Here's a shortly described presentation on molecular mechanism of drug action that I presented for my pharmacology course. I tried to include everything related to this topic shortly including receptors, ion channels, carrier molecules & enzymes. Hope it'll be helpful.

1. Molecular Mechanism
of
Drug Action

2. Group Members
1. Nafisa Mustafiz(15103036)
2. Rabeya Basri(15103012)
3. Rakibul Islam(15103042)
4. Jannatul Ferdous(15103035)
5. Ayesha Akter(15103041)

3. Contents
1. Introduction
2. Mechanism of Drug Action
3. Molecular Drug Targets
4. Characteristics of Molecular Targets
5. Receptor
– Classification of Receptor
6. Ion channels
7. Carrier molecules
8. Enzymes
9. Chemical targets
10. Bacterial, viruses & fungi targets
11. Summery

4. Introduction
 Mechanism of drug action – Pharmacodynamics
 Pharmacodynamics :
 Effects of drugs and the mechanism of their
action.
 What does a drug do & how does it do it?

5. Mechanism of drug action
 Mechanism of drug action-
– Study of drug effects
– Modification of one drug’s action by
another
 Drugs acts in four different levels-
1. Molecular
2. Cellular
3. Tissue
4. System

6. Molecular Drug Targets
 Hormone & neurotransmitter receptors
 Enzymes
 Carrier molecules
 Ion channels (ligand-gated or voltage
operated)
 Idiosyncratic targets such as, metal ions,
sufactant proteins etc.
 Nucleic acid

7. Characteristics of Molecular
Targets
• The molecular selectivity of drug action
– Determined by the similarity or divergence of
structure of different molecular targets
• The tissue selectivity of drug responses
– In accordance with the distribution of the
molecular target throughout the body
• The rapidity & persistence of the manifestation of
cellular & tissue responses.

8. Receptors
A protein molecular target for a drug
The largest no. of drugs act through them- control effectors
Endogenous substances & drugs
Regulate cell function by altering:
Enzyme activity
Permeability to ions
Conformational features
Genetic material

9. Contd.
Nature of receptor:
 Protein in nature
 Molecular weight 45-200 Kda
 Subunits, subtypes depending on tissue
 Saturable
 Have recognition & transduction properties
 Can be up-regulated & down-regulated etc.

10. Contd.
Affinity: tendency to bind to receptors.
Intrinsic activity: capacity of a single drug-
receptor complex to evoke a response.

11. Contd.
Based on affinity & intrinsic activity
 Full agonist : high affinity
high intrinsic activity(=1)
Eg. Methacholine on acetylcholine receptors
 Antagonist : only affinity
no intrinsic activity (=0)
Eg. Atropine on muscarinic receptors

12. Contd.

13. Contd.
Partial agonist: full affinity
intrinsic activity <1 (0 to 1)
Eg. Naloxene on opioid receptors
saralasin on angiotensin receptors
Inverse agonist: full affinity
intrinsic activity<0 (0 to-1)
Eg. Beta carbolines on BZP receptor.

14. Contd.
• Four types-
G-protein couple receptor
G-protein activatedG-protein binds
Signal
binds

15. Contd.
Channel-linked receptor

16. Contd.
 Enzyme linked receptor

17. Contd.
 Intracellular receptor

18. Contd.
Signaling mechanism
1. Lipid soluble ligand
2. Allosteric effect
3. Stimulation of protein kinase
4. Regulation of ion channel
5. G-protein coupled receptor

19. Ion Channel
• Also known as “ligand-gated ion channel”
• Group of transmembrane ion channel proteins
• Allows passage of Na+, K+, Ca++, and Cl- through the
membrane
• Voltage-gated channels
– Modulated endogenously by membrane potential

20. Contd.
- All share a specific number of trans-membrane
domains & extracellular & intracellular
components.
• Example: The cardiac Na+ channel

21. Contd.

22. Contd.
Drug interaction with Na+ selective VOCs
Drugs that impair Na+ channel function –Na+
channel blockers.
Used to discriminate between the role of
different types of Na+ channel in health &
disease.
Example: Tetrodotoxin
conc. 10nM blocks neuronal & skeletal muscle Na+
channel .
Conc. Needs to be 100 times higher than that to
block cardiac Na+ channels.

23. Contd.
Drug interaction with Ca++ selective VOCs
5 types of Ca++ VOCs in plasma membrane- L, T,
N, P & Q
 allow entry of Ca++ into cells
L-type is the best characterized & the most
important clinically
• Found in cardiac & smooth muscle
• Opens- during depolarization
• Closes- by voltage dependent gating

24. Contd.
• Blocked by-
1. Benzotiazepine derivatives (e.g. diltaizem)
2. Dihydropyrines (e.g. nifedipine)
3. Phenethylalkylamines (e.g. verapamil)
Drug interaction with K+ selective VOCs
 Opening of these VOCs – hyperpolarization
 Has major potential therapeutic implication for targeting
drugs
 At least 6 types of this type of VOCs has been identified

25. Contd.
Other VOCs
Recently it has become more apparent that
VOCs also exist for anions, for example, Cl-.
Cl- channels are found in both PNS & CNS.

26. Transport Carriers
• Sugars, nucleic acid, amino acid passage- energy
independent carrier molecules & energy dependent
pumps.
• Oriented proteins
• One or more binding site
• Binds weakly -> change in conformation -> translocate
the passenger across the membrane

27. Contd.
• Energy independent carrier moecules
– Transporters, symporters or antiporters
– Transporters
• Movement of one type of ion in one direction
– Symporters
• Movement of two or more ions or molecule in one
direction
• e.g. the action of furosemide (frusemide) on the
Na+/K+/2Cl– symport in the nephron
– Antiporters
• Exchange one or more ions or molecules for one or more
ions or molecules
• Na+/Ca++ exchangers

28. Contd.
• Energy dependent pumps
– Called pumps
– Enzymes
– Has facility to translocate ions or other molecules
through a central pore
– Example:
• Na+/K+ dependent adenosine triphophatase (ATPase)

29. Contd.
• Na+/K+ dependent adenosine triphosphatase
– Prevents Na+ accumulation in nerve & muscle
cells
– Corresponding loss of K+
• Due to opening & closing of ion channels
– Na+ -> outside the cell
K+ -> inside the cell
– 2 Na+ is exchanged for 3 K+
– Energy suuplied from : hydrolysis of ATP

30. Contd.

31. Enzymes
• Important target : all biological reactions under
enzyme action
• Enzyme stimulation/ enzyme inhibition

32. Contd.
STIMULATION
• Unusual with foreign substances
• Occurs with endogenous ones
• Adrenaline  adenyl cyclase; pyridoxine as cofactor
decarboxylase
• Stimulation affinity for substrate
• Enzyme induction: synthesis of more enzyme protein
activity

33. Contd.
INHIBITION
NON SPECIFIC
• Denaturing proteins:
altering tertiary
structure
• Heavy metal salts
• Strong acids
• Phenol
• Alkalies
• Too damaging for
systemic use
SPECIFIC
I. Competitive/
equilibrium type
non- equilibrium
type
II. Non competitive
A. Reversible
B. Irreversible

34. Contd.
Some enzymes & their inhibitors

35. Chemical targets
 Chelating drugs – Fe++, Fe+++ & Al+++
 Surfactants
 Certain drugs used in the treatment of GIT
disorders which absorb substances in the gut & so
alter the consistency & transmit time of bowel
contents through the GIT.

36. Bacterial, viruses, fungi targets
 Therapeutic drug acts directly
 On relevant organism – bacteria, virus, fungus or
parasite.
 MMOA of such drugs are conceptually identical to
the drugs that act on human tissue.
 i.e. modulation of receptors, enzymes.

37. Summary
• The molecular mechanism of drug action on
protein targets (receptor, ion channels,
transporters & enzymes) are summarized in the
following figure.

38. RECEPTORS
ION CHANNELS
TRANSPORT CARRIERS
ENZYMES

39. References
• Integrated Pharmacology by michael curtis & clive page
• hp://www.slideshare.net/tulasiraman/receptor-pharmacology
• https://s3.amazonaws.com/ppt-download/vj-
mechanismofdrugaction-140407201643-phpapp01.ppt?response-
contentdisposition=attachment&Signature=NWBaG6ML4jipnuVmYt
OXCPgYBTA%3D&Expires=1484243616&AWSAccessKeyId=AKIAJ6D6S
EMXSASXHDAQ
• https://s3.amazonaws.com/ppt-download/drugreceptorsfinal203-
120202090527phpapp01.ppt?responsecontentdisposition=attachme
nt&Signature=wriipvyt0%2FLN5WE1BygaF8eD698%3D&Expires=148
4243005&AWSAccessKeyId=AKIAJ6D6SEMXSASXHDAQ
• https://s3.amazonaws.com/ppt-download/mechanismofdrugaction-
131104071748phpapp01.pptx?responsecontentdisposition=attachm
ent&Signature=tSLcbZXQnSv80LPIn%2BgAvt227QM%3D&Expires=14
84227786&AWSAccessKeyId=AKIAJ6D6SEMXSASXHDAQ

41. AnyQuestions?