Lecture 18: Vasodilators Flashcards
Describe polyphosphoinositide signaling
- Gq activates membrane phospholipase C
- Hydrolyzes IP3/DAG
- IP3 releases Ca2+
- DAG stimulates PKC- IP3 dephosphorylated, DAG broken down and Ca2+ pumped out
What vasodilators increase cGMP and cause relaxation of vascular smooth muscle
NO, nitrprusside, organic nitrates, and PDE V inhibitors
What vasodilators decrease intracellular ca2+ and therefore relax vascular smooth muscle
CCB’s
CAMP increases the inactivation of ___kinase
Myosin light chain kinase
In order to promote relaxation what must happen to myosin light chain
Dephosphorylate
Vasodilators further improve ___ and reduce __ and ___ in heart failure patients
Cardiac output, edema and effusions
Vasodilators that reduce arteriolar resistance are also used in treatment of ___
Hypertension
How do ACE inhibitors effect vasodilation veins and arteries
arteries: +
Veins: +
How do nitrites effect vasodilation of veins and arteries
Arteries: +
Veins: ++
How does hydralazine effect vasodilation of arteries and veins
Arteries: +
Veins: -
How do CCB’s effect vasodilation of arteries and veins
Arteries: ++
Veins: -
How do alpha blockers effect vasodilation of arteries and veins
Arteries: +
Veins: +
What species is hydralazine commonly used in
Dogs, cats and rarely horses
Hydralazine dilates __ but not ___
Arteries but not veins
What is hydralazine most effective in treating
HF secondary to mitral valve insufficiency
Nitrates preferentially dilate ___ however dilate __ too
Veins, arteries
What vasodilators act through nitric oxide
- Hydralazine
- Nitrates
- nitroglycerin
- isosorbide dinitrate
- sodium nitroprusside
What is nitroglycerin used for
Pulmonary edema associated with HF
**vasodilate veins over arteries so assists with Left side HF symptoms
T or F: tolerance may develop with use of nitroglycerin
True
T or F: isosorbide dinitrate may develop tolerance
True
Which nitrate is a potent vasodilator that is administered as a constant infusion
Sodium nitroprusside
With the use of sodium nitroprusside, ___ toxicity may develop in patients with compromised renal function
Cyanide
T or F: tolerance develops with the use of sodium nitroprusside
False
When is sodium nitroprusside used
Pulmonary edema associated with HF and emergent hypertensive crisis
What are the two important functions of Ca2+
- Trigger muscle contractions in myocardium and vascular smooth muscle
2, required for pacemaker activity of SA node and conduction through AV node
How are vascular smooth muscle and heart calcium channels opened in the heart
B-adrenergic stimulation
How are heart and vascular smooth muscle calcium channels closed
CCB’s inhibit calcium entry
what channels do CCB’s act on
L-type channels
What do CCB’s do to transmembrane calcium current
Decrease
CCB’s cause a long lasting __ of vascular smooth muscle
Relaxation
How do CCB’s effect cardiac contractility, automaticity and conduction
Decrease
CCB’s will relax all smooth muscles that depend on calcium. ___ muscle is most sensitive but __, __, and __ is also relaxed
Vascular smooth muscle, but bronchiolar, gastrointestinal and uterine
CCB’s preferentially dilate ___ over __
Arterioles, veins
What are the major cardiac effects of CCB’s
- Negative inotropic effect due to decreased contractility
- Reduced impulse generation from SA node
- Slowed AV node conduction
What type of drug is amlodipine besylate
Long acting CCB
What does amlodipine besylate do
Vasodilate
Amlodipine besylate is the drug of choice for __
Hypertensive cats
The use of amlodipine is cautioned when __ function is poor
Liver
Amlodipine besylate can activate RAAS but this is reduced if concurrently used with
Enalapril (ACEi)
What type of drug is diltiazem
CCB
What does diltiazem do
Depresses AV and SA node for cardiac contractile depression
When is diltiazem used
HCM in cats and supraventricular tachycardia in dogs and cats
Which has a greater vasodilatory effect and causes reflex tachycardia: amlodipine or diltiazem
Amlodipine
Which has a greater depression of SA and AV node, and negative inotropic effect: amlodipine or diltiazem
Diltiazem
What type of drug is sildenafil
Selective inhibitor of cGMP specific PDE5
How does sidenafil work
By decreasing elimination of cGMP produces vasodilation
Sidenafil seems to be effective in ___ in dogs
Pulmonary hypertension
What type or drug is prazosin
Alpha1 adrenergic antagonist
When is prazosin used
- Typically for functional urethrospasm in dogs
- HF less characterized but can be considered when hydralazine is poorly tolerated
How does prazosin work
Blocks alpha1 adrenergic receptors so opposes NE vasoconstriction and dilates both arteries and veins
BP decreases
Prazosin can cause reflex __
Tachycardia
What are some adverse effects of prazosin
Hypotension, Na+ and H20 retention
