Cardiovascular PK (L4)

digoxin is an antiarrhythmic cardiac glycoside that is indicated for HF and Afib/flutter

it is a positive inotrope and a negative chronotrope, meaning it __________ HR

decreases

digoxin PK: two compartment, ______-order elimination kinetic model

first (rate of elimination is directly proportional to its plasma concentration)

digoxin PK: two compartment, first-order elimination kinetic model

______________ distribution phase

prolonged (takes 6-8hrs to distribute) (impacts when we’re giving LDs)

digoxin PK: two compartment, first-order elimination kinetic model

prolonged distribution phase and dynamic effects dependent on tissue concentrations

narrow therapeutic index: target level depends on the ___________

indication

digoxin absorption: passive, non-saturable diffusion, minimal effect from ________

food (can be taken with or without food)

digoxin absorption: passive, non-saturable diffusion, minimal effect from food (take w/ or w/o)

onset of action // peak are dependent on route of administration

PO: 1-2 hours // 2-8 hours

IV: ________ // 1-4 hours

15-30 mins

digoxin distribution: 20-30% protein bound

Vd= 6-7 L/kg in normal renal function

it does NOT distribute into ____________

adipose tissue (dosed with IdealBW)

digoxin distribution: 20-30% protein bound

Vd= 6-7 L/kg in normal renal function

___________ distribution into adipose tissue

NO (dosed with IdealBW)

digoxin distribution: 20-30% protein bound

Vd= 6-7 L/kg in normal renal function

it does NOT distribute into adipose tissue and this is why it is dosed based on _______ body weight

ideal

digoxin elimination: the half-life is affected by age, renal function, and cardiac function

renal elimination: 50-70% unchanged in urine

non-renal elimination: intestinal secretion with _____________ (causes many DDIs) and hepatic excretion

Pgp (P-glycoprotein)

___________ elimination: the half-life is affected by age, renal function, and cardiac function

renal elimination: 50-70% unchanged in urine

non-renal elimination: intestinal secretion with P-glycoprotein (causes many DDIs) and hepatic excretion

digoxin

digoxin dosing: Jellife Method

LD_total for PO= _________ x _______

- give 50% of total as 1st dose

- give 25% of total as 2nd and 3rd doses

10mcg/kg x IBW

digoxin dosing: Jellife Method

LD_total for PO= 10mcg/kg x IBW

how is that total LD given?

50% of total is 1st dose, other 50% is split up (as evenly as possible) into 2nd and 3rd doses

digoxin dosing: Jellife Method

LD_total for PO= 10mcg/kg x IBW

- give 50% of total as 1st dose

- give 25% of total as 2nd and 3rd doses

if administering IV we should ______________

reduce total dose by 25%

digoxin dosing: Jellife Method

LD_total for PO= 10mcg/kg x IBW

- give 50% of total as 1st dose

- give 25% of total as 2nd and 3rd doses

the total dose (and split up doses) are to be rounded to the nearest ________

125mcg

digoxin dosing: Jellife Method

LD_total for PO= 10mcg/kg x IBW

Maintenance dose= ______ x _____

LD x %DL (will be given %DL equation)

digoxin dosing: Jellife Method

LD_total for PO= 10mcg/kg x IBW

Maintenance dose= LD x %DL

the target serum concentration for digoxin is ____________

1.4 ng/mL (appropriate for most indications… but for HFrEF we want <1)

digoxin monitoring: generally we watch ECG, HR, renal function, electrolytes, and s/sx of toxicity

serum concentrations: at least ____________ after administration

6-8 hours (12-24 hours preferred since we want trough levels)

digoxin DDIs

Pgp-mediated: _________ and ___________ require dose reductions, CCBs, Macrolide abx, -azoles, Propafenone, and Rifampin

Amiodarone and Quinidine

___________ DDIs

Pgp-mediated: Amiodarone and Quinidine require dose reductions, CCBs, Macrolide abx, -azoles, Propafenone, and Rifampin

digoxin

digoxin DDIs (Pgp-mediated: dose reductions for Amiodarone and Quinidine)

other drug interactions: decreased renal clearance of ________, hypokalemia with __________, PPIS, and Cholestyramine

NSAIDs, diuretics

digoxin DDIs (Pgp-mediated: dose reductions for Amiodarone and Quinidine)

Drug-Disease: decreased _________ in CKD and hypothyroidism, pregnancy, and Pgp-polymorphism

Vd

digoxin DDIs (Pgp-mediated: dose reductions for Amiodarone and Quinidine)

Drug-Disease: decreased Vd in ________ and ___________, pregnancy, and Pgp-polymorphism

CKD, hypothyroidism

___________ DDIs (Pgp-mediated: dose reductions for Amiodarone and Quinidine)

Drug-Disease: decreased Vd in CKD and hypothyroidism, pregnancy, and Pgp-polymorphism

digoxin

procainamide is a class 1a antiarrhythmic drug

moderate Na⁺ and K⁺ channel blockade causes a _________ QRS and ____________ QT

widened, prolonged

procainamide is a class 1a antiarrhythmic drug

moderate Na⁺ and K⁺ channel blockade causes a widened _____ and prolonged _____

QRS, QT

procainamide is a class 1a antiarrhythmic drug

'it is indicated for stable, ___________ ______ or Afib and can be used as a last resort in pulseless VT/VF

refractory VT

procainamide absorption: route of administration is _________ only

IV (peak concentration in ~2 mins)

procainamide absorption: route of administration is IV only and peak concentration is achieved in ~________

2 minutes

procainamide distribution: 15-20% protein bound and extensive distribution into ______________

lean body tissue (dosed based on IdealBW)

procainamide distribution: 15-20% protein bound and extensive distribution into lean body tissue (dosed based on _________ body weight)

ideal

procainamide distribution: 15-20% protein bound and ___________ distribution into lean body tissue

extensive (dosed based on IdealBW)

procainamide dosing/monitoring: it should be d/c if the arrhythmia ____________, ________________, or the QRS widens >_______ of baseline

ends, hypotension, 50%

procainamide dosing/monitoring: it should be d/c if the ______________ terminates, ________________, or the _______ widens >50% of baseline

arrhythmia, hypotension, QRS

amiodarone is a class III antiarrhythmic (activity within all antiarrhythmic drug classifications)

indicated for atrial arrhythmias, stable VT, and pulseless VT/VF

route of administration: __________ formulation(s)

IV and PO

amiodarone absorption: variable bioavailability ~50%

onset of action is also variable

PO: _________ - __________

IV: hours for electrophysiologic (beta-blocking) effects, days to weeks for antiarrhythmic effects

2 days, 3 weeks (takes a longggg time which is why we give LD)

amiodarone absorption: variable bioavailability ~50%

onset of action is also variable

PO: 2 days - 3 weeks (this is why we give LD)

IV: ________ for electrophysiologic (beta-blocking) effects, __________ for antiarrhythmic effects

hours, days to weeks

amiodarone DDIs: inhibition of CYP2C9, and 3A4 (delated onset)

when given with ____________, requires a 50% reduction in ____________ dose

warfarin (warfarin is a CYP2C9 substrate —> amiodarone is inhibiting warfarin’s metabolism= warfarin working too well)

amiodarone DDIs: ____________ of CYP2C9, and 3A4 (delated onset)

when given with warfarin, requires a 50% reduction in warfarin dose

inhibition (amiodarone is inhibiting warfarin’s metabolism= warfarin working too well)

amiodarone DDIs: inhibition of __________ (delated onset)

when given with warfarin, requires a 50% reduction in warfarin dose

CYP2C9 (and CYP3A4) (warfarin is a CYP2C9 substrate —> amiodarone is inhibiting warfarin’s metabolism= warfarin working too well)

amiodarone DDIs: inhibition of CYP2C9, and 3A4 (delated onset)

when given with warfarin, requires a 50% ____________ in warfarin dose

reduction (amiodarone is inhibiting warfarin’s metabolism= warfarin working too well)

amiodarone DDIs: inhibition of CYP2C9, and 3A4 (delated onset)

when given with warfarin, requires a 50% reduction in _________ dose

warfarin (amiodarone is inhibiting warfarin’s metabolism= warfarin working too well)

_______________ DDIs: inhibition of CYP2C9, and 3A4 (delated onset)

when given with warfarin, requires a 50% reduction in warfarin dose

amiodarone

amiodarone DDIs: inhibition of Pgp

when given with _________, requires a 50% reduction in _________ dose

digoxin (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

amiodarone DDIs: ____________ of Pgp

when given with digoxin, requires a 50% reduction in digoxin dose

inhibition (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

amiodarone DDIs: inhibition of ________

when given with digoxin, requires a 50% reduction in digoxin dose

Pgp (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

amiodarone DDIs: inhibition of Pgp

when given with digoxin, requires a 50% __________ in digoxin dose

reduction (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

_______________ DDIs: inhibition of Pgp

when given with digoxin, requires a 50% reduction in digoxin dose

amiodarone (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

amiodarone DDIs: inhibition of Pgp

when given with digoxin, requires a 50% reduction in __________ dose

digoxin (digoxin is a Pgp substrate —> amiodarone inhibits digoxin’s metabolism= digoxin working too well)

lidocaine absorption: onset of action for IV is ____________ (with bolus administration)

45-90 seconds

lidocaine distribution: ______-compartment model

we give a bolus dose to achieve therapeutic plasma level, and a maintenance infusion to avoid a therapeutic gap

two

lidocaine distribution: two-compartment model

we give a __________ dose to achieve therapeutic plasma level, and a __________ infusion to avoid a therapeutic gap

bolus, maintenance

lidocaine metabolism: __________ via CYP3A4, 3A5, and 1A2 to active metabolites (and it is _________ blood flow dependent)

hepatic

lidocaine metabolism: hepatic via CYP______, 3A5, and 1A2 to active metabolites (and it is hepatic blood flow dependent)

3A4

lidocaine DDIs: lidocaine is a substrate of CYP3A4 (i.e. uses that for its metabolism)

_____________ inhibits CYP2C9 and 3A4 and requires a dose reduction when used with lido

amiodarone

lidocaine DDIs: lidocaine is a substrate of CYP3A4 (i.e. uses that for its metabolism)

amiodarone _________ CYP2C9 and 3A4 and requires a dose reduction when used with lido

inhibits

lidocaine DDIs: lidocaine is a substrate of _________ (i.e. uses that for its metabolism)

amiodarone inhibits ________ and requires a dose reduction when used with lido

CYP3A4

lidocaine DDIs: lidocaine is a substrate of CYP3A4 (i.e. uses that for its metabolism)

amiodarone inhibits CYP2C9 and 3A4 and requires a dose _________ when used with lido

reduction

___________ DDIs: it is a substrate of CYP3A4 (i.e. uses that for its metabolism)

amiodarone inhibits CYP2C9 and 3A4 and requires a dose reduction when used with it

lidocaine

IV Opioids and Acute Coronary Syndrome

Morphine and Fentanyl can __________ gastric motility

reduce

IV Opioids and Acute Coronary Syndrome

administration of morphine or fentanyl may delay the absorption and impact the activity of ____________ drugs

antiplatelet (P2Y12 agents) (ex: Ticagrelor)

oral P2Y12 Antagonists PK

___________ and ___________ are prodrugs

Clopidogrel and Prasugrel (Ticagrelor is not a prodrug)

oral P2Y12 Antagonists PK

____________ is reversible (the other two are irreversible)

Ticagrelor

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something _______ potent)

more

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in acute/early phase (within _______ of intervention): 180mg LD irrespective of timing/dosing of Clopidogrel

30 days

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in acute/early phase (within 30 days of intervention): 180mg __________ dose (what type of dose) irrespective of timing/dosing of Clopidogrel

loading

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in acute/early phase (within 30 days of intervention): 180mg LD given at what time in relation to last dosing of Clopidogrel

irrespective (can give Ticagrelor at any time! dont have to wait)

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in late/very late phase (>30 days since intervention): 90mg maintenance dose given _________ (how often) given 24 hours after last Clopidogrel dose

BID

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in late/very late phase (>30 days since intervention): 90mg maintenance dose given BID given __________ after last Clopidogrel dose

24 hours (have to wait)

switching P2Y12 agents: Clopidogrel —> Ticagrelor (going to something more potent)

in late/very late phase (>30 days since intervention): 90mg ___________ (what type of dose) dose given BID given 24 hours after last Clopidogrel dose

maintenance

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something _______ potent)

more

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in acute/early phase (within _________ of intervention): 60mg LD irrespective of timing/dosing of Clopidogrel

30 days

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in acute/early phase (within 30 days of intervention): 60mg LD given at what time in relation to last dosing of Clopidogrel

irrespective (can give Prasugrel at any time! dont have to wait)

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in acute/early phase (within 30 days of intervention): 60mg __________ dose (what type of dose) irrespective of timing/dosing of Clopidogrel

loading

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in late/very late phase (>30 days since intervention): 10mg maintenance dose given _________ (how often) given 24 hours after last Clopidogrel dose

QD

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in late/very late phase (>30 days since intervention): 10mg __________ dose given QD given 24 hours after last Clopidogrel dose

maintenance

switching P2Y12 agents: Clopidogrel —> Prasugrel (going to something more potent)

in late/very late phase (>30 days since intervention): 10mg maintenance dose QD given __________ after last Clopidogrel dose

24 hours

switching P2Y12 agents: Ticagrelor or Prasugrel —> Clopidogrel (going to something _______ potent)

less

switching P2Y12: Ticagrelor or Prasugrel —> Clopidogrel (going to something less potent)

acute/early/late/very late phase (does not matter when intervention took place): 600mg ___________ dose (what type of dose)

loading

switching P2Y12: Ticagrelor or Prasugrel —> Clopidogrel (going to something less potent)

patients are given a loading dose when they are in which phase(s)

acute or late

switching P2Y12: Ticagrelor or Prasugrel —> Clopidogrel (going to something less potent)

acute/early/late/very late phase (does not matter when intervention took place): 600mg LD given when in relation to last Ticagrelor or Prasugrel

24 hours after

switching P2Y12: Ticagrelor or Prasugrel —> Clopidogrel (going to something less potent)

acute/early/late/very late phase (does not matter when intervention took place): 600mg LD given 24 hours after last Ticagrelor or Prasugrel dose

**consider _____mg maintenance dose in patients bleeding or at high risk of bleeding (i.e. in the very very late phase)**

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