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Flashcards in antianginals 56 Deck (31):
1

Nitroglycerin (Minitran, Nitrostat)

nitrate ("nit")

"denitrated" 2x in liver, from trinitrate to mononitrate (less active: 1st pass effect)

oral, sublingual

2

Isosorbide Dinitrate (Isordil)

nitrate ("nit")

3

Nifedipine (Procardia XL)

calcium channel blocker (CCB)
act largely in arterial tissue
reduction in after load
vasospasm in a coronary artery can be reversed

4

Amlodipine (Norvasc)

calcium channel blocker (CCB)
long-acting

5

Verapamil (Isoptin SR, Calan)

calcium channel blocker (CCB)
act largely in the heart
reduce cardiac rate and contractility

6

Diltiazem (Cardizem)

calcium channel blocker (CCB)
act largely in the heart
reduce cardiac rate and contractility

7

Propranolol (Inderal-LA)

β-1 and2 Adrenergic Blocker

8

Nadolol (Corgard)

β-1 and 2 Adrenergic Blocker

9

Timolol

β-1 and 2 Adrenergic Blocker

10

Atenolol (Tenormin)

β1 (only)-Adrenergic Blocker

11

Metoprolol (Toprol-XL) New Class

β1 (only)-Adrenergic Blocker

12

Ranolazine (Ranexa)

new class: FA oxidation inhibitor
tx for chronic stable angina (in combo or alone)
-will not dec. BP

Selective inhibition of increased “late” inward-directed Na+ current caused by MI

allows for better Na+/Ca2+ exchange across myocardial cell membranes which reduces ischemia-induced calcium overload and related oxygen demand

*used for chronic stable angina* (alone or in combo)

(thought to be MOA originally: Shifting the source of fuel used by the myocardium from fatty acid to glucose, which demands less oxygen)-not so much

13

nitrate SEs

orthostatic hypotensive symptoms

throbbing headache from pulsating meningeal vasodilation

too much reflex increase in heart rate and contractility which can compromise the therapeutic goal.

systemic sodium and water retention.

14

??? can develop to nitrates


can also get rebound ???

tolerance (in part due to vascular fluid retention- offsets preload)

angina

15

can get potentially fatal interactions with nitrates and ???

Viagra and other cGMP- inactivating Phosphodiesterase-5 inhibitors used to treat erectile dysfunction

severe decrease in BP

16

nitrates contraindicated DURING a ??

inferior wall MI

17

general nitrate effects:

"become" NO-->stimulate cGMP-->smooth musc relaxation

venous>arteries

peripheral vascular dilation-->*reduced preload* (at low doses) and reduced after load (at higher doses -->reduced cardiac work

reduction in the cardiac oxygen demand

can inhib platelet aggregation

18

Calcium channel blockers (CCB)

block voltage-dependent calcium channels, esp. the L-type calcium channels in cardiac muscle (mainly verapamil and diltiazem) and arterial vascular smooth muscle (dihydropyridines) (aa>vv, so reduction of after load)

some CCBs can inhibit platelet aggregation.

preventative treatment in all forms of angina

Dihydropyridines also used to treat acute anginal attack after its onset, also can reverse vasospasm in a coronary artery

-most short-acting (problems)
-Amlodipine: long acting (safer)
-metabolized by liver

19

combination of Verapamil or Diltiazem with nitrates is useful because ??

adverse reflex effects of nitrates (e.g. tachycardia) are less likely to occur

20

CBB SEs

verapamil and diltiazem: CHF, AV blockade, and too much sinus rate depression

dihydropyridines: may reflexly increase heart rate and contractility too much (MIs)
*esp. very
rapid short-acting formulations*

21

B-blockers action

*direct inhibitory effects on the heart rate and contractility. This reduces cardiac oxygen demand*

also: decreased heart rate, cardiac contractile force, and arterial blood pressure

typically prevention, esp. excersise-induced athersclerotic angina and “silent” ischemia (not as much spastic)

useful in "silent" ischemia (no pain but O2 deficit, detected by altered EKG)

22

combination of beta-blockers with nitrates is used a lot because ??

adverse reflex effects evoked by the nitrates (e.g. tachycardia) are prevented or reduced by beta blockade.

23

B-blocker SEs

sinus bradycardia, and atrioventricular blockade

sudden withdrawal may precipitate a rebound angina (or even an M.I.).

asthmatic attacks with non-selective forms

severe hypoglycemic response to an insulin overdose may be masked

CNS adverse effects include sedation, fatigue, and sleep alterations.
-Atenolol and nadolol have less marked CNS action because they do not enter the CNS as readily as other beta-blockers (less lipid soluble).

24

Ranolazine (Ranexa) SEs

dizziness, headache, nausea, constipation

Some drugs (e.g. verapamil and diltiazem) interact to increase ranolazine plasma levels

verapamil: increasing ranolazine absorption
diltiazem: interfering with its metabolism

High concentrations can *prolong the cardiac QT interval*, thus contraindicated in patients with preexisting cardiac QT prolongation or taking QT-prolonging drugs
(e.g. quinidine, dofetilide)

25

Nicorandil (FYI?)

combo of "nitrate" plus "minoxidil" like mechanisms (BP control)

26

Dipyridamole (FYI?)

combo with warfarin to dec. thrombosis after artificial heart valve replacement (helps with coronary constriction)
anti-platelet

27

CASE: middle-aged male, HTN, hyperlipidemic, hospitalized for chest pain: heavy/squeezing pain occasionally radiating to left shoulder/arm on exertion
-no past cardiac hx (although risk factors)
-fam hx HTN

-put on treadmill: pain comes back with electrical abnormalities
-responsive to nitro
-BP and HR v. elevated

dx??

tx??

"angina of effort"
atherosclerotic angina
(atherosclerotic plaque-->
obstruction of blood flow-->oxygen deficit, switches to anaerobic metabolism-->painful metabolism)

nitroglycerin
combine with B-blocker to lower HR
or monotherapy with B-blocker for preventing future attacks (and avoiding nitro tolerance)

28

3 types of angina

*Atherosclerotic obstruction (plaque)*: classic angina pectoris, also known as angina of effort or stable angina

Reversible vasospastic reduction: Prinzmetal's angina

unstable or crescendo angina: marked platelet aggregation with clot formation at the site of a ruptured plaque. Occurs at rest as well as during exertion. May be immediate precursor of myocardial infarction (MI)

29

The overall determinant of oxygen demand is ??

4 factors that contribute to tension:

myocardial cell tension

Preload (as a function of venous blood volume and venous tone).

Cardiac Contractility (the intrinsic ability of the myocyte to contract;
controlled in part by sympathetic nerve activity).

Afterload (outflow resistance as affected largely by peripheral arterial
vascular resistance).

Heart rate (controlled in part by sympathetic nerve activity).

30

nitrate uses

treat all 3 major types of angina

acute anginal pain after it starts is the
sublingual nitroglycerin spray or tablet: fast onset and duration of 10-30 minutes

Oral (swallowed) nitroglycerin or isosorbide denigrate: onset/duration 4-8 hours

preventative: sustained release

transdermal: 8 to 14 hours

31

nitrate SEs:

orthostatic (postural) hypotensive symptoms

throbbing headache from pulsating meningeal vasodilation

reflex increase in heart rate and contractility

systemic sodium and water retention

-tolerance may develop (due to vasc. fluid retention): rebound angina
-fatal hypotensive interaction with Viagra and other cGMP- inactivating PDE-5 inhibitors
*Contraindicated DURING an inferior wall MI*