how drugs act pharmacology

2. What we do discuss here!!!
 What is a drug?
 How can we name a drug?
 Where drugs come from?
 What is Pharmacology?
 How Pharmacology differs from Therapeutics (clinical
pharmacology)
 What is the difference between PK and PD?
 Adverse drug effects and Adverse drug reaction (why and
what)?
 What is predictable and what is not?
 What do we mean by “off-label” use?
 What is the difference between side effects and secondary
effects?

3. What we do discuss here!!!
 What is the difference between “tolerance” and
“tachyphylaxix”?
 Differentiate among super sensitivity,
 Desentisation and hypersensitivity?
 How anaphylaxis differ from idiosyncrasy?
 How do drug exert their action?
 What is a drug receptor?
 What are the different types of drug receptors?
 How drugs react with their receptors?

4. Drug
“Any chemical/molecule that alters body
function(produces biological effects)”
• Beneficial – To Diagnose/Treat/Cure/Prevent (Medicine)
• Harmful – Toxic (Poison)

5. Drug Nomenclature
• Chemical- Long and unwieldy, used by chemists, pharmacist,
researchers
• Generic/ Non-Proprietary name
– Universal and official
– Approved by USAN(US Adapted Names)
– BAN (British Approved Names)
– INN (International Non-proprietary name; designed by WHO
• Brand/Trade/Proprietary- Pharmaceutical Companies

6. Generic name Chemical name Trade name
Paracetamol(BAN)INN)
Acetaminophen(USAN)
N-acetyl-p-aminophenol Panadol
Tylenol
Acetyl salicylic acid
(ASA)
2-acetoxybenzoic acid Aspirin
Nifidipine Dimethyl-2,6-dimethyl-4-(2-
nitrophenyl)-1,4-dihydropyridine-
3,5-dicarboxylate
Adalat / Procardia
Sildenafil citrate 1-[4-ethoxy-3-(6,7-dihydro-1-
methyl-7-oxo-3-propyl-1H-
pyrazolo[4,3-d]pyrimidin-5-yl)
phenylsulfonyl]-4-
methylpiperazine citrate
Viagra

7. Drugs Sources (Origin)
• Natural
– Plant: Digoxin (Digitalis) fox glove
– Animal: Premarin (menopause symp & osteoporosis)
– Microorganism: Antibiotics e.g., streptomycin
– Minerals: iron, zinc, selenium
• Synthetic: Paracetamol; ASA;etc
• Semi synthetic: Paclitaxel (Taxol)®
• Biotechnology/Genetic Engg: Human Insulin

8. Terminology
Pharmacology:
“The interaction of drugs (chemicals)
with the living systems at molecular level”
What drugs do and how they work?
Why so important (goal)?
All drugs have the potential of inducing serious adverse effects
Pharmacokinetics-What the body does to the drug (ADME)
Pharmacodyanamics-What the drug does to the body
Therapeutics-The use of drug to treat diseases

9. Adverse Drug Effects
An unwanted or unintentional effect of administered drug (very
broad term)
Why?
Unwanted selectivity
Receptors in different organs
Overlapping biochemical pathways
“Drugs are only selective not specific”

10. Classification of Adverse Drug Effects
I. Predictable (Preventable and Reversible):
Related to normal pharmacological properties of the drug and includes
1. Side effects
2. Secondary effects
3. Overdose
4. Supersentivity
5. Tolerance
6. Dependence
7. Iatrogenic diseases
8. Carcinogenicity
9. Cytotoxicity
10. Tetragenecity
11. Drug interaction

11. 1. Side Effects
Unavoidable & unwanted normal action of drugs (e.g. atropine-dry
mouth)
“All the side effects are bad”
Off label use!- Prescription of a registered medicine for a use that is
not included in the product information
Sertraline (Zolaft)® - (SSRI), and clomipramine (anafranil)®-
TCA; meant to use as antidepressant but used in PME
Propranolol (inderal)®, A BB used in hypertension, anxiety and
panic also for stage fright

12. 2. Secondary Effects: Indirect consequences of normal drug action
e.g. superinfection with broad spectrum antibiotics
3.Overdose: The ingestion or application of a drug or other
substance in quantities greater than are recommended/practiced
(results in toxicity or death)
 OD of Cocaine → tachyarrhythmia and elevated BP
 OD of Multivitamin with iron → PH imbalance (chelation
therapy) → death/permanent coma
4. Super Sensitivity: Exaggerated normal action with small dose

13. 5. Tolerance : Decreased physiological response after repeated
administration of drug
‘Tachyphylaxix’ (desensitization)- How it differs from Tolerance
6. Dependence : Intense physical disturbance when drug withdrawn
7. Iatrogenic Disease (Greek; iatros- healer): Refer to inadvertent
adverse effects or complications caused by or resulting from
medical treatment or advice (Good or Bad)
8.Carcinogenicity :The ability to produce cancer

14. 9.Teratogenecity: Developmental anomalies (isotretinoin (13-cis-
retinoic acid, BN-Roaccutane), treats acne- strong teratogen at a single
dose)
10.Cytotoxicity: cell destruction: The degree to which an agent
possesses a specific destructive action on certain cells or possession of
such an action
11.Drug interaction: A situation in which a substance affects the
activity of a drug
May decrease or increase or produce a new effect
that neither produces on its own
Drug-Drug interaction; drug-food interaction; drug-
herbs interaction

15. II.Unpredictable Adverse Effects
Abnormal response, Less common, Not dose related, more serious,
may require drug withdrawal
1.Allergey (hypersensitivity); 2. Idiosyncrasy (individualistic
reaction to a treatment)
The most severe adverse drug reaction is (anaphylactic shock)??
“Immediate allergic reaction
that can be fatal and results
in cardiovascular collapse”

16. Mechanism of Drug Action
I. Nonspecific reaction
1.Physical : Adsorption (Charcoal), Osmotic Diuretic (Mannitol),
Demulcent (Syrup)
2.Neutralisation: (NaHCO3); Chelation (BAL)
II. Interference with the metabolic pathways
Antimetabolites (Sulphonamides→ PABA in Folic acid synthesis)
III. Reaction with receptors (agonist, antagonist, inverse
agonist)
IV. Enzyme modulation-ACEI (Captopril- “capoten”)
V. Reaction with ion channel-CCB (Nifidipine)
VI. Interference with cell division

17. Drug Receptors
A macromolecule that selectively binds ligand to elicit a biological
response
ligand= drug, transmitter (or) hormone
Types of Receptors
1.coupled to Ligand-Gated ion channel
– Na+/K + Channels (non-specific):
e.g. Ach on Nicotinic receptors
– Cl- Channel: e.g. GABAA receptors
– K+ Specific channels

18. 2. G-Protein coupled receptors
G-Protein : They bind the guanine nucleotides GDP and GTP

19. 3.Coupled to Kinase activity
• Tyrosine Kinase: Growth related signals e.g. Insulin
• JAK-STAT cytoplasmic protein kinases
• Cell membrane and cytoplasme.g. Cytokines
4. Nuclear receptors
• Lipophilic ligands
• Results in DNA transcription of target gene
• e.g. Thyroid and Steroid hormones

20. • Gαq :Stimulatory
e.g. Adrenaline on β–receptors → Adenylate cylclase →
cAMP
• Gαi : inhibitory
e.g. Adrenaline on –α2receptors → Adenylate cylclase →
cAMP
• Gq :
e.g. Muscarinic receptors (M1 &M2) → Phospholipase C → IP3
Ca
2+
• Gαt: Transduction : triggers the breakdown of cyclic GMP

21. Thank You…