antianginals 56 Flashcards
Nitroglycerin (Minitran, Nitrostat)
nitrate (“nit”)
“denitrated” 2x in liver, from trinitrate to mononitrate (less active: 1st pass effect)
oral, sublingual
Isosorbide Dinitrate (Isordil)
nitrate (“nit”)
Nifedipine (Procardia XL)
calcium channel blocker (CCB)
act largely in arterial tissue
reduction in after load
vasospasm in a coronary artery can be reversed
Amlodipine (Norvasc)
calcium channel blocker (CCB)
long-acting
Verapamil (Isoptin SR, Calan)
calcium channel blocker (CCB)
act largely in the heart
reduce cardiac rate and contractility
Diltiazem (Cardizem)
calcium channel blocker (CCB)
act largely in the heart
reduce cardiac rate and contractility
Propranolol (Inderal-LA)
β-1 and2 Adrenergic Blocker
Nadolol (Corgard)
β-1 and 2 Adrenergic Blocker
Timolol
β-1 and 2 Adrenergic Blocker
Atenolol (Tenormin)
β1 (only)-Adrenergic Blocker
Metoprolol (Toprol-XL) New Class
β1 (only)-Adrenergic Blocker
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
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.
??? can develop to nitrates
can also get rebound ???
tolerance (in part due to vascular fluid retention- offsets preload)
angina
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
nitrates contraindicated DURING a ??
inferior wall MI
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
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
combination of Verapamil or Diltiazem with nitrates is useful because ??
adverse reflex effects of nitrates (e.g. tachycardia) are less likely to occur
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
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)
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.
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).
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)
Nicorandil (FYI?)
combo of “nitrate” plus “minoxidil” like mechanisms (BP control)
Dipyridamole (FYI?)
combo with warfarin to dec. thrombosis after artificial heart valve replacement (helps with coronary constriction)
anti-platelet
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)
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)
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).
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
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*
