Pharmacology PPT

1. ABSORPTION
Dr chintan Doshi
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2. PHARMACOKINETICS
• Simply means, the science which deals with
 “ What the Body does to the drug ”
• Includes 4 stages –
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PHARMACOKINETICS
ABSORPTION DISTRIBUTION METABOLISM EXCRETION

3. 3
Drug
administration
Crosses
biological membrane
Transport
Absorption
Enters
Systemic
Circulation
Reaches
body tissues
Distribution

4. ABSORPTION
30-Dec-13
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5. BIOAVAILABILITY
• DEFINITION :-
“ The Rate at which & the Extent to which the
Active Concentration of drug is available at the desired
site of action. ”
• Concept came into existence when an unusual incidence
occurred in Australia in 1968.
• Phenytoin toxicity in Epileptic patients.
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6. BIOEQUIVALENCE
 Definition :
• If two or more dosage forms of the same drug reach the
blood circulation at the same relative rate & same
relative extent, they are called Bioequivalent
preparations of the generic drug.
• Clinically important for the drugs having steep dose-
response relationship,
• e.g.
 Zero order kinetics ( phenytoin, warfarin )
 Narrow margin of safety ( Theophylline, Tetracycline )
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7. Measurement of Bioavailability
• Oral administration of 2 brand products of same drug
⇓
Plasma concentration – Time curve is obtained
⇓
3 characteristics noted & compared :
1) Cmax
2) Tmax
3) AUC
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Rate of Absorption
Extent of Absorption

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9. Quantitative Evaluation of Bioavailability
Drug Bioavailability ( % ) = AUC ( Oral ) x 100
AUC ( I.V. )
AUC (oral) = AUC obtained after oral administration of
single dose
AUC (IV) = AUC obtained after IV administration of same
drug in the same dose.
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10. Drug transport process
DRUGS ARE TRANSPORTED ACROSS
THE MENBRANE
PASSIVE DIFFUSION
AND FILTRATION
SPECIALIZED
TRANSPORT
CARRIER
MEDIATED
FACILITATED
DIFFUSION
ACTIVE
TRANSPORT
PRIMARY SECONDORY
PINOCYTOSIS
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11. Diffusion
Higher
conc.
Lower
conc.
M
E
M
B
R
A
N
E
Lipid soluble
Lipid
insoluble
DIFFUSION
FILTRATION
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12. Carrier mediated transport
• Facilitated
M
E
M
B
R
A
N
E
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13. • Active transport
AA
M
E
M
B
R
A
N
E
ATP ADP
e.g.- levodopa
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14. Active transport
PRIMARY
◦ Energy obtained directly
from ATP
◦ Eg. P glycoprotein
SECONDARY
◦ Energy obtained from
movment of other solute
(Na+)
◦ Eg- Na/K/2CL symporter
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15. • Primary Active transport
AA
M
E
M
B
R
A
N
E
ATP ADP
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16. • Secondary Active Transport
AA
M
E
M
B
R
A
N
E
Na+ K +
ATPase
ATP ADP
Na+ K +
ATPase
H+ H+
GLUCOSE
Na+
K+
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17. Pinocytosis / Cell Drinking
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• Uptake of fluid solutes

18. 18
FACTORS AFFECTING
DRUG ABSORPTION
&
BIOAVAILABILITY

19. A) Pharmacological Factors:
(1) Route of Administration :
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20. Absorption via G.I.T.
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Absorption
Site
pH
Drugs
absorbed
Example
Stomach Acidic
Lipid soluble
Non-ionized
Acidic/Neutral
Aspirin
Mouth
Lipid soluble
Non-ionized
Basic/Neutral
Isosorbide
Small
intestine Morphine
Colon Diazepam
Rectal Ergotamine

21. Absorption via Parenteral Sites :
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Intravenous injection
⇓
Direct in bloodstream
⇓
Completely absorbed,
Rapidly distributed
Intramuscular
&
Subcutaneous injection
⇓
Passive diffusion
Absorption : i.m. > s.c.

22. Absorption via Lungs :
• Rapid absorption of Lipid-soluble drugs
• From pulmonary epithelium & mucous
membrane of trachea & lungs
• Ex. - General anaesthetics ( vapourized form )
- Salbutamol ( aqueous spray )
- Disodium cromoglycate ( suspended
microfined particles)
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23. Absorption via Topical sites :
• Dermis – permeable for lipid-soluble drugs
◦ Transdermal patches for – GTN, Scopolamine.
◦ Applied on mucous membranes – Oxytocin,
Vasopressin
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24. (2) Age :
 Infants :
◦ High gastric pH
◦ Less intestinal surface & blood flow
 Elderly :
◦ Achlorhydria
◦ Less intestinal blood flow
◦ Altered gastric emptying
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25. ◦ Any factor which ↑: ↑ absorption of drug
◦ Permits drug to reach large intestinal surface
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(3) Gastric Emptying Time

26. (3) Gastric Emptying Time
• Volume of Ingested Material • Bulky material tends to empty
more slowly than liquids
• Type of Meal • carbohydrates > proteins > fats
• Body Position • Lying on the left side decreases
emptying rate,
• Right side promotes it
• Drugs
• Anticholinergics
• Narcotic analgesics
• Ethanol
• Reduction in rate of emptying
• Emotional state • Anxiety promotes,
• depression retards it
• Disease states • Hypothyroidism retards it,
• Hyperthyroidism promotes it.
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27. (4) Presence of food
FOOD INCREASES THE
ABSORPTION OF ..
Chloroquine
Griseofulvin
FOOD DECREASES THE
ABSORPTION OF ..
Ampicillin
Aspirin
Tetracycline
To be
taken
before
meals
To be
taken
after
meals
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28. Contd.
◦ Tetracycline absorption ↓ with milk
◦ Vit. C ↑absorption of iron
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29. 5)Gastrointestinial diseases
◦ Coeliac disease: Malabsorption of fat
◦ Amoxicillin show decrease absorption
◦ Gastroenteritis: oral absorption ↓
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30. 6)Drug intractions
◦ Enzyme inducer: phenobarbitone ↓ bioavalibility of other
drug
◦ Liquid paraffin: ↓ bioavaibility of VIT. A, D,E,K
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31. 7)First pass metabolism
◦ When given orally reaches direct liver for
metabolism before reaching systemic circulation
◦ Decrease bioavaibility
◦ Ex.:
◦ Levodopa
◦ Propranolol
◦ Niroglycerin
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32. 8)Pharmacogenetic factor
Slow acetalators:
◦ ↑ bioavaibility of isoniazid→ toxicity of isoniazid
◦ Seen in Americans
Fast acetalators:
o↓ bioavaibility
oSeen in Chinese, Eskimos
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33. 9)Miscelleneous factors
◦ Routes of administration
◦ Area of absorbing surface
◦ State of circulation
◦ In shock tissue perfusion ↓ and ↓ bioavalibility
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34. Pharmaceutical factors
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35. 35
Oral Administration of Drug
To fine particles
Tab or Cap
Drug in solution
Powders &
Suspensions
Solutions
Available for absorption in GIT

36. Disintegration time :
Rapid disintegration
⇓
Less disintegration time
⇓
Rapid absorption
◦ Ex.-
• Coated tablets – more disintegration time
slow absorption
• Fine dispersible tablets – less disintegration time
fast absorption
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37. 1)Particle size
◦ Microfine tablet: ↑bioavaibility
Ex:
◦ Aspirin
◦ Sprinolactone
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38. 2)Salt form
◦ Acidic drug precipitated from salt
◦ Faster dissolution and ↑bioavailability
◦ Ex.: phenytoin salts
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39. 3)Degree of ionization
◦ Non ionized lipid soluble drugs better absorbed
◦ Highly ionized drug reduce bioavailability
◦ Streptomycin
◦ Acetylcholine
◦ Neostigmine
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40. 4)Crystal form
◦ Amorphous chloramphenicol has faster dissolution and
increase bioavalibility
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41. 5)Water of hydration
◦ Anhydrous form of ampicillin has faster dissolution and
increase bioavailability
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42. Methods to Delay Absorption
1. Using Appropriate Dosage Form :
• Slow & Sustained absorption of drugs –
- Retard tablets ( pot. Chloride retard tablets )
- Depot injections ( Fluphenazine depot injectons )
- Subcutaneous implants ( testosterone pellets )
2. Changing Physical characteristics of drug :
• e.g. Procaine PnG
- Slightly water soluble
- When given i.v. ⇨ slowly absorbed & action is
prolonged
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46. Contd…
3. Adding a Vasoconstrictor Drug :
- Noradrenaline + Local Anaesthetic ( Xylocaine )
⇓
- Prolongs effect of local anaesthetic effect
- Reduces absorption into Systemic circulation &
systemic toxicity
4. Applying a Tourniquet :
- Tourniquet application ⇨ injection of L.A. below it
⇓
Delays systemic absorption
Prolongs action of L.A.
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47. Methods to Facilitate Absorption
• Addition of enzyme Hyaluronidase (breaks down
intercellular matrix)
⇓
Speeds absorption
• Increasing the local blood flow to the tissue
⇓
Increased absorption
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48. T h a n k
y o u…
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49. All of the following statements
regarding bioavailability
of a drug are true except:
◦ (a) It is a fraction of administered drug that reaches the
systemic circulation in unchanged form
◦ (b) Bioavailability of an orally administered drug can be
calculated by comparing the Area Under Curve after oral and
intravenous administration
◦ (c) Low oral availability always and necessarily means poor
absorption
◦ (d) Bioavailability can be determined from plasma
concentration or urinary excretion data.
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50. ◦ Drug transport mechanisms include:
◦ (a) Active transport
◦ (b) Passive transport
◦ (c) Diffusion
◦ (d) All
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51. All of the following are advantages of transdermal drug
delivery systems EXCEPT:
◦ (a) They produce high peak plasma concentration of the drug
◦ (b) They produce smooth and nonfluctuating plasma
concentration of the drug
◦ (c) They minimize interindividual variations in the achieved
plasma drug concentration
◦ (d) They avoid hepatic first pass metabolism of the drug
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52. ◦ Major mechanism of transport of drugs across
biological membranes is by:
◦ (a) Passive diffusion
◦ (b) Facilitated diffusion
◦ (c) Active transport
◦ (d) Endocytosis
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53. ◦ Pharmacodynamics includes:
◦ (a) Drug elimination
◦ (b) Drug excretion
◦ (c) Drug absorption
◦ (d) Mechanism of action
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