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General Pharmacology


  • H/O of Pharmacology       

Development of Modern of pharmacology in mid-1900


 Principle of experimentation rather dogma



  • 1692 – Robert Boyle: - A collection of choice of Remedies
  • 1765 – Lind: - Cinchona Bark of malaria


  • 1804-Jhonson-Discard cinchona until fever subside


  • Instead Use Calomel


  • Resulted Death (for 40 years)
  • 1858 – Robert Virchow: - Cell theory
  • 1878 – Pasteur: - Bacteria as cause of disease
  • 1847 – Buchheim: - 1st Pharmacology Institute
  • 1805 – Friederich Serturner: - Purified morphine from opium

Pharmacology in 20th & 21st Century

  • New synthetic drugs – Barbiturates, Anaesthetic
  • Antimicrobial discovery – Paul Ehlrich 1909 (arsenic for syphilis, named it as Salvasam- drug for salvation of mankind)
  • Sulfonamides – Gerhard Domagk. 1935
  • Flemming, Chain and Florey – Penicillin (during2nd world war).
  1. Discovery of Hormones, Neurotransmitters, Inflammatory mediators
  2. Concept of Receptors – Langely (1905)
  3. Biochemistry – Discovery of enzyme (As distinct branch)


Alternative Therapeutic Principle

  1. Allopathy: - James Gregory (1735-1821)
  2. Homeopathy: - Hanhemann
  3. Alternative / Complementary medicines


  1. Biotechnology
  2. Pharmacogenetics
  3. Pharmacogenomics
  4. Pharmacoepidemiology
  5. Pharmacoeconomics

Drug Development

Potential Drug Molecule (; Validated Target; may alter fraction)

  • ? Affinity & selectivity of target/ effective
  • ? Pharmacokiinetic (A, D, M, E)
  • ? Can be synthesized on large scale economically
  • ? Safety

If yes:

Animal Testing

  • 2 species of animal for Toxicity testing (Carcinogenicity, Genotoxicty, Teratogenic)


Clinical Trials in human


Phase I

Phase II

Phase III

Phase IV

1st Human

1st Patient

Multisite trial

Post marketing surveillance

0-100 number



Many thousands

Healthy volunteer

Patient with experiment drug

Patient with experiment drug

Patient in treatment with approved drug

Open label

RCT double blind

RCT Non/Blind

Open label

Safety and Tolerability

Efficacy and dose ranging

Confirm efficacy in larger population

Adverse drug reaction


Drug interaction

1 month-1 year

1-2 years

3-5 years

No fixed duration

10 million $

20 million $

50-100 $


Success rate 50%

30 %

25-50%    -



*Phase III to Phase IV: New drug application (NDA) is drafted.

Me too Drug: -
New drug structurally similar to drug in market. Deliberate attempt for profit

Orphan drugs:

Treatment of rare disease (orphan disease lack sufficient market for profit)

Example of orphan drugs:

  • Digiband, Felbamate, Fomipezole, Inborn error of metabolic disorders, N-Acetyl cysteine etc.

Routes Of Drug Administration





  • Easy
  • Preferred by patients
  • “Slow-release” preparations may be available to extend duration of action
  • Drugs can be formulated in such a way as to protect them from digestive enzymes, acid, etc.
  • Unsuitable in patients who are uncooperative, strictly “nil by mouth”, are vomiting profusely or have ileus
  • Most orally administered drugs are absorbed slowly
  • Unpredictable absorption due to degradation by stomach acid and enzymes


  • Good absorption – the haemorrhoidal veins drain directly into the inferior vena cava, avoiding hepatic first pass metabolism
  • May not be suitable after rectal or anal surgery
  • Some patients dislike suppositories

Subcutaneous or intramuscular

  • Good absorption, especially for drugs with a low oral bioavailability
  • Onset is more rapid than the above routes
  • Depending on formulation can have very long duration of action, e.g. depot antipsychotics and contraceptives
  • Absorption may still be unpredictable if peripheries are poorly perfused
  • Injections hurt, cause bruises and frighten children and needle phobics


  • Dependable and reproducible effects
  • Entire administered dose reaches the systemic circulation immediately - the dose can be accurately titrated against response
  • Requires a functioning cannula
  • More expensive and labour intensive than other routes.
  • Cannulation is distressing to some patients, especially children
  • Cannulae are prone to infection
  • IV injection of drugs may cause local reactions


  • Easy
  • Non-invasive
  • High levels of patient satisfaction
  • Most drugs have a high molecular weight and are poorly lipid soluble, so are not absorbed via skin or mucous membranes
  • Very slow absorption


  • Very rapid absorption due to the huge surface area of the respiratory endothelium
  • Bronchodilators and inhaled steroids can be targeted to lungs with low levels of systemic absorption

• Bioavailability depends on patient’s inhaler technique and the size of drug particles generated by the delivery technique


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