ADME

Question 1

Why is the ADME of a drug important to know

Answer 1

Important to know if a drug is going to be absorbed if given by a particular route - insulin cannot be given orally as it won’t be absorbed

to estimate accurate plasma concentrations (Cp) of drug as a function of time - plasma drug
concentration is dynamic - it changes with time

To know where the drug goes once inside the body – how it distributes

Drug metabolism – are the metabolites safe?

Question 2

What are the different routes of drug administration?

Answer 2

Enteral = via GI tract - oral - easiest form of administration - compliance, the patient might forget to take or cannot take if unconscious of vomiting.

Parenteral = not via GI tract
Intravenous (I.V) - thiopentone
not absorption phase and rapid effect

Intramuscular (I.M) - fluphenazine

Subcutaneous - insulin
relatively easy for the patient to self administer compared with I.M. and I.V.

Question 3

Define the oral bioavailability (F) of a drug

Answer 3

The fraction of oral dose that reaches the systemic circulation

Question 4

How do you measure oral bioavailability (F) experimentally and the equation to calculate it

Answer 4

Compare the plasma concentration vs time curves of the drug being administered orally vs iv

F= area under curve for oral administration/ area under curve for iv.

Question 5

Which factors affect oral bioavailability of a drug.

Answer 5

Poor absorption from the gut
breaking down in gut
first pass effect- when andrug is heavily broken down on their first pass through the liver not reaching the main circulatory system

Question 6

Which factors affect drug absorption at membrane.

Answer 6

Lipid solubility of the drug
Drug preparation
Area of absorbing surface
Rate of blood flow to other side of absorbing surface
Presence of food in gut
Effect of other drugs taken by patient
pKa of the drug (pH at which it is 50% ionised)
pH at absorbing surface

Question 7

Define drug distribution

Answer 7

Penetration of drug into tissues and organs from the blood

Question 8

How is drug distribution measured

Answer 8

Apparent volume of distribution (Vd) is the volume of water in which a drug would have to be distributed in to give its plasma concentration

Vd = amount of drug in body / plasma conc

vd can be volume (litres) or volume/mass (1L/kg

Question 9

Examples of drugs with high and small Vd

Answer 9

Small Vd = insulin, warphin
high Vd =prozac, imipramine

Question 10

Why is drug distribution (Vd) important to measure

Answer 10

Important when calculating dosing schedules
partly determines the plasma half-life of a drug.

Question 11

How is a drug eliminated

Answer 11

The metabolism and excretion of drugs

Question 12

Define metabolism

Answer 12

the chemical changes of drug structure.

Question 13

Define drug excretion

Answer 13

The movement of a drug from the inside to the outside of the body.

Question 14

Name sites of metabolism for drugs

Answer 14

Liver, lungs, kidney plasma

Question 15

What are the features of a first order elimination graph

Answer 15

Constant half life, most common one

Question 16

What are the features of a zero order elimination graph.

Answer 16

Constant gradient, (straight Line), happens because the metabolic pathways have become fully saturated, and cannot eliminate any faster.

Question 17

What are the features of a pseudozero order elimination graph.

Answer 17

first half looks like a 0 order line because the metabolic pathways are fully saturated, the second half looks like first order, the metabolic pathways are no fully saturated.

Question 18

What is first order elimination described by.

Answer 18

The standard exponential equation.
Ct = Co e^-k/t

Ct = plasma conc at time
Co = plasma conc when t =0
k = rate constant of elimination
t = time

Question 19

Describe the influence of body compartment pH and drug ionisation on the absorption

Answer 19

Most drugs are either weakly ionising acids or bases. weak acids tend to be absorbed better in acidic conditions and weak bases in basic conditions.
This is due to the fact that ionised drugs do not cross membranes and the pH determines how the ratio of ionised to unionised.

Question 20

Describe the influence of body compartment pH and drug ionisation on the elimination

Answer 20

Urinary excretion: The pH of urine effects how much of a drug is excreted. If the drug is weak base then more of it will be excreted if the urine is more alkaline. (e.g. aluminium chloride)
the same with acidic drug and acidic urine using sodium bicarbonate.

Question 21

Describe how drugs cross membranes and are distributed from the blood to tissue. what the extent and rate of distribution are dependant on and

Answer 21

The drug distributes into the tissues from the blood reversibly.
The degree of distribution into the tissue depends on lipid solubility, plasma protein binding (within the blood).
The rate is dependant on the rate of blood flow to the tissue/organ

Question 22

What is clearance

Answer 22

A measure of how much of a drug is eliminated. It is equal to
Rate of Elim/Cp

Question 23

What drugs are eliminated with first order kinetics

Answer 23

Ethanol, aspirin, Phenytoin

Question 24

Describe what is happening at steady state.

Answer 24

The rate of elimination of the drug is equal to its rate of absorption.

Question 25

How is steady state achieved

Answer 25

A drug is administered to a patient using i.v infusion. the plasma concentration rises until it is equal to the rate of elimination.

the drug must be eliminated using first order kinetics

Question 26

How long does it take to reach steady state

Answer 26

Roughly 4-5 half lives regardless of the rate of infusion

the

Question 27

What are the 3 process that determine renal drug excretion

Answer 27

Glomerular filtration, active secretion, passive reabsorption.

Question 28

What types of metabolites can be formed

Answer 28

Active drugs can form inactive and active metabolites
benefits of active metabolites is that it stays in the body for longer.
Inactive drugs (prodrugs) can form active metabolites.
Active drugs can also form toxic metabolites.

Question 29

Why would a prodrug be used

Answer 29

If the drug cannot get the the site of active or to decrease toxicity.

Question 30

What is the product of phase 1 hepatic metabolism and how are they formed

Answer 30

A derivative which is more reactive than the drug formed by oxidation reduction or hydrolysis.

Question 31

What is the product of phase 2 hepatic metabolism

Answer 31

Conjugate - a combination of the derivative and a polar molecule to make the conjugate less lipid soluble to Make it easier to excrete from the liver.

Question 32

Where does Phase 1 hepatic metabolism occur

Answer 32

the endoplasmic reticulum of the cells in the liver.

Question 33

Why is an paracetamol overdoes toxic

Answer 33

Paracetamol is metabolised using only phase 2 hepatic metabolism. when this metabolic pathway is fully saturated it is metabolised using phase 1 hepatic metabolism producing toxic metabolites

Question 34

Explain enzyme induction

Answer 34

Some drugs and environmental pollutants induce increased expression of cytochrome P450 enzymes over a number of days/weeks. This can cause the failure of some drugs (and itself) to produce a significant therapeutic effect.

Question 35

Explain enzyme Inhibition

Answer 35

Some drugs directly inhibit cytochrome P450 enzymes. This can increase the likelihood of seeing adverse effects/toxicity in the patient.