General Pharmacology

Muhammad Faisal Nadeem

DRUGS DRUGS

The word drug is derived from the French word drogue, a dry herb, it is defined as any substance used for the purpose of diagnosis prevention, relief or cure of a disease . In man or animals use of drug depends upon no. of factors .

1. Source 2. Chemistry 3. Absorption 4. Metabolism 5. Excretion 6. Mechanism of action 7. Side effects/ toxicity 8. Margin of safety 9. Uses

Nomenclature of the drugs 1. Chemical names: Indicates molecular structure . It is complex

and not used e.g. Acetyl-p-aminophenal.

2. Official approved name : It is the abbreviated form of chemical name used in pharmacopeia and named officially e.g. Paracetamol.

3. Proprietory name (brand / trade name) name given by the company which markets the drug . It is a commercial property of a pharmaceutical company.

To avoid confusion drugs should be prescribed by their approved name e.g

1.Chemical name: Acetylp-aminophenal

2.Official name : Paracetamol

3.Brand name : Panadol , Calpol

Origin of Drugs / Bioactive Compounds: History

Before 1800: Plants, plant extracts, inorganic material

1805: Morphine isolated from opium (sructure proposed 1935, prooved by synth. 1952)

1828: First organic synthesis (urea)

1840-1850: First synthesized org. compds used in medicine: CHCl3, Et2O anestechia)Ex of early synthetic drugs:

Choral hydrate (sleeping pill) 1869Acetyl salicylic acid synth 1853Phenazone synth 1884Benzocaine 1902Prontocil 1932

Ex of early isolated nat. prod.Quinine ca 1825Digitoxin 1841 (structure

1928)Salicylic acid, antipyretic 1875Cocaine isol. 1860, local

anestethic 1884Benzylpenicillin 1941

Traditional medicineScreeningSerendipity

Active Principles Of Crude Drugs Definition

The chemical constituents present in crude animal/vegetable preparations, responsible for their biological activity are called active principles.

Active Principles have been purified and synthetic/ semi- synthetic derivatives can be prepared and used in Therapeutics.

The Aims of Isolating Active Principles

• 1. Identification of the active ingredient(s).

• 2. Analysis of the biological effects (pharmacodynamics) of individual ingredients and of their fate in the body (pharmacokinetics).

• 3. Ensuring a precise and constant dosage in the therapeutic use of chemically pure constituents.

• 4. The possibility of chemical synthesis, which would afford independence from limited natural supplies and create conditions for the analysis of structure–activity relationships.

Sources of Drugs

Drugs may be synthesized within the body (eg, hormones) or may be chemicals not synthesized in the body, ie, xenobiotics (from Gr xenos "stranger"). Poisons are drugs. Toxins are usually defined as poisons of biologic origin.

• Drugs may be solids, liquids or gaseous.• Many drugs are weak acids or bases• Majority of drugs have molecular weights between 100

and 1000• chirality (stereoisomerism)

Drugs may be obtained from: • Plants • Animals• Mineral / Earth • Synthetic / Semi-synthetic sources• Microbiological sources• Recombinant DNA technology /Genetic engineering.

Plant / Vegetable Sources

• The oldest natural source. Even now some drugs are obtained from the plant source.

• Drugs can be obtained from all parts of the plants:

– Leaves: Digitalis purpurae ---- Digoxin

– Flowers: Papaver Somnipherum --------- Morphine

– Fruits : Senna pod --------------------- Anthracine

– Seeds: Nuxvomica seeds-------strychnine.

– Roots : Ipecacuanha root ------- Emetine

– Barks: Cinchona bark ------- Quinine

– Stem: Chondrodendron ----- d-tubocurarine

Animal Sources

• Various organs & tissue of animals are used as source of drug.

• Active principles of animal drugs are proteins, oils, fat, enzymes and hormones.

– Pancreas ………………………... Insulin

– Cod liver ……… Cod liver oil (contains Vit A & D)

Mineral / Earth Sources

Many drugs are mineral substances & their compounds.• Metals: Iron , Zinc, Gold salts• Non - metallic element: Iodine• Miscellaneous: Flourine, Selenium

Synthetic & Semisynthetic Sources

• The drugs are prepared in pharmaceutical laboratories. They may be organic or inorganic compounds or combination of both.

• 90% drugs in use are prepared synthetically. – Co-trimoxazole.– Diazepam.– Diacetyl morphine.– Ethinyl estradiol.

Microbiological Sources

These are prepared from bacteria & moulds.

Examples:• Antibiotics: Penicillin , Erythromycin• Vitamins

Recombinant DNA Technology /

Genetic engineering

The new technique for preparing certain drugs e.g. Human insulin insulin analog , Erythropoietin.

• Human Insulin & insulin analogs may be prepared by inserting human or modified pro-insulin gene into E-coli or yeast & treating the extracted pro-insulin to form the insulin or insulin analog molecules.

Advantages:

• Mass production.

• Cost effective

• Less immunological reactions.

Important active principles

• Alkaloids• Glycosides• Saponins• Fixed oils• Volatile oils • Fats• Waxes• Gums• Resins• Oleoresins• Gum resins• Balsams• Tannins • Neutral principles

Alkaloids:

The characteristics are:• Nitrogenous compounds of complex structure.• Found in plants, more than one alkaloids may be

present in one plant.• Intensely bitter.• Insoluble in water, soluble in alcohol.• Very active biologically, alkaline in reaction.• Form salts with acids which are water soluble.• Mostly solids, only a few are liquids.• English names end in ----“INE”.

Examples:

Solid Alkaloids: • Morphine, Papavarine• Atropine , Hyoscine• Quinine• Ephedrine• Strychnine

Liquid Alkaloids:• Nicotine , Pilocarpine , Lobeline

Glycosides:

The characteristics are:

1. Non nitrogenous, containing carbon, hydrogen & oxygen

2. Complex structure & very active biologically

3. Found in plants

4. Hydrolyzed by acid / enzymes into:• Sugar component or Glycone ----

Mainly determines pharmacokinetics• Non-Sugar component or Aglycone/Genin - --

Pharmacologically active

5. When sugar component is glucose, it is called glucoside

6. English names end in letter “IN”

Examples:Cardiac Glycosides:• Digoxin• Digitoxin• Gitoxin• Gitalin• Strophanthin

Saponins:

• These resemble glycosides• Neutral in reaction• Found in plants• Act as emulsifying agents• Form clear solution with water which forms froths on

shaking • They are toxic • May cause haemolysis of RBCS• Examples: Senegin, Quillia sapotoxin

Fixed Oils:

obtained from various plants or animals.• Esters of higher fatty acid (Oleic/Palmitic/ Stearic

acids) .• Insoluble in water , soluble in ether, chloroform,

alcohol. • Bland + non irritating .• Leave greasy mark on paper.• Decompose on distillation .• Form soaps with alkalies.• Used as: Nutrient , Emollient , Purgative.Examples: Castor oil , Cod liver oil , Olive oil.

Volatile Oils: (Essential Oils / Ethereal Oil)

Obtained from various parts of plants by distillation processes & are highly aromatic.

• Mostly contain liquid hydrocarbons which are monoturpenes

In addition most contain oxidized hydrocarbons.• They are usually crystalline solids, called stearoptenes • Highly aromatic, slightly water soluble – impart smell & taste.• Used as:

– Carminative e.g. cardamon oil– Diuretic e.g. oil of sandal wood– Antiseptic e.g. clove oil– Counter Irritant e.g. turpentine oil– Expectorant e.g. balsam of tolu

Examples

Usually Solids:• Camphor• Thymol• Menthol

Some Liquids: Eucalyptol

Fats:

• Fixed oils solid at room temperature• Natural ester of glycerol & fatty acids. All the

three OH groups of glycerol are esterified, so called Triglycerides

• Source Plants

Animals• Examples: Theobroma (cocoa butter) , Wool fat

Waxes:

• Esters of fatty acids with monohydric alcohols• Complex mixtures• Used in ointments & other topical preparations

used on skin.

Examples: White bee’s wax (cera alba)

Gums:

• Plant exudations• Carbohydrate in nature Starch

Cellulose• Amorphous, Transparent• Form viscous solution with water – Mucilage• Used as suspending/emulsifying agents in

preparation of suspensions & emulsions. • Examples: Gum Acacia, Gum Tragacanth

Resins:

• Solid & brittle substances, produced by oxidation of volatile oils

• Form soap with alkali• Soluble in alcohol

Examples: Colophony.

Tannins:

• Non-Nitrogenous compounds .• Precipitated by metallic salts or alkaloids.• Astringent action on mucosa.• Produce blue inky color with iron.• Some are hydrolyzed to tannic acid.

Neutral Principles:• Do not conform to any special group .• Examples: Santonin, Bitter principles .

Sources of Drugs• PlantsExample Trade Name

ClassificationChinchona BarkQuinidine Antiarrhythmic

Purple Foxglove Digitalis Cardiotonic

Poppy Plant Paregoric, Antidiarrheal,(Opium) Morphine, Analgesic,

Codeine Analgesic, Antitussive

Sources of Drugs• MineralsExample Trade Name ClassificationMagnesium Milk of Magnesia Antacid, Laxative

Zinc Zinc Oxide Oint. Sunscreen, Skin Protectant

Gold Solganal, Auranofin Anti-inflammatory;

Used in tx of Rheumatoid

Arthritis

• AnimalsExample Trade Name

ClassificationPancreas of Cow, Insulin; regular, AntidiabeticHog NPH, PZI Hormone

Stomach of Cow, Pepsin DigestiveHog Hormone

Thyroid Gland Thyroid, USP HormoneOf Animals

Sources of Drugs

Sources of Drugs• SyntheticExample Trade Name

ClassificationMeperidine Demerol Analgesic

Diphenoxylate Lomotil Antidiarrheal

Co-TrimoxazoleSeptran Anti-Infective Sulfonamide; Used in the treatment of UTI’s

Doses of Drugs

DoseMinimum doseMaximum doseDaily doseTotal doseSingle doseLoading doseMaintenance doseMedian lethal doseMedian effective doseTherapeutic indexToxic dose & fatal dose