Hypertension Management and Treatment Quiz

• Hypertension is defined as the sustained elevation of blood pressure.
  • Systolic blood pressure ≥ 140 mm Hg
  • Diastolic blood pressure ≥ 90 mm Hg
• Blood pressure is calculated by cardiac output multiplied by peripheral vascular resistance: BP = CO x PVR
• Cardiac output is calculated by heart rate multiplied by stroke volume: CO = HR x SV

Regulation of Blood Pressure

• Short-term regulation involves arterial baroreceptors, the medullary cardiovascular center, and the autonomic system.
• Long-term regulation is managed by the renin-angiotensin-aldosterone system.
  • Angiotensin II increases total peripheral vascular resistance and blood pressure and stimulates aldosterone secretion
  • Aldosterone raises blood volume and blood pressure via salt and water retention

Diagnosis of Hypertension

• According to the European Society of Hypertension, hypertension is diagnosed when systolic BP is ≥140 mm Hg or diastolic BP is > 90 mm Hg.
• The American cut-off for hypertension is ≥130/80 mm Hg, classifying 130-139/80-89 mm Hg as stage 1 hypertension.
• Diagnosis is usually based on three separate office visits and the severity of hypertension.
• Some patients may exhibit a white-coat effect, necessitating ambulatory blood pressure measurement.
• Home-based blood pressure measurements can be helpful in diagnosis.

Types of Hypertension

• Primary hypertension (essential hypertension) has no identifiable cause.
• Secondary hypertension (10–15% of patients) is related to:
  • Pheochromocytoma
  • Renal artery stenosis
  • Cushing's syndrome
  • Narrowing of the aorta (coarctation) or atheroma
• Systolic and Diastolic forms:
  • Isolated systolic hypertension (ISH)
  • Isolated diastolic hypertension (IDH)
  • Combined systolic and diastolic hypertension (Combined SDH)

Hypertensive Emergency/Malignant Hypertension

• Is an accelerated form of severe hypertension with rapidly rising BP and damage to vessels and organs.
• Can be signaled by:
  • Renal damage
  • Encephalopathy
  • Retinal hemorrhage
  • Angina
  • Stroke
  • Myocardial infarction.
• Powerful vasodilators like nitroprusside, fenoldopam, or diazoxide, in combination with diuretics and beta-blockers, are used to promptly lower blood pressure.
• Further reduction is pursued slowly afterward.

Resistant Hypertension (RH)

• Is a sustained rise in BP despite using three antihypertensive drug classes, often a long-acting CCB, ACEI or ARB, and a diuretic at maximum doses.
• Includes cases where BP requires four or more antihypertensive medications to reach target values.
• Diagnosis requires ensuring the patient is adhering to their medication regimen.

Consequences of Systemic Hypertension

• Increases risk of:
  • Coronary thrombosis
  • Stroke
  • Renal failure
  • Atherosclerosis - through arterial damage and remodeling

Goal and Options for Treatment

• Reduction in the risk of end-organ damage to the blood vessels in the kidneys, heart, retina, and brain is the goal.
  • This reduces the incidence of renal failure, coronary and cardiac disease, and stroke.
• Treatment options include non-pharmacological and pharmacological interventions.

Non-Pharmacological Interventions

• Weight reduction of 10kg can reduce systolic BP 5-10 mmHg.
• A diet rich in fruits, vegetables, and low-fat dairy products can reduce systolic BP 8-14 mmHg.
• Regular aerobic physical activity, such as 30 minutes of brisk walking, can reduce systolic BP 4-9 mmHg.
• Reduced sodium intake can lower BP by 2-8mmHg
• Limiting alcohol consumption to ≤ 21 units for men and ≤ 14 units for women per week can reduce systolic BP 2-4 mmHg.

Drugs for Hypertension

• Diuretics
  • Thiazide diuretics
  • Loop diuretics
  • Aldosterone antagonists
  • K-sparing diuretics
• Adrenergic inhibitors
  • Peripheral agents
  • Central (α-agonists)
  • Alpha-blockers
  • Beta-blockers
  • Alpha and beta-blockers
• Direct Vasodilators
• Calcium channel blockers
  • Dihydropyridine
  • Non dihydropyridine
• ACE-inhibitors
• Angiotensin-II blockers

Mechanisms of Action of Drug Groups

• Beta-Receptor Blockers and peripherally acting sympatholytics decrease cardiac output.
• Diuretics and angiotensin inhibitors decrease blood volume to lower blood pressure.
• Peripherally acting sympatholytics, calcium channel blockers, and direct vasodilators relax vascular smooth muscle, decreasing TPR.
• Centrally acting sympatholytics decrease sympathetic outflow, therefore decreasing CO and TPR.

Recommendations for Drug Treatment

• In younger white patients with normal to raised plasma renin, start with an ACEI or ARB.
• In older and those of African descent with low plasma renin, a thiazide diuretic or calcium channel blocker (CCB) is preferred.
• If blood pressure goals are achieved, reinforce lifestyle adherence.
• If blood pressure goals are not achieved, titrate medications to maximum doses or consider adding a second drug.
• Avoid excessive dose increases as it causes adverse effects and activates homeostatic control mechanisms.
• If goals are unmet, add a third or fourth drug from a different class.

Additional Info on Drug Treatment

• Adding a third or fourth drug, such as to an ARB/diuretic or ARB/calcium channel blocker combination, may be needed.
• A long-acting alpha adrenoceptor antagonist like doxazosin is an option.
• Doxazosin is administered once daily and lowers the levels of LDLs while raising HDLs.
• Beta-blockers are less tolerated than ACEIs or ARBs.
• Beta-blockers are useful when there is a need for beta-blockage such as angina and heart failure.

Staged Treatment of Hypertension

• First-line monotherapy drugs:
  • Thiazide diuretics
  • Beta blockers
• Alternative Monotherapy:
  • ACE inhibitors
  • Calcium channel blockers
  • Selective a1-blockers (prazosin)
  • α + β blockers (labetalol)
• Not for Monotherapy:
  • Hydralazine
  • Minoxidil - reflex-mediated cardiac stimulation and water retention
• Combined use of 2 drugs:
  • Diuretic + β-blocker
  • Diuretic + ACE inhibitor
  • ACE inhibitor + calcium channel blocker
  • ARB + diuretic
  • A thiazide diuretic + a K-sparing diuretic
• Combined use of 3 drugs:
  • Diuretic + sympathoplegic agent + direct vasodilator
  • Diuretic + ACE inhibitor + direct vasodilator

Considerations for specific conditions:

• Angina pectoris: Beta-blockers, calcium channel blockers.
  • Alternative include diuretics and ACE inhibitors
• Congestive heart failure: Diuretics, ACE inhibitors.
  • Avoid verapamil and beta-blockers.
• Previous myocardial infarction: Beta-blockers, ACE inhibitors.
  • Alternative choice include diuretics, calcium channel blockers
• Diabetes (IDDM): ACE inhibitors, calcium channel blockers, alpha-blockers.
  • Avoid diuretics and beta-blockers.
• Hyperlipidemia: ACE inhibitors, calcium channel blockers
  • Avoid diuretics and beta-blockers.
• Asthma, chronic pulmonary disease: Diuretics, calcium channel blockers.
  • Avoid beta-blockers.

Contraindications and Hypertensive Emergencies

• Drug treatment contraindications:
  • ACE inhibitors and ARBs are contraindicated during pregnancy.
  • Verapamil is contraindicated in congestive heart failure.
• Treatment considerations for hypertensive emergencies:
  • Vasodilators (sodium nitroprusside, diazoxide, felodopam, hydralazine)
  • Calcium channel blockers. reserpine, methyldopa, labetalol

Diuretics

• These are relatively safe and effective for hypertension, particularly in older adults.
• Administered orally, these drugs can be used alone or with other antihypertensives.
• Diuretics lower BP by depleting body sodium stores.
• Phase 1 includes a reduction of total blood volume and cardiac output, with some increase of PVR.
• Phase 2 occurs when CO returns to normal (6-8 weeks) and PVR decreases.

Thiazide Diuretics

• These diuretics, e.g., hydrochlorothiazide, chlorthalidone, indapamide, act on the distal convoluted tubule and inhibit Na+-Cl- symport.
• Suitable for combined use, and particularly useful for elderly patients, where they can counteract the effects of hydralazine
• Use carefully, monitor K+ levels, especially when digitalis is also in use.
• Reduce blood K+ and Mg2+ levels, induce hypokalemia and hyperuricemia, impair glucose tolerance, and increase serum cholesterol.
• Thiazides retain Ca2+ and decrease urine Ca2+ content.

Diuretics - Loop

• Are more powerful than thiazides, for example furosemide and bumetanide.
• Often used for treatment of severe hypertension when direct vasodilators are administered and Na+ and H₂O retention becomes a problem.
• Loop diuretics can be used in patients with poor renal function or those not responding to thiazides.
• Loop diuretics increase the level of calcium present in urine.

Diuretics - K-Sparing

• Triamterene and amiloride are Na+ channel inhibitors.
• Spironolactone and eplirenone (aldosterone antagonists), used for hypertension in patients given digitalis.
• Enhance natriuretic effects, e.g., with thiazides, and counteract K+-depleting effects of other diuretics.

Diuretics - Toxicity and Side Effects

• Depletion of K+ (except for K+-sparing diuretics), leading to hypokalemia.
• Increase uric acid concentration and precipitate gout.
• Increase serum lipid concentrations.
• Should not be used for treating hypertension in patients with hyperlipidemia or diabetes.

Sympathoplegic/Sympatholytic Agents

• Acts centrally in the brain:
  • Clonidine - reduces sympathetic and increases parasympathetic tone, leading to BP lowering and bradycardia.
  • Clonidine binds α2-Adrenergic receptors with higher affinity. Its α2-agonistic activity lowers BP due to negative feedback at presynaptic neurons.
  • Administered intravenously, stimulates a brief rise in BP, followed by prolonged hypotension. It also binds imidazoline receptors (IR).
  • Administered orally for mild to moderate hypertension. Reduces cardiac output (CO is due to decreased heart rate and relaxation of capacitance vessels, maintains renal blood flow and glomerular filtration, Half-life is 8-12 hours.

Sympathoplegic/Sympatholytic Agents - Toxicity and Side Effects

• Clonidine causes sedation, dry mouth, Na+, and H2O retention.
• Abrupt stopping of this treatment may induce hypertensive crisis, so clonidine is avoided with at risk mental health patients or those taking tricyclic antidepressants

Centrally Acting Antihypertensives

• Methyldopa is metabolized to alpha-methylnorepinephrine and reduces the sympathetic response.
• Alpha-methyl-NE is a potent alpha-adrenergic receptor agonist.
• Its CNS effect is mediated by α2-AR, reducing adrenergic outflow from the CNS and reduces total peripheral resistance.
• Cardiac output and blood flow to vital organs are maintained..
• Lowers renal vascular resistance useful for patients with renal insufficiency.
• The adverse effects and toxicity include nightmares, lassitude and even the production of autoantibodies.
• Treatment may take 4-6 hours, peaking at 24 hours
• Used for treatment of hypertension in pregnancy. -Note that ACEIs and ARBs are contraindicated

Peripheral Nervous System Antihypertensives

• Beta-Blockers:
  • Young patients tolerated these better
  • Useful for hypertension due to to myocardia infarction or heart failure
  • Propranolol antagonizes both Beta 1 and 2 AR, inhibits renin prodution is effective with elevated renin levels
  • Metoprolol is more selective antagonist of Beta 2, thus its safer to use with patients with asthma
  • Atenolol, Betaxolol, Bisoprolol, Esmolol, Acebutolol, Metoprolol, and Nebivolol are slow to metabolize (administer one dose daily)
  • Propranolol, Nadolol, Pindolol, Labetalol, Penbutolol, Sotalol and Carvedilol are non selective
• Labetalol can work in hypertensive emergencies
  • Carvedilol can be used in patients with congestive heart failure.
• Alpha-blockers (Prazosin, tetrazosin and doxazosin) can be used to antagonize reflex tachycardia

Test your knowledge of hypertension management, treatment goals, pharmaceutical interventions like ACE inhibitors, and the impact of lifestyle factors such as weight loss and diet on blood pressure. Evaluate your understanding of potential side effects from medication.