Directo Vasodilators; Cardiac Inotropes/Glycosides

Question 1

Nitroglycerin (NTG)

Answer 1

• Nitrate
• Antianginal agents, prophylactic and treatment
• SL tab/spray, patch, ointment, IV
• IV: treat acute CHF/angina/MI or severe HTN
• Ointment for tx of pain with anal fissures
• Reduced myocardial O2 demand- relaxed vascular smooth muscle–> dilation of peripheral venous vessels–> venous pooling–> decreased venous return to heart–> preload
• Decreased afterload–> decreased ventricular wall tension–> decreased SVR–> decreased systolic arterial pressure–> decreased mean arterial pressure
• Primary therapeutic use: angina
• Nitrate tolerance
• ADR’s: HA*, flushing, rash, dizziness, sweating, general hypotension (and orthostatic), reflex tachy, Methemoglobinemia (treat with methylene blue)
• C/I: increased intra-cranial pressure
• Interaction with PDE-5 inhibitors (severe hypotension)

Question 2

Isosorbide dinitrate (Isordil, ISDN)

Answer 2

• Nitrate
• Antianginal agents, prophylactic and treatment
• PO tab for angina
• BilDil (ISDN+Hydralazine) for CHG in AA patients- doesn’t rely on renin
• Reduced myocardial O2 demand- relaxed vascular smooth muscle–> dilation of peripheral venous vessels–> venous pooling–> decreased venous return to heart–> preload
• Decreased afterload–> decreased ventricular wall tension–> decreased SVR–> decreased systolic arterial pressure–> decreased mean arterial pressure
• Primary therapeutic use: angina
• Nitrate tolerance
• ADR’s: HA*, flushing, rash, dizziness, sweating, general hypotension (and orthostatic), reflex tachy, Methemoglobinemia (treat with methylene blue)
• C/I: increased intra-cranial pressure
• Interaction with PDE-5 inhibitors (severe hypotension)

Question 3

Isorbide mononitrate (ISMN)

Answer 3

• Nitrate
• Antianginal agents, prophylactic and treatment
• PO tab for angina
• Metabolite of ISDN, no first pass effect=better bioavailability and longer 1/2 life than ISDN
• Use to prevent recurrence of variceal bleed in PORTAL HTN with non-selective beta blocker (secondary prophylaxis)
• Reduced myocardial O2 demand- relaxed vascular smooth muscle–> dilation of peripheral venous vessels–> venous pooling–> decreased venous return to heart–> preload
• Decreased afterload–> decreased ventricular wall tension–> decreased SVR–> decreased systolic arterial pressure–> decreased mean arterial pressure
• Primary therapeutic use: angina
• Nitrate tolerance
• ADR’s: HA*, flushing, rash, dizziness, sweating, general hypotension (and orthostatic), reflex tachy, Methemoglobinemia (treat with methylene blue)
• C/I: increased intra-cranial pressure
• Interaction with PDE-5 inhibitors (severe hypotension)

Question 4

Phosphodiesterase (PDE)

Answer 4

• PDE-3: cardiac tissue
• PDE-4: pro-inflammatory cells
• PDE-5: in smooth muscle cells (corpus cavernosum, pulmonary arteries, prostate, bladder)
• PDE-6: photoreceptors in retinal rods/cones

Question 5

PDE-5

Answer 5

• In smooth muscle (corpus cavernosum, pulmonary artiers, prostate, bladder)
• Physiologically: breaks down (reduces) cGMP– PDE-5 activity increases post-coitus–> less cGMP= flaccid
• Inhibition: benefit in ED, BPH, pulmonary arterial HTN: more cGMP= more relaxation, priapism?, BPH benefit/mechanism not currently well understood

Question 6

PDE-5 Inhibitors

Answer 6

• Sildenafil (viagra)
• Tadalafil
• Vardenafil
• Avanafil

Question 7

Hydralazine

Answer 7

• Direct vasodilators
• Potent vasodilation of arterial SM: decreased BP and vas. resistance, potential reflex SANS activation (HR, SV, CO, EF)
• Therapeutic uses: HTN +/- emergency (primarily)- multiple daily dosing, short duration but quick onset; HF (in combo with ISDN)–> BiDil- AA pt with HF, pt’s with HF who cannot take ACEI/ARB
• ADR’s: HA, flushing, dizziness, palpitations, angina, sinus, tachy, hypotension, peripheral edema, fluid retention possible

Question 8

Minoxidil

Answer 8

• Direct Vasodilators
• Potent vasodilation of arterial SM– reduced peripheral resistance and BP (more potent than Hydralozine)
• Potential SANS activity (HR, SV, CO, EF)
• Therapeutic uses: severe, drug-resistant HTN
• ADRs: hypotension, hyertrichosis*, tachy, angina, HA, peripheral edema, fluid retention
• Medical Malpractice to use without a loop diuretic and beta blocker

Question 9

Nitroprusside (Nitropress)

Answer 9

• Direct Vasodilators
• Directly acts on arterial/venous SM to liberate NO; doesn’t affect myocardial contractility or other smooth muscle tissue– beneficial for preload/afterload, potent vasodilator with rapid onset/short duration
• Therapeutic use: IV only; HTN emergency; acute CHF
• ADR’s: hypotension, methemoglobinemia
• Metabolized to cyanide and thiocyanate; monitor for signs/sx’s of cyanide toxicity

Question 10

Milrinone

Answer 10

• PDE-3 Inhibitor
• Postive cardiac inotrope
• Breaksdown cAMP in cardiac muscle–> more cAMP–> positive inotrope (allows more Ca to enter leading to increased contraction)
• Therapeutic uses: used for short-term IV treatment of pt’s with acute decompensated HF
• ADR’s: ventricular arrhythmias (typically shorter than 48 hrs), hepatotoxicity, thombocytopenia, HA, hypo-K, tremor

Question 11

Digoxin

Answer 11

• Positive cardiac inotrope
• Cardiac glycoside
• Reversible inhibitor of Na/K-ATPase in mycardial cells– competitively binds K binding site (increases intracellular [Na])–> more intracellular [Ca]–>more contraction
• Narrow therapeutic index; need to monitor drug levels
• Renal excretion; dose adjustment in renal impairment
• Considered altered efficacy/safety in setting of electrolyte abnormalities (Ca, K)
• Therapeutic uses: CHF (improves LVEF, sx’s, and reduces hospitalization), rate control in afib (use in declining afib with other anti-arrhythmics); use is being phased out for safer and more effective drugs
• ADR’s: consider digitalis toxicity (excess digoxin in the body– consider drug-drug interactions/renal function); Hyper-K, AV block, arrhythmias, EKG changes; Xanthopsia (blurred, yellow-tinted vision/halos)
• Digibind/digifab?: binds all digoxin in the body to make them inactive and easier to excrete; antidote to digoxin

Question 12

Sildenafil (Viagra, Revatio)

Answer 12

• PDE-5 inhibitor
• In smooth muscle (corpus cavernosum, pulmonary artiers, prostate, bladder)
• Physiologically: breaks down (reduces) cGMP– PDE-5 activity increases post-coitus–> less cGMP= flaccid
• Inhibition: more cGMP= more relaxation, priapism?, BPH benefit/mechanism not currently well understood
• Indications: benefit in ED, BPH, pulmonary arterial HTN
• Do same effect as nitro’s– would never combine!!
• ADR’s: blue/green halos