This document discusses the basic types and mechanisms of drug action. It describes five basic types of drug action: stimulation, depression, irritation, replacement, and cytotoxic action. It then provides examples and explanations of each type. The document also discusses the mechanisms of drug action, including interaction with target biomolecules like enzymes, ion channels, transporters, and receptors. Agonists, antagonists, and other receptor interactions are explained in detail. Non-receptor mechanisms like changing physical properties and cell membrane permeability are also covered.

1. DR.K.S.LATHA

2.  basic types of drug action classified are
stimulation
depression
irritation
replacement
cytotoxic action

3.  Stimulation
 -refers to selective enhancement of the
level of activity of specialised cells.
 eg adr.on heart ,pilocarpine on salivary
glands
 excessive stimulation depression
Eg. High dose of picrotoxin
Resp. depression

4.  Depression-
 Selectivediminution of activity of specialised
cells
eg.barbiturates depress CNS
quinidine depress heart
some drugs stimulate one type of cells and
depress the other type
Eg.acetyl choline stimulates smooth muscle
and depress the SA node

5.  Irritation-- Non-selective often noxious
effect – applied to less specialised cells
(epithelium, connective tissue) eg. Bitters
increase salivary and gastric secretion
 Counter irritants increaseblood flow.
 Strong irritantscause crrosion ,necrosis
 Replacement-- Use of natural metabolites,
hormones or their congeners in deficiency
states Levodopa in parkinsonism, Iron in
anaemia,insulin in diabetes.

6.  Cytotoxic action-for invading bacteria
parasite, cancer cells,without effecting the
host cells
 Used for cure /palliation of infections and
neoplasms
 Eg
 Pencillins,
 chloroquin,
 zidovudine,
 cyclophosphamide.

7.  Drugs act by their physical or chemical
property
 Bulk laxatives –physical mass
 Dimethicon – physical form opacity
 PABA-absorption of UV rays
 Activated charcoal adsorptive property
 Mannitol,Mg.So4 –osmotic activity
 KMNO4 –oxidising property
 Antaacids –nuetralisation of gastric activity

8. 
 MECHANISM OF DRUG ACTION
MAJORITY OF DRUGS INTERACT WITH
TARGET BIOMOLECULES:
 Usually a Protein
 ENZYMES
 ION CHANNELS
 TRANSPORTERS
 RECEPTORS

9. 
 Enzyme Inhibition - Examples Equilibrium:
Physostigmine Vs Acetylcholine
(cholinesterase) Sulfonamides Vs PABA
(folate synthetase) Moclobemide Vs
Catecholamines (MAO-A) Captopril Vs
Angiotensin 1 (ACE) Nonequilibrium:
Orgnophosphorous compounds/Nerve gases
(cholinesterase) Non-competitive:
Acetazolamide (carbonic anhydrase),
Omeprazole (HKATPase) , Aspirin
(cyclooxygenase)

10.  Transporters Substrates are translocated across
membrane by binding to specific transporters
(carriers) – Solute Carrier Proteins (SLC),ATP
binding cassettes(ABC). Pump the
metabolites/ions In the direction of concentration
gradient or against it Drugs interact with these
transport system Examples: Probenecid (penicillin
and uric acid), Furosmide (Na+K+2Cl-
cotransport), Hemicholinium (choline uptake) and
Vesamicol (active transport of Ach to vesicles
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11.  Receptors Drugs usually do not bind directly
with enzymes, channels, transporters or
structural proteins, but act through specific
macromolecules – RECEPTORS Definition: It
is defined as a macromolecule or binding site
located on cell surface or inside the effector
cell that serves to recognize the signal
molecule/drug and initiate the response to it,
but itself has no other function, e.g. G-protein
coupled receptor 9/26/2010

12.  Some Definitions Agonist: An agent which
activates a receptor to produce an effect
similar to a that of the physiological signal
molecule, e.g. Muscarine and Nicotine)
response Ra Ri RaA Ri

13. 
 Ion Channnels Proteins take part in
transmembrane signaling and regulates
ionic composition Drugs also target these
channels: Ligand gated channels G-protein
operated channels Direct action on
channels Examples: Local anaethetics and
Class I anti arrythmics act/depress Na+
channels

14.  Antagonist: an agent which prevents the
action of an agonist on a receptor or the
subsequent response, but does not have
an effect of its own, e.g. atropine and
muscarine no response 9/26/2010
ThepowerpointTemplates.com 14 Ra Ri
RaB RiB

15. :
 Partial agonist: An agent which activates a
receptor to produce submaximal effect but
antagonizes the action of a full agonist,
e.g. pentazocine Partial response
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15 RaC+Ra Ri+RiC


16.  Enzymes – drug targets
-All Biological reactions are carried out under catalytic
influence of enzymes – major drug target Drugs –
increases/decreases enzyme mediated reactions
- In physiological system enzyme activities are optimally set
-Enzyme stimulation- is less common by drugs – common
by endogenous substrates
eg.Pyridoxine (cofactor in decarboxylase activity) Adrenaline
stimulates hepatic glycogen phosphorylase
(hyperglycaemia) throughß receptors and cyclic AMP
Stimulation of enzyme increases the affinity for the substrate
so that rate constant km of that reaction lowered
Apparent increase in enzyme activity can occur through
enzyme induction

17.  Enzyme inhibition – common mode of drug
action
 Enzyme Inhibition – Ex. Equilibrium:
Physostigmine Vs Acetylcholine
(cholinesterase) Sulfonamides Vs PABA
(folate synthetase) Moclobemide Vs
Catecholamines (MAO-A) Captopril Vs
Angiotensin 1 (ACE) Nonequilibrium:
Orgnophosphorous compounds/Nerve
gases (cholinesterase) Non-competitive:
Acetazolamide (carbonic anhydrase),
Omeprazole (HKATPase) , Aspirin
(cyclooxygenase)

18.  FUNCTIONS OF RECEPTORS :
 FUNCTIONS OF RECEPTORS To
propogate signals from outside to inside To
amplify the signal To integrate various
extracellular and intracellular regulatory
signals To adapt to long term changes in
maintaining homeostasis

19.  Slide 16:
 Inverse agonist: an agent which activates
receptors to produce an effect in the
opposite direction to that of the agonist,
e.g. DMCM on bzp receptors opposite
response 9/26/2010
ThepowerpointTemplates.com 16 Ra
Ri+RiD

Slide 17:

20.  Non-receptor Mechanisms :
 Non-receptor Mechanisms Actions on
Enzymes Enzymes = Biological catalysts
Speed chemical reactions Are not changed
themselves Drugs altering enzyme activity
alter processes catalyzed by the enzymes
Examples Cholinesterase inhibitors
Monoamine oxidase inhibitors

21. 
Non-receptor Mechanisms :
 Non-receptor Mechanisms Changing
Physical Properties Mannitol Changes
osmotic balance across membranes
Causes urine production (osmotic diuresis)


22.  TYPES OF RECEPTORS :
 TYPES OF RECEPTORS 1.Ion gated
channels 2.G- protein coupled receptors
3.Cellular receptors 4.Nuclear receptors
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23


23.  Non-receptor Mechanisms :
 Non-receptor Mechanisms Changing Cell
Membrane Permeability Lidocaine Blocks
sodium channels Verapamil, nefedipine
Block calcium channels Bretylium Blocks
potassium channels Adenosine Opens
potassium channels


24.  Ligand: any molecule which attaches
selectively to particular receptors or sites
(only binding or affinity) Affinity: Ability of a
substrate to bind with receptor Intrinsic
activity (IA): Capacity to induce functional
change in the receptor If explained Agonist:
Affinity+ IA Antagonist: Affinity+ IA (0) Partial
agonist: Affinity + IA (0-1) Inverse agonist:
Affinity + IA (0 to -1)

Drug Mechanisms :

25.  Ion channels :
 Ion channels

Slide 25:
 Ligand gated ion chanels Fastest intracellular responce, ms Binding of ligand - opening of chanel - ion (K+, Na+) in or out of cell - responce Ligands Fast neurotransmittors
ex. Acetylcholine (nicotinic reseptors) Nobel prize chemistry 2003, Roderick MacKinnon “for structural and mechanistic studies of ion channels”.
http://nobelprize.org/chemistry/laureates/2003/press.html

G-Protein coupled receptor :
 G-Protein coupled receptor Membrane bound receptors which are bound to effector system through G-proteins. These are hetero trimeric molecules having 3 subunits α,β
and ϒ. Based on α-sub unit they are further classified into 3 main varieties Gs, Gi and Gq 9/26/2010 ThepowerpointTemplates.com 26

Slide 27:
 G-Protein coupled receptors G-protein: Guanine nucleotide binding protein

Slide 28:
 Subtypes of G-proteins - Targets (Second messenger systems) Ion chanels: G12 Na+ / H+ exchange Enzyms: Gi Inhib. Adenylyl cyclase Gs Stimul. Adenylyl cyclase Gq
Stimul. Phospholipase C One ligand can bind to more than one type of G-prot. coupled receptors second messenger pathways

Slide 29:
 Subtypes of G-proteins - Targets (Second messenger systems) Ion chanels: G12 Na+ / H+ exchange Enzyms: Gi Inhib. Adenylyl cyclase Gs Stimul. Adenylyl cyclase Gq
Stimul. Phospholipase C second messenger pathways

ENZYME LINKED RECEPTORS :
 ENZYME LINKED RECEPTORS a. Intrinsic enzyme receptors intracellular domain is either protein kinase or guanyl cyclase Ex:Insulin,EGF,NGF b.JAK-STAT-Kinase
binding receptors no intrinsic catalytic domain but agonist induced dimerization affinity for cytosolic tyrosine kinase protein Ex:cytokines,growth hormone,IF 9/26/2010
ThepowerpointTemplates.com 30

Slide 31:
 Enzyme coupled receptors - Catalytic receptors STAT: Signal transducers and activators of transcription Ligands: Peptide hormones

TRANSCRIPTION RECEPTORS :
 TRANSCRIPTION RECEPTORS Receptors regulating gene expression Intracellular- cytoplasmic or nuclear Ex:All steroid hormones,thyroxine, Vit A 9/26/2010
ThepowerpointTemplates.com 32

Slide 33:
 Cytoplasmic receptors (not bound to cell membranes) (HSP-90: Heat shock protein)

Slide 34:
 Receptor subtypes Most receptor classes - several sub-types Each subtypes - differend A(nta)gonists Sub types cholinerge reseptors Nicotinerge receptors Muscarinerge
receptors Acetylcholine M1: G-Protein coupled receptors Stimulate phopholipase A M2: G-Protein coupled receptors Inhib. adenylyl cyclase Nmuscle: Ligand gated ion
chanels Incr. Na+/Ca2+ Nneuro: Ligand gated ion chanels Incr. Na+/Ca2+

Slide 35:
 Spare receptors - Partial agonist

Slide 36:
 Desensitizing Sensitizing

26.  Drug Mechanisms Receptor interactions Non-receptor mechanisms

Receptor Interactions :
 Receptor Interactions Agonist Receptor Agonist-Receptor Interaction Lock
and key mechanism

Receptor Interactions :
 Receptor Interactions Receptor Perfect Fit! Induced Fit

Receptor Interactions :
 Receptor Interactions Antagonist Receptor Antagonist-Receptor Complex
DENIED! Competitive Inhibition

Receptor Interactions :
 Agonist Receptor Antagonist „Inhibited‟-Receptor DENIED! Receptor
Interactions Non-competitive Inhibition


27.  Non-receptor Mechanisms :
 Non-receptor Mechanisms Combining With
Other Chemicals Antacids Antiseptic
effects of alcohol, phenol Chelation of
heavy metals


28.  Non-receptor Mechanisms :
 Non-receptor Mechanisms Anti-
metabolites Enter biochemical reactions in
place of normal substrate “competitors”
Result in biologically inactive product
Examples Some anti-neoplastics Some
anti-infectives