ORGANIC NITRATE

acute treatment

actions:

1)veins dilated at lowest concentrations

2) but also arterial

3)relax other smooth muscle

4) anitplatelet effect

= less stress on the wall

release NO (stimulates cGMP production = = relaxation)

Effects on O2 demand: 1) venous dilation and decreased ventricular volume (decrease radius) = decrease demand

2) increase HR and Increase contractility (reflexive, but not major effect on demand)

Effects on O2 demand:

1) some dilation of coronary arteries

2) in angiospastic angina, increase flow via collaterals

3) good for spasm angina - relieve coronary spasm and flow

Relief in patients with chronic effort-associated angina and prophylaxis of attacks

Different preparation: 1) SL 2) oral - significant first pass metabolism

3) topical prep 4) transdermal = tolerance, so don't leave on skin more than 24 hrs

Adverse Effects - headache, orthostatic hypotension, use with phosphodiesterase 5 inhibitors results in hypotensive effect (inhibiting PDE-5 = increased cGMP)

Tolerance - develops due to continous exposure; more effective to stop thereapy for 8-12 hrs each day and then resume = more effective

organic nitrate

highest bioavailability= 100%

prophylactic tx

organic nitrate

does not last as long

nitro = increase cGMP

significant hepatic first pass metabolism

Decrease O2 demand: decrease HR, BP, and contractility (decreased sympathetic outflow)

Increase O2 demand: increased ventricular end-diastolic volume and ejection time

decreased HR increases perfusion = increases delivery of oxygen

DO NOT USE with Vasospastic Angina (unapposed alpha)

Adverse: - Beta blocker withdrawl - don't take patients off of them all of a sudden - gradual tapering

calcium channel blockers - interact with L-type Ca Channels to decrease cellular uptake of Ca++

***= decrease contraction of smooth muscle = decrease BP via arterial dilation = reflexive increase HR (more in this drug than in other CCB)

***vascular selective = works systemically -  works mainly on VESSELS

AV conduction not affected by this drug

Decreased contractility

ffects on determinants of myocardial oxygen demand:

1) decrease PVR and BP = decrease O2 demand

2) decrease contractility = decrease O2 demand

3) decrease HR = "

4) decrease coronary tone in variant angina (vasospastic angina)

effective in vasospastic and chronic effort-assoc. angina

Adverse effects:

1) excessive vasodilation = dizziness, flushing, hypotension

2) constipation and peripheral edema

3) reported concerns about safety of immediate release nifedipine

DRUG interactions!!!

CCB

decrease Ca entry into cells = depolarize cells = decrease conduction through AV node

cardio selective

decrease HR (more than nifedipine)

decreased contractility

effects on determinants of myocardial oxygen demand:

1) decrease PVR and BP = decrease O2 demand

2) decrease contractility = decrease O2 demand

3) decrease HR = "

4) decrease coronary tone in variant angina (vasospastic angina)

effective in vasospastic and chronic effort-assoc. angina

Adverse effects:

1) excessive vasodilation = dizziness, flushing, hypotension

2) constipation and peripheral edema

DRUG interactions!!!

(reverses Na channel current  - pFOX inhibitor) but mechanism of action is really unknown

Little effect on HR and BP

pharm: oral; extensive metabolism; p-glycoprotein substrate

SOME ADVERSE EFFECTS:

1) Dizziness, headache, consitpation, nausea

2) Increase QT interval = Increase risk for cardiac arrhythmia (Tress. de point)

Drug interactions

??? Digoxin toxicity ???