IHD- Khan

What is the major ADR of ranolazine?

QT prolongation

What is the MOA of ranolazine?

• not fully understood

  • inhibit late Na channels

What are the 3 parameters of oxygen demand?

1. HR

2. Contractility

3. Ventricular wall stress

What are the main components of ventricular wall stress? Which one is dependent on veins, which on arteries?

preload and afterload

• preload- veins

• afterload- arteries

What is the most common cause of ischemia?

atherosclerosis

Which angina is not associated with atherosclerotic plaques?

variant angina

What is preload and afterload?

preload- stretch on the walls of the ventricles at the end of diastole

afterload- pressure ventricles have to overcome to push blood out of the heart

What group of antianginals must be first converted into NO?

nitrates

Which enzyme is stimulated by nitric oxide? What molecule is produced?

Enzyme- Guanylyl Cyclase

molecule- cGMP

What is the MAJOR effect produced by nitrates?

Decrease preload and decrease myocardial oxygen demand

Does nitroglycerin have good oral bioavailability?

no!

• we usually go for NTG sublingual (sometimes transdermal)

What are the ADRs of nitrates? What are the causes associated w/ each ADR?

• Flushing

  • dilation of blood vessels

• Orthostatic Hypotension

  • dilation of veins

• Reflex tachycardia

  • response from arteriolar dilation

• HA

  • dilation of meningeal artery

• N/V, dizzy

What are the 2 MECHANISMS of tolerance of nitroglycerin?

1. reduced # of sulfhydryl groups (-SH) = can’t turn nitrates into NO

2. presence of peroxynitrate (from making NO) = inhibits guanylyl cyclase

Nitrates should NOT be used with what class of drugs? Why?

Nitrates should not be used with PDE5 Inhibitors (-afil) because of the risk of refractory hypotension.

• basically nitrates make more cGMP and are metabolized by PDE

• PDE Inhibitors would lead to an increase in cGMP because it would inhibit the metabolism of nitrates

B1 agonism leads to what effects?

increased myocardial oxygen demand

• increase HR

• increase contractility

• increase renin release

Should beta-blockers w/ ISA or b2 blocking effects be used in IHD?

no

How do beta-blockers work do decrease cardiac muscle contraction?

inhibit cardiac muscle contraction by

• inhibiting Gs, and inhibiting the adenylyl cyclase pathway

How do beta-blockers effect the APs in nodal cells?

• decrease phase 4 depolarization

• prolong repolarization

What is the major effect of beta-blockers in IHD?

DECREASE myocardial oxygen demand

What specific beta-blockers are used in IHD?

b1 selective w/ no ISA

• metoprolol, atenolol, bisoprolol

What is the boxed warning of beta-blockers?

avoid abrupt D/C

What are the ADRs of beta-blockers?

• hypotension

• bradycardia

• hypoglycemia

• dizzy, sedation

• bronchospasm (in non-selective)

Why should beta-blockers not be used in variant angina?

beta receptors deal with vasodilation in the coronary arteries

• a beta blocker will inhibit this vasodilation and lead to vasoconstriction in the coronary arteries

  • will result in decreased blood flow

What are the structural requirements for beta-blocking activity?

aryloxypropanolamine

What group should be added to a beta-blocker for b1 selectivity?

para (4’) group with H bond acceptor

Which CCBs are vasoactive and cardioactive?

Vasoactive- DHPs

Cardioactive- non-DHPs

Where are L-type Calcium channels located at in the cell?

cell membrane

What is the MAIN effect of CCBs?

increase myocardial oxygen supply

What is the MOA of aspirin?

Covalently (irreversibly) bind to COX 1 and COX 2 enzymes

How does aspirin inhibit platelet aggregation?

COX 1 enzyme functions to make TxA2. TxA2 deals with platelet activation and aggregation. Therefore, if COX 1 is inhibited, platelets can’t aggregate.

What is clopidogrel and how is it activated?

Clopidogrel is a P2Y12 ADP receptor pathway inhibitor.

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Clopidogrel is a PRODRUG and must be activated through CYP2C19.

Why should PPIs not be used with clopidogrel?

PPIs are CYP2C19 inhibitors. Clopidogrel needs CYP2C19 to be activated, so use of a PPI would be pointless.