3. Pharmacokinetics
• Is what the body does to the drug ?......
• The magnistude of the pharmacological action of the drug
depends on its concentration at the site of action.
•Pharmacokinetics:
1. Absorption
2. Distribution
3. Metabolism
4. Elimination OR Excretion
5. Factors affecting drug absorption from site of administration:
Drug factors
• Physical and chemical ccc of the
drug
• Pharmaceuticasl preparation.
• Form of the drug
• Rate of dissolution affecting
absorption
Patient factors
• Route of drug administration: oral
sometimes associated with lower
bioavailability than parentral)
• Area of absorbing surface(Large area
is associated with rapid absorption)
• Vascularity of absorbing surface
• General circulation( lower
absorption in shock)
• State of health of absorbing surface
6. Factors affectiong oral absorption
1. GIT Motility:
2. Gastric acidity
3. Drug food and drug drug interaction
4. Health state of GIT mucosal layer
5. 1st pass metabolism(effect)
7. First-pass Effect
➢ The hepatic metabolism of a pharmacological agent when it
is absorbed from the GIT and delivered to the liver via the
portal circulation.
➢ The greater the first-pass effect, the less the agent will reach
the systemic circulation when the agent is administered
orally
➢ How to avoid it?!!! *** Use parentral route
11. Distribution
• Transport of drug from site of administration to all
body through circulation.
• Factors affecting drug distribution:
1. Same factors affecting absorption
2. Binding of drug to plasma proteins
12. • Def: The process of chemical alteration of the drug.TO
• Site: Mainly liver ,other sites include kidney, lung, GIT.
• Aim: Mainly, convert lipid soluble(hydrophobic or lipophilic ) drugs into more
polar(“hydrophilic) to be easily excreted.
• Other Effect of enzymes on drugs:
1. Conversion of active drug into inactive metabolite: the most common.
2. Conversion of active drug into active metabolite: Codeine to Morphine.
3. Conversion of inactive drug into active metabolites: L-Dopa to dopamine.
4. Conversion of non-toxic drug into toxic metabolites: Acetaminophen
Metabolism (Biotransformation)
13. Metabolism (Biotransformation)
• Oxidation, reduction or
hydroxylation reactions.
Phase Ι
•Conjugation with certain
groups to be easily
transported and then excreted
Phase ΙΙ
14. Plasma Half Life(t1/2)
• Def: It’s the time taken for elimination of 50% of the plasma
concentration of a drug to fall half of its original value.
• Clinical significance:
1. Determine frequency of drug administration/day(shorter t1/2 →
higher frequency and vice versa.
2. Determine time needed for the drug to be removed from the
body.
3. Determine the time required to reach steady state of plasma
concentration.
16. Drug excretion
1. Kidneys: the most important route of drug excretion
Renal elimination occurs through:Glomerular filtration and
Tubular secretion.
2. Alimentary tract:
• Saliva: iodides.
• Bile : Some conjugated drugs are excreted through bile to
intenstine.
3. Lungs: Gases and volatile liquid drugs as CO2and halothane
4. Skin: through Sweat as rifampin
19. Pharmacodynamics
Drugs can produce their effects through one of the
following mechanisms:
1. Physical
2. Chemical
3. Action on enzymes
4. Action on receptors
20. Mechanism of drug action….
1. Physical:
➢Drugs acting through its osmotic pressure: diuretic effect of mannitol
➢Drugs acting through its adsorbing character: pectin and kaolin in
diarrhea activated charcoal in drug and food poisoning.
2. Chemical:
Neutralization as antacids
HCL + NaHCO3 → NaCL + H2O + CO2
21. Mechanism of drug action….
3. Acting on enzymes:
Mostly enzyme inhibition as
➢Allopurinol inhibits Xanthine oxidase enzyme
➢Acetylsalicylic acid inhibits Cyclooxygenase enzyme
4.Acting on receptors:
• On binding to receptors-→physiological function
• Agonist: + receptor
• Antagonist: - receptor
22. Mechanism of drug action….
•Types of receptors:
1. G-protein linked receptors
2. Ion-Channel receptors
3. Kinase linked receptors. E.g. Tyrosine kinase
4. Receptors linked to gene transcription
5. Receptors linked to enzymes ans phospholipase A and C
• Second Messenger:
1.CAMP
2. C GMP
3. DAG
4.IP3
5. Calcium
23. Drug Antagonism
1. Chemical: 2 drugs, on binding together-→ form inactive
compound
e.g. Protamine sulphate + heparin
2. Physiological: 2 diffirent drugs acting on 2 diffirant receptors
producing opposite effects
e.g. Histamine and adrenaline on blood pressure
3. Pharmacological: antagonist prevents agonist from interacting
with its receptor.
A. Competitive: Antagonist competes with the agonist in reversible
manner for the same receptor.
e.g. Atropine on muscarinic receptors
B. Non-Competitive: Antagonist binds irreversible to receptor
inhibiting response to the agonist.
24. Side effects and Toxicity
• Exagerated pharmacological response
• Effects associated with full therapeutic dose
• 2ry effects
• Teratogenicity
• Organ toxicity on long run use
• Drug dependence
Predictable
• Idiosyncrasy: genetic aberration
• Hypersensitivity: allergic and immune mediated
• Iatrogenic effects (disease like effects) systemic lupus
with phenytoin and procainamide
• Carcinogenicity and mutagenicity
• Teratogenicity
Unpredictable
25. Predictable side effects
•Exagerated pharmacological response: mostly due to
✓Excess dose: hypoglycemia with hypoglymic drugs or hypotension
with antihypertensive drugs
✓Intolerance( to the therapeutic dose): sedation with antihistamincs
✓Drug interaction: Barbiturates+alcohol-→ more sedation
•Effects associated with full therapeutic dose
e.g. Orthstatic hypotension with antihypertensive drugs
26. Predictable side effects
• 2ry effects:other unintended actions of the drugs that can’t be omitted with intended use:
e.g. Na&water retention,osteoporosis &low immunity by corticosteroids
Folic acid deficiency with methotrexate use
Superinfection with broadspectrum antimicrobial use.
• Teratogenicity: can be expected with many drugs specially if used in 1st trimester
• Organ toxicity on long run use
Aminoglycosides → renal and ototoxicity
• Drug dependence:
Some drugs are liabe for addiction as morphine and barbiturates
