Download D - BMC Dentists 2011

PROF. Dr. ALSAYED ZAKI
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Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
It is the study of substances
that interact with living systems
to
activate or
inhibit
normal body processes.
2
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
It is the science of substances (drugs) used for:
Treatment
or
Prevention
or
Diagnostic purposes.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
3
Drugs are identified by different names
Chemical
name
Acetyl salicylic
acid
Generic name
Trade name
(official or non roprietary)
(proprietary)
Aspirin
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Rivo
4
Most of drugs are restricted for sale by
prescription only.
Some drugs can be used by the public
without a prescription
(Over-The-Counter = OTC)
e.g:Nasal & oral decongestants
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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1-Animal sources:
e.g. heparin.
2-Plant sources
e.g. digoxin.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
3-Microorganisms:
e.g. penicillin. 6
5-Mineral sources :
e.g. iodine
4-Synthetic drugs:
e.g. sulphonamides.
6-Biotechnology:
• Human insulin
• Tissue plasminogen
activator (tPA)
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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What the body does to drug
Pharmacokinetics
What the drug does to body
Pharmacodynamics
Pharmacology
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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It is a study of:
 Absorption,
 Distribution,
 Metabolism (Biotransformation)
 Excretion
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Drug administration
(I.V., Oral, etc……)
Absorption into plasma
Plasma
Sites of
action
Bound drug
Tissue
storage
Receptors
Free drug
Distribution to Tissues
Drug Metabolism
(Liver, Lung, Blood,… etc
Drug Excretion
(renal, Biliary, Exhalation,… etc
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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D
D
D
Extracellular
Membrane
Bimolecular
lipoid
(hydrophobic)
Intracellular
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
water
filled
pores
carrier
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The passage of drugs across cell membranes
occurs by any of the following processes:
1) Passive
transfer:
2) Specialized
transport:
A.Simple diffusion
B. Filtration
a. Facilitated diffusion
b. Active transport
c. Pinocytosis
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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A.Simple diffusion
It is the most important.
 Along concentration gradient
D DD D
D D
D
 No energy
Extracellular
aqueous
Membrane
 No carrier is required
lipid
Intracellular
 Not saturable.
 Not inhibited by metabolic inhibitors
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
A. Simple diffusion
It depends on:
1.concentration gradient
D
D
D
D
D
D D
D
D
Extracellular
Membrane
D
D
Intracellular
* Concentration gradient is maintained by removal
of the drug from other side of the membrane.
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A. Simple diffusion
2.Lipid solubility
It is measured by:
lipid / water partition coefficient
It is a Ratio of drug
Concentration in
Concentration in
lipid phase
water phase
D
D
DD D D
D DD
D
D D
one immiscible
lipid/water system
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
A. Simple diffusion
3. Degree of ionization
* Most of drugs are either weak acids or weak bases
A
-
B
A
non-ionized
B+
Lipid solubility
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A. Simple diffusion
3. Degree of ionization
It is determined by:
• pH of environment
• pKa of drug
PKa =
(Dissociation
constant)
non-ionized
ionized
Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
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Clinical Significance of pKa:
Aspirin
(weak acid, pKa3.5)
Non-ionized
Acid medium
stomach
A
Alkaline medium
(Intestine)
B B
B
B
B
A
A A-
A AA
A
B+
B+ B+
Non-ionized
Amphetamine
weak base (pKa9.8)
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Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Clinical Significance of pKa:
Acidification of urine
• vitamin C
• NH4Cl
Excretion
weak base drugs
B+
B+
B+
Ionized
B+
B+
In Acidic medium
B+
B+
e.g. amphetamine
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Prof.DR.AL SAYED ZAKI-BMC-SAUDIA ARABIA
Clinical Significance of pKa:
Alkalinization of urine
Excretion
NaHCO3
AA
AA
weak Acidic drugs
Ionized
In Alkaline medium
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
AAA-
e.g. aspirin
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A. Simple diffusion
It depends on:
•concentration gradient
•lipid solubility
•degree of ionization
•Molecular size.
+ +D
D D
D D
•Thickness of membrane
D
D
D
D DD
Extracellular
Membrane
Intracellular
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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B. Filtration
D
Extracellular
Membrane
Intracellular
Not affected by:
• Lipid solubility
• Not saturable
water filled
pores
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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B. Filtration
D
capillaries
It depends on:
 Hydrostatic pressure
 Osmotic pressure
 limited by blood flow
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Substances that are:
D+
D+
D+
D+
Too large
Or
Poorly lipid soluble
Carrier
(Membrane
transporters)
D+
a. Facilitated diffusion:
= simple diffusion
Require:
• Carrier
• Saturable
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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D+
ATP
D+
D+
D+
D+
c.AMP
b. Active transport:
Against concentration gradient
Energy
e.g. renal tubular secretion of organic acids
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Carrier
(Membrane
transporters)
They are proteins & control:
 Influx of ions & essential nutrients
Efflux of toxins.
They have role in selective absorption & elimination
Located in gut, liver, kidney, placenta and CSF
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Membrane carriers may be specialized for expelling
foreign
molecules e.g.
D
D
P-glycoprotein transporters
D
D
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
D
D
D
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c. Pinocytosis:
Energy dependant
where large molecules are engulfed inside cells,
e.g., absorption of B12 and intrinsic factor.
D
D
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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• Enteral
via gastrointestinal tract (GIT).
– Oral
– Sublingual
– Rectal
• Parenteral administration = injections.
• Topical application
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Advantages
Easy
Self use
Safe
Convenient
cheap
No need for
sterilization
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Disadvantages
Slow effect
No complete absorption
(Low bioavailability).
Destruction by GIT
First pass effect
GIT irritation
Food–Drug interactions
Drug-Drug interactions
Not suitable for vomiting,
unconscious, emergency.
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First pass Metabolism
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Metabolism of drug in the gut wall or portal
circulation before reaching systemic circulation
• so the amount reaching system circulation is less
than the amount absorbed
Where ?
 Liver
 Gut wall
 Gut Lumen
Result ?
Low bioavailability.
Short duration of action (t ½).
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First pass effect
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Dosage forms
Capsules
Tablets
Syrup
Suspension
Tablets
Hard- gelatin
capsule
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Soft- gelatin
Spansule
capsule
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Advantages
• Rapid effect (Emergency)
• No first pass metabolism.
• High bioavailability
• No GIT destruction
• No food drug
interaction
Dosage form: friable tablet
Disadvantages
Not for
irritant drugs
Frequent use
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Advantages
Disadvantages
Suitable for
–Vomiting & children.
&unconsciousness
– Irritant & Bad taste drugs.
– less first pass metabolism
(50%)
Not for
– Irregular
absorption &
bioavailability.
– Irritation of
rectal mucosa.
Dosage form:
suppository or enema
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Intradermal (I.D.) (into skin)
Subcutaneous (S.C.)
Intramuscular (I.M.)
Intravenous (I.V.) (into veins)
Intra-arterial (I.A.) (into arteries)
Intrathecal (I.T.) (cerebrospinal fluids )
Intraperitoneal (I.P.) (peritoneal cavity)
Intra - articular (Synovial fluids)
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Advantages
Disadvantages
• high bioavailability
• Rapid action (emergency)
• No first pass metabolism
Suitable for
–Vomiting &unconsciousness
– Irritant & Bad taste drugs.
– No gastric irritation
– No food-drug interaction
Dosage form:
Vial or ampoule Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
– Infection
– Sterilization.
– Pain
– Needs skill
– Anaphylaxis
– Expensive.
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Ampoule
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Vial
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 Produce local effect to
 Skin (percutaneous) e.g. allergy testing,
topical local anesthesia
 Mucous membrane of respiratory tract
(Inhalation) e.g. asthma
 Eye drops e.g. conjunctivitis
 Ear drops e.g. otitis externa
 Intranasal, e.g. decongestant nasal spray
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Advantages
• Mucous membrane of
respiratory system
• Rapid absorption
(large surface area)
•Provide local action
• Minor systemic effect
• Low bioavailability
• Less side effects.
• No first pass effect
Dosage form: aerosol, nebulizer
Disadvantages
Only few
drugs can be
used
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Nebulizer
Atomizer
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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a medicated adhesive patch applied to skin
* Slow effect (prolonged drug action)
* produce systemic effect
e.g. the nicotine patches
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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It is the process of entry of drug
from site of administration into
systemic circulation.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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A- Factors related
to drug
B- Factors related
to the patient:
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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A- Factors related to drug
a) Physicochemical properties :
1-Degree of ionization:
ionized
absorbed
2-Degree of solubility:
High lipid/water
partition coefficient.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
absorption
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Drug Factors
3-Chemical nature:
Inorganic
organic.
4-Valency:
Ferrous salts
ferric
so vitamin C increases absorption of iron.
b) Pharmaceutical form of drug:
Absorption of:
suspensions
or tablets.
Prof.DR.AL SAYED ZAKI-BMC-
solutions
SAUDIA ARABIA
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B- Factors related to the patient:
1-Route of administration:
alveolar
mucosa
sublingual,
small intestinal
&rectal mucosa
I.M.
Gastric
mucosa
S.C.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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2-Area and vascularity of absorbing
surface:
absorption is directly
proportional to both
Area
&
Vascularity
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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3-State of absorbing surface:
Atrophic gastritis &
Mal-absorption syndrome
rate of absorption
of drugs.
4-Rate of general circulation:
•In shock,
peripheral circulation
•I.V. route is used.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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5-Specific factors and presence
of other drugs:
•Intrinsic factor of the stomach is essential for vitamin
B12 absorption from lower ileum
•Adrenaline induces vasoconstriction so delay
absorption of local anesthetics.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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* Factors related to the drug formulation:
 Disintegration
 Rate of dissolution
 Excipients «additives»
 Molecular weight
 Lipid solubility
 Stability in gut contents
 Pka of the drug.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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* Factors related to the patient:
1-State of absorbing surface, specific factors.
2-Surface area:
Rate of absorption from intestine is greater than from
stomach.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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- Patient Factors:
3-pH within the gut:
 Where absorption of weak acidic drugs starts in
stomach
 weak base drugs are absorbed from intestine.
Destroyed by gastric juice
Drugs which are:
Or
Irritant on stomach
Administered in enteric coated form e.g. sodium salicylate.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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- Patient Factors:
4-Rate of dissolution and gut motility:
Absorption of solid form of a drug is dependent on:
Rate of dissolution
Absorption
Sustained release form
Prolong their duration.
T1 T2
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
T3
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- Patient Factors:
the rate of absorption of slowly
dissoluted drug (digoxin)
Decreased gastric emptying
that of rapidly dissoluted one
(paracetamol).
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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- Patient Factors:
5-Presence of other substance within the lumen:
•Food, calcium and iron decrease tetracycline
absorption.
•Fatty meals can enhance griseofulvin absorption.
•Grapefruit juice increases oral bioavailability of
some drugs
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
6-First pass effect
(pre-systemic metabolism):
Buccal mucosa
Benzyl penicillin
HME
pH
digestive enzymes
Insulin
mucosal enzymes
Tyramine
Rectum
Systemic circulation
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To overcome hepatic first pass metabolism:
oral dose
Propranolol
Use other routes
• IV lidocaine
• Sublingual nitroglycerin
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The percentage of drug
that reaches systemic circulation
unchanged
and becomes available for biological effect
following administration by any route.
= 100% after IV administration.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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plasma drug concentration
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
I.V. dose
Oral dose
Time
Oral bioavailability =
Area under the curve (AUC) oral x 100
Area under the curve (AUC) I.V.
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Oral bioavailability depends on:
Amount absorbed
Amount metabolized
before reaching systemic circulation
(first pass metabolism).
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
It is dependent on:
 Lipid solubility
 Ionization
Molecular size
 Binding to plasma proteins
Rate of blood flow
 Special barriers.
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The body compartments
Intracellular
compartment
Cell membrane
Interstitial compartment
Extra-cellular
Endothelium of
capillary wall
Intravascular (Plasma)
compartment
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Intracellular
compartment
Interstitial compartment
Extra-cellular
pp
Intravascular (Plasma)
compartment
2. highly bound to
plasma proteins
Dextran
1. High molecular weight
One compartment model (intravascular)
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Two compartment model (extracellular distribution) and
Intracellular
compartment
+
Interstitial compartment
Extra-cellular
Intravascular (Plasma)
compartment
Quaternary ammonium
compounds
Mannitol .
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Multicompartmental model
(extracellular and intracellular distribution)
Intracellular
compartment
+
Interstitial compartment
Extra-cellular
Intravascular (Plasma)
compartment
Alcohol
Phenytoin
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Selective distribution:
Iodide in thyroid
gland
Tetracycline in bone
and teeth
calcium in bones
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Selective distribution
Aminoglycosides as streptomycin in
Kidney
Vestibular system
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Apparent volume of distribution (Vd):
it is a kinetic parameter of a drug that correlates
dose with plasma level.
Amount of drug in body
Vd =
Plasma concentration of drug
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Total body water
42 L
Intracellular compartment
Interstitial compartment
10 L
Vd= 42 L
e.g. phenytoin &
alcohol.
12-14 L
Extra-cellular
Plasma compartment
Vd= 3-4 L
e.g. heparin
4L
Vd= 12-14 L
e.g. aspirin.
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Vd of Digoxin= 500 L
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
?
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Dialysis
Drugs with high Vd
(extensive tissue distribution).
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Estimation
of the total amount of drug in body at any time.
Amount of drug = Vd x plasma concentration of
drug at certain time.
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Loading dose
Loading dose = Vd x desired concentration.
?
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
pp
2-Bound form
1-Free form:
inert,
non-diffusible,
not available for metabolism
active,
diffusible,
available for biotransformation &
&excretion.
excretion.
It acts as a
reservoir for drug.
76
Significance of binding to
plasma proteins:
pp
e.g. diphenylhydantoin.
pp
pp
pp
free fraction of some drugs
Hypoalbuminemia or lowered binding capacity of albumin
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pp
Higher affinity
for pp binding
sites
pp
Significance of binding to
plasma proteins:
free form
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pp
pp
pp
Highly bound drug
Rapid injection
Thiopentone
Given I.V.,
↑↑free form
is given at a relatively rapid rate.
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Passage of Drugs to CNS
Blood brain
barrier
Lipid soluble
non-ionized drugs
quaternary
amines (ionized)
+
Tight junction
Endothelial cells
Basement
membrane
Astrocyte
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Passage of Drugs to CNS
Penicillins
slightly
pass through the normal barrier,
But they penetrate
readily
in acute bacterial meningitis.
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Passage of Drugs to the Foetus
First trimester
• Thalidomide ,
• Diphenylhydantoin ,
• Tetracyclines ,
• Corticosteroids ,
• Antithyroid drugs
•Aspirin .
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Redistribution:
lipid soluble drug crossing BBB
thiopentone is initially accumulated in brain
due to high lipid solubility
blood flow
then redistributed to less perfused adipose tissue
so its duration depends on
redistribution
rather than metabolism or excretion
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
Ionized drugs
lipid insoluble
(water soluble)
Excreted
unchanged
85
Volatile anesthetics
highly lipid soluble
Eliminated through
Alveoli
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Non ionized
Lipid soluble
Lipid insoluble
(water soluble)
Reabsorbed by
renal tubules
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Phases of biotransformation :
Phase I (Non synthetic) reactions :
• Oxidation
• Reduction
• Hydrolysis
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Phase I reactions :
Result in:
Drug inactivation
most of drugs
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Phase I reactions :
Result in:
Inactive
Active
Cortisone
Cortisol
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Phase I reactions :
Result in:
Active
Active
Phenacetin
Paracetamol
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Phase I reactions :
Result in:
Toxic metabolite
Methanol
Formaldehyde
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Phase II
(Synthetic) reactions:
o Glucuronic acid
Conjugation with:
o Glutathione
o Glycine
o Sulphate
o Acetic acid
o Methyl group
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Phase II (Synthetic) reactions:
Result ?
usually
Inactivation
with
few exceptions:
morphine-6- conjugate is active
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Most of drugs pass through:
phase I
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
phase II
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Isoniazid
phase I
phase II
Hydrolyzed
Acetylated
isonicotinic acid
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Sites of biotransformation
1- Microsomal Enzymes :
• Glucuronide
conjugation.
• Oxidation by
CYP450 enzymes
• Reduction.
• Hydrolysis
Affected
By
Drugs
& age
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2- Non Microsomal :
Present in liver, kidney, plasma, skin and GIT…etc
• Conjugations
• Oxidation by soluble
glucuronic acid.
enzymes in?
• Reduction.
activity is stable
• Hydrolysis.
throughout life.
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CYP450s
• Microsomal
enzymes
•Responsible for most of oxidative reactions
•Exist in multiple isoforms
•Substrate specificity
CYP1A2
smoking
CYP1A2
CYP1A2
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
theophylline
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Factors affecting drug metabolism
1-Drugs:
Synthesis
Induction:
Enzymes
Enzymes
Degradation
Prof.DR.AL SAYED ZAKI-BMCSAUDIA ARABIA
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Enzyme inducers:
Examples:
Phenobarbitone, phenytoin, carbamazepine,
Rifampicin, griseofulvin,
Testesterone, some glucocorticoids,
Tobacco smoking, ethyl alcohol (chronic).
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Importance of enzyme induction:
CYP1A2
smoking
CYP1A2
CYP1A2
theophylline
Decreases effect
of other drug.
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Importance of enzyme induction:
Pollutants
CYP450
CYP450
phenobarbitone
CYP450
phenobarbitone
Inducing its own metabolism
Tolerance
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Importance of enzyme induction:
phenobarbitone
Induces bilirubin conjugation
ttt Hyperbilirubinemia
in newborn.
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Enzyme inhibition
(drugs that inhibit drug metabolism):
Faster than enzyme induction?
serious drug interactions.
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Enzyme inhibition
Examples:
• Cimetidine
• Chloramphenicol, cotrimoxazole, ciprofloxacin,
erythromycin, ketoconazole, isoniazid,
• Oestrogen, progesterone, sodium valproate,
• MAOIs, and grape fruit.
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2-Genetics variation:
Genetically determined polymorphisms.
Acetylation rate of isoniazid :
Slow
Fast
prone to
peripheral neuritis
prone to
hepatic toxicity.
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3-Nutritional state
•conjugating agents as:
• sulphate
• glutathiaone
sensitive to body nutrient level.
protein diet
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glycine.
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Drug
accumulation
Dosage
D
D
D
D
D
D
D
D
D
D
D
Alternative
pathway
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D
D
D
D
Saturation
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5-Age:
Drug metabolism is reduced in
extremes of age.
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6- Gender:
Metabolism
 Propranolol &
 Lidocaine
 Diazepam
 Caffeine
 Paracetamol
Faster in men.
Faster in women
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7-Disease state:
Liver disease
drugs metabolism.
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7-Disease state:
Heart failure
Hepatic flow
The effect of rapidly
metabolized drugs
e.g. lidocaine
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7-Disease state:
Kidney disease
The excretion of drugs
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Factors affecting drug metabolism
8-Circadian rhythm:
In rats and mice, the rate of hepatic metabolism
of some drugs follows a diurnal rhythm.
This may be true in humans as well.
9-Route of administration:
1st pass effect occurs for drugs administered orally
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It is the
process by which
a drug
or metabolite is
eliminated from the body
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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
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Filtered
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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
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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
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