Routes of Administration: Pharmacokinetics

Question 1

Define Pharmacokinetics

Answer 1

Movement of drugs around the body
Pharmakon = medicine/drug
Kinetikos = “of motion”

Question 2

ADME acronym

Answer 2

A - absorption
D - Distribution

M - Metabolism
E - Excretion

Question 3

A - absorption

Answer 3

Movement of a drug from the site of administration to the bloodstream

Question 4

D - Distribution

Answer 4

Movement of drug around different tissues in the body

Question 5

M - Metabolism

Answer 5

Change of drugs into compounds which are easier to eliminate

Question 6

E - Excretion

Answer 6

Irreversible loss of (unchanged) drug from the body

Blood is not being metobilised

Question 7

Metabolism + Excretion =

Answer 7

“Elimination”

Question 8

Metabolism + Excretion =

Answer 8

“Elimination”

Question 8

Metabolism + Excretion =

Answer 8

“Elimination”

Question 9

Is blood considered a tissue?

Answer 9

Yes, as it is a collection of cells

Question 10

ADME – schematic representation (Aulton’s book)

Answer 10

• IV injection
• Drug at site of administration = absorption
• drug e.g. unbound drug = distribution
• Elimination > unchanged drug excreted +
  metabolises excreted

Question 11

Unbound drug / bound drug:

Answer 11

Unbound drug are the ones that can cause pharmacokinetics because the drug is unbound to proteins

Question 12

Drug can be either _____ or _____

Answer 12

bound or unbound

at equilibrium = degree of where it lies depends of types of drug

One drug can distribute the other one

Question 13

Unbound drug - distribution to =

Answer 13

1) drug at site of action
2) Tissues and fluids of distribution

Question 14

Drug plasma concentrations
(See curve on graph - slide 7)

Answer 14

• Step increase (onset) and reach
• Peak concentration
• Then descend to minimum effective concentration

Question 15

Therapeutic range:

Answer 15

This range is the target window for the drugs to be effective

Question 16

What happens if the concentration exceeds a high point?

Answer 16

May be side-effects

Question 17

Define Bioavailability;

Answer 17

The proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect

Question 18

IV administration (100% biolavailibility)

Answer 18

IV administration means the entire dose reaches the systemic circulation

Bioavailability will be lower via other routes

Question 19

Bioavailability can depend upon….

Answer 19

Permeability of the biological membrane, drug properties,and other route-dependent factors, e.g. stomach contents for oral route

Question 20

Fraction of Bioavailability =

Answer 20

F = fraction of administered dose of drug which
reaches system circulation (intact)

Question 21

First-pass (presystematic) metabolismWhere are drugs absorbed?

Answer 21

Drugs absorbed from the stomach, small
intestines and upper colon pass into the hepatic portal system —> liver

Some drugs are metabolised extensively through their “first-pass” through the liver

Question 22

What contributes to bioavailability?

Answer 22

Presynaptic metabolism is one factor

Question 23

Naloxone:

Answer 23

Used to combat opiate overdose

Rapid onset required

Undergoes first pass metabolism

Question 24

Stomach > liver

Answer 24

oral availability
0.9% to 2%

Question 25

Metabolism

Answer 25

the chemical processes that occur within a living organism in order to maintain life

The body has a number of processes for metabolising drugs

Metabolism can be affected (induced or inhibited) by other drugs

Question 26

Where does metabolism predominantly take place?

Answer 26

The liver but can happen in e.g. skin, plasma, kidney

Question 27

Metabolism - 2 phases:

Answer 27

Phase I - Simple changes
Phase II - Conjugation

Question 28

Phase I - Metabolism

Answer 28

Simple chemical changes, e.g. oxidation, reduction, hydrolysis

Cytochrome P450 isoenzyme particularly important

Products are likely to be inactive and more water-soluble

Question 29

Phase II - Metabolism

Answer 29

Involves the conjugation (or addition) of groups to the drug to increase its solubility

Conjugates include glucuronates and sulphates

Question 30

Oral administration

Answer 30

The most common route of drug administration

Solid (tablets, capsules) or liquid (suspensions, solutions) dosage forms

Dosage form travels to the main sites ofabsorption – stomach and small intestines

Drug must cross lipophilic barriers to be absorbed

Amount of drug which enters the systemic circulation depends upon the bioavailability

Question 31

Oral route is often confused with -

Answer 31

BUCCAL and SUBLINGUAL route
do not mix up!!!

Question 32

Parenteral route
(injection)

Answer 32

Parenteral formulations include:

Injections (intravenous, intramuscular, subcutaneous…)
Infusions

Sterile dosage forms

Question 33

Advantages of Partental dosage forms:

Answer 33

Useful if drug labile in GI tract

Fast-acting

Prolonged effect possible with IM

Localised effect, e.g. intra-articular

Drugs can be administered to unconscious patients

100% bioavailability for IV

Question 34

Case Study – Diazemuls®

Answer 34

> Diazepam is a lipophilic drug, i.e. it could be described “oil-loving”

> Earlier IV diazepam formulations used solvents such as propylene glycol and ethanol to aid the dissolution of the drug

> These solvents led to pain on injection
An alternative approach was to use an oily vehicle or an emulsion

> Diazemuls® consists of an oil-in-water emulsion which provides an “oily phase” in which the drug dissolves

> Plasma concentration-time curve enables us to confirm that the emulsion formulation is equivalent

Question 35

Inhalation route - where?

Answer 35

Drug is delivered directly to the lungs typically via an inhaler or a nebuliser

Question 36

What is inhalation route usually used for?

Answer 36

Typically used for a local effect, e.g. in asthma treatment but can also be used for systemic delivery

Question 37

Pharmacokinetic advantages of the inhalation route:

Answer 37

Smaller doses can be used (salbutamol oral dose = 4 mg; inhaled dose 0.2 mg)

Reduces the chance of unwanted systemic (side) effects

Fast onset because drug delivered to the site of action

Avoids first pass metabolism

Question 38

Transdermal route

Answer 38

Involves the application of a drug to the skin surface with the intention of achieving a systemic effect

Question 39

Pharmacokinetic advantages of the transdermal route:

Answer 39

Avoids first pass metabolism

Controlled rate of drug delivery (avoids the peaks and troughs found with oral delivery)

Reduces dosage frequency which can increase compliance

Question 40

Transdermal routes –»> pharmacokinetics

Answer 40

After delivery = repeated oral delivery so the therapeutic range is met (drug effective)

Question 41

Rectal route:

Answer 41

Avoids first pass metabolism
Controlled rate of drug delivery (avoids the peaks and troughs found with oral delivery)
Reduces dosage frequency which can increase compliance

[Issues with pharmacokinetics ad cultural acceptability]

Question 42

Advantages of rectal route for systemic delivery:

Answer 42

• Suitable if patient cannot easily swallow a solid oral dosage form, e.g. unconscious, child
• Drug not suited for oral delivery

Question 43

Suppository meaning?

Answer 43

a solid medical preparation in a roughly conical or cylindrical shape, designed to be inserted into the rectum or vagina to dissolve

Question 44

Why is drug incorporated into a soppusitory?

Answer 44

So it dissolves or melts within the rectum

Question 45

Foam formulations will ______ to fill the rectum (also available)

Answer 45

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