Direct Vasodilators, Cardiac Ionotropes/glycosides

Question 1

Nitrates drugs, MOA, Net effect

Answer 1

Drugs:

Nitroglycerin
isosorbide dinitrate (IDSN) - IDSN + hydralazine in CHF in African Americans 
Isosorbide mononitrate (ISMN) - portal HTN, no first pass effect, better bioavailability, longer 1/2 life

MOA: NO activates guanylate Cyclase -> increase cGMP to promote SM relaxation/vasodilation
Relaxes all segments of vascular SM from large arteries through large veins -> preload reduction

Affects afterload and preload!!!!

Net effect: vasodilation of arteries and veins -> decrease BP

Reduced myocardial O2 demand -> relaxed vasc SM -> dilation of peripheral venous vessels -> decrease venous return to heart -> decrease preload

Decrease afterload -> decrease ventricular wall tension -> decrease SVR -> decrease systolic arterial pressure

Question 2

Nitrates ADRS and Uses

Answer 2

Uses: angina - affect preload and afterload
HTN, CHF, MI, portal HTN

ADRs: hypotension, reflex tachycardia, increased intracranial pressure
tolerance, headache, flushing, rash, dizziness, sweating, hypotension

Hypoxia/cyanosis: methylhemoglobinemia
No + OxyHb = MethHb
Strong affinity for O2

Question 3

PDE-5 Inhibitors

Answer 3

Drugs: “-fil”
slidenafil, 
taldalofil (BPH+ED), 
vardenafil, 
Avanafil

MOA: inhibit breakdown of cGMP -> more cGMP.
Physiologically - break down cGMP = flaccid

Net effect: relaxation, vasodilation

Uses: pulmonary arterial HTN, BPH, ED

ADRs: hypotension

Question 4

Direct vasodilator

Answer 4

Minoxidil
Hydralazine
Nitroprusside
Alpha 1 blockers 
CCDs

Question 5

Minoxidil

Answer 5

Direct vasodilator - more potent then hydralazine
MUST combine with beta blocker and loop diuretic

MOA: vasodilation

Net effect: reduced peripheral resistance, decrease BP

Uses: servers drug resistant HTN

ADRs: peripheral edema
fluid retention, reflex tachycardia, hypotension, hypertrichosis (excessive hair growth)

Question 6

Hydralazine

Answer 6

Direct vasodilator

MOA: vasodilation of arterial SM -> decrease BP and vascular resistance
Potent reflex SANS activation - reflex tachycardia

Net effect: relaxation of arterial smooth muscle

USes:
HTN
HF - in combo with IDSN (BiDil) in AA - last resort
HR in patients who cannot take ACE/ARBs

ADRs: peripheral edema, fluid retention, reflex tachycardia

Question 7

Nitroprusside (IV)

Answer 7

Direct vasodilator

MOA: directly acts on arterial/venous Smooth muscle to liberate NO

Uses: HTN emergency, acute CHF

ADRs: hypotension, methemoglobenemia (cyanide toxicity)

Question 8

Positive cardiac ionotrope

Answer 8

E/NE
Dobutamine
Isoproterenol
Dopamine

Milrinone
Inamrnione

Digoxin

Question 9

PC ionotropes

Epi/NE
Dobutamine
Isoproterenol
Dopamine

Answer 9

MOA : increase myocardial contractibility

Net effect: Increase HR

Uses: shock, hypotension emergency

ADRs: HTN

Question 10

PC ionotropes

Milrinone
Inamrinone

Answer 10

Inamrinone - better

MOA: PDE-3 inhibitors
Inhibits breakdown of cAMP -> positive ionotrope

Net effect: Increase HR

Uses: short term IV treatment of patients with acute decompensated HR, not used in chronic HF

ADRs:
Ventricular arrythmia 
Hepatoxicity
Thrombocytopenia 
Headache
Hypokalemia (K) 
Tremor

Question 11

PC ionotropes

Digoxin

Answer 11

MOA: reversible inhibitor of Na/K Atpase in myocardial cells

Competitively binds K binding site -> increase intracellular Na

Net effect: more intracellular Na = more intracellular Ca -> more contraction

Uses: CHF, rate control afib

ADRs: 
Hyperkalemia
AV block
Arrythmia
Xanthopsia -> yellow tinted visions

Pt on Lisinopril ( inc K) -> digoxin less effect because more completion for K binding site

Pt on Hydrochlorathiazide (more Ca) give digoxin = more Ca on outside and want to bring Ca into heart -> greater effect of digoxin!