General Pharmacology

Dr Nasim Ullah Siddiqui

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

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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….

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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

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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:–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

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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:–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

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Definitions

Receptors• 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.

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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

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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

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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.

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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.

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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.

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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 .

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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:1. Acting on somatic or psychic processes or

functions2. Correction of deficiencies3. 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:– 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:– Plants– Animals / Humans–Micro-organisms–Minerals– Inorganic metals

• Semi-synthetic• Synthetic• Bio-synthetic

Sources of drugsNatural 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 drugsNatural 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 drugsBio-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 drugsBio-Synthetic Drugs:• Examples: Human Insulin's, Human Growth

Hormones, Human BCG vaccine , Human Hepatitis B Vaccine

Criteria for drug classification

1. Chemical structure:–Cholinesters,–Organophosphates,–Catecholamine's

2. Location of action:–Cardiac glycosides,–Autonomic drugs

Criteria for drug classification3. Purpose of medication:– Antihypertensive– Diuretic– Antiemetic– Analgesic

4. Name of plant:– Opium alkaloids– Cardiac glycosides– Belladonna alkaloids

Drug Nomenclature

Most drugs have at least three names:1. Chemical name 2. Generic name (Official, Approved)3. Proprietary name (Trade name,

Company name)