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RCS > L30- Antianginal Drugs > Flashcards

L30- Antianginal Drugs Flashcards

1
Q

describe the classification scale for angina

A

Class - Description:
0- asymptomatic
1- angina with strenous exercise
2- angina with moderate exertion
3- angina with mild exertion (1 flight of stairs, walking 1-2 blocks)
4- angina at any level of physical exertion

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2
Q

list the types of Angina and a brief pathophysiological explanation

A

Stable/Typical: fixed plaque / stenosis

Unstable/Crescendo: disrupted plaque with superimposed thrombus (like a MI)

Variant/Prinzmetal: intense vasospasm

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3
Q

briefly describe the pathogenensis of pain seen in angina

A

1a) inc HR, contractility, afterload, preload –> inc O2 consumption by the heart
1a) vasospasm, fixed stenosis, thrombus –> dec coronary blood flow

1a/1b –> hypoxic myocardium –> activates pain receptors in heart –> chest pain / Angina

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4
Q

describe the treatment approach(es) to angina

A

1) Inc O2 delivery:
- vasodilators
- anti-thrombic drugs

2) Dec O2 demand:
- vasodilators (reduce preload, afterload)
- cardiac depressants (β-blocker, reduce HR and contractility)

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5
Q

list each type of Angina and name the required type of therapy

A

Stable/Typical: (fixed stenosis) demand ischemia — dec O2 demand

Unstable/Crescendo: (thrombus) supply ischemia — inc O2 delivery

Prinzmetal/Variant: (vasospasm) — inc O2 delivery

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6
Q

list the drug groups used to treat Angina

A

Nitrates: isosorbide dinitrate, isosorbide mononitrate, nitroglycerin, sodium nitroprusside

β-blockers: atenolol, metoprolol, propanolol

Ca channel blockers (all): dihydropyridines (amlodipine, nifidipine), non-dihydropyridines (verapamil, diltiazem)

Na+ channel blocker: ranolazine

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7
Q

list the nitrates used in Angina

A

isosorbide dinitrate
isosorbide mononitrate
nitroglycerin
sodium nitroprusside

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8
Q

______ is the Na channel blocker used to treat Angina

A

ranolazine

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9
Q

Nitrates work by mimicing the functions of (1), with the goal being (2). The main functions of nitrates is (3), with (4) and (5) as secondary function. This is all due to the change in (6) intracellularly.

A

1- nitric oxide
2- rapid reduction in myocardial O2 demand and relief of Sxs

3- systemic vasodilation
4- anti-thrombic
5- anti-inflammatory
6- inc cGMP formation

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10
Q

list the effects of Nitrates on systemic vasculature and cardiac function

A

Systemic vasculature:

  • vasodilation, veins > arteries
  • dec venous pressure
  • slight dec in arterial pressure (slightly dec MAP does not lead to reflex tachycardia)

Cardiac:

  • reduction in preload, slight afterload reduction
  • dec myocardium O2 demand
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11
Q

what are the effect of nitrates on the coronary arteries

A
  • prevents/reverses vasospasm
  • vasodilation
  • improves subendocardial perfusion
  • inc O2 delivery
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12
Q

Clinical Applications of Nitrates:
(1) is used for unstable/crescendo angina and acute HF

(2) is first-line therapy for acute anginal symptoms
(3) is used for prophylaxis of angina symptoms

A

1- IV nitroglycerin
2- SL or spray nitroglycerin (high bioavailability/F)
3- isosorbide mononitrate (high F)

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13
Q

describe pharmacokinetics of Nitroglycerin

A
  • significant 1st pass effect, therefore given SL, IV, transdermally, buccal
  • fast acting: 2-5 min onset, lasts for ~30min
  • long-preparations available via transdermal patches
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14
Q

describe the pharmacokinetics of Isosorbide Mononitrate

A

-long onset, but long duration of action in comparison to nitroglycerin –> long-term and prophylaxis use

  • > 1hr onset
  • ~100% bioavailability

Note: metabolites have longer half-lives and significant activity

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15
Q

explain the role of tolerance in terms of using Nitrates

A

-rapid tolerance to nitrates due to vessel desensitization to vasodilation

  • over come by nitrate-free intervals of 10-12 hrs
    e. g. patches on for 12hrs, off for 12hrs
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16
Q

what are the adverse effects of nitrates

A
  • HA (cerebral vasodilation)
  • High Doses: postural hypotension, facial flushing, reflex tachycardia
  • Contraindicated with Sidenafil
17
Q

describe the interaction of Nitrates and Sidenafil

A

MOA:

  • nitrates are NO analogs => inc cGMP
  • sidenafil is a PDE5 inhibitor which inhibits cGMP –> GMP and inc [cGMP]

Result- excessive or sustained vasodilation

18
Q

The main β-blocker(s) used is(are) (1). It functions to reduce (2), (3), (4), and (5).

A

1- metoprolol, atenolol (β1 selective)&raquo_space; propanolol (non-selective β)

2- HR (β1)
3- contractility (β1)
4- O2 demand during exercise and at rest
5- frequency / severity of angina attacks

19
Q

β-blockers are used for patients with _____ angina

A
  • stable/typical (fixed stenosis)
  • unstable/crescendo (thrombus)

NOT FOR variant/prinzmetal (vasospasm)

20
Q

list the adverse effects of β-blockers

A
  • bradycardia, conduction disturbances (β1)
  • bronchoconstriction (β2)
  • worsening Sxs of peripheral vascular disease
  • fatigue
  • CNS effects (many)
  • impotence
21
Q

what are the contraindications for β-blocker use for angina

A

**Variant/prinzmetal angina (vasospasm): use nitrates or Ca channel blockers

  • cautiously for Pts with obstructive airway disease, peripheral vascular disease
  • low doses initially with HF Pts

***Never discontinue abruptly (b/c β-receptor upregulation) –> rebound HTN, angina

22
Q

Ca channel blockers are used in Angina in order to improve….

A
  • coronary and peripheral vasodilatation (better with dihydropyridines)
  • reduce contractility (non-dihydropyridines)
23
Q

describe the clinical applications of Ca channel blockers for Angina

A
  • in combination with or substitute for β-blockers if they are unsuccessful and or contraindicated (2nd line)
  • ***Variant/prinzmetal angina (1st line)
24
Q

list the adverse effects of Dihydropyridines

A

(Amlodipine / Nifedipine: Ca channel blockers, favors vasculature over heart effects)
-flushing, HA, hypotension, peripheral edema, constipation

  • minimal effect on cardiac conduction / HR
  • short-acting should be avoided unless with β-blocker b/c inc mortality
25
Q

list the adverse effects and contraindications of Verapamil

A
  • **Constipation + similar vasculature Sxs
  • neg. inotropic effects: slows AV conduction => dec HR, contractility, BP, O2 demand

Contraindications:

  • depressed cardiac function or AV conduction abnormalities
  • caution with Digoxin use (inc digoxin levels)
26
Q

list the adverse effects and contraindications of Diltiazem

A
  • similar vasculature Sxs, but lower incidences
  • neg. inotropic effects (but less than Verapamil): slows AV conduction => dec HR, contractility, BP, O2 demand

Contraindications:

  • depressed cardiac function or AV conduction abnormalities
  • caution with Digoxin use (inc digoxin levels)
27
Q

describe the mechanism of Ranolazine

A

-blocks Na+ current (efflux) that facilitates Ca influx via Ca/Na exchanger (only during times of constriction and high [Ca] intracellularly)

  • dec Ca –> reduces ventricular tension + O2 demand => myocardial relaxation
  • may modify fatty acid oxidation
28
Q

discuss the clinical application of Ranolazine for angina

A

use as last Tx when all other therapies fail (nitrates, β-blockers, Ca channel blockers)

29
Q

discuss the pharmacokinetics and adverse effects of Ranolazine

A

-metabolized via CYP3A4

AEs:

  • QT interval prolongation
  • nausea
  • constipation
  • dizziness
30
Q

In stable/typical angina:

  • (1) is used for acute attacks
  • (2) are used for maintenance therapy
  • (3) and (4) are 2nd line and 3rd line treatments respectively
A

(fixed stenosis)
1- nitroglycerine
2- long-acting nitrate (isosorbide mononitrate) and β-blockers

3- Ca channel blockers: when β-blockers fail or are contraindicated
4- Ranolazine: when all others fail

31
Q

In unstable/crescendo angina:

  • Sxs are relieved by (1)
  • (2) is often considered
  • (3) is most important to treatment
A

(unstable plaque, thrombus)
1- rest, nitroglycerine
2- nitroglycerine, β-blockers
3- treating / obliterating plaque

32
Q

In variant/prinzmental angina:

  • Sxs are relieved by (1)
  • (2) is preferred choice of (1)
A

(vasospasm)
1- nitroglycerin, Ca channel blockers
2- no preference for type of Ca channel blockers, all have equal efficacy

33
Q

Describe the effects of Nitrates on:

(1) HR
(2) MAP
(3) EDV
(4) contractility
(5) ejection time

A 
1- reflex inc (slightly)
2- dec (slightly)
3- dec
4- reflex inc
5- dec
34
Q

Describe the effects of β-blockers or Ca channel blockers on:

(1) HR
(2) MAP
(3) EDV
(4) contractility
(5) ejection time

A 
1- dec
2- dec
3- inc
4- dec
5- inc
35
Q

Describe the effects of Nitrates and β- or Ca-blockers in combination on:

(1) HR
(2) MAP
(3) EDV
(4) contractility
(5) ejection time

A 
1- slight dec
2- slight dec
3- none / dec
4- none
5- none

(idea is that in combination these effects cancel each other out)

RCS (29 decks)

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