11 11 2014 Vasodilatory drugs Flashcards Preview

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Flashcards in 11 11 2014 Vasodilatory drugs Deck (22):
1

Nitroglycerin (sublingual), Amyl nitrite, Isosorbide dinitrate

 

1. mechanism:

2. Effect on pulmonary vessel resistance at low and high doses:

3. Adverse effects

4. Overall effects:

1. release NO in smooth muscle cells NO activates Guanylate Cyclase = increase in cGMP = dephospho rylation of myosin light chain and muscle relaxation Decreases internal Ca2+ release

 

2. Low doses: decrease diastolic filling pressure; decrease pulmonary vessel resistance High doses: decrease in systemic peripheral resistance = reflex cardiac stimulation

 

3. Adverse effects: - flushing, headache, orthostatic hypotension, coronary vasodilation * all are short acting!

 

4. Decreased heart size and wall tension during systole. - reflex cardiac stimulation

2

Pharmodynamics of Nitroglycerin

-- prodrugs First pass inactivation in liver by nitrate reductase more resistant to metabolism and are less potent. Tolerance, physical dependence

3

Why is nitroglycerin useful in angina?

- acts primarily by lowering work of heart - extremely useful for suppressing acute attacks.

4

Nitroglycerin effects on perfusion? Effect on cardiac work?

no overall increase in coronary blood flow some redistribution from epicardial to endocardial ischemic regions Sublingual dose: 1. venodilation 2. arteriolar dilation 3. reflex cardiac stimulation of rate and contractility?

5

Sildenafil (Viagra), LEVITRA (Vardenafil HCl), Cialis (Tadalafil)

1. mechanism

PDE5 is an important phosphodiester mediating cGMP breakdown in tissue ( NO = normal erectile function) Sildenafil blocks PDE5 and increase cGMP = enhancing erections in males whose innervation and NOs ynthesis ability is intact.

6

Mechanism of relaxing aerial smooth muscle:

1. Hyperpolarization (open K+ channels) which

2. blocks L-Type Ca2+ channels

3. Increase cGMP = increase in NO

4. increase cAMP = beta adrenergic agonists

7

Where are L-type calcium channels?

Resistance vessel smooth muscle cells Myocardial cells Role of L-channels are contraction. They are in many cell types and they have slow activation. usually activated around -45 mV

8

Muscle contraction and what mediates tone?

Tonic -- not phasic tone is maintained by intracellular free Ca2+

9

Nifedipine 1. mechanism and binding? 2. therapeutic concentrations affect? 3. How good is it at vasodilation? 4. Reflex to cardiac activation? 5. Direct cardiac suppression? 6. overall

L-type calcium channel blocker - binds to closed L-channels and decrease frequency of opening

Therapeutic concentrations affect: 1. myocardial cells 2. vascular smooth muscle of resistance vessels

Strong vasodilation modest to strong cardiac activation modest to moderate direct cardiac suppression

 

Overall: vasodilation with modest cardiac stimulation

10

Administration/ pharmacokinetics of nifedipine?

orally large first pass metabolism Newer DHP are similar but more selective for L- ca+ channels (closed) in resistance vessels

11

Adverse effects of Nifedipine?

Flushing, headaches, hypotension, peripheral edema

12

Verapamil

1. mechanism and binding?

2. therapeutic concentrations affect?

3. How good is it at vasodilation?

4. Reflex to cardiac activation?

5. Direct cardiac suppression? 6. overall

L-type calcium channel blocker - binds to open channels -- thus frequency of opening determines extent of blockade T

herapeutic concentrations affect: 1. myocardial cells 2. vascular smooth muscle of resistance vessels

Moderate vasodialtion moderate cardiac activation moderate cardiac suppression

Overall: vasodialtion with moderate cardiac suppression

13

Pharmacology of Verapamil and adverse effects?

1. what happens on clinical dosage

2. Contraindicated?

3. Does it hit any other receptors?

4. Administration?

5. metabolism?

6. Adverse effects

Clinical dose causes: moderate vasodilation

Contraindicated in severe CHF b/c some alpha-adrenergic blockade

Oral administration

Large first pas metabolism

adverse effects: flushing, GI disturbances, LV dysfunction

14

Diltiazem 1. mechanism and binding? 2. therapeutic concentrations affect?

L-type calcium channel blocker - binds to refractory L-channels and decrease frequency of opening

Therapeutic concentrations affect: 1. myocardial cells 2. vascular smooth muscle of resistance vessels

15

Why are vasodilators useful in treating angina?

decrease vascular smooth muscle tone Decrease peripheral vascular resistance = decrease in after load = less myocardio work and decrease O2 consumption

16

Advantages to using calcium entry blockers?

No aggravation of diabetes, peripheral vascular disease, bronchospasm, blood profiles of lipids, glucose or potassium. Tolerance does not develop

17

Effect of calcium entry blockers on perfusion? Effect on cardiac work?

increase coronary blood flow resistance vessel dilation reflex cardiac effects vary with agent work of heart is decreased

18

Utility for typical angina in regards to calcium entry blockers?

-Reduce frequency of attacks -Reduce nitrate requirements -Increased exercise performance -no reducin in incidence of MI - Use when beta-blocekrs are not tolerated

19

Beta adrenergic antagonists effect on cardiac work:

- suppress cardiac activity - lower O2 consumption - prolongue diastole

20

Utility of beta-blocerks in typical angina

- most effective in reduction of cardiac ischemia

- Reduces frequency and severity of attacks

- useful for suppressing recurring myocardial infarcts

 

 

* not super effective in therapy for angian because they mostly affect the heart and not resistance.

21

Adverse effects of beta blockers:

- aggravation of peripheral insufficiency

- increased airway resistance

- produce rebound angina or MI on sudden withdrawal.

22

Typical Angina? Atypical Angina? Unstable angina?

atherosclerotic narrowing of the coronary artery

 

coronary vasospasm

 

platelet aggregation secondary to plaque rupture