Sympathomimetic-PDE III Flashcards
PDI are heterogenous group of non-catecholamine non-glycoside that exert a competitive inhibitory action of phosphodiesterase enzyme.
PDI
Multiple types of phosphodiesterase enzymes exist in different tissues: (5)
Cardiac muscle Vascular smooth muscle Platelets Liver lungs
Selective inhibitors of phosphodiesterase fraction III (PDE III) MOA
decrease hydrolysis of cAMP leading to increased intracellular concentrations of cAMP in the myocardium and vascular smooth muscle.
PDI have an indirect effect on what in vascular smooth muscle
cyclic guanosine monophosphate-dependent protein kinase
cGMP
PDI in the myocardium have what effect
increase intracellular cAMP-increase calcium-increase contractility
what is the effect of PDI and increase vascular smooth muscle increased cAMP- increased calcium
leads to smooth muscle relaxation and vasodilation
PDE III inhibitors have positive inotropic effects and smooth muscle relaxation in both arteriolar and venous beds and thus called….
inodilator
PDE III isoenzymes exist in airway smooth muscle bronchodilation - do we see this clinical effect
is not a predominant clinical effect of the current cardiac-selective PDE III inhibitors.
PDE III inhibitor
contractility and CO effects
Increased contractility
Increased CO
PDE III inhibitor
venous capacitance effects
Increased venous capacitance (The measure of a BLOOD VESSEL’s ability to increase the volume of BLOOD it holds without a large increase in BLOOD PRESSURE. Thevascular capacitanceis equal to the change in volume divided by the change in pressure.)
PDE III inhibitor
LVEDP, CVP, PCWP, Venous return to the heart, MAP, PVR, SVR
Decreased LVEDP
Decreased filling pressure (CVP and PCWP)
Decreased venous return to the heart
Decreased MAP, Pulmonary and Systemic Vascular Pressure
PDE III inhibitor
lustitropic effect
Improve the lusitropic (rate of myocardial relaxation) state of the heart
PDE III inhibitor
diastolic effect
Diastolic relaxation is facilitated by enhanced calcium removal from the sarcoplasm, thereby improving ventricular filling
PDE inhibitors do they cause arrhythmias
rarely
PDE inhibitors preload and after load affects
decrease preload and afterload
PDE inhibitors effects on wall tension and myocardial 02 consumption
decrease
PDE III inhibitors affect on beta adrenergic receptors.
PDE III inhibitors act independently of Beta adrenergic receptors and will increase myocardial contractility in patients with myocardial depression from Beta receptor blockade and in patients who have down regulation of Beta adrenergic receptors and are refractory to catecholamine therapy.
can PDE inhibitors be used with digitalis
yes an will not provoke toxicity- The hemodynamic response to selective PDE III inhibitors exceeds that of cardiac glycosides and is synergistic to actions of catecholamines
Bypyridine derivative that acts as a selective PDE III inhibitor and produces dose dependent positive inotropic and vasodilator effects manifesting as increased CO and decreased LVEDP.
amrinone (inamrinone)
amrinone effects of CI LV stroke index lv EF LVEDP, PCWP, PAP, CVP, SVR HR
Increases CI Increases LV stoke index Increases LV EF Decreases LVEDP, PCWP, PAP, Right Atrial Pressure and SVR Minimal effect on HR
protein binding of amrinone
minimal protein bound
amrinone distribution half life
1-2min
amrinone excreted unchanged %
26-40%
metabolism of amrinone
N-acetylation and glucuronidation by the liver
amrinone elimination half time
2.6-4.1hr
when is amrinone elimination half time increased
heart failure
administration form of amrinone
po & IV
what two ways does amrinone increase co
inotropic action or vasodilation mechanism
long term oral use of amrinone results in
bioavailability and increased side effects
IV loading dose of amrinone
0.5-1.5mcg/kg
after loading dose of amrinone how quickly does CO increase and last for
5 min to 2 hours persisting
maintenance infusion of amrinone
2-10mcg/kg/min
tachyphylaxis seen with amrinone?
no
max daily dose of amrinone
10mg/kg including initial loading dose
how often can you repeat a loading dose of amrinone
30 min after first injection
how do we administer bolus dose of amrinone
slow due to hypotension
who do we decrease amrinone dose for
renal dysfunction
lab side effects form amrinone
dose related thrombocytompenai (espiecially with chronic PO therapy)
po accelerated platelet loss
BP side effects of amrinone
hypotension from vasodilation
amrinone and hypotension what can you give to help BP
vasopressors
heart rate effects of amrinone
increases AV nodal conduction and decrease atrial refractoriness
what is amrinone pro arrhythmic potential
does related and associated with IV administration.
Bipyridine derivative of amrinone with almost 30 times the inotropic potency of amrinone but less adverse side effects. Thus replaced amrinone in clinical use
milrinone
how does milrinone increase CO
CO improvement by increased inotropy as well as vascular smooth muscle relaxation of peripheral and pulmonary vessels.
milrinone effects LVEDP MAP CVP, SVR Pulmonary Artery Occlusion Pressure
decreases LVEDP MAP CVP, SVR Pulmonary Artery Occlusion Pressure
milrinone dose dependent increases in CI will do what to myocardial 02 consumption
Dose dependent increases in CI occur with minimal increases in myocardial O2 consumption.
milrinone diastolic effects
improves diastolic function
milrinone IV bolus
50mcg/kg
milrinone iv maintenance
0.375 to 0.75 mcg/kg/min to maintain plasma concentrations at or above therapeutic levels.
how fast do we give milrinone bolus
over 10 min
milrinone max daily dose
1.3mg/kg/day
how much milrinone is protein bound
70%
how much milrinone is excreted unchanged by the kidenys
80%
elimination half time of milrinone
2.7hrs
what disease gets a decrease dose of milrinone
severe renal dysfunction
how is milrinone used after cardiac surgery-2 ways
wean from cardiopulmonary bypass
management of acute LV dysfunction after cardiac surgery
what can cause a reducted inotropic effect of milrinone
acidosis
does milrinone cause tachycardia
rarely
if patient has significant vasodilation or renal dysfunction which drug should they receive
dobutamine
how does milrinone affect arterial grafts
reverses vasospasm
which strange thing does milrinone have that may help after cardiopulmonary bpass
anti-inflammatory effects
if patient has elevated PAP and needs continued beta blockade and increased risk for tacyarrhythmias what medication is most appropriate
milrinone
milrinone may increase ____ in ischemic myocardium
ventricular automaticity
what arrhythmias have been reported in milrinone
ventricular and supra ventricular arrhythmia
what are milrinone effects on platelets
higher potency has less effects on platelets.
but short-term milrinone used does not cause significant changes in platelet number or function after cardiopulmonary bypass beyond the usual effects of cardiopulmonary bypass and cardiac surgery
is milronone approved for HF
not FDA approved
when might you see arrhythmias with milrinone
rapid IV loading dose
what electrical change is the major electrophysiologic effect of milrinone
enhanced AV nodal conduction
milronone with severe chronic heart failure is associated with
morbidity and mortality
how do we mitigate hypotension with milrinone
slow bolus administration/give vasopressors
