General Pharmacology

Jehan Zeb KhanPharm.D

Pharmacology

• Greek “Pharmacon” – drug, “logos” – teaching• The term "drug" means (A) articles recognized in the

official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals;

• (Mitigation means the action of reducing the severity, seriousness, or painfulness of something)

Pharmacology

• The study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules.

• Medical pharmacology is the science of substances used to prevent, diagnose and treat disease.

Sources of Drugs• Natural sources (mainly plants)

– Atropa belladonna …atropine, – Ginkgo biloba.. (Ginkgo)– Digitalis lanata- digoxin• Human and animals: such as epinphrine, insulin and

adrenocoticotrpoic hormone.

• Synthetic Sulfanilamide, acetaminophen, zafirlukast

• Minerals: as iron, iodine and zinc

• Biotechnology– Smallpox vaccine, GH, Insulin..

Routes of Administration, Classification

Classification:I. Enteral (any form of administration that involves any part of the GIT): desired effect is systemic

(non-local). Drug is given via the digestive tract

II. Parenteral: desired effect is systemic. Drug is given by injection

III.Topical: desired effect is local. Drug is applied directly where its action is desired

I. Enteral:I. by mouth (orally): many drugs such as tablets, capsules, liquids

Widely used, convenient Some capsules and tablets contain sustained release drugs, which dissolve over an extended period

of time. Administration of oral drugs is relatively easy for patients who are alert and can swallow (can not

be used in unconscious patients). Certain drugs are given by the sublingual (placed under the tongue) route. These drugs must not be

swallowed or chewed and must be dissolved completely before the patient eats or drinks. Nitroglycerin is commonly given sublingually.

II. by gastric feeding tube: many drugs and for enteral nutrition

III.Rectally: various drugs in suppository or enema form The effect of digestive enzymes is avoided Useful for unconscious patients and in vomiting cases

Routes of Administration, Classification

II. Parenteral: The most common routes of parenteral drug administration the subcutaneous (SC), intramuscular

(IM), intravenous (IV), or intradermal routes.

The most common routes of parenteral drug administration the subcutaneous (SC), intramuscular (IM), intravenous (IV), or intradermal routes.

Rapid response obtained Useful in emergencies, vomiting, and unconsciousness The drug should be in a sterile dosage form

Routes of Administration, Classification

III. Topical: epicutaneous (application onto the skin), e.g. allergy testing, antifungal creams inhalational, e.g. asthma medications enema, e.g. contrast media for imaging of the bowel eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis ear drops - such as antibiotics and corticosteroids for otitis externa intranasal route (into the nose), e.g. decongestant nasal sprays vaginal, e.g. antifungals creams

Routes of Administration, Summary

Drug Transport

• Drugs must reach and interact with or cross the cell membrane to stimulate or inhibit cellular function.

• 'A drug will not work unless it is bound‘• These critical binding sites are often referred

to as 'drug targets'

Pharmacology Concepts

Pharmacology comprise of 2 processesPharmacokinetics (PK) -

PK describes how the body affects a specific drug after administration

Or What body does to a drugPharmacodynamics (PD) –

PD describes how a drug affects the body system after administration

Or What drug does to the bodyOr drug action

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General ConceptsDrug Dose

Administration

Drug Effect or Response

Pharmaceutical

Pharmacokinetics

Pharmacodynamics

Pharmacotherapeutics

Disintegrationof Drug

Absorption/distributionmetabolism/excretion

Drug/ReceptorInteraction

Pharmacokinetics

• Involves drug movement through the body to reach sites of action, metabolism, and excretion.

Pharmacokinetics

• Processes of Pharmacokinetics• The ADME scheme– A- Absorption– D- Distribution–M- Metabolism

or Biotransformation– E- Excretion

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Pharmacokinetics…Absorption-process that occurs from the time a drug enters the body to the

time it enters the bloodstream to be circulated.• Factors affecting absorption include: lipid solubility, degree of ionization,

solubility of drugs, dosage form, route of administration, blood flow to the site of absorption, gastrointestinal function, presence of food or other drugs.

• Sites: GIT (oral mucosa, intestinal mucosa, stomach), Skin, Muscles, Vaginal mucosa.

• Bioavailability is the portion of a dose of a drug that reaches the systemic circulation and is available to act on body cells.

• IV administration is 100% bioavailable• Subcutaneous administrations has more rapid absorption than does the oral

route• Mucous membranes allow for rapid and direct absorption into the

bloodstream

Factors affecting absorption/systemic availability

• Lipid solubility, like absorb like.. Lipophillic drugs absorb rapidly across the cell membrane. Cell membrane is lipoid in nature, will readily absorb Lipophillic substances.

• Degree of ionization, an unionized drug is lipid soluble and readily absorb across the cell membrane while an ionized drug is not water soluble and will not absorb.

• Solubility of drugs, for a drug to be absorbed from the mucosa into the blood it must have sufficient water solubility to be solubilized at the site of absorption.

• Dosage form, the physical form in which a drug is administered is called a dosage from. For example syrups, tablets, capsules, parenterals, topical creams, ointments e.tc. Absorption from different dosage forms varies. Absorption from solution form is rapid than solid dosage form. The absorption from tablets depends upon disintegration and dissolution time.

• Route of administration, absorption from oral route is slower than from parenteral route. Absorption from inhaled route is faster than oral, sublingual route gives full absorption by bypassing first pass effect.

Factors affecting absorption/systemic availability

• Blood flow at the site of administration, increase blood flow at the site of absorption will increase the rate of absorption. --- local massage after IM injection.

• Gastrointestinal Tract, small intestine is the ideal place for drug absorption due to large surface area. Acidic drugs absorbed from acidic media while basic drugs from basic media. e.g. aspirin from stomach, phenobarbitone from intestines. Increased peristaltic activity decrease the absorption of drugs

• Presence of food or other drugs, Vitamin C increases absorption of iron from GIT, calcium containing food interfere with the absorption of tetracycline antibiotics.

Pharmacokinetics…

Distribution Involves the transport of drug molecules within the body.

• After the drug is absorbed into the bloodstream, it is carried by the blood or tissue fluids to its sites of action, metabolism and excretion.

• Protein binding is an important factor in drug distribution.

• Albumin is important carrier for many drugs.

Pharmacokinetics…

• Drug distribution into the CNS is limited because of the blood-brain barrier.

• Blood-brain barrier is composed of capillaries with tight walls which limits movement of drug molecules into brain tissue.

• Only drugs that are lipid soluble or have a transport system can cross the blood-brain barrier and reach therapeutic concentrations in brain tissue.

Pharmacokinetics…

Protein binding: • Most drugs form a complex with plasma proteins,

mainly albumin, which act as carriers.• Only the free or unbound portion of a drug acts on

body cells• As unbound drug acts on cells, the decrease in

plasma drug level causes some of the bound drug to be released

• Protein binding allows a part of a drug dose to be stored and released as needed

Pharmacokinetics…

Metabolism:• Method by which drugs are inactivated or

biotransformed by the body.• Some drugs yield metabolites that are also active and

exert effects on the body until they are excreted.• Most drugs are lipid soluble which aids their passage

across the cell membrane.• In metabolism lipid soluble drugs are converted into

water soluble forms.

Pharmacokinetics…

• Excretion usually is by kidneys. Need to be water soluble for this to occur. Thus, one function of metabolism is to convert fat soluble medications to water soluble ones.

• Hepatic drug metabolism or clearance is a major mechanism for terminating drug action and eliminating drug molecules from the body

• Most drugs are metabolized by the cytochrome P450 enzymes in the liver

• Liver contains complex system of enzymes, three of which are key in the metabolism of medications/drugs

Pharmacokinetics…

Excretion• Refers to the elimination of a drug from the body.• Excretion usually is by kidneys. Need to be water soluble for this

to occur.• Most are excreted by the kidneys although some are excreted in

the bile.• Kidneys: excretion is through Glomerular filtration, active tubular

secretion. Drugs having m.wt less than 300 are excreted via GF. • Bile: Drugs with a m.wt greater than 300 are excreted through

bile e.g. erythromycin, metoprolol.• Other minor routes of excretion are breast milk, lungs e.tc.

Volume of distribution• It is the volume into which the dose of a given drug appears to

have been dissolved. It is not a real but a hypothetical voume. Calculated as

• Vd=dose/Cp• It is measured in liters• If the entire drug remains in the circulation the volume of

distrubtion will be around 5litrs, equal to volume of vascular compartment. Some highly Lipophillic drugs (amitryptyline) have a volume of distribution more than 250 liters which indicate that most of the drug is present in tissue compartment.

• Drugs that are not lipid soluble have low volume of distribution e.g. amikacin, gentamicin, aspirin.

Plasma Protein Binding

• Drugs after absorption into blood occurs in two forms• Free fraction: moves freely without any complexation,

pharmacologically active, is able to be metabolized and excreted.

• Protein bound fraction: this fraction is bound to plasma protein mainly albumin, pharmacologically inactive due to large complex size, this binding is reversible.

• There is equilibrium between free and bound drug.• Drugs which are highly protein bound are phenytoin, warfain.• In renal and liver diseases the binding capacity of plasma

protein is reduced due to decrease in albumin synthesis. The concentration of free drug increases which may lead to toxicity.