Hypertension, drug classes, causes, symptoms, treatment, foods, brand generic drugs

Hypertension

Hypertension, commonly known as high blood pressure, is a chronic medical condition where the force of blood against the walls of the arteries is consistently too high. Over time, this can damage blood vessels and lead to serious health complications.

Blood Pressure Readings

Blood Pressure is measured as systolic pressure (top number) over diastolic pressure (bottom number) in mmHg.

Normal: <120/80 mmHg
Elevated: 120–129/<80 mmHg
Hypertension Stage 1: 130–139/80–89 mmHg
Hypertension Stage 2: ≥140/90 mmHg
Hypertensive Crisis: >180

Types of Hypertension

Primary (Essential) Hypertension (90–95% of cases): No identifiable cause, develops gradually due to genetics, lifestyle, or aging.
Secondary Hypertension (5–10% of cases): Caused by an underlying condition (e.g., kidney disease, hormonal disorders, medications).

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Causes of Hypertension (High Blood Pressure)

Hypertension (HTN) is classified into primary (essential, 90-95% of cases) and secondary (5-10%), where an underlying condition is the cause. Below are the major causes:

1. Primary (Essential) Hypertension

No single identifiable cause; results from a combination of genetic, lifestyle, and environmental factors:

Genetics (family history)
Obesity (↑ adipokines, insulin resistance)
High salt intake (Na⁺ retention → ↑ blood volume)
Alcohol & tobacco use (vasoconstriction)
Sedentary lifestyle (↓ vascular health)
Chronic stress (↑ sympathetic activity)
Aging (arterial stiffness)

2. Secondary Hypertension (Underlying Causes)

A. Kidney-Related

Chronic kidney disease (CKD) (↓ Na⁺ excretion)
Renal artery stenosis (↑ renin → angiotensin II → vasoconstriction)
Polycystic kidney disease

B. Endocrine Disorders

Primary hyperaldosteronism (Conn’s syndrome – excess aldosterone)
Cushing’s syndrome (excess cortisol → Na⁺ retention)
Pheochromocytoma (catecholamine-secreting tumor → episodic HTN)
Hyperparathyroidism (↑ Ca²⁺ → vascular stiffness)
Hyper/hypothyroidism

C. Cardiovascular & Vascular

Aortic coarctation (narrowing of the aorta)
Obstructive sleep apnea (hypoxia → sympathetic overdrive)

D. Medications & Substances

NSAIDs (↓ prostaglandin-mediated vasodilation)
Oral contraceptives (estrogen-induced fluid retention)
Decongestants (pseudoephedrine → vasoconstriction)
Steroids (corticosteroids, anabolic steroids)
Cocaine/amphetamines (sympathetic overstimulation)

E. Other Causes

Pregnancy-induced HTN (preeclampsia)
Liquorice abuse (glycyrrhizin → pseudoaldosteronism)

Risk Factors for Hypertension

Non-Modifiable	Modifiable
Age (↑ risk after 40)	Obesity (BMI ≥30)
Family history	High-sodium diet
Male gender (pre-menopause women have lower risk)	Alcohol excess
Black/African descent	Physical inactivity
Chronic stress
Low potassium intake

Types of Antihypertensive Medications

Antihypertensive drugs are classified based on their mechanism of action.

The major classes include:

ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors) (Blocks angiotensin II production, dilate blood vessels)
ARBs (Angiotensin II Receptor Blockers) (Block angiotensin II receptors, similar to ACEIs but no cough)
Calcium Channel Blockers (CCBs) (Relax blood vessels by blocking calcium entry into muscle cells)
Alpha-Blockers (Block alpha-1 receptors, dilate blood vessels)
Beta-Blockers (Reduce heart rate and cardiac output)
Centrally Acting Agents (Reduce sympathetic nervous system activity)
Vasodilators (Directly relax arterial smooth muscle)
Diuretics (Reduce blood volume by increasing urine output)

First-Line Treatment Choices (JNC 8 & ACC/AHA Guidelines)

General population: ACEI/ARB + CCB or Thiazide Diuretic.
Black patients: CCB or Thiazide Diuretic (ACEIs/ARBs less effective alone).
Heart disease patients: Beta-blockers + ACEI/ARB.
Chronic kidney disease (CKD): ACEI/ARB (renal protective).

ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors)

Brand Name	Generic Name	Mechanism of Action	Common Side Effects
Zestril, Prinivil	Lisinopril	Inhibits angiotensin-converting enzyme (ACE), reducing angiotensin II production and aldosterone secretion → vasodilation and decreased BP	Dry cough, hyperkalemia, angioedema, hypotension, dizziness
Vasotec	Enalapril
Altace	Ramipril
Accupril	Quinapril
Lotensin	Benazepril
Monopril	Fosinopril
Mavik	Trandolapril
Capoten	Captopril	Short-acting ACE inhibitor, same MOA	Taste disturbances, rash, proteinuria, same as others
Combination ACE Inhibitor Drugs
Zestoretic	Lisinopril / Hydrochlorothiazide (HCTZ)	ACE inhibition + thiazide diuretic →↓ RAAS activity + ↑ sodium/water excretion	Dry cough, hyperkalemia, hypotension, electrolyte imbalance
Vaseretic	Enalapril / HCTZ
Lotensin HCT	Benazepril / HCTZ
Accuretic	Quinapril / HCTZ
Monopril HCT	Fosinopril / HCTZ
Uniretic (some regions)	Moexipril / HCTZ
Tarka	Trandolapril / Verapamil	ACE inhibition + calcium channel blockade → vasodilation + ↓ HR	Bradycardia, constipation, cough, hyperkalemia

How ACE Inhibitors Work:

ACE (angiotensin-converting enzyme) inhibitors are a class of drugs primarily used to treat hypertension (high blood pressure) and heart failure.

Their mechanism of action involves:

Blocking Angiotensin-Converting Enzyme (ACE):

Normally, ACE converts angiotensin I → angiotensin II (a potent vasoconstrictor).
ACE inhibitors prevent this conversion, reducing angiotensin II levels.

Effects of Reduced Angiotensin II:

Vasodilation: Less angiotensin II → relaxed blood vessels → lower blood pressure.
Decreased Aldosterone Secretion: Reduces sodium/water retention → less fluid volume & lower BP.
Reduced Cardiac Remodeling: Protects the heart in heart failure by preventing harmful tissue changes.

Increased Bradykinin Levels:

ACE also breaks down bradykinin (a vasodilator).
Inhibiting ACE increases bradykinin, enhancing vasodilation (but may cause dry cough as a side effect).

Side Effects of ACE Inhibitors:

Dry cough (bradykinin-related)
Hyperkalemia (high potassium)
Angioedema (rare but serious)
Hypotension (first-dose effect)

ARBs (Angiotensin II Receptor Blockers)

Brand Name	Generic Name	Mechanism of Action	Common Side Effects
Cozaar	Losartan	Blocks angiotensin II from binding to AT1 receptors → vasodilation, ↓ aldosterone	Hyperkalemia, dizziness, fatigue, hypotension
Diovan	Valsartan		Hyperkalemia, headache, dizziness
Benicar	Olmesartan		Hyperkalemia, dizziness, rare: sprue-like enteropathy
Avapro	Irbesartan		Hyperkalemia, dizziness, fatigue
Micardis	Telmisartan		Hyperkalemia, back pain, dizziness
Atacand	Candesartan		Hyperkalemia, hypotension, dizziness
Teveten	Eprosartan		Hyperkalemia, headache, cough, dizziness
Edarbi	Azilsartan		Hyperkalemia, diarrhea, increased serum creatinine
ARB Combination Drugs (ARB + Thiazide)
Hyzaar	Losartan + HCTZ	Vasodilation + ↑ Na/H2O excretion	Dizziness, hypokalemia, hyperuricemia, hyperkalemia
Diovan HCT	Valsartan + HCTZ		Dizziness, fatigue, electrolyte imbalance
Benicar HCT	Olmesartan + HCTZ		Dizziness, hyperuricemia, dry mouth
Avalide	Irbesartan + HCTZ		Headache, fatigue, hypokalemia
Micardis HCT	Telmisartan + HCTZ		Dizziness, upper respiratory infection
Atacand HCT	Candesartan + HCTZ		Hypotension, back pain, dizziness
Teveten HCT	Eprosartan + HCTZ		Fatigue, headache, cough
Edarbyclor	Azilsartan + Chlorthalidone		Increased uric acid, dizziness, diarrhea

How ARBs (Angiotensin II Receptor Blockers) Work

ARBs (e.g., Losartan, Valsartan, Irbesartan) are another key class of antihypertensive drugs, often used as an alternative to ACE inhibitors.

Mechanism of Action:

Block AT1 Receptors:

ARBs selectively block angiotensin II (Ang II) receptors (AT1 subtype).
Unlike ACE inhibitors, they do not affect bradykinin metabolism (hence, no dry cough).

Effects of AT1 Blockade:

Vasodilation: Prevents Ang II-induced vasoconstriction → lowers blood pressure.
Reduced Aldosterone Release: Decreases sodium/water retention → reduces blood volume.
Cardiac & Renal Protection: Slows heart failure progression and diabetic nephropathy (similar to ACE inhibitors).

Key Notes for Pharmacy Students

ARB + HCTZ combinations enhance BP control through dual mechanisms.
Avoid in pregnancy (Category D).
Monitor: BP, potassium, renal function, signs of hypotension.
No cough, unlike ACE inhibitors (no bradykinin effect).
Watch for hyperkalemia, especially with potassium supplements or potassium-sparing diuretics.

Side Effects of ARBs:

Hyperkalemia (high potassium)
Dizziness/Hypotension (especially in volume-depleted patients)
Angioedema (rare, but less than ACE inhibitors)
Teratogenic (avoid in pregnancy, like ACE inhibitors)

ACE Inhibitors vs ARBs Comparison

Feature	ACE Inhibitors	ARBs (Angiotensin II Receptor Blockers)
Mechanism of Action	Inhibit Angiotensin-Converting Enzyme (ACE), preventing conversion of Angiotensin I → II	Block Angiotensin II from binding to AT1 receptors
Bradykinin Effects	↑ Bradykinin (leads to cough, angioedema)	No effect on bradykinin (less cough, lower risk of angioedema)
Cough	Common side effect (up to 20%)	Rare
Angioedema	More common	Less common
Preferred in	Diabetic nephropathy, post-MI, HF (with reduced EF)	Patients who can’t tolerate ACE inhibitors (due to cough or angioedema)
Side Effects	Cough, angioedema, hyperkalemia, hypotension, ↑ creatinine	Hyperkalemia, hypotension, dizziness
Contraindications	Pregnancy, bilateral renal artery stenosis, angioedema history	Same as ACE inhibitors
Combination with NSAIDs and Diuretics	↑ Risk of AKI with both classes (Triple Whammy: ACEi + NSAID + Diuretic)	Same risk with ARBs
Monitoring	Potassium, renal function, BP	Same as ACE inhibitors

Calcium Channel Blockers (CCBs) Antihypertensive Drugs

Brand Name	Generic Name	Mechanism of Action	Side Effects
Dihydropyridine
Norvasc	Amlodipine	Dihydropyridine CCB: Blocks L-type calcium channels in vascular smooth muscle → vasodilation	Peripheral edema, dizziness, flushing, palpitations
Procardia, Adalat CC	Nifedipine	Dihydropyridine CCB: Vasodilation via L-type calcium channel blockade	Headache, flushing, reflex tachycardia, edema
Plendil	Felodipine	Dihydropyridine CCB: Vasodilation	Swelling, headache, fatigue
Sular	Nisoldipine	Dihydropyridine CCB: Vasodilation	Edema, dizziness, flushing
Cardene	Nicardipine	Dihydropyridine CCB: Vasodilation	Hypotension, headache, tachycardia
Non-Dihydropyridine
Isoptin, Calan, Verelan	Verapamil	Non-Dihydropyridine CCB: Slows AV node conduction and myocardial contractility	Constipation, bradycardia, heart block, gingival hyperplasia
Cardizem, Tiazac	Diltiazem	Non-Dihydropyridine CCB: Negative chronotrope and inotrope	Bradycardia, dizziness, edema
Combination Calcium Channel Blockers Antihypertensive Drugs
Exforge	Amlodipine + Valsartan	CCB + ARB	Edema, dizziness, fatigue
Twynsta	Amlodipine + Telmisartan	CCB + ARB	Edema, back pain, dizziness
Azor	Amlodipine + Olmesartan	CCB + ARB	Edema, hypotension, dizziness
Tribenzor	Amlodipine + Olmesartan + HCTZ	CCB + ARB + Thiazide	Dizziness, hyperuricemia, electrolyte imbalance
Exforge HCT	Amlodipine + Valsartan + HCTZ	CCB + ARB + Thiazide diuretic	Dizziness, fatigue, hyperkalemia, hypotension, dehydration
Lotrel	Amlodipine + Benazepril	CCB + ACE inhibitor	Cough, edema, hyperkalemia, dizziness
Prestalia	Amlodipine + Perindopril	CCB + ACE inhibitor	Cough, dizziness, peripheral edema
Tekamlo	Amlodipine + Aliskiren	CCB + Direct Renin Inhibitor	Diarrhea, hypotension, hyperkalemia (avoid in pregnancy)
Amturnide	Amlodipine + Aliskiren + HCTZ	CCB + Direct Renin Inhibitor + Thiazide	Fatigue, dizziness, electrolyte disturbances

Types of CCBs

Class	Examples	Primary Effects	Main Uses
Dihydropyridines (DHPs)	Amlodipine, Nifedipine	Strong vasodilation, minimal cardiac effect	Hypertension, Angina
Non-Dihydropyridines	Verapamil, Diltiazem	Cardiac depression + moderate vasodilation	Arrhythmias, Angina

How Calcium Channel Blockers (CCBs) Work

Calcium channel blockers (CCBs) are a class of drugs used primarily for hypertension (high blood pressure), angina (chest pain), and arrhythmias (irregular heartbeats). They work by blocking voltage-gated calcium channels (L-type), reducing calcium influx into cells, which affects vascular smooth muscle and cardiac muscle differently.

Mechanism of Action

In Blood Vessels (Vasodilation):

CCBs block calcium entry into vascular smooth muscle cells.
↓ Intracellular calcium → relaxes arteries → reduces peripheral resistance → lowers blood pressure.
This helps treat hypertension and vasospastic angina.

In the Heart:

Dihydropyridines (e.g., Amlodipine, Nifedipine):
- Mostly affect blood vessels (minimal cardiac effect).
Non-Dihydropyridines (e.g., Verapamil, Diltiazem):
- Also block calcium channels in the heart, leading to:
  - ↓ SA node firing (↓ heart rate – negative chronotropy).
  - ↓ AV node conduction (↓ heart rate – negative dromotropy).
  - ↓ Myocardial contractility (↓ force – negative inotropy).
Useful for supraventricular arrhythmias and chronic stable angina.

Side Effects of Calcium Channel Blockers

Dihydropyridines:

Reflex tachycardia (due to vasodilation)
Peripheral edema (ankle swelling)
Headache, flushing

Non-Dihydropyridines:

Bradycardia (slow heart rate)
Constipation (Verapamil)
AV block (caution in heart failure)

Alpha Blockers – Antihypertensive Drugs

Brand Name	Generic Name	Mechanism of Action	Side Effects
Selective Alpha Blockers
Cardura	Doxazosin	Selective α1-blocker: Relaxes vascular smooth muscle → vasodilation	Orthostatic hypotension, dizziness, headache, fatigue
Minipress	Prazosin	Selective α1-blocker: Lowers peripheral resistance	First-dose hypotension, dizziness, nasal congestion
Hytrin	Terazosin	Selective α1-blocker: Vasodilation and reduced blood pressure	Drowsiness, postural hypotension, syncope
Uroxatral	Alfuzosin	Selective α1-blocker: Primarily used for BPH but may have BP-lowering effects	Dizziness, orthostatic hypotension
Rapaflo	Silodosin	Selective α1A-blocker (more prostate-specific, minimal BP effect)	Retrograde ejaculation, dizziness
Flomax	Tamsulosin	Selective α1A-blocker (for BPH; not used for BP)	Dizziness, ejaculatory dysfunction
Non-Selective Alpha Blockers
Regitine	Phentolamine	Non-selective α1/α2-blocker: Vasodilation, used for hypertensive emergencies, pheochromocytoma	Reflex tachycardia, GI upset, hypotension
Phenoxybenzamine	Phenoxybenzamine	Irreversible non-selective α1/α2-blocker: Pre-op pheochromocytoma management	Postural hypotension, nasal stuffiness, tachycardia

Note: These are not first-line agents for hypertension alone. Often used for patients with hypertension + BPH (benign prostatic hyperplasia).

How Alpha Blockers Work

Block α₁-receptors on vascular smooth muscle → vasodilation → ↓ peripheral resistance → ↓ blood pressure.
In the prostate/bladder neck, they relax smooth muscle → improve urine flow (used for BPH).

Mechanism of Action:

A. Hypertension

Not first-line (JNC8 & ACC/AHA guidelines prefer thiazides, ACEIs, ARBs, or CCBs).
Used in resistant hypertension (added to other drugs).
Preferred in patients with comorbid BPH (helps both conditions).

B. Benign Prostatic Hyperplasia (BPH)

Improves urinary symptoms by relaxing prostate/bladder neck muscles.

C. Pheochromocytoma

Phenoxybenzamine/phentolamine used preoperatively to prevent catecholamine-induced hypertension.

Side Effects of Alpha Blockers

First-dose hypotension (dizziness, syncope – minimized by starting at bedtime).
Reflex tachycardia (due to vasodilation; often requires a beta-blocker).
Dizziness, fatigue, nasal congestion.
Orthostatic hypotension (higher risk in elderly).

Beta Blockers – Antihypertensive Drugs

Brand Name	Generic Name	Mechanism of Action	Side Effects
Selective Beta-1 Blockers (Cardioselective)
Tenormin	Atenolol	Selective β1 blocker → ↓ heart rate, ↓ contractility, ↓ renin release (less preferred today)	Bradycardia, fatigue, dizziness, cold extremities
Lopressor	Metoprolol tartrate	Selective β1 blocker → short-acting	Bradycardia, fatigue, hypotension
Toprol XL	Metoprolol succinate	Selective β1 blocker → extended release	Drowsiness, depression, bradycardia
Bystolic	Nebivolol	Selective β1 blocker + nitric oxide–mediated vasodilation (vasodilatory effects (NO-mediated)	Headache, dizziness, bradycardia
Zebeta	Bisoprolol	Highly selective β1 blocker (preferred for heart failure)	Fatigue, bradycardia, insomnia
Kerlone	Betaxolol	Selective β1 blocker	Bradycardia, tiredness, visual disturbances
Non-Selective Beta-Blockers (β1 + β2 Blockers)
Inderal	Propranolol	Non-selective β1 & β2 blocker → ↓ HR, contractility; bronchoconstriction (also used for migraines, anxiety)	Bronchospasm, fatigue, depression, cold extremities
Corgard	Nadolol	Non-selective β-blocker (long-acting)	Dizziness, fatigue, bradycardia
Blocadren	Timolol	Non-selective β-blocker	Fatigue, dizziness, bronchospasm
InnoPran XL	Propranolol (ER)	Non-selective β-blocker → long-acting formulation	Hypotension, vivid dreams, cold hands/feet
Mixed Alpha/Beta Blockers
Coreg	Carvedilol	Blocks β1, β2, and α1 → ↓ HR and vasodilation (also blocks α₁ receptors (vasodilation)	Orthostatic hypotension, dizziness, weight gain
Trandate, Normodyne	Labetalol	Blocks β1, β2, and α1 → used in hypertensive emergencies and pregnancy	Dizziness, fatigue, scalp tingling
Combination Beta-Blocker
Ziac	Bisoprolol + Hydrochlorothiazide	β1-blocker + Thiazide diuretic	Dizziness, electrolyte imbalance, fatigue
Corzide	Nadolol + Bendroflumethiazide	Non-selective β-blocker + Thiazide diuretic	Hypokalemia, bradycardia, hypotension
Lopressor HCT	Metoprolol tartrate + Hydrochlorothiazide	β1-blocker + Thiazide diuretic	Dizziness, dehydration, bradycardia
Tenoretic	Atenolol + Chlorthalidone	β1-blocker + Thiazide-like diuretic	Fatigue, low potassium, cold extremities

How Beta Blockers Work

Simple mechanism of Action: Target Receptors:

Beta-blockers primarily block β1 receptors in the heart.
Some also block β2 receptors in the lungs and blood vessels.

What Happens When You Block β1 Receptors in the Heart?

🧡 Slower heart rate → less work for the heart
💪 Reduced force of contraction
🩸 Lower blood pressure
🧪 Decreased renin release from kidneys → helps control blood volume and pressure

Result:

Less strain on the heart
Improved oxygen balance
Lower blood pressure
Control of abnormal heart rhythms

Types of Beta Receptors:

Receptor	Location	Action When Stimulated	What Beta-Blockers Do
β1	Heart, kidneys	↑ Heart rate, ↑ Renin secretion	↓ Heart rate, ↓ BP
β2	Lungs, blood vessels	Bronchodilation, vasodilation	(If blocked) Bronchoconstriction
α1 (some BBs)	Blood vessels	Vasoconstriction	Vasodilation (when blocked)

Clinical Effects of Beta-Blockers

Effect	Clinical Use
↓ Heart rate	Tachycardia, Atrial fibrillation
↓ Blood pressure	Hypertension
↓ Myocardial oxygen demand	Angina, Post-MI
↓ Arrhythmias	Ventricular and supraventricular arrhythmias
↓ Cardiac remodeling	Heart failure (e.g., metoprolol, carvedilol)
↓ Tremors, anxiety	Essential tremor, performance anxiety
↓ Intraocular pressure (some)	Glaucoma (e.g., timolol eye drops)

Why Some Beta-Blockers Are Not First-Line for Hypertension?

Less effective than ACEIs/ARBs/CCBs in reducing stroke risk.
Metabolic effects (may worsen insulin resistance, lipids).
Side effects (fatigue, erectile dysfunction, cold extremities).
Exceptions (Preferred Beta-Blockers for HTN) Nebivolol (better vasodilation, fewer metabolic effects).
Carvedilol (α-blockade helps peripheral perfusion).

Centrally Acting Antihypertensive Agents

Brand Name	Generic Name	Mechanism of Action	Side Effects
Catapres	Clonidine	Stimulates central α2-adrenergic receptors – ↓ sympathetic outflow -↓ BP	Drowsiness, dry mouth, rebound hypertension, constipation
Catapres-TTS	Clonidine (transdermal patch)	Same as oral clonidine	Skin irritation, sedation, dry mouth
Aldomet	Methyldopa	Converted to α-methylnorepinephrine → stimulates central α2-receptors	Sedation, depression, hemolytic anemia, liver toxicity
Tenex	Guanfacine	Central α2-agonist (longer half-life than clonidine)	Drowsiness, dry mouth, fatigue
Kapvay	Clonidine (ER)	Stimulates central α2-adrenergic receptors – ↓ sympathetic outflow – ↓ BP (used in ADHD but also affects BP)	Drowsiness, dry mouth, rebound hypertension, constipation
Intuniv	Guanfacine ER		Drowsiness, dry mouth, fatigue
Combination Products Containing Centrally Acting Agents
Clorpres	Clonidine + Chlorthalidone	Clonidine: central α2-agonist + Chlorthalidone: thiazide diuretic	Dry mouth, drowsiness, electrolyte imbalance, dizziness
Methyldopa HCT	Methyldopa + HCTZ	Methyldopa: central α2-agonist + HCTZ: thiazide diuretic	Sedation, hypokalemia, hypotension

Notes:

Rebound Hypertension: Can occur if clonidine is stopped suddenly.
Methyldopa is safe in pregnancy (commonly used for gestational hypertension).
These drugs are not first-line agents but may be used in resistant hypertension or special populations.

How Centrally Acting Hypertensives Work

Target Site: These drugs act on the brainstem, specifically areas that control blood pressure.
Receptor Activation: They stimulate α2-adrenergic receptors in the central nervous system.
Reduced Sympathetic Outflow:
- This decreases nerve signals that normally cause the heart and blood vessels to work harder.
- Result: Heart rate and blood vessel resistance decrease.
Outcome:
- Blood vessels relax (vasodilation)
- Heart rate slows down
- Blood pressure drops

Example – Clonidine:

Clonidine binds to α2 receptors in the brain.
This reduces the release of norepinephrine (a stress hormone that increases BP).
Less norepinephrine = less stimulation of the heart and arteries = lower blood pressure.

Affects of Centrally acting Hypertensive on Body:

↓ Sympathetic nerve signals leads to ↓ Blood pressure
↓ Heart rate leads to ↓ Cardiac output
↓ Peripheral vascular resistance leads to ↓ Afterload on the heart

Risk Associated:

Rebound hypertension (Avoid sudden withdrawal, must taper clonidine).
CNS depression (drowsiness, impaired concentration).
Methyldopa: False + Coombs test, rare hepatotoxicity. Monitor LFTs, CBC

Vasodilators

Brand Name	Generic Name	Mechanism of Action	Side Effects
Apresoline	Hydralazine	Directly relaxes arteriolar smooth muscle → ↓ peripheral resistance	Reflex tachycardia, headache, flushing, fluid retention, lupus-like syndrome
Loniten	Minoxidil	Opens K⁺ channels in arteriolar smooth muscle → hyperpolarization & vasodilation	Hypertrichosis, edema, tachycardia, pericardial effusion
BiDil	Hydralazine + Isosorbide dinitrate	Hydralazine: arteriolar vasodilation; Isosorbide: venous vasodilation	Headache, dizziness, hypotension, drug-induced lupus (hydralazine)
Nitropress	Sodium nitroprusside (IV)	Releases nitric oxide → increases cGMP → vasodilation of arteries and veins	Hypotension, cyanide toxicity (with prolonged use), reflex tachycardia
Nitroglycerin (IV)	Nitroglycerin	Venous > arterial dilation via NO → ↓ preload and myocardial oxygen demand	Headache, hypotension, flushing, tolerance with continuous use
Trandate	Labetalol (has vasodilatory effects)	Mixed α1 and β-blocker → decreases BP via vasodilation and reduced HR	Dizziness, fatigue, orthostatic hypotension, bronchospasm
Coreg	Carvedilol (has vasodilatory effects)	Non-selective β-blocker + α1-blocker – ↓ HR and vasodilation	Bradycardia, dizziness, orthostatic hypotension, weight gain

Notes:

Hydralazine and minoxidil are often used with diuretics and beta-blockers to counter fluid retention and reflex tachycardia.
BiDil is specifically approved for heart failure in African American patients.
Vasodilators are not first-line for essential hypertension but are valuable in resistant hypertension or hypertensive emergencies (IV forms).

Types of Vasodilators

A. Direct Vasodilators

Arterial Dilators (↓ afterload):
- Hydralazine
- Minoxidil (also causes hair growth)
Venous Dilators (↓ preload):
- Nitroglycerin (used in angina)
- Isosorbide dinitrate/mononitrate
Mixed (Arterial + Venous):
- Sodium Nitroprusside (IV for emergencies)

B. Indirect Vasodilators (Other drug classes with vasodilatory effects)

Calcium Channel Blockers (e.g., Amlodipine)
ACE Inhibitors/ARBs (reduce angiotensin II effects)
Alpha-Blockers (e.g., Doxazosin)

Vasodilators Mechanism of Action (Basics)

Vasodilators are medications that help dilate (widen) blood vessels, leading to a decrease in blood pressure. This happens because they relax the smooth muscle in the blood vessel walls, allowing the blood to flow more freely. Let’s break down the process:

Direct Smooth Muscle Relaxation

Vasodilators act directly on the smooth muscle cells that line blood vessels.
By relaxing these muscles, the blood vessels widen, reducing the resistance that the heart has to pump against (known as afterload).
This process decreases blood pressure and improves blood flow to organs and tissues.

2. Nitric Oxide (NO) Pathway

Some vasodilators (e.g., nitroglycerin, sodium nitroprusside) work by increasing the production of nitric oxide (NO) in the endothelial cells (cells lining the blood vessels).
Nitric Oxide activates an enzyme called guanylate cyclase, which increases levels of cyclic GMP (cGMP) inside smooth muscle cells.
This process leads to smooth muscle relaxation and subsequent dilation of blood vessels.

3. K⁺ Channel Opening (Hyperpolarization)

Minoxidil and hydralazine work by opening potassium channels in the vascular smooth muscle cells.
The opening of K⁺ channels leads to hyperpolarization (making the inside of the cell more negative), which reduces the ability of the muscle to contract, causing relaxation and dilation of the blood vessels.

4. Sympathetic Nervous System Influence

Some vasodilators (like labetalol and carvedilol) also have a dual effect, acting as both alpha-blockers and beta-blockers.
They block alpha-1 adrenergic receptors (which are responsible for vasoconstriction) and beta receptors (which control heart rate and contractility). This reduces the overall sympathetic nervous system activity, leading to decreased vascular resistance and lower heart rate.

Types of Vasodilators and Their Specific Mechanisms:

Hydralazine: Direct arteriolar vasodilator; increases cGMP levels, leading to smooth muscle relaxation.
Minoxidil: Opens K⁺ channels in smooth muscle, causing hyperpolarization and vasodilation.
Sodium Nitroprusside: Releases nitric oxide (NO), leading to both arterial and venous dilation.
Nitroglycerin: Primarily venodilator; releases NO to relax vascular smooth muscle.
Labetalol and Carvedilol: Mixed alpha and beta blockers, which lead to both vasodilation and reduced heart rate.

Diuretics

Brand Name	Generic Name	Mechanism of Action	Side Effects
Thiazide Diuretics
Microzide	Hydrochlorothiazide	Inhibits Na⁺/Cl⁻ reabsorption in distal convoluted tubule	Hypokalemia, hyponatremia, hyperuricemia
Hygroton	Chlorthalidone	Inhibits Na⁺/Cl⁻ reabsorption in distal convoluted tubule
Lozol	Indapamide	Thiazide-like, inhibits Na⁺ reabsorption
Zaroxolyn	Metolazone	Thiazide-like, potent when combined with loop diuretics	Electrolyte disturbances, dehydration
Loop Diuretics
Lasix	Furosemide	Inhibits Na⁺/K⁺/2Cl⁻ symporter in thick ascending limb of loop	Hypokalemia, ototoxicity, dehydration
Bumex	Bumetanide
Demadex	Torsemide
Edecrin	Ethacrynic acid	Loop diuretic without sulfa group	Ototoxicity, GI effects
Potassium-Sparing Diuretics
Midamor	Amiloride	Blocks epithelial Na⁺ channels in distal tubule	Hyperkalemia
Dyrenium	Triamterene	Blocks epithelial Na⁺ channels in distal tubule	Hyperkalemia, nephrolithiasis
Potassium-Sparing Diuretics – Aldosterone Antagonists
Aldactone	Spironolactone	Blocks aldosterone receptors in distal nephron	Gynecomastia, hyperkalemia, menstrual changes
Inspra	Eplerenone	Selective aldosterone blocker	Hyperkalemia, less endocrine side effects
Combination Diuretic Drugs
Dyazide, Maxzide	Triamterene + Hydrochlorothiazide	Na⁺ channel blocker + thiazide	Hyperkalemia, hypokalemia, dizziness
Moduretic	Amiloride + Hydrochlorothiazide	Na⁺ channel blocker + thiazide	Hyperkalemia, nausea
Aldactazide	Spironolactone + Hydrochlorothiazide	Aldosterone antagonist + thiazide	Electrolyte imbalance
Lasilactone (EU/India)	Spironolactone + Furosemide	Aldosterone antagonist + loop	K⁺ balancing, risk of dehydration

Diuretics Comparison Table

Diuretic Type	Site of Action	Main Transporter/Target	K⁺ Sparing?
Thiazides	Distal Convoluted Tubule	Na⁺/Cl⁻ symporter	❌
Loop	Loop of Henle	Na⁺/K⁺/2Cl⁻ symporter	❌
Potassium-Sparing	Collecting Duct	ENaC (epithelial Na⁺ channel)	✅
Aldosterone Antag.	Collecting Duct	Aldosterone receptors	✅

How do Diuretics Work

Thiazide and Thiazide-like Diuretics

Examples: Hydrochlorothiazide (Microzide), Chlorthalidone, Indapamide
Site of Action: Distal convoluted tubule
Mechanism:
- Inhibit Na⁺/Cl⁻ symporter, reducing sodium and water reabsorption
- Leads to increased urine output and lower blood pressure

📌 Key Point: Often first-line for hypertension; mild/moderate diuretic effect

Loop Diuretics

Examples: Furosemide (Lasix), Bumetanide, Torsemide
Site of Action: Thick ascending limb of the loop of Henle
Mechanism:
- Inhibit Na⁺/K⁺/2Cl⁻ symporter
- Causes massive sodium, chloride, and water loss

📌 Key Point: Most potent diuretics; used in heart failure, edema, and renal disease

Potassium-Sparing Diuretics

Examples: Amiloride, Triamterene
Site of Action: Collecting ducts
Mechanism:
- Block epithelial sodium channels (ENaC), reducing sodium reabsorption
- Prevent potassium excretion

📌 Key Point: Weak diuretic effect; used with thiazides to prevent hypokalemia

Aldosterone Antagonists (also potassium-sparing)

Examples: Spironolactone (Aldactone), Eplerenone
Site of Action: Collecting ducts
Mechanism:
- Block aldosterone receptors
- Reduce sodium reabsorption and potassium excretion

📌 Key Point: Especially useful in heart failure, resistant hypertension, and hyperaldosteronism

Source

Diuretics Side Effects & Managing or Resolving Those Issues

Side Effect	Drug Examples	Why It Happens	Solution / Management
Thiazide Diuretics
Hypokalemia (low K⁺), Muscle spasms	Hydrochlorothiazide, Chlorthalidone	↑ K⁺ loss in urine	Add potassium-rich foods or potassium supplements; combine with K⁺-sparing diuretic
Hyponatremia (low Na⁺)		Excess sodium loss	Monitor Na⁺, adjust dose, ensure adequate sodium intake
Hyperuricemia / Gout		↓ uric acid excretion	Use with caution in gout patients; consider alternative
Hyperglycemia		Thiazides reduce insulin sensitivity	Monitor blood sugar in diabetic/pre-diabetic patients
Hypercalcemia		↓ calcium excretion	Monitor calcium levels, especially in hyperparathyroidism
Erectile dysfunction		Unknown mechanism	Discuss alternatives if needed
Loop Diuretics
Severe hypokalemia	Furosemide, Torsemide	High K⁺ excretion	Add potassium supplements or combine with K⁺-sparing agent
Dehydration		Excess fluid loss	Monitor fluid status, adjust dose, encourage hydration
Ototoxicity		High doses / fast IV push	Avoid rapid IV push; use lowest effective dose
Hypocalcemia, Hypomagnesemia		Increased Ca²⁺ and Mg²⁺ loss	Supplement as needed; monitor labs
Orthostatic hypotension		↓ blood volume	Rise slowly from sitting/lying; adjust dose
Potassium-Sparing Diuretics
Hyperkalemia	Amiloride, Triamterene	Blocks K⁺ excretion	Monitor K⁺, avoid in renal failure or with ACE inhibitors/ARBs
Nausea, dizziness	Amiloride, Triamterene	General drug effects	Take with food, monitor for symptoms
Potassium Sparing Diuretic – Aldosterone Antagonists
Hyperkalemia	Spironolactone, Eplerenone	↓ aldosterone = ↓ K⁺ excretion	Monitor K⁺ and renal function
Gynecomastia (Spironolactone)		Hormonal effects	Switch to Eplerenone (less hormonal effects)
Menstrual irregularities		Hormonal disruption	Monitor and assess patient concern