Lecture 27: Cardio Pharm Flashcards
What is ISA activity?
Intrinsic sympathomimetic activity
Blocks strong stimulation of beta receptors by endogenous EPI and NE but act as weak agonists at beta receptors
Useful for patients who need beta blocker but get adverse cardiac effects from too much beta receptor blockade
What are drugs with ISA activity?
Beta blockers:
Pindolol (nonselective)
Acebutolol (beta1 selective)
What are therapeutic uses for beta blockers?
Angina
HF
MI
Some cardiac arrhythmias
Explain angina pectoris
Chest pain triggered by O2 supply demand imbalance
What are determinants of MVO2 (oxygen demand)?
HR
IS
AL
How might some angina patients have low oxygen supply?
Some patients have low coronary blood flow from underlying coronary artery disease
What is the most likely explanation for efficacy of beta blockers in treatment of angina?
Beta blockers decrease HR
How do beta blockers decrease AL?
Decrease afterload by decreasing BP
How do beta blockers help with angina?
Dec. oxygen demand
Dec. HR, IS, BP (which dec. AL)
Inc. oxygen supply indirectly
Dec. HR = longer diastole (more filling time) = inc. CBF
How do beta blockers help with HF?
Dec. bad effects from sympathetic activation = dec. oxygen demand, dec. cardiac hypertrophy + remodeling
Antiarrhythmic effects
How do beta blockers help with cardiac arrhythmias?
Dec. conduction = inc. refractoriness in AV node
What are beta blocker AEs?
HF, sinus bradycardia, AV block
Inc. airways resistance in patients with asthma/COPD
DM + hypoglycemia episodes
Impaired peripheral circulation in patients with PVD (beta2 vasodilation blocked)
Only which beta blockers have established efficacy for HF?
Metoprolol
Carvedilol
Bisoprolol
What is phentolamine?
Nonselective alpha blocker
What are prazosin and tamsulosin?
Alpha1 blockers
What are therapeutics for alpha 1 blockers?
HPT (for strong)
Block vasoconstriction = dec. SVR = dec. BP
What are alpha1 blocker AEs?
Orthostatic hypotension
Less reflex tachycardia than nonselective alpha blocker
What is phenylephrine and midodrine?
Alpha1 selective agonists
What is clonidine and alpha-methyldopa?
Alpha2 selective agonists
What are therapeutic uses for alpha2 agonists?
HPT (not first line)
What is the MOA of alpha 2 agonists?
Act at alpha2 receptors in medulla oblongata to dec. sympathetic tone to CV system
Act at presynaptic alpha2 receptors to decrease NE release
What are alpha 2 agonists AEs?
Sedation
Xerostomia
What are DRIs and what do they act on?
Direct renin inhibitors
Act on renin
“Kirens”
What are ACEIs and what do they block?
ACE inhibitors
Block ACE enzyme
“Prils”
What are ARBs and what do they act on?
Angiotensin receptor blockers
Act at AT1 receptors
“Sartans”
Identify drug class for Aliskiren, Captopril, Losartan
Aliskiren = DRI
Captopril = ACE inhibitor
Losartan = ARB
What are major indications for ACE inhibitors?
HPT (1st-line)
HF
MI
What are major adverse effects of ACE inhibitors?
Cough
Angioedema
What are indications for ARBs?
HPT (1st line)
HF
MI
What are major indications for DRIs?
HPT
What is another potential adverse effect of ACEIs, ARBs, and DRIs???
HYPERkalemia
Differentiate between MOA of ACEIs and ARBs
ACEIs block synthesis of Ang II
ARBs block effects of Ang II
Where are L-type calcium channels (LTCCs) found?
Vascular SM
Cardiac myocytes
SA node
AV node
What are effects of LTCCs at vascular SM, cardiac myocytes, and pacemaker cells
Vascular SM = vasoconstriction
Cardiac myocytes = Inc. IS
SA node = inc. HR
AV node = inc. AV conduction
Describe effect of calcium influx through each LTCC
Vascular SM
Inc. Ca-calmodulin activation of MLCK = inc. phosphorylation of MLC = inc. SM contraction
Cardiac myocytes
Inc. Ca release from SR = inc. binding of calcium to TnC = inc. contractile force
SA node
Inc. phase 4 slope (automaticity) = inc. firing rate
AV node
Inc. Phase - slope/amplitude = inc. conduction velocity
Compare non-DHPs vs. DHPs
Non-DHPs = slower recovery of LTCCs in heart
DHPs result in more vasodilation
What are examples of DHPs
Nifedipine
Little effect on IS, HR or AV conduction
What are examples of non-DHPs?
Verapamil
Diltiazem
What are therapeutic uses of CCBs?
HPT (1st line, especially DHPs)
Particularly for patients with angina or cardiac arrhythmias
Cardiac arrhythmias
How do CCBs help angina?
CCBs dec. AL (by causing vasodilation which decreases BP) and inc. CBF
Non-DHPs will also dec. HR and IS
What are AEs of CCBs?
Vasodilation = hypotension, headache, peripheral edema (DHPs**)
Constipation (verapamil **)
Bradycardia, AV block, cardiac depression/HF (non-DHPs **)
What are examples of organic vs. inorganic nitrates?
Organic = nitroglycerin, isosorbide dinitrate
Inorganic = nitroprusside
How do organic nitrates help with angina?
Inc. oxygen supply via vasodilation (and inc. CBF)
Dec. oxygen demand
Vasodilation = dec. AL
Arteriole dilation = dec. BP + AL
Venodilation = dec. venous return = dec. AL
What are AEs of organic nitrates?
Vasodilation = hypotension, headache, flushing, reflex tachycardia
Tolerance
How is vasospastic angina treated?
CCBs or organic nitrates
Avoid Beta blockers because we don’t want to block vasodilation!!
What are therapeutic uses of nitroprusside?
Hypertensive emergencies
Acute HF
Production of controlled hypotension during surgery
What are AEs of nitroprusside?
Hypotension
Cyanide toxicity
What are examples of PDE inhibitors and how do they work?
Sildenafil
Inhibit PDE = dec. degradation of cGMP = inc. effects of endogenous NO
What are indications for PDE5 inhibitors?
ED
Pulmonary HTN
What are AEs of PDE5 inhibitors?
Headache, flushing
Back pain
Vision loss
Hearing loss
Dec. BP in patients taking anti-HPT drugs (most likely a problem with alpha1 blockers)
What is Riociguat and how does it work?
SGC activator - stabilizes binding of NO to sGC
What are major indications for Riociguat?
Pulmonary HPT
What are major AEs for Riociguat?
Headache, GI effects
Contraindicated in patients taking organic nitrates or PDE5 inhibitors, pregnancy
What drugs are good for pulmonary HPT?
Endothelin receptor antagonists
PGI2 analogs
PDE5 inhibitors
sGC activator
CCBs (especially DHPs)
What is digoxin?
Cardiac glycoside = inotropic drug
How does digoxin work?
Inhibits NCX (sodium-K ATPase) = Dec. electrochemical gradient for sodium = Dec. calcium extrusion by NCX = Inc. intracellular calcium = Inc. IS
What is the effect of digoxin’s increased parasympathetic and decreased sympathetic tone to heart?
Dec. AV conduction
Useful for re-entrant supraventricular tachycardia (AVNRT) and control of ventricular rate in atrial fibrillation
What is dobutamine?
Beta1 agonist that leads to increased IS
What is dobutamine used for?
Short term acute HF
