1. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
4- Excretion of drugs
It is the process by which
a drug or metabolite is
eliminated from the body
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

2. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Routes of excretion
1- Renal Excretion:
Passive glomerular filtration
Active tubular secretion in proximal tubules
Passive tubular reabsorption.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

3. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Factors affecting renal excretion:
1-Glomerular filtration rate: D
Free
Water soluble
Low molecular weight
Filtered
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

4. Ionized 2-Change in urinary pH Acidification of urine weak base drugs
Excretion
vitamin C
NH4Cl
weak base drugs B + B + B + B +
Ionized B + B + B +
In Acidic medium
e.g. amphetamine
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

5. e.g. aspirin Ionized 2-Change in urinary pH Alkalinization of urine -
Excretion
NaHCO3
weak Acidic drugs A - A - A - A -
Ionized A - A - A -
In Alkaline medium
e.g. aspirin
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

6. 2-Gastrointestinal Tract:
Morphine
Iodides
Rifampicin
Salicylates
Tetracycline
Streptomycin
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

7. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Ampicillin
Rifampicin
Biliary infection
Portal v.
Bile
Morphine
Enterohepatic circulation
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

8. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
3-Sweat:
e.g., rifampicin (red color), vitamin B1.
4-Lungs:
e.g., gases and volatile anesthetics.
5-Milk:
Morphine
Amphetamine
Chloramphenicol
Oral anticoagulants
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

9. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Pharmacodynamics
What the drug does to body
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

10. Biological & therapeutic effects of drugs
Pharmacodynamics
It is the study of the:
Biological & therapeutic effects of drugs
Their mechanisms of action
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

11. Mechanism of drug action
Physical action:
kaolin adsorbs toxins in diarrhea.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

12. Mechanism of drug action
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Chemical action:
Hcl +
NaHCO3

13. 2. selective passage of ions
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
2. selective passage of ions
1. Specific receptors
ion
Cell membrane R
Intracellular
3. Enzyme E
Nucleus
XY → X +Y Z
5. Cytotoxic action
4. Metabolic pathway

14. Action on enzyme Stimulation Inhibition Irreversible Reversible
long-lasting
short lasting
(new enzyme synthesis )
e.g:
Organophsphrous compounds
e.g:
Neostigmine
Rev
Irrev E E E
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Cholinesterase

15. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Action on Specific receptors
Bind
specifically
with a ligand:
Drug
ligand
Hormone
Neurotransmitter R
Cell membrane R R
Biological response
Nucleus
Intracellular
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

16. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Affinity
= tendency to bind receptors
Potency
= how much drug is required to elicit a response.
ligand R
Efficacy =
Biological response
Nucleus
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

17. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Agonists
Antagonists
Affinity
Affinity
Efficacy
No efficacy
Rapid dissociation rate
slow dissociation rate
Prevent action of agonist
ligand
ligand
ligand R R
initiate changes
without initiating change

18. R R Competitive antagonism Non-Competitive antagonism
Displaced by an excess agonist
Not displaced by an excess agonist
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

19. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Partial agonists
Stimulate and block receptors
Affinity
Efficacy (less than full agonist)
Moderate dissociation rate
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

20. Inverse agonists Produce effects opposite to that of agonist
Benzodiazepines
Carbolines
Inverse agonists of the Bz receptors
Agonists of Bz receptors
Sedation,
Muscle relaxation
Anxiolytic action
Convulsions
Anxiety.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

21. dosage & action of drugs
Factors modifying
dosage & action of drugs
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

22. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
1) Age:
Newborn infants especially premature are
more susceptible to drugs due to:
Underdevelopment of microsomal enzymes
Low plasma protein and low binding capacity
Reduced excretory function
Immaturity of blood brain barrier
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

23. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
1) Age:
In infants use:
Clark's formula = adult dose x weight in kg 70
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

24. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
1) Age:
Children require small dose than adults
They may metabolize some drugs more rapid
& so may need high dose of digitalis
In children use
Young's formula = adult dose x Age in years
Age +12
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

25. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
1) Age:
between years
3/4 of adult dose
Elderly:
above 70 years
½ the dose.
This is due to:
Ageing of liver microsomal enzymes
Underweight
Reduced renal function
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

26. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
2) Body weight and surface area:
The bigger the body weight the larger the dose
Oedema
The increase in weight due to: Or
Fat
Is not taken into consideration
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

27. Surface area is more accurate parameter for dose calculation
In obese patients:
Dose of fat soluble drugs
Dose of water soluble drugs.
Surface area is more accurate parameter for dose calculation
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

28. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
2) Sex:
need smaller dose than
This is due to:
Fat content
Enzyme inhibiting effect of female sex hormones
Enzyme inducing effect of male sex hormone
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

29. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
2) Sex:
During menstruation avoid :
salicylates and castor oil.
During pregnancy avoid :
teratogenic drugs,
cathartics and uterine stimulants
During lactation avoid:
chloramphenicol,
oral anticoagulants
phenolphthalein
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

30. > > > > 3) Route of administration: I.V
sublingual & inhalation
I.M.
S.C
oral
Affect the dose:
I.V dose less than oral.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

31. 3) Route of administration:
Affect the Action:
Magnesium sulphate:
Orally is purgative
Rectally is dehydrating agent
I.V. it is anticonvulsions & antagonizes Ca++
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

32. dose 4) Drugs intolerance = supersensitivity = hypersusceptibility:
Exaggerated action to normal dose of a drug
it may be due to:
• Decrease clearance of drug or
• Upregulation of receptors.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

33. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
5)Tolerance:
Failure of response to the usual dose of a drug.
It may be:
2. Acquired:
1. Congenital:
a) Racial:
b) Species:
c) Individual variation
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

34. 2. Acquired Tolerance: e.g.: Reversible Morphine, Ethyl alcohol
Nitrates,
Ephedrine
Reversible
It may develop to some actions only
& not to all actions
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

35. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Special types of tolerance:
Tachyphylaxis e.g:
ephedrine on B.P.
2) Cross tolerance
(tolerance between related drugs)
e.g:
between ethyl alcohol & general anaesthesia.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

36. R R R D D D D Variation in drug response may be due to: Variation in:
1. Drug concentration D D
2. Concentration of endogenous transmitters D D R R R
3. Number or
function
of receptors
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

37. Immune response 6) Hypersensitivity (allergic) reaction: D D
Does not occur on first exposure
Hapten
Not dependent on dose
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

38. 7) Idiosyncrasy = pharmacogenetics:
Abnormal reaction to drug due to:
genetic or
enzyme defect:
Succinylcholine apnea
cholinesterase enzyme
Malignant hyperthermia with
succinylcholine or halothane
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

39. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
7) Idiosyncrasy = pharmacogenetics:
Anaemia & methemoglobinemia
G-6-PD
Peripheral neuritis with
slow isoniazid acetylator
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

40. Emotional distress 8) Drug dependence:
Habituation:
Emotional or psychological dependence on the drug
when stopped
Emotional distress
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

41. severe withdrawal reaction
8) Drug dependence:
Addiction
Psychic craving for and physical dependence on the drug
when stopped
severe withdrawal reaction
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

42. Aspirin lowers fever temperature to normal,
9) Pathological State:
Aspirin lowers fever temperature to normal,
but no effect on normal one.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

43. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
10) Cummulation:
>
Rate of drug administration
elimination
e,g, digitalis and guanethidine
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

44. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
11) Emotional State (Placebo effect):
Placebo are inert dosage forms which produce their effect psychologically.
They are used in testing new drugs
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

45. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
12) Drug Combinations:
a. Addition or summation:
b. Synergism:
c. Potentiation:
1) Physiological
d. Antagonism:
2) Chemical
3) Pharmacological
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

46. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Toxicity of Drugs
Adverse (unwanted) drug effects
A) Unpredictable
1- Allergy (hypersensitivity reaction)
2- Idiosyncrasy.
B) Predictable
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

47. 4- Long-acting sulphonamides can produce jaundice in premature babies.
B) Predictable:
1- Overdose toxicity.
2- Teratogenic effects
3- Iatrogenic drugs
4- Long-acting sulphonamides can produce jaundice in premature babies.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

48. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
5- Blood dyscrasias by chloramphenicol,
6- Carcinogenic effect, e.g. smoking and radiation.
7- Hepatic toxicity, e.g., halothane.
8- Nephrotoxicity by:
sulphonamides, aminoglycosides, phenacetin.
9- Nerve damage, e.g.:
streptomycin can produce 8th cranial nerve damage
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

49. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
10- Secondary effects, e.g.:
prolonged use of broad spectrum antibiotic
• superinfection
&
• Vit. B & K deficiency.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

50. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
11-Intolerance.
12-Drug dependence and addiction.
13-Drug interactions.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

51. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Dosage of Drugs
(Posology)
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

52. Therapeutic dose: the average adult dose required
to produce a therapeutic effect.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

53. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Maximal tolerated dose:
largest safe dose that can be taken.
Lethal dose:
dose that produces death
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

54. Loading dose :
the dose given at the onset of therapy to achieve rapid increase in
plasma drug concentration to reach Css within therapeutic range.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

55. It is the dose needed to keep the plasma drug concentration constant
Maintenance dose :
It is the dose needed to keep
the plasma drug concentration constant
at the steady state
i.e. to compensate for drug loss
in between doses.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

56. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Therapeutic index :
LD50/ED50
it is measure for safety of drugs
LD50 (median lethal dose):
minimum dose that produces death
in 50% of experimental animals.
ED50 (median effective dose):
dose that produces
a certain pharmacological effect
in 50% of experimental animals.

57. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Elimination half life t
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

58. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Plasma half life of a drug (t ½):
= 4 hours ? 24 6 12 18
Decline by
one half
Time
Drug concentration
in Plasma
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

59. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Plasma half life of a drug (t ½):
It depends on drug clearance
It is a measure for drug elimination
Half-life (t1/2) is important to indicate
the time required to attain steady state
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

60. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Types of drug elimination kinetics
First order kinetics:
a constant proportion of drug is absorbed, metabolized or eliminated
depending on the drug concentration
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

61. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Types of drug elimination kinetics
Zero order kinetics:
where a constant number of moles are absorbed or eliminated
irrespective of the total amount present.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

62. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
First order kinetics
Zero order kinetics
Rate of the process
Rate of the process α ≠
the amount of drug
the amount of drug
t ½ is constant
t ½ increases with dose
Linear disappearance curve if log dose is used
Non-linear disappearance curve if log dose is used
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

63. Methods to prolong duration of action of drugs
1-Delay absorption
add vasoconstriction
e.g adrenaline to local anaesthetics.
b) Add oil
e.g. vasopressin.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

64. e.g. protamine zinc insulin.
c) Use of suspensions
e.g. protamine zinc insulin.
d) S.C pellet implantation
e.g. contraceptives
e) Use of sustained release (SR)
or controlled release (CR)
or timed release (TR)
long acting preparations
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

65. Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
2-Increase protein binding:
e.g. sulfonamides.
3-Decrease metabolism
e.g. enzyme inhibitors
4-Delay renal excretion:
probenecid to decrease penicillin excretion.
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA

66. SEE YOU NEXT TIME
Prof.DR.AL