Dr Nasim Ullah Siddiqui General Pharmacology Dr Nasim Ullah Siddiqui

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

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….

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

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

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

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

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.

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

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.

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

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.

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

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

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.

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.

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.

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 .

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.

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

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

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, ..)

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

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)

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

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

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

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

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

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

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

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

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

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

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