2.
It is the study of physiological & biochemical
effects of drugs & their mechanism of action at
organ system /subcellular /macromolecular levels.
It deals with what the drug does to the body.
Whereas Pharmacokinetics deals with what the body
does to the drug
3.
This may be desirable therapeutic effects or
undesirable adverse effects (A/E)
The A/E may be expected effects of the drug as side
effects or toxicity( Quantitative effect)
Unexpected A/ E are seen as hypersensitivity
( allergy ) or Idiosyncrasy ( Qualitative effect)
4.
Stimulation - Adrenaline on heart/ Pilocarpine on
salivary gland
Depression - Diazepam on CNS/ PPI on Gastric acid
Replacement - Hormones - Insulin , Thyroxin/ levodopa
in parkinsonism
Cytotoxicity - Anticancer drugs , Antibiotics
Irritation
5.
1.
2.
3.
4.
Most drugs act by binding to a particular target
protein as follows:
Receptors
Ion Channels
Enzymes
Carrier or Transport proteins
Certain drugs have no particular target
Eg: Alcohol, GA
6.
7. Receptor
It is a macromolecular or binding site located on the
surface or inside the effector cell that serves to
recognize the signal molecule / drug & initiate the
response to it, but itself has no other function
Sites of receptors- cell membrane, cytoplasm, nucleus
8.
Paul Ehrlich
The idea that drugs act upon specific
sites (receptive substance) began with
John New Port Langley (1852-1926)
of Cambridge.
The word ‘receptor’ was given by
Paul Ehrlich (1854- 1915).
The receptor concept which forms a
key note in the development of
molecular pharmacology became
firmly established by the quantitative
work of
Alfred Joseph Clark
(1885-1941),
a
professor
of
pharmacology at Kings College
London.
10.
Ligand :
Any molecule that binds selectively to a specific
receptor is called ligand
Affinity :
It is the ability of the molecule to bind to a receptor
Intrinsic activity/Efficacy :
It is the ability of the molecule to elicit a response
after binding with the receptor
11. Agonist
Has both affinity and intrinsic activity
IA= +1
Eg : Adrenaline - α & β receptors,
Morphine- opioid receptors
Antagonist
Has affinty but no intrinsic activity (IA=0).
They oppose the action of agonist
Eg : Propronolol- β blocker,
Atropine-M receptor
12. PARTIAL AGONIST:
Have affinity & submaximal intrinsic activity
IA =between 0 & +1
Eg : Nalorphine, Pentazocin on opioid receptors
Inverse Agonists:
These drugs have affinity but produces actions
opposite to those produced by agonist.
IA = between 0 & -1
Eg: Beta Carboline on BZD receptor
14. SPARE RECEPTORS:
These are reserve receptors present in the body,
gets stimulated only at special situations.
SILENT RECEPTORS:
These are receptors to which an agonist binds
but does not produce a response.
15.
Continued use & stimulation of receptors by agonist
drugs may decrease the number and sensitivity of
the receptors.
This phenomenon is called down regulation
Eg: Constant use of β2 agonist (salbutamol) reduce
therapeutic response in Asthma
16.
Continued use and inhibition of receptors by
antagonist drugs, may increase the number and
sensitivity of the receptors.
This phenomenon is called up regulation.
Eg: sudden withdrawal of anti-anginal drug
(Propranolol) may precipitate angina.
17. 1) Ion channel receptor
2) Transmembrane receptor
3) G-protein coupled receptor
4) Nuclear receptor
Receptor which regulate gene transcription.
18. 1. Ion channel linked
2.
Transmembrane linked
3.
G protein linked
4.
Nuclear (gene) linked
19. -Voltage gated ion channel
-Ligand gated ion channel
-Stretch activated ion channel
-Temperature activated ion channel
20.
Protein pores in the
membrane
Ions include Na+, K+, Ca2+ , Cl.
plasma
Nerves, Skeletal & smooth
muscle cells, cardiac tissue
Channels open when there is
Depolarization of membrane
from its resting potential
Voltage gated Na+ Channeleg. Local An.-lidocaine
Voltage Dependent Ca Channel
eg. Nifedipine
21. Protein pores in the
plasma membrane
Ions include Na+, K+, Ca2+ , Cl.
GABA gated Cl- Ion channel - eg. BZD
Glutamate gated cation Ch. (NMDA r)-
eg. Ketamine, Galantamine
Action occurs very fast in millisecond
24. GPCR Structure:
• Single polypeptide chain
threaded back and forth
resulting in serpentine
shaped 7 transmembrane
alpha helices with 3 loops
extracellularly & 3 loops
intracellularly.
1
2
3
4
•There’s a G protein
attached
to
the
cytoplasmic side of the
membrane.
6
5
Gα
GDP
7
β
γ
• Amino
terminal
lies
extracellularly & carboxy
terminal on cytosolic side.
25. Guanine nucleotide binding proteins:
participate in reversible, GTP-mediated interactions.
Common features:
bind GDP and GTP with high affinity, but adopt different
structure depending on the bound nucleotide.
GTP-bound complex has high affinity for other proteins
(“acceptor’), affecting their enzymatic activity
possess intrinsic GTPase activity which converts GTP to
GDP
Contains ,
and subunits
-subunit contains the GTP/GDP binding site,
26.
27.
Gs – Adenyl cyclase Stimulator & Ca channel
opener
Gi – Adenyl cyclase Inhibitor & K+ channel
opener
Gq – Phospholipase C activator
Go – Ca channel inhibitor
32.
Structure:
• Receptors exist as individual
polypeptides
• Each has an extracellular
signal-binding site
• An intracellular tail with a
number of tyrosines & a
single å helix spanning the
membrane
• Receptor action is slow &
occurs in hours
Eg: Insulin receptors, EGF &
NGF, PDGF, ANF, TGF
receptors.
36.
Receptors are seen intracellularly in the cytoplasm,
Agonist(drug) cross cell membrane and bind with receptor
and form Drug Receptor complex .
DR complex moves to nucleus, interact with DNA, regulate
gene transcription , synthesise specific proteins which
produce cellular effects.
Nuclear receptor action is very slow and occurs with in hours
or days
Egs: Corticosteroids, Sex hormones ,Thyroxine,
Vitamin D, Vitamin A
41. 1) Physical
Bulk laxative
eg.- Agar
Osmotic purgative
- Mgso4, Mannitol
Adsorption
- Charcoal
Demulscent
- Glycerine
Astringent
-tannic acids
2) Chemical
-Neutralisation of Gastric Hcl by antacids,
-Chelating agents with Heavy metals
3) Physico-Chemical
-Alcohol
42.
This is a graph showing dose response relation.
Dose is plotted on X-Axis and Response is
plotted on Y-Axis.
There are two types of DRC:
-Graded/simple DRC
- Log DRC
In Log DRC – dose is converted to logarithmic
scale and is plotted
Log DRC is more convenient and used
44.
Large variations in doses can not be plotted on a
single graph paper.
Comparison between other drug responses is not
possible
45.
Being logarithmic scale , less space
only is
required for plotting & large variations of dose
can be recorded on single graph paper.
Comparison between different drug responses
are possible
46.
To compare the efficacy & potency of drugs
To distinguish between Competitive &
Noncompetitive antagonism of drugs
For calculating the Therapeutic Index or Safety
margin of drugs
47.
Efficacy is the maximum effect produced by the
drug. The maximum height of DRC shows the
efficacy. Clinically efficacy is more important.
Potency is the amount of drug required to
produce the response. in case of less potent drug ,
DRC shifts to right.
Steeper slope of DRC indicates marked increase
in response with slight increase in dose
51. % Max response
AG alone
AG + NC ANT
AG + higher dose
NC ANT
Log Drug Concentration
52.
The gap between therapeutic effect DRC and adverse
effect DRC defines the safety margin or therapeutic
index (TI)
It can be calculated as ratio between LD50 and ED50
TI = median Lethal Dose
= LD50
median Effective Dose
ED50
TI should be more than one , it indicates safety of drug.
Greater the TI , more will be the safety of the drug
53.
Median effecive dose means the 50% of test
population showing therpeutic effect.
Median lethal dose means the 50% of test
population showing lethal effect.
Drugs with wide TI – Diazepam , Penicillin
Drugs with narrow TI – Digoxin , Lithium,
phenytoin,Theophyllin
54.
55.
56.
57. This is the dose range of drug bounded by the
dose which produces minimal therapeutic effect
and the dose which produce maximal
acceptable adverse effect.
Also known as Therapeutic Window.
59. Combined effect of Drug
Synergism
Antagonism
-Physical Antagonism
Additive
synergism
Supradditive
synergism
-Chemical Antagonism
-Physiological Antagonism
-Receptor Antagonism
60. 1.
Additive synergism:
If the total effect of drugs is equal to sum of their
individual effects, it is called additive synergism
( eg: 2+2 = 4)
Egs: Aspirin + paracetamol (analgesic effect)
Theophyllin + ephedrine (Br.Asthma)
2.
Supra additive synergism :
If the added up effect is greater than sum of their
individual effects, it is called supra-additive
synergism ( eg: 2+2 > 4)
Egs: Levodopa + carbidopa (Parkinsonism)
61. 1.Physical antagonism:
The effect of one drug is inhibited by physical
property of another drug.
Eg: Charcoal adsorbs poisons on its surface &
useful in alkaloid poisoning
2.Chemical antagonism :
Here two drugs interact chemically and one drug
neutralise the effect of the other.
Egs :Antacids neutralise gastric acidity
Ca EDTA useful in lead poisoning
62. Here two drugs act on different receptors/ sites; but their
pharmacological effects are opposing each other
functionally
Examples:
Histamine (H1) produce bronchospasm
Adrenaline (β2) produce bronchodilation
Insulin reduce blood sugar
Glucagon increase blood sugar
63. A. Competitive reversible
Both agonists & antagonist drugs compete for same
receptor.
Antagonistic effect is completely reversible.
Eg: Morphine & naloxone on opioid receptor
Adrenalin & Prazosin on alpha receptor
65. B. Competitive irreversible
both drugs act on the same receptor . But
Antagonistic effect is not reversible .
Eg: Adrenaline & Phenoxybenzamin (α rec.)
C. Non Competitive antagonism
The drugs act at different sites of the same receptor
or pathway.
Eg: Adrenaline & Verpamil.
66. % Max response
AG alone
AG + NC ANT
AG + higher dose
NC ANT
Log Drug Concentration
