Antihypertensive Drugs and Hypertension Management

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Questions and Answers

Which type of antihypertensive drug is primarily used to reduce cardiac output?

Beta-blockers (correct)

Calcium channel blockers

ACE inhibitors

Thiazide diuretics

What is the primary mechanism of action for thiazide diuretics in managing hypertension?

Reduced peripheral vascular resistance

Inhibition of the renin-angiotensin-aldosterone system

Increased sodium and water excretion (correct)

Blockade of calcium channels

Which of the following classes of antihypertensive drugs is contraindicated during pregnancy?

Beta-blockers

Calcium channel blockers

Thiazide diuretics

ACE inhibitors (correct)

How does angiotensin II primarily affect blood pressure?

By stimulating aldosterone secretion Signup and view all the answers

Which subtype of angiotensin receptors is most closely associated with increases in blood pressure?

AT1R Signup and view all the answers

What is the primary treatment of choice for managing hypertension during pregnancy?

Labetalol Signup and view all the answers

Which of the following medications is contraindicated during pregnancy for treating hypertension?

ACE inhibitors Signup and view all the answers

In a hypertensive emergency, which intravenous medication is effective for acute management?

Esmolol Signup and view all the answers

What characterizes primary (essential) hypertension?

Accounts for approximately 93% of adult hypertension cases Signup and view all the answers

Which class of antihypertensive medications typically ends with the suffix '-dipine'?

Calcium channel blockers Signup and view all the answers

What type of hypertension is indicated by normal readings in a doctor's office but elevated readings elsewhere?

Masked hypertension Signup and view all the answers

Which class of medications is often utilized to inhibit the Renin-Angiotensin-Aldosterone System (RAAS)?

ACE inhibitors Signup and view all the answers

What is a common treatment for secondary hypertension caused by obstructive sleep apnea?

Management of the underlying condition Signup and view all the answers

Which class of antihypertensive drugs should be avoided in patients with bronchial asthma?

β-blockers Signup and view all the answers

What is the primary mechanism of action of Aliskiren in treating hypertension?

Inhibition of renin enzymatic activity Signup and view all the answers

In which scenario are ACE inhibitors particularly beneficial?

Patients with diabetes and renal disease Signup and view all the answers

Which of the following is a common adverse effect of ACE inhibitors?

Dry cough Signup and view all the answers

What is a key characteristic of calcium channel blockers in hypertension management?

They promote vasodilation without manipulating RAAS Signup and view all the answers

Which combination drug includes Aliskiren for hypertension treatment?

Aliskiren + HydroChloroThiazide Signup and view all the answers

What is the primary role of ACE in the renin-angiotensin-aldosterone system (RAAS)?

Conversion of angiotensin I to angiotensin II Signup and view all the answers

What is a recommended alternative to ACE inhibitors for hypertensive patients, especially those who may experience dry cough?

ARBs (Angiotensin II Receptor Blockers) Signup and view all the answers

Study Notes

Pharmacology of AntiHypertensives

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Learning Objectives

Identify examples of antihypertensive drugs in each class.
List major antihypertensive drugs and their clinical uses.
Explain the mechanism of action of major antihypertensive drugs.
Discuss the pharmacokinetics and drug interactions of antihypertensive drugs.
Describe common and severe adverse effects of antihypertensive medications.
Summarize major contraindications of antihypertensive drugs.

Renin-Angiotensin-Aldosterone System

Regulates blood pressure (BP), sodium (Na), and water balance.
Plays a role in cardiovascular and renal homeostasis.

Angiotensin Receptors

AT1R subtype is the most well-understood Ang II receptor.
G-protein coupled receptors embedded in the plasma membrane of target cells (smooth muscle, adrenal gland).

BP Regulation

BP = Cardiac Output (CO) x Systemic Vascular Resistance (SVR).
β-blockers decrease CO. Thiazide diuretics decrease SVR.

Drugs Relevant to Hypertension

Diuretics (loop, thiazide)
RAAS Inhibitors (renin inhibitors, ACE inhibitors, ARBs)
Calcium channel blockers
Sympatholytics
Nitrates

ABCDs of Antihypertensives

ACE inhibitors: 'pril' (e.g., lisinopril)
ARBs: 'sartan' (e.g., losartan)
Alpha blockers: 'osin'
Beta blockers: 'lol' (e.g., metoprolol)
Calcium channel blockers: 'dipine' (e.g., amlodipine)
Diuretics, Dilators
ACE inhibitors and ARBs are contraindicated in pregnancy.
Other options are safe.

Multifactorial Disease

Essential Hypertension (93% of cases).
Does not have a known cause
- Risk factors include genetics, smoking, stress, poor diet, obesity, family history, and sedentary lifestyle.
Secondary Hypertension (7%):
- Caused by other medical conditions (renovascular disease, adrenal disorders, thyroid issues, medications).

HTN Emergencies

Sudden, life-threatening elevation of BP.
Intravenous vasoactive medications (labetalol, esmolol, nicardipine, nitroglycerin) are typically used in emergencies.
Oral medications (clonidine, nifedipine) are not useful in emergencies.

Pregnancy

Labetalol is the preferred treatment.
Hydralazine or methyldopa can also be used.
Avoid ACE inhibitors and ARBs.

Patient with Asthma

Low-dose diuretics, ARBs, and calcium channel blockers are acceptable options.
Avoid beta-blockers and alpha-2-blockers.
ACE inhibitors are not recommended due to dry cough and increased airway sensitivity.

Renin Inhibitors

High-renin hypertension (~15% of cases), commonly in young men.
Aliskiren blocks renin.
Block the synthesis of all angiotensin peptides.

Aliskiren

MOA: Direct renin inhibitor.
Ultimately blocks conversion of Angiotensinogen.
Often combined with other drugs (e.g. Hydrochlorothiazide).

ACE Inhibitors

Beneficial in patients with diabetes, heart failure, chronic kidney disease, and hyperuricemia.

Angiotensin Converting Enzyme (ACE)

ACE converts inactive Ang I into Ang II.
A zinc-metalloenzyme that can be inhibited by metal-chelating agents.
Also degrades bradykinin.

Drugs Inhibiting ACE

Used to reduce circulating and local levels of Ang II, and aldosterone & ADH secretion.
Often end in "pril" (e.g., lisinopril, ramipril).
Used for hypertensive patients with renal disease.

Captopril

Treatment for hypertension (normal or impaired renal function)
MOA: Inhibits conversion of Ang I to Ang II.
Keeps vessels dilated and prevents aldosterone secretion.
PK: Renal elimination.
AE: Proteinuria, skin rashes, altered taste, neutropenia, worsening proteinuria.

ACE Inhibitors: Adverse Effects

Dry cough, often due to increased bradykinin.
Angioedema, severe swelling under the skin in mucous membranes.

Lisinopril

Longer half-life
Hydrophilic, does not bind to proteins.
Not broken down by the liver.
Excreted unchanged by the kidneys.

ARBs

Treatment for hypertension when patients cannot tolerate ACE inhibitors.
Losartan, valsartan, candesartan are examples.
Do not affect bradykinin metabolism.

Losartan

Common ARB.
Works well with low-dose hydrochlorothiazide.
Blocks Ang II receptor (AT1).
Oral, once daily. Extensively metabolized by the liver.

Sacubitril-Valsartan

1^st agent in a new class: angiotensin receptor neprilysin inhibitor (ARNI).
An alternative to ACE inhibitors or ARBs
Approved for pediatric patients with heart failure.
MOA: Blocks neprilysin (prevents the breakdown of natriuretic peptides), lowers blood pressure, reduces aldosterone. Valsartan blocks Angiotensin receptor

α-agonists & antagonists

Treatment for hypertension in pregnancy (a-methyldopa).
a-blockers (prazosin) can cause orthostatic hypotension when first started.

α-adrenergic Receptor Modulators

MOA: affects the sympathetic nervous system to decrease systemic vascular resistance.
Lowering BP
Adverse effects: orthostatic hypotension, bradycardia
Examples: methyldopa, clonidine, prazosin

Methyldopa

Centrally acting alpha-2 adrenergic agonist.
Treatment for hypertension, especially in pregnancy.
No teratogenic effects.

Clonidine

Centrally acting alpha-2 adrenergic agonist.
Treatment for hypertension and ADHD.
Often used to manage severe hypertension.

Prazosin

Alpha-1 adrenergic antagonist.
Treatment for hypertension (not first-line)
Marked effects: First dose orthostatic hypotension.

Beta-Blockers

Treatment for hypertension in patients with heart disease history
'lol' (e.g., metoprolol, atenolol, carvedilol, labetalol, esmolol)
MOA: blocks beta receptors.
Side effects: bradycardia, contraindicated in bronchial asthma.

Labetalol

Combined beta- and alpha- blocker.
Non-selective.
Also promotes glucose uptake and reduces glycogenolysis/gluconeogenesis.
Used for hypertensive emergencies and in pregnancy.

Atenolol

Selective beta-1 blocker.
Used for hypertension and atrial fibrillation.
Does not cause postural hypotension.

Other Beta-Blockers

Metoprolol
Carvedilol
Esmolol

Calcium Channel Blockers

Treatment for hypertension in patients with asthma
Blocks the system causing contraction, relaxes vessel muscles
Examples: verapamil, diltiazem, nifedipine, amlodipine
Side effects include flushing, syncope, peripheral edema, constipation

Nicardipine

Short-acting dihydropyridine calcium channel blocker.
Treatment for hypertensive emergencies.
MOA: Lowers BP by reducing Ca2+ influx into vascular smooth muscle cells.

Direct-Acting Vasodilators

Treatment for severe refractory hypertension, malignant hypertension, and hypertensive emergencies.
Examples: hydralazine, minoxidil

Hydralazine

Dilates arterioles, decreases systemic vascular resistance.
Used for hypertension and chronic heart failure when combined with nitrates.

Minoxidil

Arterial vasodilator.
Treatment for severe hypertension.

Nitrates

Cause vasodilation by releasing nitric oxide (NO).
Used for hypertension (especially hypertensive emergencies).
Nitroglycerin (short-acting), isorbide dinitrate (long-acting), and nitroprusside (IV).

Nitroprusside

Non-selective vasodilator to prevent end-organ damage during severe hypertension.
Water-soluble salt comprised of ferrous iron complexes with nitric oxide (NO) and five cyanide ions.
MOA: Acts as a prodrug, reacts with sulfhydryl groups on erythrocytes and other proteins to produce nitric oxide (NO).
PK: IV infusion (rapid onset <1').
AE: Cyanide accumulation.

Fenoldopam

Dopamine-1 receptor agonist.
Treatment for hypertensive emergencies.
MOA: Affects dopamine-1 receptors in mesenteric, coronary and renal arteries, thus increasing renal perfusion.
PK: Short half-life (10 minutes), administered by a continuous IV infusion.

Diuretics

Treatment for newly diagnosed hypertension.
Thiazide diuretics (hydrochlorothiazide, chlorthalidone, indapamide)
K+-sparing diuretics (spironolactone, eplerenone) are used for refractory hypertension and counteract potassium depletion from other diuretics.

Hydrochlorothiazide

Diuretic that reduces peripheral vascular resistance.
Reduces blood volume via inhibiting Na-Cl symporter.
Often used as first-line treatment for essential hypertension.

NSAIDS and ACEI

NSAIDs reduce ACEI efficacy.

First-Line Agents

ACEI, ARBs, CCBs, thiazide diuretics
- Patients with pre-existing diabetes: ACEIs or ARBs.
- Patients not with pre-existing diabetes: Thiazide diuretics.
- Patients with migraine: Nifedipine
- Patients with MI: Beta-blocker
- Pregnancy and Children should avoid ACEI drugs.

When to Treat Hypertension

BP thresholds and recommendations for treatment.
A stepped approach

Site of Drug Action

Summary of drug action locations in the body, categorized by drug mechanism

Untreated Hypertension

Angiotensin II can remodel cardiomyocytes, leading to heart attacks.

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Description

This quiz focuses on key concepts related to antihypertensive drugs and their mechanisms in managing hypertension. Topics include drug classes, contraindications during pregnancy, and characteristics of hypertension. Test your knowledge on effective treatments and critical management strategies for hypertension.