Pharmacology

1. Pharmacology-I
Course code PMS-614
By
Dr. Junaid Athar Khattak
INTRODUCTION TO PHARMACOLOGY
AND ITS BASIC PRINCIPLES
3rd Semester, Chapter # 1
Institute of paramedical sciences,
Khyber Medical University Peshawar
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2. Introduction to Pharmacology
Definition1: “Study of substances that interact with living system through chemical
process, especially by binding to regulatory molecules and activating or inhibiting
normal body process”. OR
Definition2: The branch of medical sciences which deals with the study of action of
drug on living tissues
Origin:
• Pharmacology is derived from two words; Pharmacon means drugs or medicine
and logos means study
• It has two divisions as follows
• Pharmacokinetics: It means the movement of drugs in the body (absorption,
distribution, Metabolism (biotransformation), and excretion).
• Pharmacodynamics: The mechanism by which the drug exerts its effect. For
example, how aspirin work as an analgesic.
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3. PHARMACOKINETICS
DEFITITION:
It means the movement of drugs in the body (absorption, distribution,
Metabolism (biotransformation), and excretion). OR
What the body does to the drug.
Pharmacokinetics consists of the following divisions, so will discuss all of
these in detail.
 Absorption
Distribution
Metabolism
 Excretion 3

4. ABSORPTION (PHARMACOKINETICS)
• DEFINITION: The transfer of a drug from the site of administration to the blood
stream.
• The process of absorption is complete, when the drug given by iv route
reaches the systemic circulation
• But when the drug is given by oral route, it must cross the cell membrane to reach
the systemic circulation, and its absorption may be partial.
• The cell membrane consist of two layers with protein layer on each side. The cell
membrane consist of hydrophilic and hydrophobic part. lipids soluble drugs
passing through hydrophobic part. Most of the drugs given passes through the
pores present in the cell membrane.
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5. FACTORS AFFECTING DRUG ABSORPTION
• Drug concentration: Greater the concentration of drug greater will be the
absorption because of greater concentration gradient between the site of
administration and local blood vessels.
• Lipids solubility : The drug with high lipids solubility will be rapidly
absorbed as compare to those with less lipids soluble or water soluble drugs.
e.g. vitamin A and D.
• Surface area : It is the area of the body which is directly exposed to drug.
Greater the surface area, greater will be the absorption of drug. e.g. intestine
have greater surface area than stomach so greater amount of drug will
be absorbed in intestine.
• PH of the medium: Acidic drugs will be better absorb in acidic medium
like aspirin, phenobarbitone. Basic drugs show better absorption from basic
media like Ephedrine.
• Weight of the body: Greater the weight of the body greater dose will be
require in order to show quick action. 5

6. DRUG DISTRIBUTION
• DEINITION: It is the process by which a drug reversibly leaves the blood
stream and enters the interstitium (Extracellular fluid) and / or the cells of
the tissues.
• After absorption the drug did not remain in the plasma.
• It is distributed in the body and all tissues, which includes adipose tissues, muscles
and brain etc.
• When the drug is distributed into the tissues, it will produce a therapeutic
effect 6

7. FACTORS AFFECTING DRUG DISTRIBUTION
• Dose of the drug: Greater the dose of the drug, higher will be the distribution of the
drug.
• Route of administration: Intravenous injection produce a rapid rise in the drug
concentration while oral rout gives slow rise in drug concentration and intramuscular
is an between these two.
• Lipid solubility: Drugs which have high lipids solubility are rapidly absorb and
distributed to different tissues as well as the CNS. But the drugs which are ionized at the
PH of blood will be poorly absorbed from the blood and distributed to the tissue and also
have poor penetration to the CNS e.g. tetracycline. While the drugs like
chloramphenicol and sulphadiazine are lipid soluble and readily penetrated into
the CNS.
• Pathological condition: Pathological condition also effect drug distribution.
• It increase the permeability of blood brain barrier e.g. in meningitis the permeability of
blood brain barrier is increase.
• In order to produce a certain level of effect ceftriaxone is used to treat this condition.
• Due to the increased permeability of BBB, the drug can easily reach the infected area.
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8. FACTORS AFFECTING DRUG DISTRIBUTION cont
• Binding of drugs to plasma protein and storage: Drugs which are bounded to
plasma proteins like albumin and globulin are slowly released and slowly
distributed to different tissue in order to produce a certain level of effect.
• Drugs can also be distributed to some other areas e.g.
• Thiopentone and griseofulvin adipose tissues
• Tetracycline bones and teeth
• Chlorpromazine brain
• Chloroquine liver
• Digoxin skeletal muscles
• Iodine thyroid glands
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9. DRUG METABOLISM OR BIOTRANSFORMATION
• DEFINITION: Metabolism is change in the chemical structure of the drug
from one form to another, which is readily execrable.
• Ethanol is a CNS depressant drug change to acetaldehyde which is ready for
excretion.
• When the drug is metabolized, its pharmacological activity is diminished.
• In short the metabolism convert the drug into more polar form which is readily
excreted from the body.
• The effect of the metabolism is the conversion of drug into inactive form but some
drugs are converted into active form .
 Active drugs to active metabolites are
• Phenylbutazone to oxyphenylebutazone
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10. DRUG METABOLISM OR BIOTRANSFORMATION
 Pro drug or inactive drug to active metabolites e.g.
• Levodopa dopamine
• prednisone prednisolone
 Active drugs to toxic metabolites
• INH acetyl hydrazine
• sulphonamides acetyl derivatives
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11. SITES OF DRUG METABOLISM OR
BIOTRANSFORMATION
• Metabolism takes place various parts of the body such as liver, kidneys, lungs,
skin and occur almost in all parts of the body except in nails and hairs.
• Liver is the major organ for the metabolism of drugs because the microsomal
enzymes (CYP-450) responsible for metabolism are present in the liver.
• Enzymes such as Esterases, Amidases, Dehydrogenases, Transferases and p-450
are responsible for the metabolism of drugs .
• Biotransformation may also takes place in mitochondria and plasma
membrane. 11

12. TYPES OF METABOLIC REACTIONS
There are two main types of metabolic reactions
A) Oxidation A) Acetylation
B) Reduction B) Methylation
C) Hydrolysis C) Glucuronide conjugation
D) Sulphate conjugation
E) Amino acid conjugation
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1) Phase 1 reactions 2) Phase 2 reactions

13. 1) PHASE 1 REACTIONS
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• Phase 1 reactions includes the following
 A) Oxidation reaction:
o Oxidation reactions mean the addition of oxygen and removal of hydrogen from a
drug molecule.
o It can be a microsomal which takes place in the liver (SER) and non-microsomal
which takes place other parts of the body enzymes in mitochondrion of the cell.
 Reduction reaction:
o It involve the halogenated and nitrated compounds. These reaction takes place in
the liver. Nitrobenzene is converted into aniline.
 Hydrolysis:
• These reactions take place in the liver and are carried out by the Esterases and amidases
which hydrolyze the ester and amide group of the drug e.g. aspirin is hydrolyzed by
esterase into salicylic acid.

14. 2) PHASE 2 REACTIONS
• Phase 2 reactions are also called biosynthetic reaction.
• It is the process by which drug combine with endogenous substance usually
carbohydrate or amino acids or their derivatives resulting causes the inactivation
of drug nearly all conjugates are inert and water soluble in nature and can pass
easily in urine.
• It involves the following reactions
A) Acetylation:
• It involve the addition of acetyl group to a drug thus drug is converted into
metabolites.
• For example, in case of isoniazid (anti-tubercular drug) acetyl group is added and
converted into acetyl ionized.
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15. 2) PHASE 2 REACTIONS
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2) Methylation:
• It involve the addition of methyl group to the drug and is converted into its
metabolites.
• Example: Dopadihydroxy phenyl alanine (anti-Parkinson drug) is converted
into Methyl Dopa.
• Glucuronide conjugation: It takes place in phenols and alcohols or in
compounds containing hydroxyl and carboxylic group these are easily
conjugated with glucuronic acid e.g. aspirin, phenacetin etc.
• Sulphate conjugation: The phenolic and steroidal compounds are sulphated
by sulphokinase e.g. salicylamide is converted into salicylamide Sulphate.
• Amino acid conjugation: Drugs like nicotinic acid, salicylic acid and
benzoic acid are combined with amino acid to form conjugates. These
reactions are carried out by transferase enzyme.
• large conjugates are excreted in bile while small conjugates are excreted
in urine.eg glycine + benzoic acid yield Hippuric acid.

16. DRUG EXCRETION/ ELIMINATION
• Excretion of drug: The process where the drug is transferred inversely from
internal to external environment through renal and non-renal route.
• Major routes of drug excretion : These are renal , biliary , faecal and alveolar.
• Minor routes of drug excretion: These are milk , hair, sweat, skin and saliva.
• Renal excretion: It is the most major route.
• Kidneys are the most important organs for the removal of drug there are three
processes that determine excretion through are
a):Glomerular excretion
b):Active tubular secretion
c):Passive tubular reabsorption
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17. ROUTES OF DRUG ADMINISTRATION
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• A route of administration in pharmacology and toxicology is the path by which a
drug, fluid, or other substance is taken into the body
• The followings are the various routes of drug administration
• Enteral route
• Parenteral route
• Inhalational route
• Topical route

18. ROUTES OF DRUG ADMINISTRATION
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19. 1: ENTERAL ROUT
Enteral Route:
o Enteral word is derived from a Greek word enteron which means Gut or intestine
e.g.. the administration of drug through GIT.
It has been divided into following types.
• Oral
• Sublingual
• Buccal
• Rectal
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20. 1: ENTERAL ROUTE
A). Oral Route:
• The administration of drug by mouth.
• The most commonly used rout for the administration of drug.
• The drug given orally is absorb through GIT and maximum absorption occur in
small intestine.
• Most common dosage form available are tablets, capsules, syrup, suspension and
elixir etc.
• This rout can also be used for the local action of drugs like anthelminthic and
purgatives etc.
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21. 1: ENTERAL ROUTE
Advantages of oral route:
• Natural route
• It is a common route
• Inexpensive route
• Safe route
• Convenient route
• Acceptable route
• Painless route
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22. 1: ENTERAL ROUTE
• Painless rout This rout can be used for the local action of drugs
• This does not require a medical assistance
Disadvantages of oral route:
• It can't be use in emergency situations
• It can't be used for the patient suffering from vomiting
• It can't be used for unconscious patient
• Irritant drugs can't be given through this rout
• Can't be used for the drug destroyed by the gut e.g. insulin
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23. 1: ENTERAL ROUTE
B). Sublingual route:
• Sub means beneath and lingual means tongue so in this rout the drug is given by
placing it under the tongue.
• The absorption takes place through buccal mucosa because in the buccal mucosa
there is a bed of capillaries through which the drug is rapidly absorbed and reach
the systemic circulation.
• For example angised, which is an antianginal drug is used to place under the
tongue.
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24. 1: ENTERAL ROUT
C). Buccal Rout:
• It is the administration of drug where the drug is placed between the gums and
inner walls of the cheeks and drug is absorbed by the buccal mucosa.
Advantages:
• Avoid first pass metabolism
• Rapid action
• Drug remain stable
Disadvantages:
• It is an inconvenient rout
• It has a very small dose limit
• Drug will lose its effect if swallowed
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25. 1: ENTERAL ROUT
D). Rectal Rout:
• In this way the drug is administer through rectum
• This rout can be used for local as well as for systemic effect.
• Suppositories, lotion, ointment and enemas can be used through this rout.
Advantages:
• This rout is used for the local action of certain drugs
• It is a common rout used for babies
• This rout can be used for unconscious patient and for those who are suffering from
vomiting
Disadvantages:
• Inconvenient
• Absorption is slow
• Inflammation to the rectal mucosa
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26. 2: PARENTERAL ROUT
Parenteral rout:
• The word parenteral is derived from a Greek word para mean away and enteron means
gut or intestine
• Here the drug is directly administered through injection.
• This is further divided into the following routes.
Intravenous
Intramuscular
Subcutaneous
Intra arterial
Intra articular
Intra thecal
Intra dermal
 Intra cardiac
 Intrapleural 26

27. 2: PARENTERAL ROUT
Intra venous :
• The administration of drug directly into the vein
• Here the drug directly introduce into the blood.
• This is route of choice for aqueous preparations.
• This route provides most rapid and quick response.
• The drug is rapidly distributed into the tissues.
Advantages of Intra venous rout:
• Bioavailability through this route is 100%
• large quantity of drug can also be administered through this route
• Irritant drugs can also be given through this route
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28. 2: PARENTERAL ROUT
• This route can also be used in emergency situations
• First pass effect is avoided
• Gastric manipulation can be avoided
Disadvantages of Intra venous route:
• It is non economical and expensive route
• require technical person and aseptic techniques
• Not suitable for oily preparations or for suspension
• It can cause thrombophlebitis and bacteremia
• it is less convenient and painful also require technical person
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29. 2: PARENTERAL ROUTE
Intra muscular routes:
• By this route the drug is usually given into gluteal are deltoid muscles.
• Absorption from this areas is high because of rich blood supply to these areas.
• The rate of absorption of drug depend upon the concentration and blood flow to
this area.
Advantages:
• Quick absorption of drug
• Route of choice in emergency situations
• Does not require patient cooperation
• Patient may got some psychological satisfaction
• It require technical assistance and aseptic techniques
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30. 2: PARENTERAL ROUTE
Disadvantages of Intra muscular routes:
• Expensive and painful route require medical assistance
• There may a danger of infection and chances of abscess
• There may be chances of breakage of needle in the muscles
• There may be chances of injury to the bone and nerves
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31. 2: PARENTERAL ROUTE
Subcutaneous route:
• By this route the drug is given below or under the skin.
• The absorption may be less than intramuscular route.
• The irritant substance may cause pain and local necrosis.
Advantages:
• The action of the drug is quick to produce local action
• Vaccine can be given through this rout
• There is uniform distribution of the drug
Disadvantages:
• It is expensive route
• Skilled handed person is require
• This route can be use for limited numbers of drugs 31

32. 2: PARENTERAL ROUTE
Intra-arterial route:
• By this route drug is given into the artery for localized effect.
• Anti-cancer drugs are usually given through this route.
• This is also used for the diagnosis of peripheral vascular disease.
Intra articular route:
• This route is used for the administration of antibiotics and corticosteroids into
the cavities of inflamed joints through injection like hydrocortisone is injected in
rheumatoid arthritis.
Intrathecal route:
• This route is used for the administration of drug to the subarachnoid space of
the spinal cord.
• This route is used for getting anesthesia
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33. 2: PARENTERAL ROUTE
Intra cardiac route:
• This is directly administered in the cardiac muscles to achieve an immediate
effect.
• Adrenaline injection is usually given through this route to enhance cardiac
contractility.
Intra dermal route:
• This route is used to inject the drug into the skin or dermis.
• This route is used to check the sensitivity of certain drug e.g. penicillin; iron etc.
Intrapleural route:
• This route is mainly used to give drug into the pleural cavity, which is a thin
membrane covering the lungs
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34. 2: PARENTERAL ROUTE
Topical/Local routes:
• The drug given through this route is usually to produce local effect to the inflamed
surface of mucosal membrane.
• The drug in applied on the external surface of the skin as well as mucosal surface
of the lungs, eyes, ears and vagina.
• It has the following types
Skin:
• Various drugs like antibiotics, antiseptic, cream and applied on skin for treating
various skin problems.
Eyes and ears:
• Most of the drugs are usually given through these routes for treating ears and eyes
problem in the form of drops. 34

35. 2: PARENTERAL ROUTE
Vagina:
• Most of the antifungal drugs are given through this route for treating fungal
infection.
Lungs:
• Inhalers are used to be given by this route for local effect. Bronchodilators are
given through this route in respiratory disorders.
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36. PHARMACODYNAMICS
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37. Contiued…
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38. PRINCIPLES OF DRUG ACTIONS
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47. TYPES OF AGONISTS
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48. TYPES OF AGONISTS
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50. TYPES OF ANTAGONISM
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51. 3. PHYSIOLOGICAL OR FUNCTIONAL ANTAGONISM
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52. 3. PHYSIOLOGICAL OR FUNCTIONAL ANTAGONISM
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• There are two sub types of physiological antagonism
A) Competitive Antagonism and
B) NON Competitive Antagonism

53. 3. PHYSIOLOGICAL OR FUNCTIONAL
ANTAGONISM
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B) NON COMPITATIVE ANTAGONISM

54. 54

55. SIGNAL TRANSDUCTION MECHANISM FOR
1. LIGAND GATED ION CHANNEL RECEPTORS
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56. SIGNAL TRANSDUCTION MECHANISM FOR
1. LIGAND GATED ION CHANNEL RECEPTORS
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57. SIGNAL TRANSDUCTION MECHANISM FOR
2. G PROTIENE COUPLED RECEPTORS
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58. SIGNAL TRANSDUCTION MECHANISM FOR
2. G PROTIENE COUPLED RECEPTORS
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59. SIGNAL TRANSDUCTION MECHANISM FOR
3. ENZYME-LINKED RECEPTORS
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60. SIGNAL TRANSDUCTION MECHANISM FOR
3. ENZYME-LINKED RECEPTORS
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61. SIGNAL TRANSDUCTION MECHANISM FOR
4. RECEPTORS REGULATING GENE EXPRESSION
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62. DOSE RESPONSE RELATIONSHIP
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63. DOSE RESPONSE RELATIONSHIP
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64. DOSE RESPONSE RELATIONSHIP
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65. DOSE RESPONSE RELATIONSHIP
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66. DOSE RESPONSE RELATIONSHIP
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67. DOSE RESPONSE RELATIONSHIP
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68. DOSE RESPONSE RELATIONSHIP
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69. DOSE RESPONSE RELATIONSHIP
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70. DOSE RESPONSE RELATIONSHIP
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71. DOSE RESPONSE RELATIONSHIP
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72. Any Question?

73. 73