Pharmacokinetics

Question 1

Define pharmacokinetics

Answer 1

Use math equations to describe what body does to drug in terms of absorption, distribution, metabolism and elimination

Question 2

Applications of pharmacokinetics

Answer 2

1. Therapeutic drug monitoring
   1.1 Guide/optimise drug dosing (dose and frequency of admin)
   1.2 Identify drug-drug interactions
   1.3 Troubleshoot failure to respond to therapy
2. Toxicology
   2.1 Estimate amount of drug/toxin in body
   2.2 Evaluate clearance of drug/toxin to direct decontamination efforts

Question 3

Factors affecting pharmacokinetics

Answer 3

Age
Gender
Body weight
Diet
Environment
Pregnancy
Genetics
Pathology - disease, infection, inflammation
Drug-drug /Food-drug interactions

Question 4

6 differences in body composition that affect

Answer 4

1. Total body water
2. Percent body fat
3. Muscle mass
4. Organ size
5. Blood volume and flow
6. Enzyme metabolism

Question 5

Polar drugs are _____ in water and are primarily distributed to __________ and eliminated by ____________

Answer 5

Polar drugs are soluble in water and are primarily distributed to the blood and eliminated by the kidneys.

Question 6

Non-polar drugs are soluble in _________ and are primarily distribute to ________________ and eliminated ____________

Answer 6

Non-polar drugs are soluble in lipids and are primarily distributed to the CNS, tissue and fat and are eliminated in faeces and bile.

Question 7

Drug distribution is dependent upon?

Answer 7

Blood perfusion. Takes minutes to distribute to plasma and well perfused organs (eg heart, liver, kidneys and brain), minutes to hours to distribute to muscle and skin and hours to days to distribute to fat stores

Question 8

Limitations of Volume of distribution

Answer 8

based on total body water
doesn’t estimate sites of actual distribution
individual differences in ptn binding or tissue binding
requires distribution to be complete

Question 9

Define bioavailability

Answer 9

Percentatge of drug from original drug formulation that enters systemic circulation unchanged

Question 10

Factors influencing bioavailability

Answer 10

Route of admin
Formulation - salt, crystal suspension, gel, capsule, SR
Stability in GI tract
Characteristics of drug for absoprtion and biotransformation
Pt patho/physiology - GI pH, motility, blood perfusion, GI flora, malabsorption states, kidney/liver/cardiac fn, genetics

Question 11

Why do IV drugs have 100% bioavailability?

Answer 11

Bypass first pass metabolism

Question 12

Which protein(s) do acidic drugs bind to?

Answer 12

Albumin

Question 13

Which protein(s) do basic drugs bind to?

Answer 13

Alpha1-acid glycoprotein and lipoproteins

Question 14

Name some factors affecting protein binding of drug

Answer 14

Competition with other protein binding drugs - drug that binds more tightly will displace the others
Hypoalbuminaemia - more free drug
Increased acute phase reactants - more protein bound drug
Hyperbilirubinaemia/increased fatty acids change protein binding
Renal disease changes negative charge on albumin

Question 15

Pharmacological activity is proportional to bound or unbound concentration in blood?

Answer 15

Unbound/free

Question 16

Effects of drug metabolism

Answer 16

1. Terminate pharmacologial activity
2. Activate prodrugs
3. Decrease bioavailability (1st pass)

Question 17

Difference between Phase I and Phase II metabolism reactions

Answer 17

Phase I - oxidation/reduction/hydrolysis by cytochrome P450 enzymes
Phase II - conjugation reactions
Both make drugs more soluble in preparation for elimination

Question 18

Most drug metabolism occurs in?

Answer 18

Hepatocytes

Question 19

Kinetic models of metabolism

Answer 19

First order - amount of drug eliminated is dependent on concentration of compound and follows a logarithmic relationship over time; clearance dn Vd does not change with dose or concentration
Zero order - rate of elimination NOT dependent on drug concentration eg ethanol, phenytoin, salicylates
Non-linear - “capacity limited”, rate of elimination shifts from first to zero order based on saturation of elimination mechanisms

Question 20

Define drug clearance

Answer 20

Elimination of drug from blood and body

Question 21

How is clearance expressed?

Answer 21

Concentration of drug/unit volume of blood/unit time

Question 22

Define elimination half-life

Answer 22

The amount of time it takes for the plasma drug concentration to be reduced by half

Question 23

Factors affecting drug elimination

Answer 23

Body weight
Body surface area
Cardiac output
Drug-drug interactions
Genetics
Liver and kidney function
Plasma protein binding

Question 24

In pharmacokinetics, what compartments comprise the two compartment model?

Answer 24

1. Blood and well perfused organs
2. Poorly perfused organs (eg muscle, fat)