1. Dr Nasim Ullah Siddiqui
General Pharmacology
Dr Nasim Ullah Siddiqui

2. What is Pharmacology? Pharmacology:
Pharmacon (drugs) + Logos (studies)
The study of drugs

3. Drugs & Medicines Drugs:
Any substance that, when absorbed into the body of a living organism, alters (changes) normal body function
Examples:
aspirin,
Antibiotics,
Nicotine,
alcohol,
Marijuana….

4. Drugs & Medicines Medicines:
In pharmacology, a drug is a chemical substance used in the:
treatment, cure, prevention, or diagnosis of disease
Or used to enhance physical or mental well-being

5. Drugs & Medicines
Drug is called medicine when used in proper dosage form for safe administration
All medicines are drugs but all drugs are not medicines

6. Clinical / Experimental
Clinical Pharmacology
deals with the study of drug effects in humans beings, i.e. healthy volunteers and patients
Experimental Pharmacology
deals with the study of drug effects in laboratory animals
In vitro – Isolated tissue
In vivo – Intact organism

7. Definitions Toxicology: Pharmacogenetics:
deals with adverse (undesired) reactions of drugs & their treatment
Pharmacogenetics:
How genetics influence the mode of drug actions (e.g.. Metabolism) and biological variations of drug responses

8. Definitions
Pharmacogenetics is generally regarded as the study or clinical testing of genetic variation that gives rise to differing response to drugs.
Pharmacogenetics refers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.

9. Definitions Pharmacokinetics: Pharmacodynamics:
How the body handles the drug
Includes absorption, distribution , biotransformation, and elimination
Pharmacodynamics:
How drug handles the body
Deals with the biochemical and physiological effects of drugs on man

10. Receptors Definitions
Biochemical receptors are large protein molecules that can be activated by the binding of a ligand (such as a hormone or drug).
Receptors can be membrane-bound, occurring on the cell membrane of cells, or intracellular, such as on the nucleus or mitochondrion.
Binding occurs as a result of noncovalent /covalent interaction between the receptor and its ligand, at locations called the binding site on the receptor.

11. Definitions
Potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.
A highly potent drug (e.g., morphine) evokes a larger response at low concentrations.
while a drug of lower potency (acetylsalicylic acid) evokes a small response at low concentrations
It is proportional to affinity and efficacy

13. Definitions Affinity is the ability of the drug to bind to a receptor.
Efficacy is the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level.
The response is equal to the effect(E), and depends on both the drug binding and the drug-bound receptor then producing a response; thus, potency depends on both affinity and efficacy.

14. Drug Responses How are drug responses produced?
By interaction with active binding sites called RECEPTORS
Drug may be agonist or antagonist for the receptors

15. Definitions
The agonist (ligand, drug or hormone) that binds to the receptor and initiates the response.

16. Definitions
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks agonist-mediated responses.
The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally-defined binding sites on receptors.
Antagonists have affinity but no efficacy for their receptors, and binding will disrupt the interaction and inhibit the function of an agonist at receptors.

17. Antagonist
Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist receptor binding.
Physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by α-adrenergic receptor activation.

18. Definitions
Tachyphylaxis : Rapidly developed tolerance is tachyphylaxis, is a medical term describing a decrease in the response to a drug due to previous exposure to that drug.
Caused by depletion or marked reduction of the amount of neurotransmitter responsible for creating the drug's effect, or by the depletion of receptors available for the drug or neurotransmitter to bind to. Examples: Amphetamine, ephedrine (indirectly acting drugs)
Tachyphylaxis is characterized by the rate sensitivity i.e, a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished response also known as desensitization.

19. Definitions
Physiological tolerance or drug tolerance is a subject's reaction to a drug (such as an opiates painkiller, benzodiazepine drug) is reduced at a later time even though the dose or concentration at the effect site is the same.
This means that larger doses are required to achieve the same effect.
Drug tolerance can involve both psychological & physiological drug tolerance factors.
It is reversible
Physiological tolerance occurs after repeated exposure .

20. Definitions
Idiosyncrasy (idiosyncratic drug reaction) denotes a non-immunological hypersensitivity to a substance, without connection to pharmacological toxicity.
Is an individual based on a specific condition of the one who suffers it. Most commonly, this is caused by an enzymopathy, congenital or acquired.

21. Drugs actions Drug actions are mediated by 3 ways:
Acting on somatic or psychic processes or functions
Correction of deficiencies
Toxic action on pathogenic microorganism

22. Ideal drug effects Drug effects should be: Selective Temporary
Dose-related (controllable)
Show close relationship with bioavailability

23. Nature of drugs Physical: Chemical structure: Solid (aspirin)
Liquid (nicotine, ethanol)
Gas (nitrous oxide)
Chemical structure:
Protein, lipid, carbohydrate
To be weak acid or weak base
Amine (primary, secondary, tertiary, ..)

24. Sources of drugs Natural from: Semi-synthetic Synthetic Bio-synthetic
Plants
Animals / Humans
Micro-organisms
Minerals
Inorganic metals
Semi-synthetic
Synthetic
Bio-synthetic

25. Sources of drugs Natural from Plants:
Active principles are found in roots, leaves and seeds in 2 forms:
Glycoside, e.g
Cardiac glycoside Digoxin ( from the Foxglove plant)
Alkaloid, e.g
Morphine (from Poppy capsules),
Atropine (from Belladonna leaves)
Quinine (from bark of Cinchona tree)
Castor oil (from castor seed)

26. Sources of drugs Natural from animals / humans: Hormones:
Heparin from Pig or Ox liver,
Insulin from Pig or Ox pancreas
Gonadotrophins from urine of pregnant women
Plasma or serum from blood
Thyroxin from Pig or Ox thyroid gland
Cod Liver Oil from Cod fish Liver

27. Sources of drugs Natural from micro-organisms: Antibiotics:
Penicillin from Penicillium notatum,
Streptomycin from Streptomyces griseus,
Bacitracin from Bacillus

28. Sources of drugs Minerals & Inorganic metals :
Calcium, Magnesium, Aluminium, Sodium, Potassium & Iron salts
Liquid paraffin from petroleum.

29. Sources of drugs Semi synthetic drugs:
Prepared by chemical modification of natural drugs in labs.
Ampicillin from Penicillin-G,
Semisynthetic cephalosporin's from 7-amino cephalosporinic acid

30. Sources of drugs Synthetic Drugs:
Prepared by chemical synthesis in pharmaceutical laboratories
Sulphonamides
Salicylates
Barbiturates
Benzodiazepines

31. Sources of drugs Bio-Synthetic Drugs:
Prepared by cloning of human DNA into bacteria like E.Coli.

32. Sources of drugs Bio-Synthetic Drugs:
Technique is called Recombinant DNA technology or Genetic Engineering
Cells from animals or human that produce active substance
Isolation of DNA
Transfer to bacteria (E-coli) by plasmids (Gene cloning)
A new E-coli synthesizes the new substance
Cloning of ‘new’ E-Coli means production of identical subjects like parent

33. Sources of drugs Bio-Synthetic Drugs:
Examples: Human Insulin's, Human Growth Hormones, Human BCG vaccine , Human Hepatitis B Vaccine

34. Criteria for drug classification
Chemical structure:
Cholinesters,
Organophosphates,
Catecholamine's
Location of action:
Cardiac glycosides,
Autonomic drugs

35. Criteria for drug classification
Purpose of medication:
Antihypertensive
Diuretic
Antiemetic
Analgesic
Name of plant:
Opium alkaloids
Cardiac glycosides
Belladonna alkaloids

36. Drug Nomenclature Most drugs have at least three names: Chemical name
Generic name (Official, Approved)
Proprietary name (Trade name, Company name)