Sketchy Pharm Cardio

Where do thiazide diuretics act?

distal convoluted tubule

MOA: Thiazide diuretics

Inhibit Na+/Cl- cotransport

What is the difference in mechanism of Ca2+ reabsorption in DCT vs. TAL?

(1) DCT: Active transport

(2) TAL: Driven by (+) lumenal voltage

What effect do thiazide diuretics have on Ca2+ reabsorption?

Enhances reabsorption

(opposite in loop diuretics)

5 indications for thiazide treatment

1. Hypertension

2. Heart failure

3. Nephrogenic Diabetes Insipidus

4. Ca2+ stone prevention

5. Osteoporosis

7 adverse effects of thiazides

1. Hyponatremia

2. Hypercalcemia

3. Hyperlipidemia

4. Hyperglycemia

5. Hypokelimia

6. Hyperuricemia

7. increase Li+

Which segment of the nephron is impermeable to water?

Thick Ascending Loop of Henle

Note: DCT is relatively impermeable to water as well

What transporter do loop diuretics inhibit?

Na-K-2Cl (on lumenal membrane)

MOA: Furosemide

Inhibits Na+/K+/2Cl- Cotransporter

What ions do loop diuretics promote excretion of indirectly?

(1) Mg2+

(2) Ca2+

Do loop diuretics have a larger effect on serum Mg2+ or Ca2+?

Mg2+

Ca2+ levels are corrected by ↑ intestinal absorption due to Vitamin D, ↑ renal absorption due to PTH

Which class of diuretics induce the expression of COX-2?

Loop diuretics

Which class of pain medication can interfere with loop diuretics?

NSAIDs

Indications (3) : Loop diuretics

1. Pulmonary edema/CHF (1st line drug for CHF with edema)

2. Ascites

3. Hypertension

True or false. Loop diuretics are potassium wasting.

True

Inhibition of Na+/K+/2Cl- cotransporter ⇒ ↑ lumenal Na+ concentration and ∴ increased activity of Na+/K+ ATPase

Adverse Effects (5) : Loop diuretics

1. Ototoxicity

2. Sulfa drug allergy

3. Interstitial nephritis

4. Hyperuricemia

5. Contraction alkalosis

Name a loop diuretic that is NOT a Sulfa drug

Ethacrynic acid

Suffix: ARBs

-sartan

MOA: Aliskiren

direct renin inhibitor

What effect does Angiotensin II have on renal electrolyte handling?

↑ Na+/HCO3- in PCT

Suffix: ACE inhibitors

-pril

Name 4 physiologic effects of ACE inhibitors/ARBs

(1) Dilate efferent arteriole

(2) ⇒ ↓ GFR

(3) ↓ Aldosterone release

(4)⇒ ↓ Na+/HCO3- reabsorption in PCT

Name 2 solute abnormalities caused by ACE inhibitors

(1) ↑ Creatinine

(2) Hyperkalemia

What is a common initial side effect for heart failure patients started on ACE inhibitors?

Fainting

(Sudden drop in AngII ⇒ Vasodilation ⇒ Syncope)

Indications (4) : ACE inhibitors

(1) Heart failure

(2) Myocardial infarction

(3) Hypertension

(4) Diabetic nephropathy

Do ACE inhibitors ↓ mortality in heart failure?

yes

(By inhibiting AngII mediated remodeling)

When are diabetic patients placed on ACE inhibitors?

Albuminaria with BP >130/80

What is the most distinctive side effect of ACE inhibitors?

Dry cough

(Due to increased bradykinin)

What genetic disease is an absolute contraindication to ACE inhibitors?

Hereditary angioedema

Which antihypertensive is a teratogen?

ACE inhibitors

What drugs are an absolute contraindication to ACE inhibitors?

NSAIDs

What is the difference in target of dihydropyridines and non-dihydropyridine calcium channel blockers?

(1) Dihydropyridine: ∝ Smooth muscle

(2) Non-dihydropyridine: ∝ Cardiac muscle

Suffix: Dihydropyridines

-dipine

Name the CCB with the strongest cardiac effect

Verapamil

(∴ Verapamil > Diltiazem for angina)

Name the CCB which causes both vasodilation and an intermediate cardiac effect

Diltiazem

(Diltiazem = 2 = Affects both smooth muscle and heart)

What calcium channel blocker can be used in pregnancy?

Nifedipine

Indications (9) : Calcium channel blockers

(1) Hypertension

(2) Malignant hypertension

(3) Hypertension in pregnancy

(4) Raynaud's

(5) Subarachnoid hemorrhage

(6) Stable angina

(7) Migraine prophylaxis

(8) Prinzmetal angina (1st line)

(9) Arrhythmia

Walk around the room counterclockwise ~sketchy tip

Which CCB is used for migraine prophylaxis?

Verapamil

(Verapamil for Very-Painful-Migraines)

Adverse Effects (3) : Dihydropyridines

(1) Lightheadedness and headache

(2) Peripheral edema

(3) Reflex tachycardia

Which calcium channel blocker is known to exacerbate myocardial ischemia?

Nifedipine

Name the distinctive side effect of Verapamil

Constipation

What enzyme do nitrates activate?

Guanylyl cyclase ⇒ ↑ cGMP

Describe the effect nitrates have on the vasculature

(1) Significant venous dilation

(2) Moderate dilation of large arteries

Which hemodynamic factor [afterload, preload] do nitrates predominantly affect?

Preload (decrease)

Indications (3) : Nitrates

(1) Stable angina

(2) Prinzmetal angina

(3) Acute coronary syndrome

ROA: Nitroglycerin

(route of action)

Sublingual

ROA: Isosorbide Nitrate

Oral

When are nitrates contraindicated in treatment of MI?

Right sided MI

(Due to ↑ sensitivity to preload)

Why would β-blockers be given with nitrates?

Prevent reflex tachycardia

(Venous vasodilation ⇒ ↓ Preload ⇒ ↓ MAP ∴ Body compensates by ↑ HR)

How can nitrates cause hypoxia?

Oxidize heme Fe2+ → Fe3+

Causes methemoglobinemia

(Nitrates have many oxygens ∴ oxidizing agents ∴ oxidize iron)

How is nitrate tolerance avoided?

Nitrate free interval every day or

low dose interval

What drug class is an absolute contraindication to nitrates?

PDE-5 inhibitors i.e. Sildenafil

(Viagra)

What type of heart disease are nitrates contraindicated in?

Hypertrophic cardiomyopathy

(↓ Chamber vol. exacerbates outflow obstruction and mitral regurgitation)

Indications (3) : Clonidine

(1) Hypertension

(2) ADHD

(3) Tourette's syndrome

Treatment: Gestational hypertension

α-methyldopa also

Nifedipine

Adverse Effect: α-methyldopa

Drug induced lupus

(Also Coombs-positive hemolytic anemia)

What sympatholytic is used to treat PTSD?

Prazosin

MOA: Clonidine

α2 agonist

Adverse Effects (2) : α1 antagonists

(1) Orthostatic hypotension

(2) ⇒ Reflex tachycardia

Suffix: α1 antagonist

"-osin"

What type of sympatholytic are useful in chronic stable angina?

β blockers

What are the primary indications for the cardio-selective β-blockers?

(1) MI

(2) CHF

Name 2 non-selective β + α1 blockers

(1) Carvedilol

(2) Labetalol

Which β-blocker is the most acceptable to use while pregnant to treat HTN?

Lavetalol

Which class of sympatholytic is useful in hypertrophic obstructive cardiomyopathy?

β-blockers

(↓ Ventricle volume ∝ ↑ Outflow resistance ∴ β-blockers mediated ↓ in stroke volume helps with symptoms)

What drug is a selective β1-blocker with partial agonist activity?

Acebutolol

What drug is a non-selective β-blocker with partial agonist activity?

Pindolol

Which β-blockers are contraindicated in heart failure?

Partial agonists

Partial agonist activity (pindolol, acebutolol) should be avoided with patients with heart failure + history of MI

Treatment: β-blocker poisoning

Glucagon

What new EKG finding may present when on β-blockers?

Heart block (due to excessive suppression of AV node conduction)

How can you identify a β1 selective antagonist?

Name start with A-BEAM

1. Atenolol

2. Betexalol

3. Esmolol

4. Acebutolol

5. Metropolol

Name 2 reasons β-blockers are helpful in CHF

1) Prevents remodeling (due to excess catecholamines)

(2) ↓ Renin (and ∴ prevents fluid overload and AngII mediated remodeling)

Adverse Effects (3) : β-blockers

(1) ⇒ Heart block

(2) Exacerbate asthma

(3) Impotence

How is dietary cholesterol sent to the liver?

(1) Converted to cholesterol esters

(2) Packaged in chylomicrons

Which apoliproteins do chylomicrons have?

A-E

(A, B, C, E)

What enzyme releases FFAs from chylomicrons and VLDLs?

LPL

(Lipoprotein Lipase)

What is the receptor and ligand for receptor mediated endocytosis of chylomicrons?

Receptor: LDL receptor

Ligand: ApoE

What is the product of HMG-CoA reductase?

Mevalonate

First-intermediate in de novo cholesterol synthesis

What apolipoprotein is found on "bad cholesterol"?

ApoB100

What is the receptor and ligand for receptor mediated endocytosis of LDL?

Receptor: LDL receptor

Ligand: ApoB100

(Also scavenger receptor)

What enzyme converts free cholesterol to cholesterol esters for transport by HDL?

LCAT

(Lecithin cholesterol acyltransferase)

What are two mechanisms HDLs transfer cholesterol to the liver?

(1) Deliver to LDLs via CETP

(2) Receptor mediated endocytosis via SR-1

CETP= cholesteryl ester transfer protein

MOA: Statins

Inhibits HMG-CoA reductase

(↓ Intracellular Cholesterol ⇒ Upregulation of LDL receptors ⇒ ↑ Rate of peripheral cholesterol removal)

What part of the lipid fraction do statins reduce?

(1) ↓↓↓ LDL

(2) ↓ TGs

(3) ↑ HDL

What is the first line treatment for hypercholesterolemia?

Lifestyle modification + statins

What is the most effective lipid-lowering drug to prevent future cardiovascular events?

Statins

Only lipid lowering drug consistently proven to reduce risk of atherosclerotic heart disease

Adverse Effects (3) : Statins

(1) Myopathy

(2) ↑ LFTs

(3) Teratogen

LFTs= liver function test

What is the only statin drug not metabolized by the CYP-450 system?

Pravastatin

(Primadonna-statin = Too good for CYP-450 system)

What enzyme catalyzes the final step of coagulation cascade?

Thrombin

(Factor II, and crosslinking of fibrin occurs via Factor XIII)

What coagulation factor activates thrombin?

Factor 10a + 5a

Route of Entry: Direct factor Xa inhibitors

Oral

What protein mediates Heparin's effects?

Antithrombin III

Which coagulation factors does Heparin inhibit?

(1) Factor IIa (Thrombin)

(2) Factor Xa

Which clotting time does heparin most affect?

PTT

Activated partial thromboplastin time

Indications (3) : Heparin

(1) DVT prophylaxis

(2) Pulmonary embolism prophylaxis

(3) Acute MI

Route of Entry: Heparin

IV

What is the antigenic target in Heparin Induced Thrombocytopenia?

Platelet Factor 4

Antibodies against heparin are bound to plately factor 4 cause heparin induced thrombocytopenia (HIT)

Adverse Effects (4) : Heparin

(1) Heparin induced thromboytopenia

(2) Hypoaldosteronism (leads to hyperkalemia)

(3) Osteoporosis

(4) Type IV RTA

(Type 4 renal tubular acidosis)

What drug reverses the effects of Heparin?

Protamine sulfate

What is the difference LMWH and Heparin?

LMWH is more specific for Factor Xa