04.22 - IHD Pharm (Ostrom) Flashcards by Ryan Lee

What determines myocardial demand?

HR, Contractility, Wall tension (afterload)

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2 Main CV effects of Nitrates

(1) Venodilation reduces Preload; (2) Coronary Vasodilation

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2 major non-dihydropyridine CCB’s, and which is better

Verapamil > Diltiazem

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2 mechanisms of Ranolazine

Late sodium current inhibitor; Partial FA oxidase inhibitor –> Increase glucose oxidation and efficiency of O2 utilization in heart

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2 Non-Dihydro CCB’s

Verapamil, Diltiazem

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3 Widespread Uses of CCB’s

Angina, HTN, Supraventricular Arrhythmias

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5 Dihydro CCB’s

Nifedipine, Nicardipine, Isradipine, Felodipine, Amlodipine

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Absolute Contraindication for Nitrates

PDE inhibitors

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Action of Ca2+ in cardiac muscle cell

Binding to Troponin C reduces inhibition of actin-myosin cross-bridges

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Action of Ca2+ in smooth muscle cell

Binding to Calmodulin activates MLCK, which phosphorylates myosin and triggers contraction

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Adverse Effects of Nitrates

Hypotension, Headache, Drug Rash

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Adverse reactions with Ranolazine

Dizziness, headache, constipation, nausea (4-6%)

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AE’s caused by all CCB’s

Hypotension, Peripheral Edema

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AE’s of DHP CCB’s

Excessive Vasodilation, GI, Per Edema, Coronary Steal

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AE’s of Verapamil, Diltiazem

Bradycardia, Asystole, AV Block; Constipation; CHF

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All patients with CHD should receive

Aspirin

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Another source of concern for CCB’s

may increase cancer risk (not shown in ALLHAT)

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Are CCB’s good at treating HTN

One study says yes, other no

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Best choice for oral anti-HTN in patient with Prinzmetal’s would be

DHP CCB

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Cardiac cells rely on L-type Ca channels for

Contraction (contractile cells) and Upstroke of AP in Nodal Cells

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CCB’s act on what type of Ca channels

L-Type

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CCB’s are highly effect for relief of symptoms in

Exertional and Vasospastic Angina

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CCB’s in patients with CAD

fail to consistently reduce reinfarction or CAD mortality; Imparied LV function

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Chemical class of Diltiazem

Benzothiazepines

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Chemical class of Verapamil

Phenylalkylamines

Con to Ranolazine

Cost; Will not relieve acute angina attacks

Conclusion: When should CCB's be used

Unable to tolerate BB's; Or add-on for angina uncontrolled by BB + nitrate

Contraindications for All CCB's

Hypotension, Advance HF

Contraindications for Non-DHP CCB's only

Sinus Bradycardia, AV conduction defects (also Hypotension, Advance HF)

DHP =

Vasodilation = Baroreceptor Reflex

Direct effects of Non-Di CCB's predominate to

Reduce Heart Work: HR, Contractility, Slowed AV conduction

Do BB's prevent vasospasm?

Drug of choice in Angina overall

Beta blockers

Effect of Nitrates on BP and HR

BP unchanged or slight decrease, HR unchanged or slight increase

Effect of Nitrates on Coronary Arteries

Vasodilate, Prevents or reverses coronary vasospasm

Effect of Nitrates on Pulmonary Vascular Resistance and CO

PVR decreased, CO reduced slightly

Effects of Nitrate Venodilation

Decreased Preload --> Reduces wall stress and MvO2, Subendocardial blood flow increased

For Exertional Angina, use BB why?

Reduces HR, contractility

For Unstable Angina, use BB's with

Nitrates, ASA, and Heparin

For Vasospastic Angina, use BB why?

DON’T

How do CCB's effect CV function w/out significant side effects

Specific for L-type Ca Channels

How do CYP inducers affect Verapamil, Diltiazem

Reduce their levels

How do Di CCB's reduce MvO2

Vasodilation = Reduced afterload

How do Non-Di CCB's reduce MvO2

Reduce heart work (demand)

How does increased Diastole affect coronary perfusion?

Increases

Indications of Ranolazine

Chronic, stable agina in combo with Amlodapine, BB, or Nitrates

Major Contraindications of Ranolazine

Digoxin (conc. increases); CYP; Long QT

Mechanisms of Tolerance to Nitrates

Volume Expansion, Neurohumoral Activation, Depletion of Tissue Cysteine Stores

MOA of Milrinone

PDE4 inhibitor

Most common side effects of DHP's are due to

Vasodilation

Most common ventricular dysfunction

Heart Failure

Notable pharmacokinetics for CCB's

Extensive First-Pass metab; CYP3A4; Short plasma half-life; Bolus effect

Pharmacodynamic interactions with Verapamil, Diltiazem

BB's increase risk of Nodal Block

Primary drug class of choice for most types of angina

Nitrates

Problem with Di CCB's

Reflex cardiac stimulation: HR, Contractility

Properties of L-Type Ca Channels

V-dep, Large Conductance, Slow inactivation

Rationale for combining BB with CCBs (Di)

Prevent coronary vasospasm, reduce systemic vascular resistance

Rationale for combining BB with Nitrates:

Reduces LVEDP, LV Volume, Dilates coronary arteries

Situations favoring Di CCB

With BB for Coronary Vasodilation, reduced afterload; Sinus brady, Nodal block; Valvular insufficiency

Special effect of non-Di CCB's on coronary arteries

Coronary Vasodilation: Prevents or reverses Vasospasm

Special feature of lipophilic BB's

Can reduce afterload thru CNS effects

Vascular specificity of CCBs

Induce relaxation of arterial SM but not Venous (reduce afterload, not preload)

What does voltage-dep binding of Nifedipine select for smooth muscle ca channels?

SM voltage less variable

What is target of nitrates?

*--> NO --> GC --> Increase cGMP

What type of Ca channels mediate NT release in neurons

N- and P-type

When should Renolazine be used:

Increase exercise tolerance and time to onset of angina; Adjunct when refractory to other tx's

When would Non-Di CCB's be indicated

Pt can't use BB: Asthma/COPD, Insuline-dep DM, PVD

Which anti-anginal(s) doesn't vasodilate coronaries?

Which anti-anginal(s) doesn’t reduce HR

Nitrates, Dihydro CCBs

Which anti-anginal(s) reduce afterload?

All

Which anti-anginal(s) reduce preload?

Nitrates

Which CCB causes constipation

Verapamil

Which CCB class binds in use-dependent way

Non-DHP

Which CCB class binds in voltage-dependent way

DHP

Which CCB class is a selective vasodilator

Dihydro --> Can cause reflex

Which CCB class needs to be used with Beta blocker

Dihydropyridine to prevent reflex cardiac stimulation

Which CCB worsens CHF

Verapamil

Which CCB's are CYP3A4 substrates

Verapamil, Diltiazem

Which CCB's slow the recovery of the L-type channel?

Verapamin, Diltiazem (non-dihydro)

Which class of CCB's affect AV node conduction

Non-Di CCB's slow

Which is preferred, Di or Non-Di CCB's?

Dihydropyridine, unless patient can't tolerate BB

Which of the following decrease CHD events: BBs, Nitrates, CCBs

BBs do, Nitrates don't, CCBs are variable

Why do Nitrates cause Headache

Vasodilation of Meningeal arteries

Worst choice of oral anti-HTN in patient with Prinzmetal's

Beta Blocker

04.22 - IHD Pharm (Ostrom) Flashcards

(84 cards)