pcol p6

CARDIOVASCULAR SYSTEM

• ANTI-HYPERTENSIVE DRUGS

• ANTI-HYPERLIPIDEMIA

• ANTI-ANGINAL DRUGS

• DRUGS FOR HEART FAILURE

• ANTI-ARRHYTHMIC DRUGS

• ANTITHROMBOTIC & THROMBOLYTIC DRUGS

REGULATION OF BLOOD PRESSURE

ANTI-HYPERTENSIVE DRUGS

• DIURETICS

• Sympatholytic Drugs

• Angiotensin Inhibitors

• Vasodilators

DIURETICS

• Loop

• Thiazides

• K-Sparing

• Carbonic anhydrase inhibitors

• Osmotic Diuretics

Loop Diuretics

Less effective in treating HPN vs. thiazides

Thiazides

Most frequently used

K-Sparing

Combined with thiazide/loop to prevent hypokalemia

Thiazides

• MOA → inhibit the Na⁺/Cl⁻ symporter (EARLY distal tubules)

a.

b.

c.

• S/Es

Loop Diuretics

• Aka high-ceiling diuretics

• MOA → inhibit the Na⁺, K⁺, 2Cl⁻ symporter in the ascending limb of the loop of Henle

Loop Diuretics

Drugs

a. semide

b. semide

c. Bumetanide

d. Ethacrynic acid

Loop Diuretics

Uses

a.

b.

c.

Effects:

a. _____________

b. Hyper

c. Hyper

d. Hyper____

Potassium-Sparing Diuretics

• impressive ability to lower blood pressure when combined with other drugs

• MOA →

• (–) Aldosterone = ↓ Na⁺ reabsorption, ↑ K⁺ secretion (spironolactone)

• (–) Na⁺-channel = ↓ Na⁺ reabsorption, ↑ K⁺ secretion (amiloride)

spironolactone

(–) Aldosterone = ↓ Na⁺ reabsorption, ↑ K⁺ secretion

amiloride

(–) Na⁺-channel = ↓ Na⁺ reabsorption, ↑ K⁺ secretion

Carbonic Anhydrase Inhibitors

a. ________zolamide

b. ________zolamide

Uses → treatment of

a.

b.

c.

Osmotic Diuretics

Use → management of high ICP

a. Mannitol

b. Glycerol

Sympatholytic Drugs

• MOA → (–) adrenoceptor = ↓ sympathetic activity

• alpha-2 agonist = ↓ NE activity

Result → Sympatholytic effect

Sympatholytic Drugs

• α-Adrenoceptor Antagonists

• β-Adrenoceptor Antagonists

• Centrally-Acting Drugs

α-Adrenoceptor Antagonists

• MOA → (–) α1 = vasodilation

• Suffix → -zosin

• S/Es:

a. Reflex tachycardia

b. lightheadedness, dizziness, and syncope at initiation of therapy (first-dose phenomenon)

c. Orthostatic hypotension

β-Adrenoceptor Antagonists

• MOA → Blockade of cardiac β1-receptors

a. ↓ HR

b. ↓ contractility

c. ↓ renin secretion

β-Adrenoceptor Antagonists

• Uses → HPN + CVD (myocardial ischemia, arrhythmia, HF)

β-Adrenoceptor Antagonists

S/Es:

• B

• A

• D

• F

• I

• S

• H

Properties of Beta-Blockers: Solubility

Lipid-soluble

• Use → migraine prophylaxis

1.

2.

3.

Properties of Beta-Blockers: Solubility

Water-soluble

• Adv → less CNS S/E (fatigue, nightmares)

1.

2.

3.

Properties of Beta-Blockers: Generations of Beta-Blockers

First-generation

• Non-selective

Second-generation

• β1-selective

Third-generation

• may be selective or nonselective

• Vasodilatory

First-generation Beta-Blockers

Second-generation Beta-Blockers

Third-generation Beta-Blockers

Mixed Beta-Blockers

Intrinsic Sympathomimetic Property

Membrane-Stabilizing Property

Local anesthetic property

Centrally-Acting Drugs

(+) α2-receptor = ↓ sympathetic outflow

Centrally-Acting Drugs

Drugs

a. clonidine

b. guanfacine

c. methyldopa

Centrally-Acting Drugs

• Converted to → α-methyl norepinephrine

• Can be used for pregnant

• S/Es → sedation, Coombs-positive hemolytic anemia (methyldopa)

Angiotensin Inhibitors

• ACE Inhibitors

• Angiotensin Receptor Blockers

ACE Inhibitors

• Use

a.

b.

• Examples

a.

b.

c.

d.

ACE Inhibitors

A/Es

a.

b.

c.

Angiotensin Receptor Blockers

MOA → block AT1 receptor

• Use

a.

b.

*adv → less dry cough

Angiotensin Receptor Blockers

Drugs

a. Candesartan

b. Losartan

c. Olmesartan

d. Valsartan

e. Eprosartan

f. Irbesartan

g. Telmisartan

*New → Azilsartan, Fimasartan

Vasodilators

• Calcium Channel Blockers

• Direct-acting vasodilator

• Dopamine-1 agonist

Calcium Channel Blockers

• Dihydropyridines

• Non-dihydropyridines

Dihydropyridines

• Have vascular selectivity

• Drugs:

Non-dihydropyridines

• A/Es:

Non-dihydropyridines

• Have cardioselectivity, but also vasodilators

• Drugs:

Non-dihydropyridines

A/Es:

_____cardia

Constipation (particularly, __________)

Direct-acting vasoDopamine-1 agonistdilator

H

• A/E → __________

N

• A/E → __________

D

• A/E → __________

M

• A/E → __________

Angina Pectoris

• Ischemia = restricted blood supply → shortage of oxygen

• Problem → ________oxygen SUPPLY = _______oxygen DEMAND

Stable Typical Angina

• Most common

• Angina of _________

• Mx → Rest or Nitroglycerin

• Chronic stable angina

a.

b.

c.

Unstable Typical Angina

• Rest angina, preinfarction

• Medical emergency

• Mx:

a. oxygen therapy

b. statins

c. antiplatelets

d. anticoagulants

Atypical Angina: Variant / Prinzmetal angina

• Rare

• Mx → __________

ANTI-ANGINAL DRUGS

Drugs:

• Increase supply → increase blood flow and regional flow distribution

ANTI-ANGINAL DRUGS

Drugs:

• Decrease myocardial wall tension

*Preload (venous pressure) → Drugs → _________________

*Afterload (arterial pressure) → Drugs →

ANTI-ANGINAL DRUGS

• VASODILATORS

  • Organic Nitrites and Nitrates

• CALCIUM CHANNEL BLOCKERS

  • Dihydropyridines

  • Non-dihydropyridines

• BETA-ADRENOCEPTOR BLOCKERS

  • atenolol, metoprolol, nadolol, and propranolol

• Ivabradine

• Ranolazine

• Trimetazidine

Organic Nitrites and Nitrates

MOA → converted to ________ which (+) guanylate cyclase = ___ CGMP = ____________

Organic Nitrites and Nitrates

• Amyl nitrite

• Nitroglycerin

• Isosorbide dinitrate and isosorbide mononitrate

Amyl nitrite

*poppers = increases libido

• inhalational

Nitroglycerin

• Sublingual, transdermal, topical, oral, IV

• A/Es:

CCB: Dihydropyridines

• relax ___________ smooth muscles

• decrease

CCB: Non-dihydropyridines

• decrease __________ & _______________

• decrease demand

BETA-ADRENOCEPTOR BLOCKERS

• atenolol, metoprolol, nadolol, and propranolol

• often used in __________ angina and __________

BETA-ADRENOCEPTOR BLOCKERS

Uses:

In typical angina:

• prevent exercise-induced tachycardia

• reflex tachycardia

Acute MI:

• decrease recurrence of MI and improve survival

Ivabradine

• MOA → inhibit If current in SA node (pacemaker current) = decrease HR

• treatment of:

a. chronic angina (if ________ to beta blockers)

b. HFrEF

Ranolazine

preferred for chronic stable angina with __________ or ___________

Trimetazidine

• blocks ketoacyl coA thiolase, resulting in decrease FA metabolism

• Use: Angina (if intolerant to other drugs)

Hyperlipidemia

• high LDL, low HDL

• increases the risk of atherosclerosis (build-up of fats, cholesterol, and other substances in the artery) → stroke, MI

LIPOPROTEINS

• Chylomicron

• Very low density lipoprotein

• Low density lipoprotein

• High density lipoprotein

Chylomicron

• Transport ___________ triglycerides (fats) from the intestine to tissues throughout the body.

Very low density lipoprotein

• Produced in the liver

• Transports TGs produced in the liver to tissues for energy production and storage

• VLDL becomes LDL as they lose triglycerides

Low density lipoprotein

• Bad cholesterol (buildup of ___________ in the arteries)

• Transport cholesterol from the liver to tissues

High density lipoprotein

• Good cholesterol (remove excess cholesterol from the bloodstream and transport to the liver for excretion)

Hyperlipidemia

↑ LDL

↑ VLDL

↑ LDL & VLDL

↓ HDL

HYPOLIPIDEMIC AGENTS

• HMG-CoA Reductase Inhibitors

• Bile Acid–Binding Resins

• Ezetimibe

• Niacin (Nicotinic Acid) Fibric Acid Derivatives

HMG-CoA Reductase Inhibitors

• Statins

• First-line for _________________

a. ______vastatin

b. ______vastatin

c. ______vastatin

d. ______vastatin

HMG-CoA Reductase Inhibitors

Effects:

• ____ LDL (~60%)

• ____ HDL (~10%)

• ____ VLDL (~30%)

HMG-CoA Reductase Inhibitors

A/Es:

• GIT upset

• R

• H

Bile Acid–Binding Resins

a. Choles_______________

b. Coles_____________

c. Cole______________

Bile Acid–Binding Resins

• Use: Hypercholesterolemia ______

• MOA: increase fecal excretion of bile acid

Bile Acid–Binding Resins

Effects:

• ____LDL (~30)

• minimal effect on HDL

• No effect on VLDL

Bile Acid–Binding Resins

A/Es

• Constipation

• fecal impaction

Ezetimibe

• inhibits the absorption of ___________________

• used alone or in combination with statins for hypercholesterolemia

Niacin (Nicotinic Acid)

• only hypolipidemic vitamin

• MOA: inhibits formation & secretion of VLDL

• Use: hypertriglyceridemia

Niacin (Nicotinic Acid)

Effects

• _____VLDL

• _____LDL

• _____HDL

Niacin (Nicotinic Acid)

A/Es

• Niacin _____________

• Hepatitis

• Hyperglycemia

• Hyperuricemia

Fibric Acid Derivatives

a. Clofibrate (no longer available)

b. Gemfibrozil

c. Fenofibrate

Fibric Acid Derivatives

• MOA: (+) PPAR-→ → activation of LPL → low VLDL

• Effects

• ____VLDL (30-50%)

• ____LDL-C

• ____ HDL-C

Fibric Acid Derivatives

A/Es

• GI problem

• blood cell deficiencies (rare)