Pharmacology

1. PHARMACOLOGY
2ND
CHAPTER

2. Pharmacology
• Greek word , Pharmakon- Drug and Logos – Study
• The study of interaction of drugs with living organism. It embraces all knowledge
concerning drugs
• History, source , physiochemical properties, dosage form, method of administration,
distribution, mode of action, biochemical changes produced in the body,
biotransformation, excretion, adverse effect
Drug : French word drogue means Dry herb.
According to WHO A drug is a substance or product that is used or intended to be used
to modify or explore physiological system or pathological state for the benefit of the
recipients.
The benefit of the recipient means the diagnosis, prevention, control or cure of the
diseases.
Ex: insuline metronidazole
Drugs are distinguished from endogenous biochemical by being introduced from outside
of the body.

3. •Groups of drugs: Different drugs have different biological effect. Some
drugs perform similar action with different strength though they have
different physical properties and chemical structure.
Ex: Antibiotics: Amoxyciline HCl, Ciprofloxacine HCl, Azythromycine HCl.
Antacid Mg(OH)2
, Al(OH)3
•Prodrug: There are some drugs or substances which do not produce
any pharmacological effect until they are chemically altered within the
body, such a substance are called prodrugs.
•A prodrug is a substance that are administrated in an inactive form and
is metabolized in vivo into active metabolite.

4. Purposes of prodrug
•Increase the administration from the GI track or other site of
administration
•Reduce the presystemic biotransformation
•Increase the specificity of the drug receptor site
•Reduce the adverse effect
•Ex: Aspirin has the biologically active form Salicylic acid

5. Sources of drug
1. Natural : plant/animal, time consuming to collect , amount is less
▪Plant source: Alkaloids
Glycoside
oil
Antibiotics
Gum and Mucilage
Carbohydrates and relative compounds
Plant sources are root, bark , stem, leaf, seed flowers
H2
O soluble
H2
O insoluble

6. • Alkaloids: Basic nitrogenous compound and or corresponding salt reacting with acid . They are white
crystalline substance having bitter taste. They are soluble in alcohol, insoluble in water. Salts are soluble in
water. They are easily identified by the word (ine) in the end of the name . Most of the alkaloids are
extracted from flower plants. Ex, Morphine, Nicotine
• Glycoside: The glycoside is the condensation product of sugar with various hydroxy organic compound. IT is
non- nitrogenous colorless, crystalline solid, Which can be splits up into sugar part and non-sugar part. The
non-sugar part is called aglycon, and is pharmacologically active part of glycoside. ( Bark, seed, leaf) ex,
Doxin, Digitoxin
• Oil: a) Fixed or non volatile ( high M.W) oil that's a mixture glycerol ester of high M.W aliphatic acid ex:
plamic acid, Stearic acid, This oil is lighter than water, insoluble in water but soluble in chloroform. It has no
smell. b) Volatile Low M.W oil: Odorous compound as it evaporates when exposed to air . So it is called
volatile oil or essential oil.
• Gum and mucilage: They are secretory and hydrocolloidal product of plant origin, chemically non-ionic ,
anionic, polysaccharide which on hydrolysis produce sugar. Gum is differentiated by the basis of solubility .
Gum readily soluble in water and mucilage form slimy mass. Ex: Psyllium seeds (gum), Tragacants
(mucilage)
• Antibiotics: majority of antibiotics are produced by antiniomycetes (58%) Fungy( 80%), Higher plant (12%),
and 9% other bacteria , 3% other algae . Ex: Erythromycene, Genetumgecene
• Carbohydrate and relative compounds: Naturally occurring organic compounds 65% aq. Solution of sugar
can be used as preservative

7. 1. ANIMAL SOURCES: Toad skin due to diseases lack of vit-A. From cod fish
the deficiency of vit A can filled. Insulin hormone is extracted from the
pancreas of bovine , a cattle like buffaloes.
2. Mineral sources: Various clay is used for diarrhea or constipation. Mercury
in calomel is used to treat congestive cardiac failure.
3. Laboratory source: Most of the drugs are artificially synthesized with two
or more elements. This synthetic source of drug is less time consuming,
safer than plants, low cost and can be produced in a large scale.

8. Route of administration
• To produce the pharmacological effect, it is important for the drugs to reach the
site of the action. There should be a minimum concentration of drug in blood to
be biologically active . This concentration is called the therapeutic concentration
• The drug works in two ways 1. Administration of the drug 2. The release of the
active ingredient in action.
• Delivery system
Local drug ( Directly on skin) Systemic drug (In blood)

9. What are the factors therapeutic conc.
Depends on?
•Volume of distribution: The amount of drug taken
•Biotransformation: how the drug is biologically active after
metabolism
•Excretion: release of the excess drug from the body.

10. Selection of routes depend on the following
factors
1. Physical properties: the physical properties of a drug determine which route is
ideally suitable for action. Ex: a. Antacid is well in gastric environment whereas
benzyl penicillin antibiotic will get in activated in the stomachs acidic
environment { Because penicillin is a weak acid with pKa value of 2.7 . It is
highly ionized in plasma. The gastric absorption of penicillin G is poor because
it rapidly hydrolyzed inn the acid of stomach} b. Morphine is given by injection
as it is absorbed in stomach after oral administration.
2. Site of action: Ther are some drugs which are route specific. . Ex: Ansthetic
vapour is suitable for inhalation. 0.5% Timalol solution is greatly effective than
10 g timalol taken orally.
3. Onset of action: For rapid onset action, the plasma level has to be reached
quickly. For this inhalation or intravenous route become more necessary

11. 4. Maintenance / Prolongation of action: For sustainable action transdermal
(into skin) or subcutaneous (under the skin) drugs are applied. Ex: Insuline
is more effective transdermally than injection.
5. Adverse effect: The route selection sometimes prevents the adverse
effect. Ex: Sulbutamol is well tolerated inhalationally than the oral
administration

12. Membrane
First pass
a. Oral or rectal
(out of the body)
b. Intravenous /Intraarterial
(Injection)
c. Intramuscular/ sublingual/
subcutaneous
Metabolism
Bioavailability in blood
Bioavailability in blood

13. Routes of Administration
Enteral Parenteral Tropical or Site
specific
Oral administration ( tablet, capsule , powder, solution, suspension)
Rectal administration ( Gas or acid sensitive drug/ Solution, Suppository, ointment)
Nasogastric administration ( Patient is unconscious, semiconscious, uncooperative/ Solution, suspension)
Colonic administration ( Directly into the colon through anus/ liquid )
Buccal administration( Between the chick and gum/ tablet, )
Sublingual ( Under the tongue/ tablet , aerosol, capsule)

14. Parenteral ( Dosage form solution only)
Intradermal Ad.(applied within the layers of skin/ solution, suspension)
Subcutaneous ( applied between the skin and cell)
Intermuscular Ad. ( Inside the muscle penetrating the skin and subcutaneous tissue)
Intravenous ( Into the vein for instant action)
Intraarterial Ad.( Bioavailability 100%)
Intrathecal Ad. ( On the spinal cod)
Epidural Ad. ( On the joint of the spine)
Intracardiac Ad. ( During cardiac or Bypass surgery)
Intraperitoneal ad. ( Beside the naval)
Intrapleural Ad. ( into the cell of the body, under the skin)
Intraarticular( on the joint of bones)

15. Tropical or Site specific
Epidermal ( Outer layer of skin/ Cream , ointment)
Transdermal ( Just under the skin)
Conjunctive ( Under the eye/ injection)
Inhalation ( asthma)
Nasal ( nose drop)
Vaginal ( Suspension / suppository)

16. Pharmacogenetics
•Pharmacogenetics ( pharmacogenomics) is generally regarded as the
study or clinical testing of genetic variation that gives rise to different
responses to drug. Pharmacogenetics refers to genetic difference in
metabolic pathway which can affect individual response to drugs both
in therapeutic and adverse effect.
•Pharmacogenetic technology : There are rapid development of gene
and protein sequence machine that determines the amino acid
sequence. Two recent developments
1. Phenotyping
2. Genotyping

17. Phenotyping Classification
•Functional phenotyping : Determines the presence and activity of
particular metabolic enzyme
•Metabolic phenotyping: It measures the level of metabolites in a
person after administration of drug
Genotyping: It determines the specific genetic code of individual.
* Difference between phenotyping and genotyping

18. Pharmacodynamics
•Pharmacodynamics means what a drug does to the body
Pharmacodynamics is the study of how a drug affects an organism. It
is concerned with the effects of drugs and the metabolism of their
action. Ex:

19. HOW DO DRUGS WORK?
Cell Membrane
Bound Endogenous Activator (Agonist) of Receptor
Active Cell Surface Receptor
Extracellular
Compartment
Intracellular
Compartment
Cellular Response

21. Mechanism of drug action
•Some drug act by interacting with their 1.specific receptor, some
drugs response 2. Modifying ion channel 3. Interacting with enzyme 4.
Physical and chemical rection
•Receptor: Receptor is the component of the cell to which a ligand
specifically bind and produce responses. Receptor are located at the
plasma membrane steroid, thyroid, hormone inside the cell.

22. Classification of receptors:
• Ion- channel coupled receptor : Ion channel receptors are usually
multimeric proteins located in the plasma membrane. Each of
these proteins arranges itself so that it forms a passageway or
pore extending from one side of the membrane to the other. these
passageways, or ion channels, have the ability to open and
close in response to chemical or mechanical signals. When an
ion channel is open, ions move into or out of the cell in
single-file fashion.
• Protein- coupled receptor
• receptor
• DNA-linked receptor

23. G-Protein- coupled receptor
• G protein-coupled receptor (GPCR), also
called seven-transmembrane receptor or heptahelical
receptor, protein located in the cell membrane that binds extracellular
substances and transmits signals from these substances to an
intracellular molecule called a G protein (guanine nucleotide-binding
protein). GPCRs are found in the cell membranes of a wide range of
organisms, including mammals, plants, microorganisms,
and invertebrates.

24. Ion channels
• Ion channels( membrane protein) are pores that open and close in all or
nothing fashion in a time scale of 0.1 to 10msec. Provide the aqueous
channel through the plasma membrane that that ion can transverse.
• The ion channel are either voltage sensitive or ligand gated.
• Classification of ion channels: Sodium channel, Calcium channel, Potassium
channel, Chloride channel
• shaping action potentials and other electrical signals by gating the
flow of ions across the cell membrane, controlling the flow of ions
across secretory and epithelial cells, and regulating cell volume. Ion
channels are present in the membranes of all cells.[
Ion channels are
one of the two classes of ionophoric proteins, the other being ion
transporters.

25. Tyrosine-Kinase link membrane
https://www.youtube.com/watch?v=ObrsQl-vPA4&app=deskto
p&ab_channel=HeyNowScience

27. Depending on the receptor involved, the chemical structure of the ligand and the tissue that is being affected,
nuclear receptor ligands may display dramatically diverse effects ranging in a spectrum from agonism to
antagonism to inverse agonism.
Agonists
The activity of endogenous ligands (such as the hormones estradiol and testosterone) when bound to their
cognate nuclear receptors is normally to upregulate gene expression. This stimulation of gene expression by
the ligand is referred to as an agonist response. The agonistic effects of endogenous hormones can also be
mimicked by certain synthetic ligands, for example, the glucocorticoid receptor anti-inflammatory
drug dexamethasone. Agonist ligands work by inducing a conformation of the receptor which favors
coactivator binding (see upper half of the figure to the right).
Antagonists
Other synthetic nuclear receptor ligands have no apparent effect on gene transcription in the absence of
endogenous ligand. However they block the effect of agonist through competitive binding to the same binding
site in the nuclear receptor. These ligands are referred to as antagonists. An example of antagonistic nuclear
receptor drug is mifepristone which binds to the glucocorticoid and progesterone receptors and therefore
blocks the activity of the endogenous hormones cortisol and progesterone respectively. Antagonist ligands
work by inducing a conformation of the receptor which prevents coactivator and promotes corepressor
binding (see lower half of the figure to the right).
Inverse agonists
Finally, some nuclear receptors promote a low level of gene transcription in the absence of agonists (also
referred to as basal or constitutive activity). Synthetic ligands which reduce this basal level of activity in
nuclear receptors are known as inverse agonists.