Pharmacokinetics (DONE) Flashcards Preview

PH3110 > Pharmacokinetics (DONE) > Flashcards

Flashcards in Pharmacokinetics (DONE) Deck (16):
1

Why use therapeutic drug monitoring?

Narrow therapeutic window/index
Recognised inter-individual variability in PK
Toxic effect that is related to concentration and not easily identified or differentiated early by clinical signs

2

What are concentration-time profiles determined by?

PK parameters e.g. dose, volume of distribution, elimination rate constant

3

What can the elimination half life tell us?

It can inform us about how much drug remains in the body or how much drug has been eliminated

4

How long does it take to reach Css?

Five half lives

5

What one parameter is Css dependent on?

Elimination half life

6

What are the indications for digoxin?

Controlling ventricular response in persistent or permanent atrial fibrillation and atrial flutter
Congestive heart failure

7

Pharmacology of congestive heart failure

Inability of the heart to provide adequate blood flow to sustain normal tissue perfusion
Systolic dysfunction- myocardial muscle function loss
Activation of sympathetic nervous system and the renin-angiotensin-aldosterone system: vasoconstriction, increased heart rate, resistance to cardiac output, stress on heart due to continued heart stimulation, reduced blood flow to kidney

8

What is the drug treatment for CHF?

Loop diuretics- reduce congestion and fluid accumulation
ACE-I/ARB- reduce effects of angiotensin and aldosterone
Beta-blockers- reduce sympathetic tone
Digoxin- positive inotrope, declining use

9

What is digoxin's place in therapy of CHF?

Improves clinical status and improves heart failure symptoms
Withdrawal can cause re-emergence of symptoms
Provides no mortality benefit
May be added on to patients who continue to have symptoms despite optimal therapy

10

Pharmacology of atrial fibrillation and flutter- digoxin

Rate control, not rhythm control- increased vagal tone, parasympathetic activity
Block conduction through the AV node- decreases conduction velocity and prolongs the refractory period of the AV node, prolongs PR interval on ECG and slows ventricular response rate
Less effective than beta blocker or calcium channel blocker- especially during exercise

11

What is the pharmacological target of CHF?

Positive inotropic effect caused by binding to Na/K/ATPase
Decreased Na transport out of the myocardial cells, increased intracellular Na promotes increased intracellular Ca, increased intracellular Ca affords augmented action potential induced Ca release increasing force of contraction
Reduced sinoatrial firing rate and reduced conduction velocity through AV node- increased parasympathomimetic vagal efferent activity to the heart

12

TDM for digoxin

Intra/inter-patient variability
Narrow therapeutic index
Side effects: GI, CNS, cardiac

13

When to sample digoxin?

Plasma concentrations are only meaningful in terms of relating to myocardial effects when obtained after 4-6 hours following IV dose and after 6-8 hours following oral dose
(digoxin displays two compartment distribution)

14

Digoxin loading dose

Acute setting, particularly for atrial fibrillation where addition of digoxin is viewed as beneficial
Loading dose achieves therapeutic levels quickly rather than slow accumulation over 7 days +
Principle is loading dose based on knowledge of target concentration and V
In reality loading dose is administered in divided doses to evaluate any toxicity associated with the relatively high dose administration

15

Phenytoin adverse effects

Narrow therapeutic index
CNS side effects related to plasma concentration
Mechanism of action

16

Capacity limited metabolism

Metabolism reaches its maximum at therapeutic concentrations
Disproportionate changes in plasma concentration with dose i.e. small increases in dose can result in significant change in plasma concentration
Mix of first order linear and nonlinear PK