It is the
process by which
a drug
or metabolite is
eliminated from the body
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
1
o Passive glomerular filtration
o Active tubular secretion in proximal tubules
o Passive tubular reabsorption.
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Factors affecting renal excretion:
1-Glomerular filtration rate:
D
• Free
• Water soluble
• Low molecular weight
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Filtered
3
2-Change in urinary pH
Acidification of urine
• vitamin C
• NH4Cl
Excretion
weak base drugs
B+
B+
B+
Ionized
B+
B+
In Acidic medium
B+
B+
e.g. amphetamine
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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2-Change in urinary pH
Alkalinization of urine
Excretion
NaHCO3
AA
AA
weak Acidic drugs
Ionized
In Alkaline medium
AAA-
e.g. aspirin
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Tetracycline
Streptomycin
oIodides
oRifampicin
oSalicylates
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Ampicillin
Rifampicin
Biliary infection
Morphine
Enterohepatic circulation
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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-BMCSAUDIA ARABIA
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What the drug does to body
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It is the study of the:
 Biological & therapeutic
effects of drugs
 Their mechanisms of action
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Physical action:
kaolin adsorbs toxins
in diarrhea.
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Chemical action:
Hcl
+
NaHCO3
12
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
2. selective passage of
ions
1. Specific receptors
ion
Cell membrane
R
Intracellular
3. Enzyme
Nucleus
XY
→ X +Y
Z
4. Metabolic pathway
5. Cytotoxic action
13
Action on enzyme
Stimulation
Inhibition
Irreversible
long-lasting
(new enzyme synthesis )
e.g:
Organophsphrous
compounds
Irrev
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
E
Reversible
• short lasting
• e.g:
Neostigmine
Rev
E
E Cholinesterase
14
Action on Specific receptors
• Drug
Bind
specifically
with a ligand:
ligand
• Hormone
• Neurotransmitter
Cell membrane
R
R
R
Nucleus
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Biological response
Intracellular
15
Affinity = tendency to bind receptors
drug is required
Potency = how muchligand
to elicit a response.
R
Efficacy = Biological response
Nucleus
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Agonists
• Affinity
• Efficacy
• Rapid dissociation rate
ligand
Antagonists
• Affinity
• No efficacy
• slow dissociation rate
• Prevent action of agonist
ligand
ligand
R
R
initiate changes
without initiating change
17
Competitive
antagonism
Non-Competitive
antagonism
Ag
antag
Ag
Ag
Ag
Ag
Ag
antag
R
Displaced by an
excess agonist
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R
Not displaced by an
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excess agonist
Partial agonists
 Stimulate and block receptors
 Affinity
 Efficacy (less than full agonist)
 Moderate dissociation rate
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Inverse agonists
•Produce effects opposite to that of agonist
•Benzodiazepines
•Agonists of Bz
receptors
•Carbolines
•Inverse agonists of
the Bz receptors
• Sedation,
• Muscle relaxation
• Anxiolytic action
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
• Convulsions
• Anxiety.
20
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1) Age:
Newborn infants especially premature are
more susceptible to drugs due to:
Underdevelopment
Low
of microsomal enzymes
plasma protein and low binding capacity
Reduced excretory function
Immaturity
of blood brain barrier
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1) Age:
In infants use:
Clark's formula =
adult dose x weight in kg
70
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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
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1) Age:
between 60-70 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
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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
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In obese patients:
Dose of fat soluble drugs
Dose of water soluble drugs.
Surface area is more accurate parameter
for dose calculation
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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
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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
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3) Route of administration:
I.V
>
sublingual &
inhalation
>
I.M.
>
S.C
>
oral
Affect the dose:
I.V dose less than oral.
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3) Route of administration:
Affect the Action:
Magnesium sulphate:
• Orally is purgative
• Rectally is dehydrating agent
• I.V. it is anticonvulsions &
antagonizes Ca++
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4) Drugs intolerance
= supersensitivity
= hypersusceptibility:
dose
Exaggerated action to normal dose of a drug
it may be due to:
• Decrease clearance of drug
or
• Upregulation of receptors.
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5)Tolerance:
Failure of response to the usual dose of a drug.
It may be:
1. Congenital:
2. Acquired:
a) Racial:
b) Species:
c) Individual variation
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2. Acquired Tolerance:
e.g.:
• Morphine,
•Ethyl alcohol
• Nitrates,
•Ephedrine
Reversible
It may develop to some actions only
& not to all actions
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Special types of tolerance:
1) Tachyphylaxis e.g:
ephedrine on B.P.
2) Cross tolerance
(tolerance between related drugs)
e.g:
between ethyl alcohol & general anaesthesia.
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Variation in drug response may be due to:
Variation in:
1. Drug concentration
D
D
D D
R
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
2. Concentration of
endogenous
transmitters
R R
3. Number
or
function
of receptors
36
6) Hypersensitivity (allergic) reaction:
D
Immune response
D
Hapten
Does not occur
on first exposure
Not dependent on
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
dose
37
7) Idiosyncrasy = pharmacogenetics:
Abnormal reaction to drug due to:
genetic
or
enzyme defect:
o Succinylcholine apnea
cholinesterase enzyme
o Malignant hyperthermia with
succinylcholine or halothane
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7) Idiosyncrasy = pharmacogenetics:
o Anaemia
&
methemoglobinemia
G-6-PD
o Peripheral neuritis with slow isoniazid acetylator
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8) Drug dependence:
Habituation:
Emotional or psychological
dependence on the drug
when stopped
Emotional distress
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8) Drug dependence:
Addiction
Psychic craving for and physical
dependence on the drug
when stopped
severe withdrawal reaction
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9) Pathological State:
Aspirin lowers fever temperature to normal,
but no effect on normal one.
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10) Cummulation:
Rate of drug administration
>
elimination
e,g, digitalis and guanethidine
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11) Emotional State (Placebo effect):
•Placebo are inert dosage forms which produce
their effect psychologically.
•They are used in testing new drugs
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12) Drug Combinations:
a. Addition or summation:
b. Synergism:
c. Potentiation:
d. Antagonism:
1) Physiological
2) Chemical
3) Pharmacological
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Toxicity of Drugs
Adverse (unwanted) drug effects
A) Unpredictable
1- Allergy (hypersensitivity reaction)
2- Idiosyncrasy.
B) Predictable
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B) Predictable:
1- Overdose toxicity.
2- Teratogenic effects
3- Iatrogenic drugs
4- Long-acting sulphonamides can produce
jaundice in premature babies.
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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
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10- Secondary effects, e.g.:
prolonged use of broad spectrum antibiotic
•
•
superinfection
&
Vit. B & K deficiency.
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11-Intolerance.
12-Drug dependence and addiction.
13-Drug interactions.
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Therapeutic dose:
the average adult dose required
to produce a therapeutic effect.
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Maximal tolerated dose:
largest safe dose that can be taken.
Lethal dose:
dose that produces death
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Loading dose :
the dose given at the onset of therapy to
achieve rapid increase in
plasma drug concentration to reach Css
within therapeutic range.
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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.
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Therapeutic index :
LD50/ED50
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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.
56
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Plasma half life of a drug (t ½):
= 4 hours ?
24
6
18
12
Decline by
Time
one half
Drug concentration
in Plasma
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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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-BMCSAUDIA ARABIA
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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-BMCSAUDIA ARABIA
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Types of drug elimination kinetics
Zero order kinetics:
 where a constant number of
moles are absorbed or eliminated
irrespective of the total amount
present.
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First order kinetics
Rate of the process
α
the amount of drug
Zero order kinetics
Rate of the process
≠ the amount of drug
t ½ is constant
t ½ increases with dose
Linear disappearance
Non-linear disappearance
curve if log dose is used
curve if log dose is used
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Methods to prolong duration
of action of drugs
1-Delay absorption
a) add vasoconstriction
e.g adrenaline to local anaesthetics.
b) Add oil
e.g. vasopressin.
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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) long acting
or timed release (TR)
preparations
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2-Increase protein binding:
e.g. sulfonamides.
3-Decrease metabolism
e.g. enzyme inhibitors
4-Delay renal excretion:
probenecid to decrease penicillin excretion.
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SEE YOU NEXT TIME
Prof.DR.AL
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