Time Course of Delayed Drug Effects Flashcards

1
Q

What are the three possibilities for a drug time course?

A
  1. Immediate (drug effects are immediately related to drug concentration)
  2. Delayed (drug effects are delayed related to drug concentration)
  3. Cumulative (drug effects determined by the cumulative action of the drug)
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2
Q

What are the mechanisms that can explain delayed drug effects?

A

Distribution to the receptor site (pharmaco-kinetics)
Binding to and unbinding from receptors (receptor-kinetics)
Turnover of a physiological mediator of effect (physio-kinetics)

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3
Q

Explain why distribution to effect site could cause a delay in drug response

A

It takes time for the drug to perfuse from the blood to a target tissue. This is driven by the central blood volume. (thiopentone in brain)

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4
Q

What is an effect compartment in determining the time course of distribution?

A

Effect compartment is used to deduce the time course of drug concentration at the site of action. The time needed to reach steady state when receiving constant input is determined by the elimination half life of the plasma compartment

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5
Q

What is equilibration half life?

A

The effect compartment half life. Determined by the volume of the effect compartment and the clearance of the effect compartment. Eg. Thiopentone has rapid clearance so has an equilibration half life of 1 min

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6
Q

How can binding to a receptor cause a drug delay?

A

Some drugs (usually potent ones eg. digoxin) dissociate slowly from their receptors which causes a delay

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7
Q

Why does digoxin effect compartment reach its peak before the average tissue concentration?

A

The heart as rapid perfusion compared with other tissues

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8
Q

Why is the half life of digoxin slow despite rapid perfusion?

A

Slow unbinding from Na/K ATPase caused delayed onset of effects

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9
Q

What are the actions of warfarin?

A

Action: inhibition of Vitamin K recycling (VitK reductase)
Rapid effect: decreased synthesis of clotting factors
Delayed response: prolongation of coagulation time

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10
Q

What is INR?

A

International normalised ratio -time measure

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11
Q

How is the time to reach steady state INR with different warfarin doses different?

A

It is unchanged by the C50 because the only determinant is the half life of clotting factors

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12
Q

How long does it take warfarin to reach steady state?

A

2-3 days as half life of prothrombin complex is 14 hours

C50 for synthesis is 1.5 mg/L

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13
Q

What are the two types of drugs used in heart failure?

A

Dixogin, ACE inhibitors and beta blockers: used to improve survival
Diuretics (Frusemide): provide relief from symptoms

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14
Q

What is the relationship of Frusemide intake and sodium loss?

A

Sigmoidal curve with an Emax of 180mmhol/h C50=1.5 mg/L Hill coefficient of 3

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15
Q

How does Frusemide intake compare with loss with a large dose (120 mg)?

A

The loss of effect is quicker than the plasma concentration of Frusemide disappears due to steep concentration effect relationship

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16
Q

How does dose relate to effect in 40 mg vs 120 mg Frusemide?

A

40 mg always has 1/3 of the concentration of the 120 mg dose, but the maximum effect of 40 mg is almost equal to the 120 mg

17
Q

What is AUCe?

A

The area under time versus sodium excretion curve (cumulative sodium excretion)

18
Q

What is schedule dependence?

A

Total loss of sodium and its effect on heart failure depends not just on the total dose but also the dosing schedule. Eg 3 x 40mg dose of Frusemide causes greater sodium excretion than 1 x 120mg dose

19
Q

Which drugs do not show schedule dependence?

A

Irreversible anti cancer agents:
Action: irreversible binding to cell structure
Delayed effect: block of cell division
Cumulative: slowing of tumour growth

20
Q

What is dose individualisation in busulfan?

A

Measuring concentration after first dose in necessary to adjust subsequent doses as response is due to cumulative exposure