Pharmacokinetics

Question 1

What is Pharmacokinetics

Answer 1

What the body does to the drug

Question 2

What does ADME stand for

Answer 2

Absorption - GI system and small intestine and systemic/hepatic circulation
Distribution - systemic circulation to tissues
Metabolism - in liver
Excretion - kidneys

Question 3

What factors can effect absorption?

Answer 3

• drug formulation
• particle size
• drug interactions
• pH of the drug
• gut content
• gut motility
• blood flow to stomach and small intenstines

Question 4

Describe FIRST PASS METABOLISM via oral route

Answer 4

• if a drug gets passed the barriers of A, there are inactivating enzymes in gut wall and liver.
• drugs are absorbed, then transported via portal circulation to the liver
• drug is metabolised by hepatic enzymes before it’s returned to systemic circulation for distribution.

Question 5

What is BIOTRANSFORMATION

Answer 5

The parent compound is metabolised, maybe or maybe not changing efficacy, before it’s returned to the bloodstream.

Question 6

What is BIOAVAILABILITY

Answer 6

The proportion of the drug or other substance which enters the circulation when introduce into the body and is able to have an effect (amount of drug that reaches systemic circulation)

Question 7

what is the bioavailability of IV medication and why?

Answer 7

100%, as it bypasses first pass metabolism and absorption, and goes straight into systemic circulation

Question 8

Factors affecting distribution (2 bodily factors, 4 drug factors)

Answer 8

• blood flow - organs like heart and kidneys will uptake drugs faster due to being very vascular
• slower build up in bone, fat, muscle and skin
• molecule size
• plasma protein binding
• lipid solubility and the blood brain barrier (BBB)
• storage sites where some drugs accumulate

Question 9

in circulation, a drug is either….

Answer 9

unbound (active)
protein bound (inactive)

Question 10

what is the protein called in plasma protein binding?

Answer 10

Albumin

Question 11

describe what happens to protein bound drugs in circulation

Answer 11

the complex becomes too large to leave the blood capillaries and enters the tissue fluid surrounding the body’s cells.

Question 12

What happens to an unbound protein in circulation

Answer 12

they leave the circulation normally, and more molecules are released from plasma proteins to re-establish the ratio

Question 13

what is the risk of protein bound drugs involving albumin?

Answer 13

some drugs compete to bind with Albumin, and displacement of one drug with another could have serious consequences

Question 14

What is the blood brain barrier (BBB)

Answer 14

in the CNS, and lacks ion channels and lipid cell membrane
- only lipid soluble drugs or transported drugs can pass the BBB

Question 15

What type of drugs will fatty tissues store?

Answer 15

lipid soluble drugs

Question 16

what types of drugs can accumulate in calcium-containing structures like bone?

Answer 16

drugs that are bound to calcium

Question 17

who are more likely to store lipid soluble drugs?

Answer 17

Obese people

Question 18

who are more likely to store fat soluble drugs?

Answer 18

elderly people as they have a greater fat:muscle ration

Question 19

Define VOLUME OF DISTRIBUTION (a.k.a apparent volume (V))

Answer 19

how much of the drug is left in the bloodstream after all of it has been absorbed and distributed

Question 20

Define ‘drug propensity’

Answer 20

the likelihood that the drug will remain in the plasma or redistribute to other tissue compartments

Question 21

How is V affected if the plasma concentration is high

Answer 21

if plasma concentration is HIGH, V is low

Question 22

How is V affected if the plasma concentration is low

Answer 22

if plasma concentration is low, V is high as the drug is leaving plasma and getting into tissues, thus maybe being stored.

Question 23

How is V affected if the distribution rate of a drug is high?

Answer 23

for highly distributed drugs, V is high

Question 24

Describe Metabolism

Answer 24

• occurs in the liver
• transforms drugs for excretion
• split into phase 1 and phase 2
• occurs via cytochrome P450 (CYP450) enzymes

Question 25

What are the 4 factors that effect metabolism?

Answer 25

• hepatic blood flow
• hepatic function
• CYP450 enzyme induction and inhibition
• biotransformation

Question 26

what is PRODRUG?

Answer 26

a compound with no pharmacological activity that metabolises into the body and converts into an active drug compound (e.g. clopidogrel or codeine)

Question 27

what are the 3 main steps of EXCRETION?

Answer 27

1- glomerular flirtation
2- tubular secretion
3 - passive reabsorption

Question 28

5 factors that effect EXCRETION

Answer 28

• renal blood flow
• renal function (increased in pregnancy, decreases in elderly)
• acute illness and dehydration
• LTC’s
• other drugs (some effect renal function)

Question 29

Define HALF LIFE

Answer 29

the time required for the concentration or amount of drug in the body to be reduced by half, a.k.a T 1/2

Question 30

how many half lives does it take for a drug to be fully excreted?

Answer 30

5 half lives

Question 31

what do you need to do if a drug has a narrow therapeutic range/window?

Answer 31

monitor levels (e.g. Warfarin = INR levels OR gentamicin = check GENT levels)

Question 32

what is a steady state in regards to drug levels in the body?

Answer 32

the ideal levels of drug in the body that doesn’t fall below or above therapeutic range

Question 33

what is below therapeutic range called?

Answer 33

sub-theraputic

Question 34

what is above therapeutic range called?

Answer 34

toxic

Question 35

what can be done if a patient needs to get to a ‘steady state’ quickly?

Answer 35

a loading dose of the drug can be given to avoid the timely climb it takes to normally reach a ‘steady state’.