Dental Pharmacology -Pharmacokinetics

1. PHARMACOKINETICS

2. Pharmacokinetics
• Pharmacokinetics is derived from two words:
Pharmaco- meaning drug and -kinesis meaning
movement.
• In short, it is ‘what the body does to the drug’.
It includes absorption (A), distribution (D),
metabolism (M) and excretion (E) of a drug.

4. 1. Drug Absorption
• The movement of a drug from the site of
administration into the blood stream.
• Factors Influencing Drug Absorption :
1. Physicochemical properties of the drug:
a. Physical state:
– Liquid form of the drug is better absorbed than solid
formulations.
b. Lipid-soluble and unionized form of the drug:
– is better absorbed than the water-soluble and ionized
form.
c. Particle size:
– Drugs with smaller particle size are absorbed better
than larger ones.

5. Factors Influencing Drug Absorption
d. Disintegration time:
– It is the time taken for the formulation (tablet or
capsule) to break up into small particles
e. Dissolution time:
– It is the time taken for the particles to go into
solution. Shorter the time, better is the
absorption.
f. Formulations:
– Pharmacologically inert substances like lactose,
starch, calcium sulphate, gum, etc. are added to
formulations as binding agents.

6. Factors Influencing Drug Absorption
2. Route of drug
administration:
– Drugs like insulin are
administered parenterally
because they are degraded in
the GI tract on oral
administration.
3. pH and ionization:
– Strongly acidic (heparin) and
strongly basic (gentamycin)
drugs usually remain ionized
at all pH; hence they are
poorly absorbed.

7. Factors Influencing Drug Absorption
4. Food:
– Fatty meal increases the absorption of some drugs.
– some drugs should be taken on an empty stomach.
5. Presence of other drugs:
– Concurrent administration of two or more drugs may
affect their absorption,
– e.g. ascorbic acid increases the absorption of oral
iron. Antacids reduce the absorption of thyroxine.
6. Pharmacogenetic factors:
– In pernicious anaemia, vitamin B12 is not absorbed
from the gut due to lack of intrinsic factor.

8. Factors Influencing Drug Absorption
7. Area of the absorbing surface:
– Normally, drugs are better absorbed in the small
intestine because of a larger surface area.
– Resection of the gut decreases absorption of
drugs due to a reduced surface area.
8. Gastrointestinal diseases:
– In gastroenteritis, there is increased bowel
movement that reduces the drug absorption.

9. Bioavailability
• It is the fraction of a drug that reaches the
systemic circulation from a given dose.
• Intravenous route of drug administration gives
100% bioavailability, as it directly enters the
circulation.
• The term bioavailability is used commonly for
drugs given by oral route.
• If two formulations of the same drug produce
equal bioavailability, they are said to be
bioequivalent.

10. Factors Affecting Bioavailability
• Factors that affect drug absorption also affect
bioavailability of a drug. With other factors:
1. First-pass metabolism:
– The net result is a decreased
bioavailability of the drug
and diminished therapeutic
response.
– certain drugs get
metabolized and are
removed or inactivated
before they reach the
systemic circulation.

11. Factors Aff ecting Bioavailability
• 2. Hepatic diseases:
– They result in a decrease in drug metabolism; thus
increasing the bioavailability of drugs that
undergo first-pass metabolism, e.g. lignocaine.

12. 2. Drug Distribution
• Distribution is defined as the reversible transfer
of drugs between body fluid compartments.
• Drug Reservoirs or Tissue Storage
– Some drugs are concentrated or accumulated in
tissues or some organs of the body, which can lead to
toxicity on chronic use. For example, tetracyclines—
bones and teeth.
• Blood–Brain Barrier
– The capillary boundary that is present between the
blood and brain.
– Only the lipid-soluble and unionized form of drugs can
pass through BBB and reach the brain, e.g. diazepam.
• Placental Barrier
– The lipid membrane between mother and fetus

13. Plasma Protein Binding
• Many drugs bind to plasma proteins like
albumin, α1 – glycoprotein.

14. Plasma Protein Binding
• Plasma protein binding delays the metabolism
of drugs.
• Bound form is not filtered by kidney; so,
excretion of highly plasma protein- bound
drugs is delayed.
Highly protein-bound drugs have a longer
duration of action
Low plasma protein. there will be an increase
in the free form of the drug, which can lead
to drug toxicity.

15. 3. Drug Metabolism
• The metabolism of a drug usually converts the
lipid-soluble and unionized compounds into
water-soluble and ionized compounds to be
excreted.
• Sites: Liver is the main site for drug metabolism;
other sites are GI tract, kidney, lungs, blood, skin
and placenta.
1. Active drug to inactive metabolite:
Phenytoin p-Hydroxyphenytoin
2. Active drug to active metabolite:
Diazepam Oxazepam
3. Inactive drug to active metabolite:
Levodopa Dopamine

16. Prodrug
• It is an inactive form of a drug that is
converted to an active form after metabolism.
Uses of prodrug (advantages):
1. To improve the bioavailability.
2. To prolong the duration of action.
3. To improve the taste.
4. For site-specifi c drug delivery

18. 4. Drug Excretion
• Removal of the drug and its metabolite from
the body.
• The main channel of excretion of drugs is the
kidney; others include lungs, bile, faeces,
sweat, saliva, tears, milk