KG - Pharm 2 Exam 2, Antianginal Drugs Flashcards
etiology - “classic” angina
atheromatous obstruction of large coronary vessels, esp w/ exercise
treatment - “classic” angina
if uncontrolled by drugs may require coronary bypass or angioplasty
etiology - “varian” or “angiospastic” or “Printzmetal’s” angina
spasm or constriction in atherosclerotic coronary vessels
treatment - “varian” or “angiospastic” or “Printzmetal’s” angina
reversed by nitrates or CCBs
- you can’t stent a spasm so you must dilate w/ drugs
nitrates/nitrites MOA
- vasodilation via NO –> cGMP
- UNEVEN VASODILATION
- large veins dilated, increased venous capacity, decreased preload
- arterioles not dilated as much but still decreases afterload
DOC for ACUTE ANGINAL ATTACK?
nitrates/nitrites
nitrates/nitrites - the GOOD
- decreased cardiac workload: decreased preload & afterload
nitrates/nitrites - the BAD
- increased cardiac workload: decreased BP (so increased baroreflex) –> increased HR & contractility, decreased diastolic perfusion time
nitrates/nitrites provide ANGINAL RELIEF by ____
predominantly: decr myocardial O2 requirement
secondarily: redistribution of blood flow from normal to ischemic areas (even though total bflow unchanged)
nitrates also relax ___
smooth muscle in bronchi, GI, GU tracts
nitrates/nitrites pharmacokinetics
- oral nitrates - have HIGH FIRST PASS, rapid liver metabolization
- inhalation, sublingual, transdermal
why is sublingual nitrate/nitrite preferred?
- AVOID HEPATIC DESTRUCTION
- rapid absorption
- immediate relief, short duration
which nitrate/nitrite is fastest acting?
inhaled Amyl nitrite:
- volatile liquid
- inhaled
which nitrate/nitrite is IV?
nitroprusside, also fast acting
describe isosorbide dinitrate
- solid
- sublingual or oral tablet
nitrates/nitrites adverse effects
due to vasodilation:
- orthostatic hypotension
- tachycardia
- THROBBING HEADACHES
- frequent exposure to nitrates leads to TOLERANCE OR MARKED REDUCTION of most effects - CAN NOT USE LONG TERM
which CCB is indicated for HTN only?
slow release nifedipine - may provoke angina pectoris
which CCB increases HR?
nifedipine
which CCB decreases HR?
verapamil
what are CCBs good for in relation to angina?
for CHRONIC TREATMENT, not immediate relief
BENEFICIAL EFFECTS nifedipine/other -dipines
coronary vasodilation –> increased myocardial O2 supply & decr afterload
HARMFUL EFFECTS nifedipine/other -dipines
enhanced by development of MI
- rapid hypotension –> baroreflex –> incr cardiac workload
BENEFICIAL EFFECTS verapamil/diltiazem
(due to decr cardiac workload)
- decr myocardial contractility
- bradycardia caused by decr SA node automaticity/AV conduction
HARMFUL EFFECTS verapamil/diltiazem
potential for SERIOUS CARDIAC DEPRESSION that can end in arrest, AV block, CHF
which CCB is most likely to produce tachycardia?
nifedipine (highest vasodilation –> marked hypotension –> reflex tachycardia)
why don’t verapamil and diltiazem not likely to elicit reflex tachycardia?
weaker dilatory effects, directly depress SA/AV node function
beta blockers - effects
- major = cardiac & vascular
- ANGINAL RELIEF (less sympathetic activation, less cardiac activity, less vasoconstriction, hypotension/bradycardia, decr cardiac workload, decr myocardial O2 demand)
what are the CV effects of beta blockers?
- heart: decr CO (blocks receptors on heart)
- kidneys: decr renin
- CNS: decr sympathetic vasomotor tone
BETA ADRENERGIC BLOCKADE IS INEFFECTIVE IN _____
PRODUCING CORONARY VASODILATION
beta blockers - adverse effects
- bronchoconstriction
- increase triglycerides
- recovery from insulin-induced hypoglycemia DELAYED
- CNS side effects (fatigue, depression, sleep)
- can be potentially HARMFUL IN VARIANT ANGINA bc by slowing HR/prolonging ejection time you incr LV end volume & increase myocardial O2 requirement
ranolazine MOA
- partial fatty acid oxidation (PFOX) inhibitor (decr O2 consumption)
- inhibitors late inward Na+ current (decr contractility)
ranolazine indications/therapeutic effects
- decreased LVent wall stiffness
- improves coronary circulation
- USED WHEN OTHER ANTI-ANGINAL MEDS DO NOT WORK
DOC for VARIANT or ANGIOSPASTIC ANGINA?
nitrates and CCBs (beta blockers will not dilate spastic vessels)
how to get best effects of angina treatment?
use combos of 3 major drug classes
most effective drug combos for angina pectoris?
beta blockers + vasodilator for long term
how to prevent harmful effects of CCBs or beta blockers?
combine with nitrates
how to minimize reflex tachycardia?
combine nitrates w/ CCBs or beta blockers
asthma least & most preferred drugs? (for pts w/ angina)
Most: CCB, nitrate
Least: beta blocker
DM least & most preferred drug? (for pts w/ angina)
most: CCB, nitrate
least: beta blocker
heart failure least & most preferred drug? (for pts w/ angina)
most: nitrate
least: beta blocker, diltiazem, verapamil
HTN least & most preferred drug? (for pts w/ angina)
most: beta blocker, CCB
least: nitrate
peptic ulcer least & most preferred drug? (for pts w/ angina)
most: beta blocker, nitrate
least: CCB
Sildenafil (Viagra) MOA
selective inhibitor of cGMP - specific PDE5
Sildenafil (Viagra) indications/therapeutic effects
- tx male ED
- pulmonary HTN
Sildenafil (Viagra) pharmacokinetics
- oral
- rapidly absorbed, 40% bioavailability
- PHK dose proportional through dose range
- max conc. reached 30-120 min
- 1/2 life 4 hrs
- metabolized by CYP3A4
Sildenafil (Viagra) adverse effects
- transient to mild to mod effects
- HA, flushing, dyspepsia, congestion, UTI
- visual impairment w/ BLUE TINGE to vision, photophobia or blurred vision
Sildenafil (Viagra) contraindications
- NOT for pregnant/lactating women
- NOT for nitrates/nitrite use
- use w/ alpha blockers can lead to hypotension
what drugs could reduce Sildenafil clearance (inhibitors of CYP3A4), resulting in increase of adverse effects?
- Ritonavir, saquinovir
- ketoconazole
- cimetidine (zantac)
- macrolides
- quinidine
- zafirlukast, zileuton
ALSO: grapefruit juice
which new PDE5 inhibitors have less visual disturbances than Sildenafil?
Vardenafil
Tadalafil
- more selective for PDE5 than PDE6
info: Vardenafil
- achieves max concentration SOONER than sildenafil - faster onset of action
info: Tadalafil
duration (24-36 hrs) is LONGER than Sildenafil
- Spontaneity!
