Vasodilators

Front 1

Nitroglycerine/Nitrate
1. mechanism
2. vessels affected
3. common uses

Back 1

1. direct effect; induce endothelial cells to release NO causing inc in cGMP and vasodilation via dephosphorylation of myosin light chain
2. mostly venous
3. angina, HF, HTN emergency

Front 2

Isosorbide
1. mechanism
2. vessels affected
3. common uses

Back 2

1. direct effect; conversion to NO causing inc in cGMP and vasodilation
2. primarly venous
3. angina, HF

Front 3

Sodium nitroprusside
1. mechanism
2. vessels affected
3. common uses

Back 3

1. direct effect; conversion to NO resulting in inc cGMP and vasodilation
2. venous and arteriolar
3. HTN emergency, acute HF

Front 4

Nesiritide
1. mechanism
2. vessels affected
3. common uses

Back 4

1. BNP; binds guanylate cyclase receptors inc cGMP
2. venous and arteriolar
3. acute HF

Front 5

Hydralazine
1. mechanism
2. vessels affected
3. common uses

Back 5

1. direct effect; may increase NO
2. arteriolar
3. HTN, HF

Front 6

Minoxidil
1. mechanism
2. vessels affected
3. common uses

Back 6

1. direct effect; potassium channel agonist
2. arteriolar
3. HTN

Front 7

Sildenafil, vardenafil, tadalafil
1. mechanism
2. vessels affected
3. common uses

Back 7

1. inhibit PDE5
2. vasculature in penis
3. ED, pulmonary HTN

Front 8

Angina
1. what causes it?
2. typical
3. atypical

Back 8

1. transient myocardial ischemia caused by an imbalance of myocardial oxygen supply-demand relationship
2. typical: CP on exertion, usually due to CAD
3. atypical: CP at rest, usually due to coronary vasospasm

Front 9

Clinical Syndrome of Heart Failure

Back 9

salt and water retention, pulmonary congestion, edema, low CO, diastolic dysfunction

Front 10

Compensatory Mechanisms of Heart Failure (due to dec CO/TPR > arterial underfilling)

Back 10

1. activation of symp system (release NE)
2. activation of RAAS
3. secretion of ADH/vasopressin
4. activation of thirst

Front 11

Hypertension
1. what determines it?
2. how is TPR determined?
3. vasodilators
4. vasoconstrictors

Back 11

1. CO X TPR
2. by small arterioles (not large arteries)
3. atrial and Btype natriuretic peptides, NO, prostacyclin, bradykinin
4. Norepi, ang II, aldosterone, endothelin, vasopressin/ADH

Front 12

Neurohormonal compensatory effects of Vasodilation
1. examples
2. how can they be inhibited to allow effectiveness of vasodilators?

Back 12

sympathetic stimulation (inc HR, CO), renin secretion (inc Na/H2O resorption, inc fluid volume)
2. beta blocker (propranolol) can be used to dec symp activity and renin activation, diuretic can be used to increase Na/H2O excretion

Front 13

Nitrate/Nitroglycerin Effects
1. myocardial oxygen demand
2. myocardial oxygen supply
3. other non-coronary effects

Back 13

1. reduce end diastolic volume/pressure/fiber length (preload), reduce afterload = reduced oxygen demand
2. redirect blood flow to ischemic areas = inc oxygen supply
3. bronchodilation, bililary tract relaxation, decreased esophageal tone (may relieve atypical CP due to biliary/esophageal spasm)

Front 14

Pk of Nitroglycerin vs. Isosorbide dinitrate vs. Isosorbide mononitrate

Back 14

1. Nitroglycerin: sublingual, oral, topical/cutaneous works best (half life 1-4mins)
2. Iso dinitrate: usually only oral (half life 30min-2hrs- 4-6X day)
3. Iso mononitrate: oral, extended release, less first pass clearance so can take less often (half life 3-7hrs- 1-2X day)

Front 15

Common Side Effects of Nitrates (NG, dinitrate, mononitrate)

Back 15

HA, postural hypotension, syncope, nausea, dizziness, flushing, reflex tachy

Front 16

Tolerance and Dependence with Nitrates (NG, dinitrate, mononitrate)
1. what causes tolerance?
2. how can tolerance be avoided?
3. what indicates dependence?

Back 16

1. frequent exposure to high doses of nitrates leads to development of tolerance (may be due to depletion of cysteine/sulfhydryl groups)
2. brief periods of no therapy may avoid tolerance
3. MI may occur in pts withdrawaing from long-term nitrate exposure (indicates dependence)

Front 17

Drug Interactions with Nitrates

Back 17

1. concomitant administration of agents capable of lowering BP
2. sildenafil and nitroglycerin: both increase cGMP concentrations (sildenafil via PDE5 inhibition) which can lead to profound hypotension and inc risk of angina

Front 18

Therapeutic Uses of Nitrates

Back 18

1. acute angina pectoris: take as needed sublingual, lingual, or buccal
2. heart failure: reduces preload, SVR, and pulmonary resistance; combine w/ hyralazine to reduce mortality rate
3. initial tx in patients with unstable angine or MI: use w/ beta blocker or CCB to decrease risk of reflexive tachy

Front 19

Administration/Dosing of Nitrates for acute anginal pain

Back 19

give every 3-5mins until pain is relieved. Seek medical attention after 3 inadequate doses. Store in glass containers protected from light, moisture, and heat

Front 20

Sodium Nitroprusside MOA
1. metabolism
2. NO effect
3. tolerance
4. effect on CO

Back 20

1. metbolized to release NO and cyanide (forms its own NO, unlike NG which causes release of endogenous NO)
2. NO stimulates guanylyl cyclase, increasing cGMP leading to vasodilation; acts equally on both arterioles and venules
3. do not develop tolerance
4. decreases CO in healthy pts (dec preload outweighs, dec afterload); increases CO in pts with heart disease (dec afterload outweighs dec preload)

Front 21

Pk of Nitroprusside
1. administration
2. Vd
3. metabolism
4. half life, duration of action

Back 21

1. only IV
2. distributes to volume of ECF
3. binds Hb forming methemoglobin and liberates 5CN-, one CN binds metHb and the others goto liver and are converted to thiocyanate
4. onset of action in seconds, half life of 2mins

Front 22

Nitroprusside
1. Adverse Effects
2. Drug Interactions
3. Administration/Dosing

Back 22

1. profound hypotension, reflex tachy; CN and thiocyanate toxicity (fatigue, anorexia, nausea, pyschosis, smell like almonds, blue skin)
2. concomitant use with antihypertensive meds > profound hypotension; sympathomimetic agents may negate effects of nitroprusside
3. give IV, use opaque/foil wrapping around IV bag to prevent decomposition w/ light exposure

Front 23

Therapeutic Uses of Nitroprusside

Back 23

1. rarely first line agent for pts w/ hypertensive crisis or exacerbations of HF
2. proven useful for tx of hypertensive emergency w/ careful monitoring for excessive hypotension, reflex tachy, and CN toxicity

Front 24

Nitroglycerin vs. Nitroprusside MOA
1. how are they similar?
2. how are they different

Back 24

1. both are nitro-vasodilators (use NO to induce relaxation of smooth muscle)
2. nitroprusside releases NO spontaneously while NG requires an enzymatic process to form NO (does not directly release NO)

Front 25

Nesiritide
1. what is it?
2. MOA
3. end result
4. tolerance

Back 25

1. recombinant human B-type natriuretic peptide (BNP released by ventricles in response to increased volume or pressure
2. directly binds guanylate cyclase receptors > inc cGMP > arterial/venous dilation; suppresses RAA and NE; does not require liberation of NO
3. increases SV and CO w/o development of tachy
4. does not appear to occur

Front 26

Adverse Effects of Nesiritide

Back 26

1. hypotension: may be prolonged (>2hrs even w/ discontinuation), need close BP monitoring esp during first few hours of therapy and with increasing rate of infusion
2. may promote azotemia via inhibition of RAAS (still not contraindicated in pts with renal disease, just need to monitor Cr and urine output)

Front 27

Nesiritide
1. therapeutic use
2. administration

Back 27

1. pts with acutely decompensated CHF who have dyspnea at rest or with minimal activity
2. IV

Front 28

Direct Vasodilators
1. examples
2. MOA

Back 28

1. hydralazine, minoxidil, diazoxide
2. interfere w/ Ca movements responsible for contractile state, resulting in dec TPR, and reflexive inc in HR and CO (give BB or diuretic to combact compensatory mechanisms)
2.

Front 29

Hydralazine
1. what is it?
2. MOA
3. adverse effects
4. therapeutic use

Back 29

1. direct vasodilator
2. direct vasodilatory action on arterial circulation; give with beta blocker, nitrate, diuretics and/or ACEI to prevent reflex tachy and activation of RAAS
3. immune mediated: lupus is most common (fever, arthralgia, rash, positive ANA, inc risk >200mg/day), may see pyridoxine-treatable polyneuropathy
4. hypertension (combined w/ BB, caution in elderly and ischemic heart disease pts), hypertensive emergency (including preeclampsia- safe for fetus), systolic HF (give w/ nitrates to dec mortality)

Front 30

Minidoxil
1. what is it?
2. MOA
3. dosing
4. adverse effects
5. therapeutic uses

Back 30

1. direct vasodilator
2. activates K+ ATPAse in vascular smooth mm causing K+ influx, hyperpolarization, and vasodilation (acts on arterial circulation)
3. orally for HTN (always give with diuretic/BBs), or topically for baldness (Rogaine)
4. salt and water retention (prevent w/ diuretic), may worsen outcomes in pts w/ ischemic heart disease or LVH, pericardial effusion, flatten and inverted T waves, hypertrichosis
5. HTN in pts refractory to other threapies (added as 4th/5th agent)- too many side effects

Front 31

Diazoxide
1. what is it?
2. MOA
3. adverse effects
4. therapeutic use

Back 31

1. direct vasodilator (old drug, won't see used anymore)
2. relaxes arterial smooth muscle via activaiton of K+ ATPase allowing K+ influx; induces reflexive symp activity and salt/water resorption
3. hyperglycemia, hyperuricemia, hypotension
4. HTN emergencies, tx of hypoglycemia secondary to insulinoma

Front 32

Ranolazine
1. MOA
2. Therapeutic Uses
3. dosing
4. Adverse Effects

Back 32

1. reduces Na+ entry into myocardial cells, shifts ATP production away from fatty acid oxidation in favor of glucose oxidation (reduces O2 demand w/o decreasing ability of tissue to do work)
2. reduces chest pain
3. used in combo w/ amlodipine, beta blockers, or nitrates
4. QT interval prolongation (minimal)

Front 33

Phosphodiesterase Inhibitors (type 5)
1. examples
2. MOA
3. Pk (absorption, half life)
4. drug interactions
5. adverse effects
6. therapeutic uses

Back 33

1. sildenafil, verdanafil, tadalafil
2. inhibit PDE5 (whic metabolizes cGMP) > inc cGMP in corpora cavernosa> improves blood flow to penis > sustainable erection
3. BA of S and V is altered by food and they must be taken 60mins prior to sexual activity, T has longer half life, so those restrictions don't apply
4. concomitant use with nitroglycerin can cause severe hypotension; S and V should not be used with alpha blockers (doxazosin, prazosin)
5. HA, flushing, dyspepsia (similar to nitrates), abnoraml vision (S, V), QT prolongation (V), myalgias/back pain (T), and priaprism
6. erectile dysfunction (do not induce erection, rather they improve likelihood of erection upon sexual stimulation), pulmonary hypertension (limited success)