel blocker plus thiazide arm and finally the patients enrolled in the trial were all at high risk of cardiovascular events so it’s not clear how generalizable the results are to lower risk populations nonetheless this remains the generally recommended combination therapy I’ll end with a few final pearls about anti hypertensive medications ARVs have virtually identical indications and contraindications to ACE inhibitors but due to increased cost should generally be reserved for patients intolerant to ACE inhibitors due to the side effect of COFF remember to monitor electrolytes and renal function after initiation and any dose increase of an ace ARB or diuretic and using combination therapy if poor compliance is not a concern it is preferable to give at least one medication at bedtime twice daily dosing of lisinopril may be more effective than once daily there is both theoretical and empirical evidence to favour using cloth aldohn over hydrochlorothiazide even though the latter is heavily favored in the u.s. admittedly the clinical difference between the two thighs ides is probably very small and finally atenolol should never be used for hypertension ever there’s a large amount of evidence that atenolol is no better than placebo at preventing a number of important adverse cardiovascular events and all it does is expose your patient to side-effects and unnecessary cost that concludes this video on anti hypertensive medications I hope you found it interesting and useful if you have not already done so please consider subscribing for many more medical videos

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