3. PRINCIPLES OF DRUG ACTION
1. STIMULATION: it indicates an increase in the activity of
specialised cells. E.g- adrenaline stimulates heart.
Excessive stimulation lead to depression . E.g- picrotoxin
2. DEPRESSION: decrease in normal activity of specialised cells.
E.g- quinidine depresses heart
3. IRRITATION : non selective noxious effect, applied to less
specialised cells like epithelium , connective.
- mild irritation and strong irritation
4. 4. REPLACEMENT: use of natural metabolites ,
hormones or their congeners in deficiency states.
E.g- levodopa, insulin, iron
5. CYTOTOXIC ACTION: selective action on invading
parasites and cancer cells. E.g- penicillin,
chloroquine, zidovudine, cyclophosphamide
5.
6. MECHANISM OF DRUG ACTION
Mainly based on physical and chemical property:
Action examples
Neutralisation Antacids
Chelation EDTA, dimercaprol, penicillamine,
deferoxamine
Ion exchangers- cholestyramine exchanges Cl- from
bile salts
Radioactivity I 131
and other radioisotope
7. action examples
Physical mass Bulk laxatives like isphaghula
Osmotic activity MgSO4 as purgative, mannitol
Adsorption Simethicone adsorb gases used as anti-
flatulent
Absorption of UV rays PABA
Oxidizing property Potassium permanganate
Demulcents Menthol in cough syrups
Sequestration of cholesterol in
gut
cholestyramine
8. • Drug action associated with extracellular
processes- viz., thrombois, inflammation and
immune response.
• Drug action utilised by anti- infective agents-
target microbial proteins
9. TARGETS OF DRUG ACTION
• ENZYMES
• ION CHANNEL
• TRANSPORTER
• RECEPTORS
10. ENZYMES
• Enzymes are proteins catalysts which facilitate
the conversion of substrates into products.
• Drugs either increase or decrease the rate of
enzymatically mediated reactions.
11. Influence of enzymes
Induction Stimulation Inhibition
Enzyme inhibition
Specific
Competitive
Non
competitive
Non
specific
12. ENZYME INDUCTION
• Apparent increase in
enzyme activity occur by
enzyme induction i.e.,
synthesis of more enzyme.
• Km- no change
ENZYME STIMULATION
• Stimulation of enzyme
increase its affinity for the
substrate
• Km- lowered
• E.g.- pyridoxine stimulate
decarboxylase activity
13. Non specific inhibition
Denaturation of enzymes by drugs and
chemicals.
E.g.- heavy metal salts
• Strong acids and alkalies
• Alcohol
• Formaldehyde
• phenol
14. • Km- the substrate concentration at which velocity is exactly
one half of maximal velocity ( ½ Vmax).
• Vmax- it is the number of substrate molecules converted
into product by an enzyme molecule in a unit time when the
enzyme is fully saturated with substrate.
• ½ Vmax
15. COMPETITIVE INHIBITION
EQUILIBRIUM TYPE
• Drug similar to normal
substrate
• Km- increase
• Vmax- unchanged
NON EQUILIBRIUM TYPE
• Same enzyme & same drug
but either form strong
covalent bond or have high
affinity bond.
• Km- increased
• Vmax- decreased
• E.g- organophosphates react
covalently with esteric site of
ccholinesterase
Substrate
+ enzyme
No product
Non
functional
product
16.
17.
18. Non competitive inhibitor Enzyme
Acetazolamide Carbonic anhydrase
Aspirin, indomethacin Cyclooxygenase
Disulfiram Aldehyde dehydrogenase
Omeprazole H+ K+ ATPase
Digoxin Na+K+ ATPase
Theophylline Phosphodiesterase
Lovastatin HMG-CoA reductase
NON COMPETITIVE INHIBITION
• Reacts with adjacent site, not with catalytic
site.
• Alters the enzyme
• Km unchanged but Vmax reduced.
19.
20. ION CHANNELS
• Ion channels facilitate the flow of ions such as
sodium, potassium and calcium across cell
membranes and are a site of action for various
neurotransmitters.
21.
22. Two important types are ligand-gated channels
and voltage gated channels.
LIGAND GATED VOLTAGE GATED
PHYSIOLOGICAL LIGANDS ACh , GABA, 5HT None (activated by
membrane depolarization)
EFFECTORS AND
TRANSDUCERS
Na+, Ca2+, K+, Cl– Na+, Ca2+, K+, other ions
EXAMPLE DRUGS Nicotine, gabapentin Lidocaine, verapamil
24. TRANSPORTER (Carrier molecules)
• These proteins control the influx of essential
nutrients and ions and the efflux of cellular
waste, environmental toxins, drugs, and other
xenobiotics.
• 7% of total number of genes codes for
transporter proteins
25.
26. ABC ( ATP BINDING CASSETTE
TRANSPORTER)
SLC (SOLUTE CARRIER
TRANSPORTER)
Primary active transporter Secondary active transporter
DRUG EFFLUX (OUT) DRUG UPTAKE (IN)
unidirectional BIDIRECTIONAL
Function – efflux or excretion of drugs and
their metabolites, bile salts , and
phospholipids.
Function- mediates uptake of organic
anions, cations and bile salts.
E.g- MDR1, BRCP, P-gp, CFTR e.g- OATP, OCT, SERT, DAT
It has 2 major super families:
27.
28. Examples of transporter
DRUG ACTION TRANSPORTER
NAME
Desipramine, cocaine block neuronal
reuptake or noradrenaline
norepinephrine
transporter (NET)
Fluoxetine (and other
SSRls)
inhibit neuronal
reuptake or 5-HT
Via serotonin
transporter (SERT)
Amphetamines blocks dopamine
reuptake in brain neurons
Dopamine
transporter (DAT)
Furosemide inhibits Na+K+2CI- cotransporter in the
ascending limb of loop of Henle
Probenecid inhibits active transport of
organic acids (uric acid, penicillin) in
renal tubules
Via organic anion
transporter (OAT)
Hydrochlorothiazide Inhibits NaCl symporter in the distal
convoluted tubule.
29. REFERENCES
• Brunton LL, I lilal-Dandan R, Knollman BC(Eds):Goodman and
Gilman's The Pharmacological Bci5is of Therapeutics: 13th
edn: McGraw-Hill,New York
• Katzung B.G.(Ed.),Ed. Bertram
G. Katzung.eds. Basic & Clinical ... Basic & Clinical
Pharmacology, Fourteenth Edition
• Tripathi, K. D. (2018). Essentials of medical pharmacology (8th
ed.). Jaypee Brothers Medical.
• Ritter, James. Rang and Dale's Pharmacology. Ninth edition.
Edinburgh: Elsevier, 2020.
