14. pKa – pH value at which one half
of the drug is present in ionic
form
pKa = pH + log (HA)
(A-)
15. Drugs and ionisation
Theory
The more acidic the pH for an acidic
drug the more of it is unionised, and
vice versa for a basic drug
The Unionised fraction is lipid soluble
and thus crosses cell membranes
more easily than the Ionised fraction
16. Drugs and ionisation: Which of the
following statements are correct?
1. Ionised drugs do not easily cross lipid
barriers such as the gut, placenta and
blood brain
2. Acidic drugs are well absorbed in the
acidic medium of the stomach, basic
drugs in the alkaline medium of the
small bowel
17. Factors Affecting GI Absorption
Gastric Emptying Time
Intestinal Motility
Food
Formulation Factors
“First Pass Effect”
18. First Pass Metabolism
Bioavailability: the fraction of the administered
dose reaching the systemic circulation
Dose
Destroyed
in gut
Not
absorbed
Destroyed
by gut wall
Destroyed
by liver
to
systemic
circulation
20. Bioavailability
The liver (and gut wall) removes drugs
by ‘first pass’ metabolism and binding
so only a proportion reaches the
hepatic veins and the systemic
circulation
22. Factors Affecting Drug
Distribution
Affecting Rate of Distribution
Membrane Permeability
Blood Perfusion
Affecting extent of distribution
Extent of plasma protein binding
Regional differences in pH
Lipid solubility
Available transport mechanisms
Intracellular Binding
25. Metabolism
Active Drug Inactive metabolite
Active Drug Active or toxic
metabolite
Inactive Prodrug Active drug
Unexcretable drug Excretable
metabolite
26. Drug Metabolism
Side effects are results that are different
from the primary, or therapeutic, effect, for
which a drug is taken.
First-pass metabolism drug-metabolizing
enzymes in either the cells of the GI tract
or the liver can markedly reduce the
amount of drug that reaches the
bloodstream.
32. Organs Involved
Kidney – Glomerular Filtration,
active tubular secretion and
passive tubular reabsorption.
Lungs
Faeces
Bile
Skin, Saliva, Milk.
33. Half life is the time taken
for the concentration (in the
plasma) to fall by one half
Plasma Half-life (t½)
34. HALF LIFE AND PERCENT OF DRUG
REMOVED (wash out)
Number of Percent of Drug Percent of Drug
Half-lives Remaining Removed
0 100 0
1 50 50
2 25 75
3 12.5 87.5
4 6.25 93.75
5 3.125 96.875
35. Zero order
kinetics:
• a fixed
amount of the
drug is
metabolised
in unit time
(e.g. alcohol)
First order
kinetics:
• a fixed
fraction of the
drug is
metabolised
in unit time
Zero-Order and
First order Kinetics