Pharm II - CVS drugs Flashcards
What are the CVS effects of cardiac glycosides (CGs)? (6)
- increase contractility/excitability
- increase CO
- Diuresis
- Reduces edema
- Decrease HR
- Decrease venous Pressure
Is diuresis a prominent feature of Digitalis?
No. It is 2ry to circulatory improvement
How does Digitalis cause diuresis (2)?
- Increases renal blood flow
2. Decreases aldosterone secretion
Will Digitalis induce diuresis if the edema is not cardiogenic in nature?
No
CO depends on what 3 things?
- Intrinsic response of cardiac mm. to change in myofiber length
- HR
- Contraction force of heart
Compensatory mechanisms of the the CVS? (4)
- Activation of Sympathetic NS
- Renin-andiotensin-aldosterone system
- Myocardial hypertrophy
- CHF
CGs are a ____ compound linked by an _____ atom to one or more ____ molecules.
neutral
oxygen
sugar
What are Ionotrophic drugs generally used for?
- increase myocardial contractile force
2. TX CHF
What are the iontropic drugs (6)?
Digitalis Inamrinone Milrinone Pimbendan Dobutamine Aminophylline
Digitalis collectively refers to what 3 drugs?
Digoxin
Digitoxin
Ouabain
Where does the cardioactivity of CGs reside?
principally in the aglycone moiety & sugar molecules attached to aglycone
How does digitalis affect cardiac rate & rhythm?
stimulates vagal afferents & directly depresses SA node conduction = decrease HR
How does digitalis affect cardiac excitability?
reduces the diastolic potential to threshold level, enhancing excitability
Higher bioavailability
(75-95%) is achieved when digoxin is administered in what form?
elixir form
Which species are CGs poorly absorbed? Why?
Ruminants
due to metabolism by ruminal micro-organisms
Does digoxin bind to PP?
Yes, poorly (25%)
What BW should be used to calculate digoxin dosage?
Lean BW (not well distributed to fat)
Does digitalis undergo enterohepatic circulation?
yes, gives it a long 1/2 life
List the half life for a single IV dose of digitalis by species shortest to longest. (6)
sheep- 7.2 hrs Cattle- 7.8 hrs Horses- 23 hrs Dogs- 28 hrs Cats- 35 hrs Humans - 39+ hrs
How can digitalis be administered for maintenance therapy?
PO or parenteral
What is digitalization?
involves initial admin of a large amt of digitalis (loading dose) in several divided doses over 24-48 hrs followed by a daily maintenance dose to maintain therapeutic efficacy
What is the main aim of digitalis therapy?
to determine the smallest amt of CG that will effectively maintain cardiac compensation w/o signs of toxicity
What is the slow method of oral digitalization?
Admin loading dose in 5 equal parts over 48 hrs
What is the rapid method of oral digitalization?
Admin loading dose in 3 equal parts every 6 hrs
What is the intensive method of digitalization?
ER!!
- Give 1/2 loading dose
- Give 1/4 loading dose 6 hrs later
- Give 1/8 loading dose at 4-6 hr intervals
- Use maintenance dose
When is the steady state conc. of digitalis attained? What do you do then?
6th to 8th day of maintenance therapy
assess for response to TX
Which 2 organ fxns should be assessed before beginning digitalis tx?
Liver & kidneys
What should you do with the digitalis dose in patients w/ renal & hepatic dz?
Reduce the dose levels
When is IV admin of digitalis recommended?
animal does not retain oral meds or has acute cardiac decompensation or respiratory distress
Why is careful monitoring required after giving digitalis IV?
It can induce toxic arrhythmias
Can you give digitalis IM?
Not recommended, causes pain & swelling
What is the MOA of CGs?
Inhibits Na/K ATPase –> increases INTRAcellular Ca –> excess Na is exchanged for Ca by the Na/Ca pump (3:1) –> increases [Ca] –> activates inotropic action
What is digoxin safety margin?
Narrow
Should steady state plasma [digoxin] be done?
yes
How do you monitor digitalis toxicity? (3)
- ECG
- [plasma/serum]
- serum [K]
Serum ___ & ____ influence myocardial sensitivity to digitalis action?
K & Ca
K+ ______ digitalis binding to Na/K ATPase?
inhibits
____kalemia increase digitalis binding w/ Na/K ATPase & toxicity?
Hypokalemia
How does Quinidine increase digitalis steady state concentration?
- displaces digitalis from its tissue binding site
2. inhibits P-glycoprotein in GIT & Kidney –> increases absorption & decreases excretion of digitalis
Increased ____ may enhance the toxic effect by increasing intracellular Ca stores?
Ca
How does Cholestyramine resin TX digitalis toxicity?
binds glycoside w/in GIT & inhibits enterohepatic circulation = increases elimination of digitalis
When is digitalis contraindicated?
in case of AV block!
What should you do when administering digitalis & Quinidine together?
Reduce digitalis dose by 1/2 6-8 days prior to therapy w/ Quinidine
What adjunct therapy should be used along with CGs?
Diuretics –> reduces cardiac preload
Furosemide is a ____ diuretic? Where does it act?
Loop-acting
Ascending LoH
MOA of Furosemide?
inhibits Na/K/Cl co-transport mechanism
Which animals show decreased response to furosemide?
animals w/ low CO & poor renal perfusion
List the diuretics (3) used in CVS therapy.
Furosemide
Thiazide diuretics
K sparing diuretics
MOA of thiazide diuretics
inhibit Na/Cl symport in DCT–> increasing K excretion & enhancing Ca reabsorption
Which diuretic increases the risks of digitalis toxicity?
Thiazide diuretics due to effects on serum [K] & [Ca]
What is the preferred diuretic to use in CVS therapy?
K sparing diuretics –> decreases K in urine
MOA of K sparing diuretics?
interferes w/ Na/K exchange mechanism in renal collecting tubules
What is the problem w/ K sparing diuretics?
slow onset of action