1. (Pharmacokinetics; drug administration and absorption)
General pharmacology
(Pharmacokinetics; drug administration and absorption)
Prof. Hanan Hagar
Dr.Ishfaq Bukhari
Pharmacology Department

2. What is Pharmacology? From the Greek pharmakon (drug),
and legein (to speak or discuss)
Broadly defined as the study of how chemical agents affect living processes.
e.g Hormones, Neurotransmitters and drugs

3. What is Pharmacology
Pharmacology studies the effects of drugs and how they exert their effects.
Acetylsalicylic acid (ASA) or Aspirin can reduce
inflammation, , pain and fever
It inhibit the action of a human cell membrane enzyme known as cyclooxygenase, which is
responsible for the synthesis of a number of
inflammatory mediators.
Penicillin cures certain bacterial infections
disrupt the synthesis of cell walls in susceptible
bacterial strains by inhibiting a key enzyme.

4. Some Pharmacology Definitions and Areas of Study
Pharmacokinetics
Study the fate of drugs once ingested. It covers , How the body absorbs, distributes,
metabolizes, and excretes drugs (what the body does to a drug?)
Pharmacodynamics
Study the mechanisms by which drugs work ,Also study endogenous agents (what the drug does to the body?)

5. Pharmacokinetics (Drug absorption)
The student should be able to
Discuss the different routes of drug administration
Identify the advantages and disadvantages of various routes of drug administration
Know the various mechanisms of drug absorption
List different factors affecting drug absorption
Define bioavailability

6. Recommended books
Lippincott’s illustrated reviews (Pharmacology) by Howland and Mycek
Basic and Clinical Pharmacology by by Katzung

7. PHARMACOKINETICS:
Pharmacokinetics:It is the study of what the body does to the drug i.e ADME
ABSORPTION
DISTRIBUTION
METABOLISM
EXCRETION
of the drug
Note: Pharmacodynamic is what the drug does to our body

8. Routes of drug administration

9. Routes of drug administration

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

11. Oral administration Self use Safe convenient - cheap
Disadvantages
Advantages
- Slow effect
No complete absorption
- Destruction by pH and enzymes
- GIT irritation
- Food - Drug interactions
Drug-Drug interactions
First pass effect
(low bioavailability).
Not suitable for
vomiting & unconscious patient
emergency & bad taste drugs
- Easy
Self use
Safe
convenient
- cheap
- No need for sterilization

12. Factors affecting absorption from GIT
GIT motility changed by drug / diseases
Presence of food
Blood flow/surface area
GIT juices
pH of GIT fluids
Chemical/drug interactions
dosage form of a drug
Most of the drug is absorbed with in 1-3 hours,mostly it occurs in small intestine ,rate of absorption depends on lipid solubility ,ionization and pH.

13. Factors affecting absorption from GIT
Drugs administered in aqueous solution are absorbed faster & completely than tablet or suspension forms.
Drugs such as the tetracyclines, which are highly ionized, can complex with Ca++ ions in membranes, food, or milk, leading to a reduction in their rate of absorption.
Factors that accelerate gastric emptying time, permitting drugs to reach the large absorptive surface of the small intestine sooner, will increase drug absorption unless the drug is slow to dissolve.

14. 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
Results ?
Low bioavailability.
Short duration of action of drugs (t ½).

16. First pass effect

17. Stomach pH
The low pH of the gastric contents (pH 1–2) may influence absorption of drugs because it can affect the degree of drug ionization. e.g, the weak base diazepam will be highly Ioninized in the gastric juice, and absorption will be slow.
weak acid drug, acetaminophen will exist mainly in its unionized form and can more readily diffuse from the stomach into the systemic circulation.

18. Small intestine
The small intestine, with its large surface area and high blood perfusion rate, has a greater capacity for absorption than does the stomach.
Conditions that shorten intestinal transit time (e.g., diarrhea) decrease intestinal drug absorption, while increases in transit time will enhance absorption by permitting drugs to remain in contact with the intestinal mucosa longer.

19. Oral Dosage Forms (oral formulations)
Tablets (enteric coated tablets)
Capsules (hard and soft gelatin capsules)
Syrup
Suspension
Emulsion

20. Spansule
Tablets
Soft- gelatin capsule
Hard- gelatin capsule

21. 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

22. Rectal administration
Disadvantages
Advantages
Irregular absorption & bioavailability.
Irritation of rectal mucosa.
Suitable for
children
Vomiting or unconscious
patients
Irritant & Bad taste drugs.
less first pass metabolism
(50%)
Dosage form:
suppository or enema

23. Parenteral administration
Intradermal (I.D.) (into skin)
Subcutaneous (S.C.) (under skin)
Intramuscular (I.M.) (into muscles)
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)

25. Intravenous administration
Disadvantages
Advantages
Infection
Sterilization.
Pain
Needs skill
Anaphylaxis
Expensive.
Not suitable for oily solutions or poorly soluble substance
Rapid action (emergency)
High bioavailability
No food-drug interaction
No first pass metabolism
No gastric irritation
Suitable for
Vomiting &unconsciousness
Irritant & Bad taste drugs.
Dosage form:
Vial or ampoule

26. Ampoule Vial
Single use
Repeated use

27. Injection Special Utility Limitations
I.D.
Minute volume (0.1 ml)
Suitable for vaccinations
& sensitivity test
Not suitable for large volumes
S.C.
0.1 ml – 1 ml
Suitable for some poorly soluble suspensions and for instillation of slow-release implants e.g. insulin zinc preparation
I.M.
larger volume 3-5 ml Suitable for moderate volumes, oily vehicles, and some irritating substances
Not suitable for irritant drugs
I.V.
Suitable for large volumes and for irritating substances
Not suitable for oily solutions or poorly soluble substances
Must inject solutions slowly as a rule

28. Drugs are mainly applied topically to produce local effects
Drugs are mainly applied topically to produce local effects. They are applied to
Skin (percutaneous) e.g. allergy test, topical antibacterial and steroids prep and 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

29. 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
Less side effects.
No first pass effect
Dosage form: volatile gases (anesthetics), aerosol, nebulizer for asthma

30. Nebulizer Atomizer

31. Transdermal patch
a medicated adhesive patch applied to skin to provide systemic effect (prolonged drug action)
e.g. the nicotine patches (quit smoking)
Scopolamine
(vestibular depressant)

32. Drug absorption
Is the passage of drug from its site of administration to its site of action through various cell membranes.
Except for intravenous administration, all routes of drug administration require that the drug be transported from the site of administration into the systemic circulation.

33. Sites of Administration Sites of action
Drug absorption
Is the passage of drug from its site of administration to its site of action through cell membranes.
Cell membrane
Sites of
Administration
Sites of
action

34. Absorption & distribution
Elimination
Sites of
Administration

35. Mechanisms of drug absorption
The transport of drugs across membranes occurs through one or more of the following processes:
Simple diffusion = passive diffusion.
Active transport.
Facilitated diffusion.
Pinocytosis (Endocytosis).

36. Cell membrane

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

40. Simple diffusion
Low conc
High conc

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

42. Simple diffusion
Drugs exist in two forms ionized (water soluble) nonionized forms (lipid soluble) in equilibrium.
Drug ionized form + nonionized form
Only nonionized form is absorbable.
Nonionized / ionized fraction is determined
by pH and pKa
As general basic drugs are more ionized and less diffusible in a relatively acidic medium, on the contrary basic are more lipid soluble and more diffusible in a relatively alkaline medium

43. PKa of the drug
(Dissociation or ionization constant): pH at which half of the substance is ionized & half is unionized.
The lower the pKa value (pKa < 6) of the acidic drug the stronger the acid e.g aspirin (Pka= 3.0 ),
The higher the pKa value (pKa >8) of a basic drug, the stronger the base e.g propranolol ( pKa= 9.4)

44. 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.

45. 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)?
Propranolol pka= 9.4

46. Active Transport Relatively unusual.
Occurs against concentration gradient.
Requires carrier and energy.
Specific
Saturable.
eg.
Sugar, amino acids and Iron absorption.
Uptake of levodopa by brain.

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

50. 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
saturable
Not saturable
Selective
Not selective
energy is required
No energy

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

52. Phagocytosis (Endocytosis & Exocytosis)
Endocytosis: uptake of membrane-bound particles.
Exocytosis: expulsion of membrane-bound particles.
Phagocytosis occurs for high molecular weight
Drugs or highly lipid insoluble drugs.

53. (Exocytosis)
(Endocytosis)
OUT IN IN
OUT

54. Mechanisms of drug absorption

55. Factors modifying drug absorption
GENERAL FACTORS
lipid solubility
Degree of ionization
Drug solubility (aqueous sol better than oily,susp,sol)
Dosage forms (depending on particle size and disintegration)
Concentration of drugs
Circulation at site of absorption
Area of absorbing surface (small intestine has large surface area)
Route of administration.

56. Bioavailability I.V. provides 100% bioavailability.
Is the fraction of unchanged drug that enters systemic circulation after administration and becomes available to produce an action
I.V. provides 100% bioavailability.
Oral usually has less than I.V.