Pharmacokinetics Flashcards
Where does the majority of drug metabolism occur?
Liver
Where does drug excretion occur?
Kidneys
What is the pharmaceutical process and what does it depend on?
If the drug is getting into the patient
Depends on: formulation and compliance
Rate of action depends on …
Dissolution
What is topical administration?
Giving the drug directly to the target (eg. Inhaled steroids for asthma)
What are the advantages of topical administration?
Less systemic absorption
Less off-target (side) effects
Define oral bioavailability
The proportion of drug given orally (or any route except IV) that reaches circulation unchanged
What is the formula for bioavailability?
(AUC oral / AUC injected) x100
AUC = area under curve where x=time, y=plasma conc of drug
What is the formula for therapeutic ratio?
LD50 / ED50
Maximum tolerated dose / minimum effective dose
Does warfarin have a narrow or wide therapeutic window, and what does this mean?
Narrow
Easy to produce unwanted effects
Define toxic concentration
The concentration that starts to produce unwanted, adverse effects
Which drugs are less likely to reach toxic conc, fast or slow release?
Slow release
With fast release drugs the conc rises very rapidly
Describe first pass metabolism
Drugs administered orally are exposed to the liver first and may be extensively metabolised. This means much less drug is received by the systemic circulation.
Name alternative routes that avoid first pass metabolism
Parenteral (IV, IM, SC)
Rectal
Sublingual
Define volume of drug distribution
The theoretical value into which drug is distributed if this occurred instantaneously
How do we obtain the value for volume of distribution?
Extrapolation of the plasma drug concentrations on a graph back to time zero
Protein binding interactions are important when the object drug:
Is highly bound to albumin
Has a small volume of distribution
Has a low therapeutic ratio
What is another name for the object drug?
Class I drug
What is another name for the precipitant drug?
Class II drug
Describe a class I drug alone
Dose lower than number of albumin binding sites
Most drug molecules bound to albumin
Free drug concentration low
Little effect
Describe a class II drug alone
Doses greater than the number of binding sites
Most albumin sites contain a drug molecule but the free drug concentration is still significant
More effective alone than class I is alone
Describe class I and class II drugs together
Displacement of class I from binding sites Free concentration of class I drug increased Class I drug effect increased than if it were alone
Define 1st order kinetics
The rate of elimination is proportional to drug concentration in the body
Define zero order kinetics
Rate of elimination is constant, no matter the drug concentration in the body
How do you spot 1st order kinetics on a graph?
x = time
y = plasma conc (linear or log)
Linear scale - graph is curved
Log scale - graph is straight line
How do you spot zero order kinetics on a graph?
x = time
y = plasma conc in linear scale
Graph will be a straight line
At lose doses, drug concentration has ……kinetics
1st order
At high doses, drug metabolism has ……. kinetics
Zero order
As maximum rate of elimination is reached
On repeated drug administration, how long does it take to reach a steady state?
5 half lives
Define bolus
The administration of a distinct amount of drug in order to raise its concentration in blood to an effective level
Which kinetics have a more predictable therapeutic response and why?
1st order kinetics
(Double dose = double action)
The therapeutic response of zero order kinetics can suddenly escalate as elimination mechanisms saturate
What occurs during phase I of drug metabolism?
Oxidation, reduction and/or hydrolysis
Drug usually inactivated
What occurs during phase II of drug metabolism?
Conjugation products formed
Conjugated to make them more soluble
Drugs usually completed inactivated by the end of this phase
What type of enzymes work at phase II?
Mixed function oxidases
Name 3 properties of mixed function oxidases
Affinity for lipid soluble drugs
Low substrate specificity
Inducible and inhibitable
Drug interactions matter most clinically when:
Drug has a low therapeutic ratio
Drug is being send at the minimum effective concentration
Drug metabolism follows zero order kinetics
What are the effects of drug metabolism enzyme inducers and give an example?
Increase rate of drug metabolism
Drug is less effective
Rifampicin is an enzyme inducer of the oral contraceptive pill
What are the effects of drug metabolism enzyme inhibitors and give an example?
Inhibits drug metabolism
Drug concentration can be excessive, may be toxic
Cimetidine is an enzyme inhibitor of warfarin
If the drug is a weak acid, what conditions will increase and decrease reabsorption in the kidneys?
Acid urine = increases reabsorption of drug (drug is less likely to dissociate into its ions)
Alkali urine = decreases reabsorption
If the drug is a weak base, what conditions increase and decrease reabsorption of the drug in the kidneys?
Acid urine = decreases reabsorption
Alkali urine = increases reabsorption
How do we speed up aspirin elimination if someone has an overdose?
Aspirin is a weak acid therefore we must infuse the patient with bicarbonate (alkali) to speed up elimination
What are the pH ranges for acidic and alkali urine?
Acid - pH
Describe the effects of renal disease on drug excretion
Drugs will have a longer half life due to less excretion from kidneys
Patient needs a lower maintenance dose of drug
Takes a longer time to reach the steady state
