1. Pharmacology Department
General pharmacology
(Pharmacokinetics)
Grade I
Prof. Hanan Hagar
Pharmacology Department

2. Basic and Clinical Pharmacology by Katzung
Recommended books
Basic and Clinical Pharmacology by Katzung
Pharmacology
by Rang

3. Pharmacokinetics of drugs
(ADME)
Are studies of
Absorption
Distribution
Metabolism
Excretion of drugs

6. Drug absorption
Is the passage of drug through cell membranes to reach its site of action.
Mechanisms of drug absorption
Simple diffusion = passive diffusion.
Active transport.
Facilitated diffusion.
Pinocytosis (Endocytosis).

7. Cell membrane

9. Simple or passive diffusion
water soluble drug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane.
Lipid soluble drug (nonionized or non polar) is readily absorbed via cell membrane itself.

11. Simple diffusion Characters pka of drug - pH of medium.
common.
Occurs along concentration gradient. Non selective
Not saturable
Requires no energy
No carrier is needed
Depends on lipid solubility.
Depends
pka of drug - pH of medium.

12. Simple diffusion
Low conc
High conc

13. pKa- pH= log protonated / non-protonated
Simple diffusion
Drugs exist in two forms ionized (water soluble & nonionized forms (lipid soluble) in equilibrium.
Drug ionized + nonionized
Only nonionized form is absorbable.
Nonionized / ionized fraction is determined
by pH and pKa according to Henderson-
Hasselbach
pKa- pH= log protonated / non-protonated

14. Affects ionization of drugs.
PKa of the drug
(Dissociation or ionization constant):
pH at which half of the substance is ionized & half is unionized.
pH of the medium
Affects ionization of drugs.
Weak acids  best absorbed in stomach.
Weak bases  best absorbed in intestine.

15. Which one of the following drugs will be best absorbed in stomach (pH=3)?
Aspirin pka=3.0
warfarin pka=5.0
Arrange the following drugs in ascending order from least to greatest in rate of absorption in small intestine (pH=7.8)?
9.4 Propranolol pka=

16. Active Transport Relatively unusual.
Occurs against concentration gradient.
Requires carrier and energy.
Specific
Saturable.
Iron absorption.
Uptake of levodopa by brain.

18. Carrier-mediated Facilitated Diffusion
Occurs along concentration gradient.
Requires carriers
Selective.
Saturable.
No energy is required.

20. Carrier-mediated facilitated diffusion Active transport Needs carriers
along concentration gradient
(From high to low)
Against concentration gradient
(From low to high)
Needs carriers
Selective, saturable
No energy is required
Energy is required

21. against concentration gradient Along concentration gradient
Active transport
Passive transport
against concentration gradient
(From low to high)
Along concentration gradient
(From high to low)
Needs carriers
No carriers
Selective, saturable
Not selective
Not saturable
energy is required
No energy

22. Phagocytosis (Endocytosis & Exocytosis)
Endocytosis: uptake of membrane-bound particles.
Exocytosis: expulsion of membrane-bound particles.
High molecular weight drugs or
Highly lipid insoluble drugs

24. Routes of drug administration
Enteral
via gastrointestinal tract (GIT).
Oral
Sublingual
Rectal
Parenteral administration = injections.
Topical application

25. Oral administration Disadvantages Advantages 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.
Easy
Self use
Safe
Convenient
cheap
No need for sterilization

26. First pass Metabolism
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).

27. First pass effect

28. Dosage forms Capsules Tablets Syrup Suspension Hard- gelatin capsule
Soft- gelatin capsule
Tablets
Spansule

29. Sublingual Disadvantages Advantages Not for irritant drugs
Frequent use
Rapid effect (Emergency)
No first pass metabolism.
High bioavailability
No GIT destruction
No food drug
interaction
Dosage form: friable tablet

30. Rectal administration
Disadvantages
Advantages
Not for
Irregular absorption & bioavailability.
Irritation of rectal mucosa.
Suitable for
Vomiting & children. &unconsciousness
Irritant & Bad taste drugs.
less first pass metabolism
(50%)
Dosage form:
suppository or enema

31. Parenteral administration
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)

33. Parenteral administration
Disadvantages
Advantages
Infection
Sterilization.
Pain
Needs skill
Anaphylaxis
Expensive.
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

34. Ampoule Vial

35. Topical application 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
Topical application

36. Only few drugs can be used
Inhalation
Disadvantages
Advantages
Only few drugs can be used
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

37. Nebulizer Atomizer

38. Transdermal patch a medicated adhesive patch applied to skin
* Slow effect (prolonged drug action)
* produce systemic effect
e.g. the nicotine patches

39. Bioavailability
Is the fraction of unchanged drug that enters systemic circulation after administration and becomes available to produce action
I.V. provides 100% bioavailability.
Oral usually has less than I.V.
Bio = AUC oral / AUC IV X 100

41. Factors Affecting Bioavailability:
Molecular weight of drug.
Drug Formulation (ease of dissolution).
(solution > suspension > capsule > tablet)
Drug solubility of the drug
Chemical instability in gastric pH (Penicillin & insulin )
First pass metabolism reduces bioavai

42. Greater blood flow increases bioavailability
Factors Affecting Bioavailability (BAV):
Blood flow to absorptive site
Greater blood flow increases bioavailability
Intestine has greater blood flow than stomach
Surface area available for absorption.
Intestinal microvilli increases it
Rate of gastric emptying
rapid gastric emptying fast transit to intestine
pH of gut

43. Intestinal motility (Transit Time)
Diarrhea reduce absorption
Drug interactions
Food
slow gastric emptying
generally slow absorption
Tetracycline, aspirin, penicillin V