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Pharm 2 - Cardio 1

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isabellepjk's version from 2017-10-11 16:04

Inotropic Drugs

Cardiac Glycosides

Question Answer
What are the drugs in Cardiac Glycosides?Digoxin, Digitoxin & Ouabain
What is the MOA for Cardiac Glycosides? (to ↑ inotropy)Increase myocardial contraction in normal AND failing heart
Acts by inhibition of Na+/K+ ATPase enzyme in the sarcolemma membrane of cardiac tissue, which ↑ intracellular Na concentration in sarcomere & then the excess Na+ is exchanged for Ca by Na+/Ca++ pump → ↑ Ca++ conc in the contractile proteins leading to better inotropy
*What are the main uses of Cardiac Glycosides? (digoxin)Congestive heart failure & atrial arrhythmias
How do Cardiac Glycosides affect heart rate? Rhythm? How does it do this?↓ heart rate (stimulation of vagal tone & depression of SA node conduction) & slows atrio-ventricular (AV) impulse conduction (used to tx fast arrhythmias of the atria, so you'd want to slow it down!)
**How do Cardiac Glycosides affect the force of contraction/contractility/output (excitability)?Positive ionotropic action on heart leading to ↑ contractility & output – (↑ Na & ↓ K ↑ excitability)
DIGOXIN/DIGITALIS DOES NOT INC AV CONDUCTION IT DECREASES THEM
How do Cardiac Glycosides affect urination?They ↑ heart output which ↑ renal blood flow → ↑ GFR → ↑ diuresis. ALSO reduces Aldosterone (However, diuresis doesn't happen if the edema wasn't cardiogenic) (can remember like sugar in urine & peeing I guess)
What are the signs of cardiac glycoside toxicity & why?They cause protracted (long lasting/continuous) vomiting & diarrhea (bc it stimulates the CTZ (Chemoreceptor Trigger Zone) in the brain which is responsible for vomiting.
Also arrhythmias & weight loss will start to occur (Arrhythmia bc still messing w/ SA & AV node impulse conduction)
What bad side effect can Digitalis have on the heart?
How do you fix this?
Digitalis mediated arrhythmias - Txed w/ Phenytoin, Propranolol & Lidocaine (Atrial Arrhythmias arent PHENTO have. But if youre brave enough to numb your heart w/ LIDOCAINE, PROPs to you, lol)
Which kind of arrhythmias are Cardiac Glycosides used to Tx? How does it work?Atrial arrhythmias – Digoxin reduces sinus rate (vagal stim) & slows AV node impulse conduction to abolish atrial arrhythmias. (What causes the atria to beat is the electrical signal activating each mm fiber as it moves from the SA to the AV. if you slow this conduction down, it takes longer for the full contraction of the atria to occur, slowing down the time it takes for a beat, leaving less room for irregular beats to take place)
How do you administer Cardiac Glycosides?Given orally & parenteral (IV) IM not recommended bc it is painful (would you want flowers shoved in your muscles?)
IV is good for when oral meds can't be retained, and when there is acute cardiac decomp/resp distress
IV/IM can cause arrythmias
What is the distribution of Cardiac Glycosides like?Goes everywhere but FAT!!!!! NEED TO CALC DOSE BASED ON LEAN BODY MASS (also doesn't go into edema fluid, so calculate that weight out of the dose as well) (think glyc=sugar=fat)
What ↑s the half-life of Cardiac Glycosides? (Not a drug, just a natural property of them)They undergo enterohepatic circulation which ↑ half-life
LONGEST in cats, shortest in SHEEP
What is digitalization?
What are the initial signs after digitalization?
The admin/effect of giving Digitalis
Cough relief, less labored breathing, decreased fatigue, improved diruesis, decreased edema, decreased BW, decrease ventricular rate

All basically due to decreasing CO or diuresis
Describe the slow/fast/intensive method of dosing (digitalizing) Digitalis(in general, it is giving a large (loading) dose to reach therapeutic levels & then smaller maintenance doses) for slow dosing, loading dose is divided by 5. For rapid, loading dose is divided by 3, for intensive method, 1st loading dose is half of it, then 1/4, then 1/8.
What are some considerations you need to think about when dosing (digitalizing) Cardiac Glycosides?Drug wont go into FAT or into EDEMA, so need to calc dose MINUS that weight (need lean body mass). ALSO dose should be reduced in animals w/ hepatic & renal dysfunction
What are the signs on toxicity? How can you monitor a Digitalis toxicity? Explain.Signs- vomiting, GIT disturbances, chronic weight loss, arrhythmias.
(1) Watch ECG pattern
(2) Monitor plasma/serum level of drug
**(3) You can watch serum electrolyte levels! K inhibits Digitalis binding to Na/K/ATPase enzyme & normal serum K levels would ↓ arrhythmias. Hypokalemia would cause an ↑ in arrhythmias. An ↑ in Ca+ ↑ toxic effects bc there would be more Ca for the mm to use which also INC toxicity
*How does K+ levels affect arrhythmias caused by Digoxin?HYPERkalemia antagonizes arrhythmias (competitive bindings w/ Digitalis)
HYPOkalemia potentates arrhythmias (easier to depol)
K inhibits the binding of digitalis to Na, K-ATPase enzyme becuase K and digitalis compete for the same binding sites.
*How does Ca2+ affect digitalis?HYPERcal = inc Ca for contraction and that increases toxic effects
*How can you tx digitalis toxicity?mild to mod = stop therapy, put it in a comfy cage, and give oral K supplement (HYPOkalemia=digitalis induced arrythmias)
severe= give cholestyramine, tx with anti-arryths like lidocaine, propranolol or phenytoin, or give atropine
What are the safety margins of Cardiac Glycosides?NARROW safety margin
What is Quinidine's relation to Cardiac Glycosides? (Explain mechanism)Quinidine will almost DOUBLE Digoxin conc by INHIBITING the P-glycoprotein in the intestine/kidney .
P-Gp facilitates more absorption & ↓ elimination through kidney, so if it is inhibited, the concentration INC
ALSO ↑ in DISPLACEMENT of Digoxin from tissue binding sites (Which means more avail to interact w/ heart)
If you want to admin Quinidine w/ Digoxin, what do you gotta do? (Dose regimen)Give 1/2 dose Digoxin, wait for 6-8 days & then administer Quinidine
Why would you want to give a diuretic w/ Digoxin?↓ preload/workload of failing heart (by ↓ fluid content in general) so improves efficiency of heart
How does Digoxin affect the AV node?Slows AV impulse conduction
What should you know about the diuretic effect of Cardiac Glycosides?NOT A DIRECT EFFECT! It’s 2⁰ to circulatory changes, it is not directly affecting the kidney
How is Digitalis anti-arrhythmic? How is it arrhythmogenic?Anti = stops ventricular arrhythmias associated w/ Quinidine. Also Txs atrial arrhythmias by itself
Pro = ↑ excitement so possibly arrhythmegenic
Describe the oral bioavailability, and absorption of digoxin?variable absorption; LOW IN RUMS d/t microorgs
Bioavail is high for elixir forms but lower in HORSES
memorize

Diuretics

Question Answer
**What is the fx or furosemide?acts on the luminal membrane of the ascending LoH; interferes with reabsorption of K, Mg, and Ca
Induces significant Ca loss
Liver metabolism
Glucuronidated
What can DEC the action of furosemide?Low CO and poor renal perfusion
*What are the MoAs of thiazide diuretics?
What is the effect?
Inhib Na/Cl symporter in DCT which INC diuresis ; Inc urinary K excretion; Inc renal tubular Ca reabsorption; INC toxic potential of glycosides d/t effects on K and Ca
Increase urine output AND endothelium effect
*How do K sparing diuretics work?
What are some of the drugs?
What is a drawback?
interfere the Na/k exchange mech
aldost ANTagonist=spironolaction
Triameterene and amiloride inhibit Na reabsorption
Drawback-slow diuresis
Triam/spiro is K sparing so can give with DIGOXIN to reduce K loss
*What is a desirable combo of K sparing diuresis?Hydroflumethazide + spironolactone
memorize

Phosphodiesterase Inhibitors

Question Answer
What are the PI drugs?Inamrinone, Milrinone, Pimobendan (In Rin, Mi Rin, bendan over)
How do Phosphodiesterase Inhibitors affect the heart? BVs?Inotropic effect on heart, vasoDILATOR (so they are called "inodilators" )
*What is the main use for a Phosphodiesterase Inhibitor?ACUTE myocardial failure (& CHF) (a cAMPing trip is ACUTE way to relax your vessels & invigorate your heart)
PIMO, MILRIN, IAMRINONE
What is the MOA of Phosphodiesterase Inhibitors? What are the 2 effects of this?It inhibits the Phosphodiesterase 3 enzyme, which leads to an accumulation of cAMP (does intracellular signal transduction) → ↑ cardiac contraction & vasodilation
*Whats unique about Inamrinone?Produces positive inotropic action w/o ↑ myocardial O2 consumption (In Rin you don't need air)
DEC Preload and afterload
treatment of acute mycardial failure in dogs and cats when given IV
Pimobendan has what unique feature?Improves binding efficiency of Ca++ for cardiac myofibers to further improve positive inotropic action (↑ binding efficiency of cardiac myofibril to Ca ions) (bendan over so I can stick some more Ca in you)
NO EFFECT of oxygen demand, and will not cause arrythmias
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β-1 adrenergic agonists

Question Answer
What is the drug for this category?Dobutamine (Beta dobutamine...βutt)
What are dobutamine features?B1 adrenoreceptor agonist
+ inotropic
decrease vent filling pressure (preload), WEAK + chronotropic action
VASOCONSTRICTOR AND VASODILATOR
Clinical use of DobutamineCongestive heart failure & cardiogenic shock (shock is an emergency situation, need a fast acting injectable inotropic & vasodilating agent)
(hypotension in horses (seeing a butt for the 1st time is shocking)
Unwanted SFx of β-1 adrenergic agonists?Can cause arrhythmias when there are ischemic heart conditions & tachyphylaxis w/ chronic use (give that butt some air, or it's going to freak out!! It's addicted after all)
How do you admin Dobutamine? What is its period of action?IV admin, period of action is only 4min (Injecting Butts IV wont last for long)
will need continuous IV admin
How is it biotransformed?COMT
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Aminophylline

Question Answer
What is the 1⁰ effect of Aminophylline?BRONCHODILATION (Ami phylline the paperwork for her inhaler → bronchodilator)
aminophylline MOA?Inhibits Phosphodiesterase enzyme in cardiac tissue (ami is filing the paperwork for her inhaler, for P (D) E Class)
*Why would you use Aminophylline?Indicated for taking care of Acute Pulmonary Edema associated w/ CHF (also weak inotropic action & mild diuresis) (Bronchodilator for Pulmonary Edema (associated w/ CHF), makes sense)
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Check yo'self

Question Answer
What are the 4 groups of inotropic drugs?Cardiac Glycosides, Phosphodiesterase Inhibitors, β-1 Agonists, Aminophylline
What are the drugs in Cardiac Glycosides?Digoxin, Digitoxin & Ouabain
What are the drugs in the Phosphodiesterase Inhibitors?Inamrinone, Milrinone, Pimobendan (rin would go camping w/ me in the desert)
What are the drugs in the Β 1 agonists? DOES IS CONSTRICT OR DILATEDobutamine (Β 1 is the β receptor on the heart!)
VASODILATOR
Chemoreceptor trigger zone → what group am I thinking of?Cardiac Glycosides. The stim of this zone leads to vomiting & protracted diarrhea, which is how you know they are having toxic effects
Works by inhibition of Na+, K+-ATPase enzyme in the sarcolemma membrane of cardiac tissueCardiac Glycosides
Accumulation of cAMPPhosphodiesterase
(3) inhibitors
Inhibits Phosphodiesterase enzymePhosphodiesterase Inhibitors (inhibit PDE3) & also Aminophylline
↑ binding efficiency of cardiac myofibril to Ca ionsPimobendan (PDE3 inhibitor)
Positive inotropic action w/o ↑ myocardial O2 consumptionInamrinone (PDE3 inhibitor)
BronchodilationAminophylline
What are the inodilators?The Phosphodiesterase Inhibitors (MILRINONE, IMAMRINONE, PIMOBENDAN) & also Dobutamine
memorize

By Drug → which group?

Question Answer
DigoxinCardiac Glycosides
DigitoxinCardiac Glycosides
OuabainCardiac Glycosides
InamrinonePhosphodiesterase Inhibitors
MilrinonePhosphodiesterase Inhibitors
PimobendanPhosphodiesterase Inhibitors
Dobutamineβ-1 agonist
Inamrinone (Amrinone)Phosphodiesterase Inhibitors
MilrinonePhosphodiesterase Inhibitors
Pimobendan (Inodilators)Phosphodiesterase Inhibitors
Dobutamineβ-1 adrenergic agonist
AminophyllineIn its own category (technically its a bronchodilator)
memorize