ANTI-HYPERTENSIVE AGENTS

A1 stimulation causes

Smooth muscles: vasoconstriction

Kidneys: tubular reabsorption of sodium

B2 stimulation causes

Smooth muscles: vasodilation

Kidneys: renin release

B1 stimulation causes

increase in myocardial contraction

A2 stimulation acts as a

Inhibitor / negative feedback for NE release

Major endogenous vasodilator

Nitric oxide

Major endogenous vasoconstrictor

Endothelin

Loop diuretics MOA

Located at the think ascending limb and act on the Na/K/2Cl carrier to inhibit the reabsorption of these ions

The most powerful diuretic

Loop diuretic

Names of the loop diuretics

Furosemide, Torsemide, Bumetanide, and Ethacrynic acid

Names of the Thiazide Diuretics

Hydrochlorthiazide, Chlorthiazide, Chlorthialidone, and Indapamide

Thiazide diuretics MOA

Located at the distal convoluting tubule targeting the Na/Cl carrier

Adverse effects of Thiazide and Loop diuretics

Hypokalemia and ischemic ventricular fibrillation leading to sudden death

Thiazide and Loop diuretics should be avoided by

Nursing mothers as it appears in breast milk

K+ sparing diuretics include

Amiloride, Thiamterene, Spironolactone, and Eplerenone

K+ sparing diuretics MOA

Target ENaC channels, preventing sodium re-absorption from the collecting ductA

Adverse effect of K+ sparing diuretics

Hyperkalemia

B1 blockers will cause a reduction in

myocardial contractility, heart rate, cardiac output, peripheral resistance, renin secretion thus Ang II levels

Adverse effects of beta blockers

Rebound hypertension → sudden discontinuation of beta blockers can produce withdrawal syndrome likely due to up regulation of beta receptors

You should not take a nonselective beta blocker for patients with

reactive airway disease because it will exacerbate asthma

Both nonselective and B1 selective beta blockers should not be taken for patients with

myocardial conduction defects such as SA or AV nodal dysfunction

Nonselective beta blocker and epinephrine combined will cause

Hypertension

Beta blocker combined with a calcium channel blocker such as Verapamil/Diltiazem will cause

Conduction block leading to death

A1 adrenergic antagonists

Prazosin, Alfuzosin, Tamsulosin, Terazosin, and Dozazosin

A1 adrenergic antagonist MOA

reduce anterior resistance and increase venous capacitance

Adverse effects of A1 antagonists

hypotension, pretension of salt and water leading to peripheral edema

Labetalol is prescribed for

Hypertensive emergency

Labetelol is combined of what antagonists

A1 antagonist and nonselective beta antagonist

Carvedilol is prescribed for

Adjunctive therapy with diuretics and ACE inhibitors

Carvedilol is combined of what antagonists

A1 antagonist and nonselective beta antagonists

Carvedilol contraindication

Decompensated heart failure

Methyldopa prodrug conversion

a-methyldopamine → a-methylnorepinephrine

Methyldopa MOA

Acts on the presynaptic A2 in the CNS to prevent further release of NE

Do not prescribe methyldopa to patients with

Renal insufficiency and who are pregnant

Clonidine, Guanabenz, and Guanfacine MOA

Stimulate the a2A subtype receptors in the brainstem to reduce NE release and plasma NE

Clonidine, Guanabenz, and Guanfacine adverse effects

Severe bradycardia, sinus arrest, and hepatotoxicity

Calcium channel blockers MOA

block L-type calcium channels exhibiting their effects on cardiac muscle and vascular smooth muscle to slow down heart rate and decrease peripheral vascular resistance

Clevidipine

Ultra short acting 3rd generation calcium channel blocker that has an onset of action between 1-3 minutes

The indirect result of calcium channel blockers

Evokes a baroreceptor response to the decrease in vascular resistance which will mediate a sympathetic discharge and result in tachycardia.

Calcium channel blocker combined with beta blocker results in

Negative chronotrophic effect (decreased heart rate)

Do not prescribe calcium channel blockers for patients with history of

SA nodal block, myocardial infarction, angina, or severe cardiovascular events

Aliskiren MOA

Directly and competitively inhibits renin release, leading to Ang I being completely blocked

Adverse effect of Aliskiren

Angioedema

Aliskiren contraindication

Pregnant women due to fetal damage

ACE inhibitor names

Captopril, Lisinopril, Enalapril, Ramilpril, and Benazepril

ACE inhibitor MOA

Inhibits ACE preventing Ang II generation

Primary benefit of vasoconstriction and binding to its AT-1 receptor (activates the receptor)

Inhibition of aldosterone levels by blocking aldosterone Na+ uptake and associated edema

Relationship between ACE inhibitor with bradykinin

ACE breaks down bradykinin, therefore an ACE inhibitor will increase bradykinin leading to coughing

ACE inhibitor adverse effect

Angioedema → swelling of the mucosal dermal and subcutaneous tissue leading to vascular leakage. This is life threatening

Coughing due to bradykinin accumulation

ACE inhibitor contraindications

Pregnancy due to heavy risk to fetal health and in patients with compromised renal function or renal failure

ACE inhibitors combined with K+ sparing diuretics causes

Hyperkalemia

AT1 receptor antagonists names

Losartan, Valsartan, Telmisartan, Candesartan, Eprosartan, and Ibesartan

AT1 receptor antagonists MOA

Antagonizing the effects of Ang II on the AT1 receptors causing a relaxation of the smooth muscles promoting vasodilation.

Prevents aldosterone release promoting renal salt and water excretion, decreasing plasma volume.

AT1 receptors antagonists adverse effects

hyperkalemia, hypotension, and reduced renal function

Negative feedback loop of AT1 inhibition

leads to increased levels of renin and Ang II

Hydralazine

One of the most orally active drugs for arterial vasodilation

Hydralazine MOA

Causes a decrease in intracellular calcium by preventing IP3 mediated release of Ca from sarcoplasmic reticulum

Minoxidil

Arterial vasodilator that is inactivated. It is activated by converting into an active metabolite minoxidil NO sulfate

Minoxidil MOA

activates ATP modulated K+ channel, thus opening the K+ channel and promoting efflux of K+ in smooth muscle cells, causing relaxation.

Adverse effects of Minoxidil

Hirsutism (excess hair growth), pseudoacromegaly (enlarged hands and feet, and facial features but has no effect of GH), and pericardial effusion (box warning)

Nitroprusside

Arterial and venous dilator must be given through IV

Nitroprusside MOA

Immediate release of NO which activates guanylyl cyclase leading to vasodilation

Nitroprusside contraindications

Renal and hepatic failures and compromised function

What is something to look out for with Nitroprusside?

The drug releases cyanide so cyanide poisoning can occur

This is due to the conversion of nitroprusside to cyanide and thiocyanate

Adverse effects of Nitroprusside

Cyanide toxicity which can lead to lactic acidosis, anorexia, nausea, fatigue, and toxic psychosis

Two treatment options for cyanide poisoning

1. administer thiosulfate along with nitroprusside administration to prevent cyanide poisoning

2. administer hydroxocobalamin which will combine with cyanide to form cyanocobalamin (vitamin B12)

First line of therapy for hypertension drugs

Thiazide. calcium channel blockers, ACE inhibitors, and AT-1 receptor antagonists (ARBs)

Widaplik

New combination drug that combines 3 drugs into one

Aprocitentan

Endothelin receptor antagonist that treats hypertension

CANNOT BE USED WHILE PREGNANT - females must be on birth control while using this drug