Anti-hypertensive

Question 1

Thiazide, etc.

Answer 1

Class: Diuretics

MOA: Lower BP initially by ↓ blood volume, ↓CO (↓ Na+ and H2O in body) → later ↓ peripheral resistance. After several weeks, C.O returns normal but peripheral resistance falls.

Adverse Effects: Hypokalemia, volume depletion/azotemia, hyponatremia, hypomagnesemia → start with lower dose (e.g. 12.5-25mg) do avoid side effects.

Clinical Pearls: Thiazide: used alone for mild
hypertension. Diuretics often used in combination with sympatholytics and vasodilator drugs b/c these drugs tend to cause volume retention. Drug of choice when first starting diuretic due to long DOA (18-24hr) → loop diuretics have shorter DOA (6hrs). Kidney retains water and Na after 6
hrs, lose antihypertensive effect.

Question 2

Clonidine

Answer 2

Class: Sympatholytic agents

MOA: Stimulates alpha-2- adrenergic receptor in medulla of brain (alpha 2 agonist) → ↓ sympathetic and ↑ parasympathetic outflow from medulla → ↓BP, ↓HR, reduces vasomotor tone (Lower BP by ↓ peripheral vascular resistance or ↓ cardiac output)

Adverse Effects: Dry mouth, sedation, depression, rebound hypertension if stopped abruptly

Clinical Pearls: Oral and transdermal patch

Question 3

Methyldopa

Answer 3

Class: Sympatholytic agents

MOA: Analog of L-dopa-, also stimulates central alpha- adrenoreceptors

Adverse Effects: Sedation and depression

Clinical Pearls: used in hypertension of pregnancy

Question 4

Guanethidine

Answer 4

Class: Sympatholytic
agents- Adrenergic neuron blocking agents

MOA: Blocks release of norepinephrine from postganglionic sympathetic nerve endings

Adverse Effect: Postural hypotension, diarrhea

Clinical Pearls: Rarely used due to side effects (better
drugs available with less side effects)

Question 5

Reserpine

Answer 5

Class: Sympatholytic
agents- Adrenergic neuron blocking agents

MOA: Blocks ability of aminergic transmitter vesicles to take up and store biogenic amines: depletion of norepinephrine, dopamine, serotonin

Adverse Effects: Sedation and depression

Clinical Pearls: Rarely used due to side effects

Question 6

Propranolol

Answer 6

Class: Non-selective Beta blockade

MOA: BP lowering effect due to ↓ in C.O. Inhibits stimulation of renin production by catecholamines

Adverse Effects: Bradycardia, Bronchospasm (non-selective beta blockade)

Clinical Pearls: First beta blocker used for hypertension and angina

Question 7

Metoprolol, atenolol

Answer 7

Class: Beta 1 blockade (cardioselective)

MOA: BP lowering effect due to ↓ in C.O. Inhibits stimulation of renin production by catecholamines

Clinical Pearls: Most widely used beta-blockers. Less bronchial constriction than
propranolol

Question 8

Labetalol, Carvedilol

Answer 8

Class: Alpha 1, Beta 1, Beta 2 blocker

MOA: Have Beta-blocking and vasodilating effects (alpha 1 blockade)

Clinical Pearls: Potent, used in hypertensive emergencies (i.v.). Oral and iv available.

Question 9

Nebivolol

Answer 9

Class: Beta 1 blocker

MOA: Beta 1 blocker with vasodilating properties due to ↑ release of nitric oxide (NO)

Question 10

Prazosin, Terazosin, Doxazosin

Answer 10

Class: Sympatholytic
Agents- Alpha 1 adrenergic blockers

MOA: Selectively block alpha-1 receptors in arterioles and venules → dilate both arteries and veins

Adverse Effects: Postural hypotension (first dose phenomenon → start with
low dose, have patients take the med before bed). Dizziness, palpitations, headache.

Clinical Pearls: NOT a first line therapy for HTN. Works best when used with another agent

Question 11

Hydralazine

Answer 11

Class: Oral Arterial vasodilators

MOA: Relax smooth muscle of arterioles (MoA unclear), may cause membrane hyperpolarization by opening K+ ATP channels and/or inhibition of Ca release from sarcoplasmic reticulum Evoke *compensatory physiologic
responses (limit effectiveness) → works best with other agents

Adverse Effects: Headaches, nausea, palpitations (reflex tachycardia)

Clinical Pearls: Not a first line agent b/c of need for frequent dosing and tachyphylaxis. Most effective when used with other agents b/c of compensatory responses (which is ↑ Na and Water reabsorption by kidney → beta blocker use is helpful → enhance BP effect and prevent tachycardia)

Question 12

Minoxidil

Answer 12

Class: Oral vasodilators

MOA: Opens potassium channels (K+ ATP) in plasma membrane of smooth muscle
cells, prevents Ca2+ channel opening (inhibits contractions) → dilates arterioles

Adverse Effects: Reflex sympathetic stimulation (tachycardia). Salt and water retention (Edema). Headache,
sweating, hypertrichosis (hair growth).

Clinical Pearls: MORE POTENT

Question 13

Sodium nitroprusside

Answer 13

Class: Intravenous vasodilators

MOA: Release of nitric acid (NO) → dilates arterial and predominantly venous blood vessels

Adverse Effects: Hypotension Accumulation of thiocyanate, can cause weakness, seizures,
death

Clinical Pearls: Hypertensive emergencies → rapidly lowers BP within minutes, short half life

Question 14

Fenoldopam

Answer 14

Class: Intravenous vasodilators

MOA: Agonist of dopamine D1 receptors, dilates peripheral arteries

Adverse Effects: Reflex tachycardia, HA, flushing

Clinical Pearls: Hypertensive emergencies → rapidly lowers BP within minutes, short half life

Question 15

Phenylalkylamines (Verapamil)

Benzothiazepines (Diltiazem)

Dihydropyridines (Nifedipine, Felodipine, Amlodipine)

Answer 15

Class: Calcium channel blocking agents

MOA: Block L type Ca2+ channel in cardiac and smooth muscle cells (channels have 4 subunits, different classes bind to different sites on the alpha 1 subunit) In smooth muscle cells, keeps [Ca2+] low, ↓ activation of myosin light chain kinase → ↓ smooth muscle contraction ↓ BP by dilating blood vessels, particularly arterioles.

Adverse Effects: Dihydropyridines: Headache,
dizziness, flushing, peripheral
edema. Verapamil, diltiazem:
Bradycardia, cardiac depression. Verapamil: constipation.

Clinical Pearls: Dihydropyridines: greater vasodilatory effect, less cardiac depressant effect than verapamil and diltiazem. Non-DHP (Diltiazem, Verapamil): more likely to cause negative inotropic/chronotropic effects in heart and constipation.

Question 16

Aliskiren

Answer 16

Class: Renin Inhibitor

MOA: Binds to active site of renin → inhibits binding of renin to angiotensinogen → blocks conversion of angiotensinogen to angiotensin I → Reduce peripheral vascular resistance and blood volume.

Clinical Pearls: Most recently developed class of antihypertensive drugs. Comparable BP lowering effect to ACE-inhibitor and angiotensin II receptor blockers (but Aliskerin is more expensive).

Question 17

Benazapril
Captopril
Enalapril
Fosinopril
Lisinopril
Moexipril
Perindopril
Quinapril
Ramipril
Trandopril

Answer 17

Class: ACE Inhibitors

MOA: Block production of Angiotensin II → block contraction of vascular smooth muscle,Thirst, Vasopressin release, Aldosterone secretion, Release of adrenal catecholamines, Increase sympathetic tone, Cellular hypertrophy and hyperplasia. Prevent degradation of bradykinin, a potent vasodilator. Reduce peripheral vascular resistance and blood volume.

Adverse Effects: Cough (due to ↑ bradykinin → fluid accumulation into alveoli). Fetopathy (can’t use in
pregnancy), Angioedema (bradykinin mediated), Hyperkalemia, Hypotension. Acute renal failure, Skin rash

Clinical Pearls: Hypertension Left ventricular systolic dysfunction (congestive HF), Acute myocardial infarction (M.I.), Chronic kidney disease (slow progression).

Question 18

Candesartan
Eprosartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan

Answer 18

Class: ARBs

MOA: Bind to angiotensin II type 1 receptor (AT1) with high affinity. Inhibit biological effects of angiotensin II → same as ACEi except no effect on breakdown of bradykinin (no cough). Equally effective to ACEi in ↓BP.

Adverse Effects: Same as ACEi except no cough, angioedema much rarer.

Clinical Pearls: Hypertension. Left ventricular systolic dysfunction. Acute myocardial infarction. Chronic kidney disease. The best tolerated of all antihypertensive drugs - lowest discontinuation rate (more expensive).