Pharmacokinetics (DONE) Flashcards
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
What are concentration-time profiles determined by?
PK parameters e.g. dose, volume of distribution, elimination rate constant
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
How long does it take to reach Css?
Five half lives
What one parameter is Css dependent on?
Elimination half life
What are the indications for digoxin?
Controlling ventricular response in persistent or permanent atrial fibrillation and atrial flutter
Congestive heart failure
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
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
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
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
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
TDM for digoxin
Intra/inter-patient variability
Narrow therapeutic index
Side effects: GI, CNS, cardiac
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)
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
Phenytoin adverse effects
Narrow therapeutic index
CNS side effects related to plasma concentration
Mechanism of action
