principles of pharmokinetics

Question 1

define pharmokinetics

Answer 1

the action of drugs in the body (absorption, distribution, metabolism, excretion)

Question 2

define absorption

Answer 2

the process of transfer from the site of administration into the general or systemic circulation

Question 3

what are the routes of administration

Answer 3

Oral
Intravenous
Intra-arterial
Intramuscular
Subcutaneous
Inhalational
Tropical
Sublingual
Rectal
Intrathecal
Most drugs (except IV/IA) must cross at least one membrane from site of generation to general circulation.

Question 4

what are the methods of passage across membranes?

Answer 4

Passive diffusion through the lipid layer
Diffusion through pores or ion channels
Carrier mediated processes
Pinocytosis

Question 5

what is ionization

Answer 5

Ionization is a basic property of most drugs that are either weak acids or weak base

Question 6

why are ionisable groups important?

Answer 6

Ionizable groups are essential for the mechanism of action of most drugs as ionic forces are part of the ligand receptor interaction

Question 7

is ionised more water or lipid soluble

Answer 7

most water sol

Question 8

is un-ionised more water or lipid soluble

Answer 8

lipid

Question 9

what are the obstacles the drug needed to overcome before it reaches the systemic circulation?

Answer 9

drug structure
drug formation
gastric emptying
first pass metabolism

Question 10

how is the drug structure an obstacle before it reaches the systemic circulation?

Answer 10

Drugs need to be lipid soluble to be absorbed from gut
Some drugs unstable at low pH or in presence of digestive enzymes so have to be given by alternative route

Question 11

how is the drug formation an obstacle before it reaches the systemic circulation?

Answer 11

The capsule/ tablet must disintegrate and dissolve to be absorbed
Some formulated to dissolve slowly or have a coating that is resistant to the acidity of the stomach

Question 12

how is gastric emptying an obstacle before it reaches the systemic circulation?

Answer 12

Rate of gastric emptying determines how soon a drug taken orally is delivered to small intestine
Can be slowed (food/drugs) or speeded up (gastric surgery)

Question 13

how is first pass metabolism an obstacle before it reaches the systemic circulation?

Answer 13

Drugs taken orally have to pass 4 major metabolic barriers to reach circulation;
Intestinal lumen
Intestinal wall
Liver
Lungs

Question 14

describe Intradermal and subcutaneous absorption

Answer 14

Avoids barrier of stratum corneum
Mainly limited by blood flow
Small volume can be given

Question 15

when is intradermal and subcutaneous absorption used

Answer 15

Use for local effect or to deliberately limit rate of absorption

Question 16

describe Intramuscular absorption

Answer 16

Depends on blood flow and water solubility
Increase in either enhances removal of drug from injection site
Can make a depot injection by incorporating drug into lipophilic formulation which releases drug over days or weeks

Question 17

describe inhalation absorption

Answer 17

large SA and blood flow but limited by risks of toxicity to alveoli and delivery of non-volatile drugs
Largely restricted to volatiles such as general anesthetics and locally acting drugs such as bronchodilators in asthma
Asthma drugs non-volatile so given as aerosol or dry powder

Question 18

describe protein binding- is it reversible?

Answer 18

Many drugs can bind to plasma or tissue proteins
This may be reversible or irreversible

Question 19

what Is the most common reversible protein binding?

Answer 19

with the plasma protein albumin

Question 20

what does binding with the plasma protein ablumin do?

Answer 20

Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination

Question 21

what happens if a drug bind irreversibly?

Answer 21

Some drugs bind irreversibly and cannot re-enter the circulation and is equivalent to elimination

Question 22

describe drug distribution

Answer 22

Lipid soluble drugs easily pass from blood to brain
The brain does little metabolizing and drugs are removed by diffusion into plasma, active transport in the choroid plexus or elimination in the CSF
Lipid soluble drugs readily cross placenta
Large molecules do not cross placenta

Question 23

describe foetal liver drug distribution

Answer 23

Foetal liver has low levels of drug metabolizing enzymes, so relies on maternal elimination

Question 24

what is elimination

Answer 24

The removal of a drugs activity from the body

Question 25

what does elimination involve

Answer 25

May involve metabolism – the transformation of the drug molecule into a different molecule
Or excretion – the molecule is expelled in liquid, solid or gaseous waste

Question 26

what is metabolism necessary for

Answer 26

for the elimination of lipid soluble drugs

Question 27

what are the lipid soluble drugs converted to by the metabolism?

Answer 27

They are converted to water soluble products that are readily removed in the urine (if they remained lipid soluble they would be reabsorbed)

Question 28

what does metabolism produce as a result ?

Answer 28

Metabolism produces one or more new compounds which may show differences from the patent drug

Question 29

describe phase 1 of drug metabolism

Answer 29

Phase 1 – these reactions involve the transformation of the drug to a more polar metabolite
done by unmasking or adding a functional group
oxidations are the commonest reactions catalyzed by CP450

Question 30

describe phase 2 of drug metabolism

Answer 30

Phase 2 – involves the formation of a covalent bond between the drug or its phase 1 metabolite and an endogenous substrate
Resulting products are usually less active and readily excreted by the kidneys

Question 31

what are drugs and metabolites excreted in?

Answer 31

Fluids – important for low molecular weight polar compounds (urine, bile, sweat, tears, breast milk)
Urine excretion: Total excretion = glomerular filtration + tubular secretion – reabsorption
Solids – faecal elimination
Gases – expired air important for volatiles