Pharmacokinetics is the study of how the body affects a drug over time, including aspects like absorption, distribution, metabolism, and excretion of drugs. The four main pharmacokinetic properties that determine the onset, intensity, and duration of a drug's effects are absorption, distribution, metabolism, and excretion. Understanding a drug's pharmacokinetics allows clinicians to design optimal dosing regimens by considering factors like the route of administration, dose, dosing frequency, and duration of treatment.

3. Derivation
Pharmacology =>
Pharmakon = Active Principle/Active
Ingredient or equivalent to drug, medicine or
poison &
Logia = study.
PHARMACOLOGY
means:
“THE SCIENCE OF DRUGS”

4. Pharmacology:
 Is the study of substances that interact with
living systems through chemical process,
especially by binding to regulatory molecules &
activating or inhibiting normal body process.
 Includes, history, source, properties,
compounding, biochemical and physiological
effects, PK and PD, therapeutic and other uses,
precautions, adverse effects, interactions and
contra-indications of drugs.

5.  A French word ‘Drogue’ which means dry herb.
 Any substance that brings about a change in biologic
function through its chemical action.
 Alters state in the body:
=>can’t create new function but alter existing
function.
 Are poisons if they used irrationally.
 Poisons are drugs that have almost exclusively harmful
effects. However, Paracelsus famously stated that
"the dose makes the poison,"
 “Poisons in small doses are the best medicines; and
useful medicines in too large doses are poisonous.
“Every drugis a medicine buteverymedicine is not a drug!!!”

6. Receptors
 Specialized target macromolecules present on
the cell surface or intracellularly.
 The biological molecule plays a regulatory role.
 Drugs bind with receptors & initiate events
leading to alterations in biochemical activity of a
cell, and consequently, the function of an organ.
 Some times, the drug may act through non-
specific physicochemical mechanisms.
– Osmotic properties (bulk laxatives, saline
purgatives, mannitol)
– Adsorbents (kaolin, charcoal)

7. Basic Areas of Pharmacology
 Pharmacokinetics (Biodisposition of drugs)
 Pharmacodynamics
 Pharmacokinetics: deals with absorption, distribution,
biotransformation & excretion of drugs.
 Pharmacodynamics: study of biochemical &
physiological effects of drugs & their MOA
(Mode of Action).
 Pharmacotherapeutics: use of drugs in prevention &
treatment of disease.
 Chemotherapy: effect of drugs upon microorganisms,
parasites and neoplastic cells living & multiplying in living
organism.

8. Basic Areas of Pharmacology
 Pharmacokinetics (Biodisposition of drugs)
 Pharmacodynamics
 Toxicology: branch of pharmacology which deals with
the undesirable effects of chemicals on living systems.
 Pharmacogenomics: relationship of individual’s genetic
makeup to his/her response to specific drugs.

9. History of Pharmacology
 Prehistoric people recognized beneficial & toxic
effects of many plant & animal materials.
 Preceding the modern era, there were attempts
to introduce rational methods into medicine.
 But none were successful owing to the
dominance of systems of thought [without
experimentation & observation].
 Around end of 17th century, reliance on
observation & experimentation began.
 About 60yrs ago, controlled clinical trial
reintroduced; expansion of research efforts;
 Drug action & receptor.
 Now, the molecular mechanism of action of many
drugs is known.

10. Application of
pharmacology
 To control speed of onset, intensity of the drug's
effect, and duration of action. Hence decide on
route of administration, the amount and frequency
of each dose, and the dosing intervals.
 To identify the possible side effect, and
withdrawal symptoms of drugs and take measures
to manage.
 To avoid adverse effects from drug interaction
and contraindicated drugs.
 To avoid adverse effects in special populations
like geriatrics, paediatrics, pregnant and lactating
mothers.
 To avoid treatment failure due to tolerance &
resistance.
 To control misuse of drugs by the patient & health
professionals.

11. Drugs
 Drugs mostly interact with a specific molecule in
a biologic system that plays a regulatory role
[receptor].
 Clinically, drugs used for:
–Diagnosis: Barium salts,
–Prevention: Vaccines, chemoprophylaxis
–Treatment: Antiretroviral Therapy(ART)
–Cure: Antibiotics
–Alteration of physiological processes:
Hormones & their derivatives (insulin, GH,
contraceptives….)
–Global effect: General anesthetics

12. To interact chemically with its receptor, a
drug molecule must have the appropriate:
 Size (MW100-1000Dalton),
 For specificity of action, the ability to move
within the body (e.g., from the site of
administration to the site of action).
 Electrical charge (bonding)
 Shape (complementary to that of the receptor
site in the same way that a key is complementary
to a lock).
 Atomic composition.

13.  A number of useful or dangerous drugs are
inorganic elements, e.g. lithium, iron, & heavy
metals.
 Many organic drugs are weak acids or bases.
– This fact has important implications for the
way they are handled by the body, because pH
differences in the various compartments of
the body may alter the degree of ionization of
such drugs.

14. Source of
Drugs
 Drugs are obtained from various sources.
 Drugs may be synthesized within the body
(hormones) or not. i.e. xenobiotics (from the
Greek xenos, meaning "stranger").

15.  According to sources they are:-
1.Natural drugs
A. Plants
E.g. . Digoxin from Digitalis purpurea
. Atropine from Atropa belladonna
. Quinine from Cinchona officinalis
B. Animals
E.g.. Insulin from pork/beef
. Cod liver oil from Cod fish liver.
C. Minerals: Iron, Iodine, Potassium salts.
D.Micro – organisms: Penicillin from penicillium
notatum, Chloramphenicol from Streptomyces
venezuelae (Actinomycetes).

16. 2. Synthetic drugs: prepared by chemical
synthesis in pharmaceutical laboratories.
E.g. Sulphonamides, quinolones, barbiturates.
3. Semi-synthetic drugs: prepared by chemical
modification of natural drugs.
E.g. . Ampicillin from penicillin G.
. Dihydroergotamine from ergotamine.
4. Biosynthetic drugs: prepared by cloning of
human DNA in to the bacteria like E.coli.
E.g.. Human insulin (humulin), human GH.

17. Drug Nomenclature
• Existence of many names for each drug causes
lamentable & confusing situation.
• A drug has at least three types of names;
 Chemical name (IUPAC) or scientific name,
 Based on molecular structure of the drug
 Very long, too complex to use in common practice.
 International Nonproprietary/generic name,
- Given by FDA/WHO while approved, the short hand
version of chemical name.
- Recommended in RX.
 Proprietary/trademark/Brand name,
- Given by the pharmaceutical company.
- Costly.

18. Examples:
 2-acetoxybenzoic acid
 Aspirin
 Jusprin®
 Ethyl 4-(8-chloro-5,6-dihydro-11 H-benzo[5,6]
cyclohepta[1,2-b] pyridin-11-ylidene)-1-piperidine
carboxylate.
 Loratadine
 Claritin®

19. DOSAGE FORMS
(PREPARATIONS)
Dosage forms (DFs) are the means by which drug
molecules are delivered to sites of action within
the body.

20. Types of Dosage forms
According to route of administration:
Oral
Rectal
Vaginal
Parenteral
Inhaled
Topical
Ophthalmic
Otic

21. Types of Dosage forms…
According to physical form of a drug;
1. Solid
a. Tablets – Conventional
- Chewable
- Sublingual
- Extended release
b. Capsules – Hard gelatin & Soft gelatin
c. Powders – Effervesent granules
- Insufflations
- Dentrifices
- Powder for injections
d. Suppositories

22. 2. Liquid – Solutions, Suspensions, Emulsions
3. Semisolids – Ointments
- Creams
- Pastes
- Jellies
- Pessaries
4. Gases (pressurized) - aerosols

23.  Orally (swallowed)
 Through Mucus Membranes
– Oral Mucosa (e.g. sublingual)
– Nasal Mucosa (e.g. insufflated)
 Topical/Transdermal
(through skin)
 Rectally (suppository)
According to on set of
action Slow
Absorption

24. Faster
Absorption
90⁰ 45⁰
 Parenterally (injection)
– Intravenous (IV)
– Intramuscular (IM)
– Subcutaneous (SC)
– Intradermal(ID)-15⁰
– Intraperitoneal (IP)
 Inhaled (through lungs)

25. Medication
Administration
– Right Medication
– Right Dosage
– Right Time
– Right Route
– Right Patient
– Right Documentation

26. Routes of Drug administration
Is the path by which a drug, fluid, poison
or other substance is brought into contact
with the body.

27. Commonly Used Routes of Drug Administration
28
IV = intravenous;
IM = intramuscular;
SC = subcutaneous.

28. Enteral Routes
 Enteral - drug placed directly in the GI tract:
–sublingual - placed under the tongue
–Oral - swallowing (p.o., per os)
–Rectal - absorption through the rectum

29. Oral Route
ADVANTAGES
 Safe
 Convenient
 Economical
 Usually good absorption
 Can be self
administered
action
drugs
DISADVANTAGES
 Slow absorption slow
 Irritable and unpalatable
 Un co-operative &
unconscious pts.
 Some drugs destroyed
 First-pass effect

30. Sublingual Route
ADVANTAGES
 Economical
 Quick termination
 First-pass avoided
 Drug absorption is quick
 Can be self administered
DISADVANTAGES
 Unpalatable & bitter drugs
 Irritation of oral mucosa
 Large quantities not given
 Few drugs are absorbed

31. Rectal Route
ADVANTAGES
Used in children
DISADVANTAGES
Inconvenient
Little or no first pass effect Absorption is slow and erratic
Used in vomiting/unconsciuos Irritation or inflammation of
Higher concentrations rapidly rectal mucosa can occur
achieved
Vaginal Routes
 Drug may be administered locally in the vagina in
the form of pessaries.
E.g. Antifungal vaginal pessaries

32. First-pass Effect
 The first-pass effect is the term used for the
hepatic metabolism of a pharmacological agent
when it is absorbed from the gut and delivered to
the liver via the portal circulation.
 The greater the first-pass effect, the less the
agent will reach the systemic circulation when the
agent is administered orally.

33. First-pass Effect cont’d…
Magnitude of first pass hepatic effect:
 Extraction ratio (ER)
ER = CL liver/Q
 Where, Q is hepatic blood flow (usually about 90 L per
hour for 70 kg adult).
 Systemic drug bioavailability (F) may be
determined from the extent of absorption (f) &
the extraction ratio (ER),
F = f x (1-ER)

34. First-pass Effect
cont’d…

35. Systemic Routes
Parenteral
First-pass
metabolism
can occur
with orally
administered
drugs.

36. Needle insertion for
parenteral drug:
A. Intradermal
injection @15⁰.
B. Subcutaneous
injection @45⁰.
C. Intramuscular
injection @90⁰.
D. Intravenous
injection

37. 1. Absorption phase is bypassed (100% BA)
2. Precise, accurate and almost immediate onset of
action.
3. Large quantities can be given, fairly pain free
4. Greater risk of adverse effects
a. High concentration attained rapidly
b. Risk of embolism and cannot be recalled by
strategies such as emesis or by binding to
activated charcoal
5. IV is the most common parenteral route for
drugs that are not absorbed orally.

38. Intramuscular Route(IM)
Advantages
 Absorption reasonably
uniform
 Rapid onset of action for
drugs in aqueous solution.
 Mild irritants can be given
 Repository and slow release
preparations
 First pass avoided
 Gastric factors can be
avoided
Disadvantages
 Only up to 10ml drug given
 Local pain and abscess
 Expensive
 Infection
 Nerve damage

39. Subcutaneous route(SC)
1. Slow and constant absorption
2. Absorption is limited by blood flow, affected if
circulatory problems exist
3. Concurrent administration of vasoconstrictor will
slow absorption

40. 1. Aerosols (gaseous & volatile agents)-lungs
2. Rapid onset of action due to rapid access to
circulation
A. Large surface area
B. Thin membranes separates alveoli from
circulation
C. High blood flow

41.  Mucosal membranes (eye drops, nasal drops,
antiseptic, sunscreen, callous removal etc.)
 Skin
A. Dermal - rubbing in of oil or ointment (local
action)
B. Transdermal - absorption of drug through
skin (systemic action)
i. Stable blood levels
ii. No first pass metabolism
iii. Drug must be potent or patch
becomes to large

42.  Intravenous 30-60 seconds
 Intraosseous 30-60 seconds
 Endotracheal 2-3 minutes
 Inhalation 2-3 minutes
 Sublingual 3-5 minutes
 Intramuscular 10-20 minutes
 Subcutaneous 15-30 minutes
 Rectal 5-30 minutes
 Ingestion 30-90 minutes
 Transdermal (topical) variable (minutes to hours)

43. The ROA is determined by:
 Physical characteristics of the drug,
 Speed which the drug is absorbed and/or released,
 The need to bypass hepatic metabolism and achieve
high conc. at particular sites
Important
Info

44. Pharmacokinetics (The life cycle of a Drug)
 Pharmacokinetics:
– Pharmakon: drug
– Kinesis: motion
 Action of body on drug/ how body handles drugs
 Pharmacokinetics: ADME
 Four pharmacokinetic properties determine the
onset, intensity & duration of drug action.
 Using knowledge of pharmacokinetic parameters;
clinicians can design optimal drug regimens;
including the route of administration, dose,
frequency & duration of treatment.
44

45. General Pharmacology 45
Absorption
 Absorption is the process by which a drug enters
the bloodstream without being chemically altered
or
 The movement of a drug from its site of
application into the blood or lymphatic system
How drugs transfer form site of administration?
1. Filtration [aqueous diffusion]-passage of drugs
through aqueous pores.
Size should be less than size of pore
 Has to be water soluble.
E.g. Na+, glucose, caffeine.

46. General Pharmacology 46
2. Diffusion: drugs supposed to pass membrane.
Drugs must be lipid soluble.
High partition coefficient  high absorption.
3. Carrier mediated absorption
a. Facilitated diffusion
- Passive but facilitated.
E.g. levodopa & amino acid into brain.
b. Active transport
- Use ATP & carrier proteins.
- Against the concentration gradient.
E.g. levodopa & methyldopa from the gut.

47. 4. Phagocytosis & pinocytosis
- Process by which large molecules are engulfed by
the cell membrane forming a vesicle & releases
them intracellularly.
E.g. protein, toxin
General Pharmacology 47

48. General Pharmacology 48
Drug absorption
• Transfer of a drug from its site of
administration to the bloodstream.
• The rate and efficiency of absorption depend on
the route of administration.
– For IV delivery, absorption is complete; that
is, the total dose of drug reaches the systemic
circulation.
– Drug delivery by other routes may result in
only partial absorption and, thus, lower
bioavailability.

49. General Pharmacology 49
Factors affecting GI absorption
PH of media & pKa of the drug
Area of absorbing surface
Particle size of the drug
Formulation
Gut motility
GIT blood flow
Gastric secretion
Drug interaction

50. General Pharmacology 50
 A drug must be in solution to be absorbed, since
most drugs are either weak acids or weak bases,
pH affects their solubility and hence absorption.
 Weak bases are absorbed more rapidly from the
intestine than stomach.
 Small intestine is the major absorption site
because:
–It has large surface area (microvilli
200M2)
–There is good blood supply (1L blood/min
compared to 150mL/min stomach)
–Permeability to drugs is greater

51. General Pharmacology 51
Bioavailability (F)
• Fraction of administered drug that reaches the
systemic circulation in a chemically unchanged
form.
– Amount of drug available in the circulation/site
of action
– It is expressed in percentage
– It is 100% for drugs given IV.
• For example, if 100 mg of a drug is administered
orally and 70 mg of this drug are absorbed
unchanged, the bioavailability is 0.7 or 70%.
Factors affecting bioavailability
– Extent of absorption
– First pass effect

52. Plasma
Concentration
Oral Dose
Time
Bioavailability (F)
General Pharmacology 52

53. General Pharmacology 53
Drug distribution
 Reversible movement of drug from bloodstream
to interstitium (extracellular fluid) and/or cells.
Factors affecting drug distribution
1.Plasma protein binding
– Albumin [acidic & hydrophobic drugs]
– -glycoprotein [basic drugs]
2.Tissue uptake of drugs/tissue binding
-Adipose tissue [DDT]
-Bone [TTC]
-Liver [chloroquine]
-Thyroid gland [iodine]

54. 3. Barriers –capillary permeability
 Blood brain barrier (BBB)
 Placental blood barrier (PBB)
 Cell membrane
4. Rate of blood flow
 Brain,
 Kidney,
 Liver &
 Lung
highly perfused
5. Plasma concentration
General Pharmacology 54

55. General Pharmacology 55
Drug metabolism
 Enzymatically mediated alteration in drug
structure.
 Transforms lipophilic drugs into more polar
readily excretable products.
 Liver - major site for drug metabolism, but
specific drugs may undergo biotransformation in
other tissues, such as the kidney and the
intestines.
 Note: Some agents are initially administered as
inactive compounds (pro-drugs) and must be
metabolized to their active forms.

56. General Pharmacology 56
Inducers
 The cytochrome P450 enzymes are an important
target for pharmacokinetic drug interactions.
 Certain drugs, most notably phenobarbital,
rifampin, and carbamazepine, are capable of
increasing the synthesis of one or more CYP
isozymes.
 This results in increased biotransformations of
drugs.
1. Decreased plasma drug concentrations.
2. Decreased drug activity if metabolite is
inactive.
3. Increased drug activity if metabolite is
active.
4. Decreased therapeutic drug effect.

57. Inhibitors
 Inhibition of CYP isozyme activity is also an
important source of drug interactions that leads to
serious adverse effects.
 The most common form of inhibition is through
competition for the same isozyme.
 For example, omeprazole is a potent inhibitor of
three of the CYP isozymes responsible for
warfarin metabolism.
 If the two drugs are taken together, plasma
concentrations of warfarin increase, which leads to
greater inhibition of coagulation and risk of
hemorrhage and other serious bleeding reactions.
64

58. Inhibition of drug metabolism may lead to;
- Increased plasma levels over time with long-term
medications.
- Prolonged pharmacological drug effect.
- Increased drug-induced toxicities.
Microsomal enzyme inducers
Phenobarbitone
Phenytoin
Rifampicin
Carbamazepine
Sulphonamides
St. John’s Wort
Cigarette smoking
General Pharmacology 58
Microsomal enzyme inhibitors
 Isoniazid
 Disulfiram
 Cimetidine
 Allopurinol
 Chloramphenicol
 Erythromycin
 Metronidazole
 Grape fruit juice

59. First-Pass Effect: significant metabolic
inactivation of some drugs by the liver following
oral administration.
- Drugs absorbed from the GI tract enter the
portal circulation and are carried to the liver
before entering the systemic circulation.
General Pharmacology 59

60. General Pharmacology 60
Drug excretion
 Removal of a drug from the body occurs via a
number of routes.
 The major routes of excretion include renal
excretion, hepatobiliary excretion & pulmonary
excretion.
 The minor routes of excretion are saliva, sweat,
tears, breast milk, vaginal fluid & hair.
 The rate of excretion influences the duration of
action of drugs.
 If the drug is excreted slowly, the concentration
of drug in the body is maintained and the effects
of the drug will continue for longer period.

61. General Pharmacology 61
Routes of drug excretion
a. Renal excretion
 For water soluble and non volatile drugs.
 The three principal processes that determine the
urinary excretion of a drug.
– Glomerular filtration
– Active tubular secretion
– Passive tubular reabsorption
 The function of glumerular filtration and active
tubular secretion is to remove drug out of the
body, while tubular reabsorption retain the drug.

62. General Pharmacology 62
b. Hepatobiliary Excretion
 The conjugated drugs are excreted by
hepatocytes in the liver.
 After excretion of drugs through bile to the
intestine; certain amount of drug is reabsorbed
in to the portal vein leading to an entrohepatic
cycling which can prolong the action of drug.
 E.g. Chloramphenicol, estrogen.

63. General Pharmacology 63
c. Gastro intestinal excretion
 When a drug is administered orally, part of the
drug is not absorbed and excreted in the faeces.
 The drug which do not undergo enterohepatic
cycling after excretion in to the bile are
subsequently passed with stool.
 E.g. Aluminum hydroxide changes the stool
color in to white, Ferrous sulphate darkens it
and Rifampicine gives orange red colour to the
stool.

64. General Pharmacology 64
d. Pulmonary excretion
 Many inhalation anesthetics and alcohol are
excreted through the lungs.
e. Sweat
 E.g. Rifampcine, metalloids like arsenic are
excreted in to the sweat.