2. Pharmacokinetics Flashcards

1
Q

Where does drug metabolism usually occur?

A

liver

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2
Q

What is the aim of drug metabolism? Describe in general the processes involved.

A

Enhances drug elimination.

Phase 1 - usually inactivates drug

  • oxidation, reduction or hydrolysis to create/expose polar groups on drug
  • cytochrome P450 (CYP) enzymes

Phase 2 - make it soluble

  • drug conjugation with eg. glycine, glutatione, glucuronide
  • conjugating enzymes
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3
Q

Suggest possible factors affecting CYP enzyme activity.

A
  1. genetics
  2. age
  3. gender
  4. enzyme inducing/inhibiting drugs
  5. smoking or alcohol consuption
  6. liver disease
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4
Q

Name examples of CYP inducers.

A

Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin

Griseofulvin
Phenobarbitone
Sulphonylureas

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5
Q

Name examples of CYP inhibitors.

A

Sodium valproate
Isoniazid
Cimetidine
Ketoconazole

Fluconazole
Alcohol (acute)
Chloramphenicol
Erythromycin
Sulphonamides

Ciprofloxacin
Omeprazole
Metronidazole

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6
Q

What is the main route of drug elimination?

A

Kidney

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7
Q

Describe the 3 processes involved in drug elimination via the kidney.

A
  1. Glomerular filtration
    - only unbound (free) drugs
    - proportional to GFR
  2. Active secretion - PCT
    - via OATs and OCTs
  3. Passive reabsorption - DCT and CDs
    - water is reabsorbed along length of tubule, increasing drug conc. If lipophilic, is reabsorbed down conc. gradient.
    - decreases rate of effective elimination
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8
Q

What is the main determinant of drug clearance rate?

A

GFR

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9
Q

Explain the difference between 1st order and 0 order kinetics.

A

1st order:

  • rate of elimination is proportional to drug level, with constant fraction of drug eliminated in unit time
  • T1/2 can be defined
  • most drugs

0 order:

  • rate of elimination is constant, independent of drug conc.
  • some drugs (eg alcohol, phenytoin, aspirin, warfarin) and many drugs when at very high concs. as Rs/enzymes become saturated
  • more likely to result in toxicity
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10
Q

How many t1/2 are required for a steady state to be reached during repeated drug administration?

A

3-5 t1/2

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11
Q

Why is a loading dose required when prescribing digoxin?

A

Large apparent Volume of Distribution (>200L) and thus long t1/2 (40hrs).

So need loading dose to achieve rapid therapeutic effect.

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12
Q

Do loading dose and maintenance doses need to be reduced in renal failure?

A
  • Loading dose can remain the same (unless renal failure is very severe).
  • Maintenance doses need reducing if renal failure leads to reduced clearance.
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13
Q

How is loading dose calculated?

A

Loading dose = Vd x [drug]target

= Vd x drug Cpss

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