INTRODUCTION TO PHARMACOLOGY DEFINITION:

Pharmacology is the science that deals with the study of drugs and their interaction with the living systems.

The word Pharmacology is derived from Greek –pharmacon means drug and logos means study.

DRUG:

Drug is a substance used in the diagnosis ,prevention or treatment of disease.

PHARMACOKINECTICS:

Pharmacokinectics is the study of the absorption distribution ,metabolism and excretion of drugs,i.e what the body does the drug (in greek kinesis = movement).

INTRODUCTION TO PHARMACOLOGY DEFINITION:

PHARMACODYNAMICS :

Pharmacodynamics is the study of the effect of the drugs on the

body and their mechanism of action ,i.e what the drug does the

body.

THERAPEUTICS:

Therapeutics deals with the use of drugs in the prevention and

treatment of disease.

TOXICOLOGY :

Toxicology deals with the adverse effect of the drug and also the

study of poisons,i.e detection ,prevention and treatment of

poisoning.(Toxicon =poison in greek.

INTRODUCTION TO PHARMACOLOGY CHEMOTHERAPHY :

Chemotheraphy is the use of chemicals for the treatment of infections.the term now also includes the use of chemical to treate malignancies.

PHARMACY :

Pharmacy is the science of identification , compounding and dispensing of drugs .It also includes collection , isolation, purification , synthesis and Standardization of medical substances.

SOURCES OF DRUGS The sources of drugs could be natural or synthetic ,

NATURAL SOURCES:

1.PLANTS,e.g Atropine ,Morphine ,Quinine

,digoxine,pilocarpine,physostigmine.

2.ANIMALS e.g . Insulin ,heparin ,gonadotrophins and

antitoxic sera.

3.MINERALS,Magnesium sulphate , Aluminium hydroxide

,iron ,sulphur and radio active isotopes.

4.MICROORGANISMS ,Antibacterial agents are obtained

from some bacteria and fungi.we thus have

pencillins,cephalosporins,tetracycline and other antibiotics.

SOURCES OF DRUGS 5.HUMAN: some drugs are obtained from man ,e.g

Immunoglobulin from blood,growth hormone from anterior pituitary and chorionic gonadotrophins from the urine of pregnant woman.

SYNTHETIC :

Most drugs are now synthesized .e.gquinolones,omeprazole,sulfonamides,pancuronium,neostigmine.

Many drugs are obtained from cell culture ,e.g urokinase from cultured kidney cells.

some are now produced by recombinant DNA technology ,e.ghuman insulin, tissue plasmogen activator and some drugs by Hybridoma technique, e.g monoclonal antibodies.

ROUTES OF DRUG ADMINISTRATION Drugs may be administered by various routes .the choice

of the route in a given patient depends on the properties of

the drug and the patients requirements.A knowledge of

advantage and disadvantage of the routes of drug

administration is essential.

The route can be broadly divided into:

Enteral

Parenteral

Local

ENTERAL ROUTE (ORAL INGESTION ) This is the most common ,oldest and safest routes of drug

administration.the large surface area of the GI ,the mixing of its

content and the differences in pHat different parts of the gut help

effective absorption of the drugs given orally.

ADVANTAGES:

1.Safest route

2.Most convenient

3.Most economical

4.Drugs can be self-administered

5.Non-invasive route

DISADVANTAGES 1.Onset of action is slower as absorption needs time.

2.Irritant and unpalatable drugs cannot be administered.

3.Some drugs may not be absorbed due to certain physical

characteristics, e.g streptomycin.

4.There may be irregularities in absorption.

5.Irritation to the GIT may lead to vomitting .

6.Some drugs may be destroyed by gastric juices.e.g insulin.

7.Cannot be given to unconscious and uncooperative patients.

8.Some drugs may undergo extensive first pass metabolism in

liver.

9.Patients may forget to take the tablet which is the practical

problem.

ENTERIC COATED TABLET Some tablets are coated with substances like cellulose-

acetate, phthalate,gluten,etc., which are not digested

by the gastric acid but get disintegrated in the alkaline

juices of the intestine.

This will

1.Prevent gastric irritation.

2.Avoid destruction of the drug by the stomach.

3.Provide higher concentration of the drug in the small

intestine.

4.slow the absorption ,and there by prolong the

duration of action.

ADVANTAGES :

Frequency of administration may be reduced.

Therapeutic concentration may be maintained for along

time specially when noctural symptoms are to be treated.

DISADVANTAGES :

It is more expensive.

There may be releaes of the entire amount of the drug in a

short time leading to toxicity.

PARENTERAL ROUTE Routes of administration other than the enteral route are

known as parenteral routes.Here the drugs are directly

delivered into tissue fluids or blood.

ADVANTAGES :

Action is more rapid and predictable than oral

administration.

These routes can be employed in unconscious or

uncooperative patients.

Gastric irritant can be given parenterally and therefore

irritation to the GIT can be avoided.

It can be used in patients with vomitting or those unable to swallow.

In emergencies parenteral routes are very useful.

Digestion by the gastric and intestinal juices and the first pass metabolism are avoided.

DISADVANTAGES :

Asepsis must be maintained.

Injection may be painful.

More expensive less safe and incovenient.

Injury to nerve and other tissues may occur.

Parenteral route include:

1.Injections

2.Inhalation

3.Transdermal route

4.Transmucosal route

INJECTION

Intradermal

The drug is injected into the layers of the skin by:

1.Raising a bleb ,e.g . BCG vaccine ,tests for allergy.

2.By multiple punctures of the epidermis through a

drop of the drug, e.g. Smallpox vaccine.

Only a small quantity can be administered by this

route and it may be painful.

Subcutaneous (SC) injection

Here the drug is deposited in the SC tissue ,e.g.insulin,

heparin.As this tissue is less vascular, absorption is

slow and largely uniform and this make the drug long-

acting.

DISADVANTAGES :

As SC tissue is richly supplied by nerves ,irritant drugs

cannot be injected.

In shock absorption is not dependable because of

vasoconstriction.

Repeated administration at the same site can cause

lipoatrophy resulting in erratic absorption.

Drugs can also be administered subcutaneously as :

1.Dermojet :

In this method ,a high velocity jet of drug solution is

projected from a fine orifice using a gun . The solution

gets deposited in the SC tissue from where it is

absorbed .As needle is not required ,this method is

painless.It is suitable for vaccines.

2.pellet implantation :

Small pellets packed with drugs are implanted SC.The

drug is slowly released for weeks or months to provide

constant blood levels,e.g

,testosterone,desoxycortocosterone acetate.

3.sialistic implants :

The drug is packed in sialistic tubes and implanted SC .

The drug gets absorbed over months to provide constant

blood levels ,e.g .hormones and contraceptives. The

empty nonbiodegradable implant has to be removed.

INTRAMUSCULAR:

Aqueous solution of the drug is injected into one of the

large skeletal muscle –deltoid, triceps, gluteus or rectus

femoris .

Absorption into the plasma occurs by simple diffusion . Large molecules enter through the lymphatic channels .As the muscle are vascular ,absorption is rapid and quite uniform.

Drugs are absorbed faster from the deltoid region than gluteal region especially in women .The volume of injection should not exceed 10ml .For infants rectus femoris is used instead of gluteus which is not well-developed till the child start walking .oily solution or suspension ,the absorption is slow and steady . smaller volume (1-2ml) deltoid muscle is used if large volumes gluteal muscles should be used .

Soluble substances ,Mild irritant ,depot preparations , suspensions and colloids can be injected by this route.

ADVANTAGES :

Intramuscular route is reliable.

Absorption is rapid.

DISADVANTAGES :

IM injection may be painful.

It may result in an abcess.

Risk of nerve injury –irritant solutions can damage the

nerve if injected near the nerve.The needle may also be

puncture the blood vessel.

INTRAVENOUS (IV) Here ,the drug is injected into one of the superficial veins

so that it directly reaches the circulation and is immediately available for action.

Drug can be given IV as :

1.A bolus: the drug is dissolved in a suitable amount of vehicle and injected slowly.An initial large dose is given,e.g .heparin.

2.slowly : over 15-20 min,e.g.aminophylline.

3.slow infusion: when constant plasma concentration are required ,e.g.oxytocin in labor or when large volumes have to be given,e.g.dextrose, saline.

ADVANTAGES : IV route is useful in emergencies because the drug is

immediately available for action.

It gives 100% bioavailability.

Large volume and irritants can be given,they quickly diluted in blood.

Rapid dose adjustments are possible-if unwanted effectesoccur,infusion can be stopped.

DISADVANTAGES :

Once injected ,the drug cannot be withdrawn.

Irritation of the vein may cause thrombophlebitis.

Self medication is difficult.

The solution should be sterile and strict aseptic measures should be taken.

Administration of IV solutions Maintain strict asepsis.

Before starting infusion the IV line should be flushed with saline.

Watch for sign of extravasation of fluid and thrombophlebitis.

Make sure that there are no air bubbles in syringe and tubing.

Intraperitonial :

Peritonium offers a large surface area for absorption .

This route is also used for peritonial dialysis.

Intrathecal :

Drugs can be injected into the subarachnoid space for

action on the CNS,e.g .spinal anesthetics.some antibiotics

and corticosteroids are also injected by this route to

produce high local concentrations.

Intra-articular:

Drugs are injected directly into a joint for the treatment of

arthritis and other diseases of the joints.strict aseptic

precautions are required,e.g .hydrocortisone is injected

into the affected joint,in rheumatoid arthritis.

Intra-arterial:

Here the drug is injected directly into the arteries.it is used only in the treatment of peripheral vascular disease, local malignancies and angiograms.

Intramedullary:

This route involves injection into a bone marrow –now this rarely used.

Inhalation :

Volatile liquids and gases are given by inhalation,e.gGA.Solution of drug particles and the fine droplets are inhaled as aerosol, e.g . Salbutamol.Inhaled drugs and vapour may act and absorbed on the pulmonary epithlium and mucous membranes of the respiratory tract.

ADVANTAGES :

Almost instaneous absorption of the drug is achieved because large surface area of the lungs.

Hepatic first pass metabolim is avoided.

Absorption and excretion through lunges.

DISADVANTAGES :

Irritant gases may enhance pulmonary secretions and should be avioded by this route.

TRANSDERMAL ROUTE:

Highly lipid soluble drugs can be applied over the skin for

slow and prolonged absorption ,e.g nitroglycerin ointment

in angina pectoris . Adhesive units, inunction,

iontophoresis and jet injection are some forms of

transdermal drug delivery.

Adhesive units :

Adhesive patches of different sizes and shapes made to

suit the area of application .site of the application are

chest, abdomen , upperarm ,back or mastoid region,e.g

hyosine, nitroglycerin fentanyl,estrogen,testosterone

transdermal patches.

ADVANTAGES :

Duration of action is prolonged.

Provide constant plasma levels.

Patient compliance is good.

Inunction :

In this route of administration the drug is rubbed in to the skin and it gets absorbed to produce systemic effects.

Iontophoresis :\

In this procedure ,galvanic current is used for bringing about penetration of lipid insoluble drugs into the deeper tissues where its action is required,e.g .salicylates, fluoride iontophoresis is used in the treatment of dental hypersensitivity.

Jet injection :

As absorption of drug occurs across the layers of the skin ,

TRANSMUCOSAL:

Druga are absorbed across the mucous membranes. It includes sublingual,nasal and rectal routes.

Sublingual :

Here, the tablet or pellet containing the drug is placed under the tongue.it dissolved and the drug is absorbed across the sublingual mucosa,e.g. Nitroglycerin, nifedipine,buprenorphine.

ADVANTAGES :

Absorption is rapid –within minutes the drug reaches the circulation.

First pass metabolism is avoided.

After the desired effect is obtained ,the drug can be spat out to avoid the unwanted effects.

DISADVANTAGES :

Buccal ulceration can occur.

Nasal :

Drugs can be administered through nasal route .e.g. Oxytocinspray ,oxymetazoline, budesonide for allergic rhinitis.

Rectal :

Rectum has a rich blood supply and drugs can cross the rectal mucosa to be absorbed for systemic effect.

Drugs absorbed from the upper part of the rectum are carried

by the superior hemorrhoidal vein to the portal circulation.e.g

indomethacin, chlorpromacine, diazepam can be given rectally.

ADVANTAGES :

Gastric irritation is avoided.

Can be administered by unskilled persons.

Useful in geriatric patient and others with vomiting and those

unable to swallow.

DISADVANTAGES :

Irritation of the rectum can occur.

Absorption may be irregular and unpredictable.(enema )

Enema is the administration of a drug in liquid form into the rectum.enema may be evacuant or retensionenema.

Evacuant enema: In order to empty the bowel,about600ml of soap water is administered per rectum.it is given prior to surgeries ,obstetric proceduresandradiological examination of gut.

Retention enema: The drug is administered with about 100ml of fluids and is retained in the rectum for local action.e.g prednisolone enema in ulcerative colitis.

TOPICAL:

Drugs may be applied on the skin for local action as ointment

,cream , gel ,powder, paste,etc,drugs may also be applied on

the mucous membrane ascin the eyes ,ears , and nose as

ointment ,drops and sprays.

Drugs may be administered as suppository for rectum ,bougie

for urethra and pessary (oval shape) and douche for

vagina.e.g antifungal pessaries in vaginal candidiasis.

SPECIAL DRUG DELIVERY SYSTEM:

In order to improve drug delivery ,to prolong the duration

of action and improve the patient compliance ,special drug

delivery system are used.some such systems are ocusert,

progestasert, transdermal adhesive unit , prodrug ,osmotic

pumps,computerized pumps and methods using

monoclonal antibodies and liposomes as carriers.

Ocusert :

Ocusert systems are thin elliptical units that contains the

drug reservoir which slowly release the drug by

diffusion.e.g pilocarpine ocusert used in glaucoma is

placed under the lid can deliver the pilocarpine for 7 days .

Progestasert is inserted into the uterus where it delivers progesterone constantly for one year.

Trans dermal adhesive units:

Prodrug is an inactive form of a drug which gets metabolized to the active derivative in the body .e.gdopamine does not cross BBB but levo dopa a prodrugcrosses BBB and it is converted to dopamine in the CNS . Bacampicillin a prodrug of ampicillin.

Osmotic pumps are small tablet shape units containing the drug and an osmotic substances in two different chambers.the tablet swallowed and reaches the gut ,water enter into the tablet through SPM .the osmotic layers swells and pushes thedrug slowly.

Computerized miniature pumps: These are Programed to release drugs at a definite rate and continuously.e.g inslin and anticancer drugs.

Monoclonal antibodies are antibodies against the tumor .

Liposome are phospholipids suspended in aqueous vehicles to form minute vesicles .Drugs encapsulated in liposomes .mainly used for malignant tumors.

NURSES RESPONSIBILITIES :

Ensure the correct drug is administered by therightroute and in the right dose.

History of allergy should be taken particularly before parentral administration of the drugs.

Moniter the adverse effect.

Drugs should be kept in safe place.

Check the prescription ,drug label and the patients name before the administration of drugs.

PHARMACOKINETICS

PHARMACOKINETICS Pharmacokinetics is the study of the absorption

,distribution , metabolism and excretion of the drugs, i.e the movement of the drugs into ,within and out of the body.

once drug is administered it is absorbed ,i.e .enters the blood,is distributed to different parts of the body,reaches the site of action ,is metabolized and excreted.

All these processes involve passage of the drug molecules across various barriers – like the intestinal epithelium ,cellmembrane, renal filtering membrane,capillary barrier.

.

Drugs may be transported across the membrane by passive or active transport.

Passive transport:

The drug moves across a membrane without any need for energy.

Active transport It is the transfer of drugs against a concentration of drugs

against a concentration gradient and needs energy.It is

carried by a specific carrier protein.

only drugs related to natural metabolites are transported

by this process,

e.g levodopa, iron , aminoacids, penicillin and probenecid

are given together ,the excretion of penicillin is delayed by

probenecid.

ABSORPTION Absorption is defined as the passage of the drug from the site of

administration into the circulation.for a drug to reach its site of action,it must pass through various membranes depending on the route of administration .

Absorption occurs by one of the processes i.e .passive diffusion or active transport.Thus except for IV route, absorption is important for all other route of administration .

several factor influence the rate and extent of absorption of a drug.they are:

1.Disintegration and dissolution time :The drug taken orally should break-up into individual particles to be absorped.then it has to dissolve in the GI fluids.In case of drugs given SC or IM ,the drug molecules have to dissolve in the tissue fluids.liquids are absorped faster than solids.

Delay in disintegration and dissolution result in delayed absorption.

2.formulation :Inert substance used with drugs as diluents like starch and lactose may sometimes interfere with absorption.

3.Particle size: small particle size is important for better absorption of drugs.Drugs like corticosteroids ,griseofulvin,digoxin ,asprin and tolbutamide are well absorped when given as small particles.

4.Lipid solubility: lipid soluble drugs are absorbed faster and better by dissolving in the phospholipids of the cell membrane.

5.pHand ionization :Ionized drugs are poorly absorbed

while unionized drugs are lipid soluble and are well

absorbed.

Acidic drugs remain unionized in acidic medium of the

stomach and are rapidly absorbed,e.g aspirin,barbiturates.

Basic drugs are unionized when they are reach the alkaline

medium of intestine from where they are rapidly

absorbed,e.g pethidine,ephedrine.

strong acid and bases are highly ionized and therefore

poorly absorbed ,e.g heparin, streptomycin.

6.Area and vascularity of the absorbing surface:larger

area of the absorbing surface and more the vascularity –

better is the absorption.Thus most of the drug absorbed

from the small intestine.

7.Gastrointestinal motility: Gastric emptying time-if

gastric emptying is faster ,the passage of the drug to the

intestines is quicker and hence absorption is faster.

Intestinal motility – when motility is highly ed as in

diarrhea,drug absorption is reduced.

8. Presence of food : Drugs may form complexes with

food,such complexes are poorly absorbed.e.g. Tetracycline

chelate Ca present food ,so absorption ed.

9.Metabolism : Some drugs may be degraded in

gut,e.g.nitroglycerin,insulin.

10.Diseases: The disease of the gut like malabsorption

and achlorhydria result in reduced absorption of drugs.

First pass metabolism First pass metabolism is the metabolism of the drug during its

passage from the site of absorption to the systemic

circulation.it is also called presystemic metabolism or first pass

effect.

Drugs given orally may be metabolized in the gut wall and in

the liver before reaching the systemic circulation.the extent of

FPM differs from drug to drug and person to person.

FPM may result in partial to total inactivation of the drug.when

it is partial , it can be compensated by giving higher dose of

particular drug,e.g nitroglycerin,salbutamol.

Bioavailability is the fraction of the drug that reaches the systemic circulation following administration of any route. IV -100% Bioavailability ,chlortetracycline 30%,chloroquin 80% ,diazepam 100%.

Bioeqivalence :it is the study of comparison bioavailability of different formulation of the same drug.

Distribution After a drug reaches the systemic circulation ,it gets

distributed to various tissues . it should be cross several

barrieers before reaching the site of action.

like absorption distribution also involves the same

process,i.e filtration,diffusion ,and specialized transport.

Various factors determine the rate and extent of

distribution, they are lipid solubility,ionization,blood flow

and binding to plasma proteins and cellular protein.

unionized and lipid soluble drugs are widely distributed

through out the body.

Plasma protein binding On reaching the circulation ,most of the drug bind to plasma

protein ;acidic drug mainly bind with albumin and basic drugs

to -acid glycoprotein.The free or unbound fraction of the drug

is the only form available for action,metabolism and excretion,

The protein bound form serves as areservoir . PB prolongs the

duration and action of drug.e.g warfarin 99%,morphine

35%,ethosuximide and lithium 0%.

One drug may displaces another binding site and result in

displacement interaction,warfarin 99% PB indomethacin

reduces its binding to 95%.free warfarin level incresed it

produce toxicity.

Tissue binding : some drugs get bound to certain tissue constituent because of special affinity for them. TB delays excretion and thus prolongs the duration of drug.

Lipid soluble drug like thiopentone sodium are bound to adipose tisssue,bone-tetracycline,retina-chlorquine,thyroid-iodine.

Blood brain barrier (BBB) :The endothelial cells of the brain capillaries have tight junctions.moreover glial cells envelope the capillaries and together these form the BBB.Only lipid solublle and unionized drugs can cross BBB.

E.G . Penicillin readily penetrates BBB.

Placental barrier: Lipid soluble ,unionized drugs readily cross the placenta.

Metabolism Metabolism or biotransformation is the process of

biochemical alteration of the drug in the body.Body treats most of the drugs as foreign substance and tries to inactivate and eliminate them by various biochemical reactions.

Theses processes convert the drugs into more polar ,water soluble compounds so that they are easily excreted through the kidneys.

Some of the drugs are largely unchanged in urine,e.gfrusemide,atenolol.mainly drugs are metabolized in liver some are metabolized kidney,lungs,blood and skin.

The chemical reactions of biotrasformation can take place in two phases,

1.phase I (Non-synthetic reactions) : convert the drug to more polar metabolite by oxidation,reduction,orhydrolysis.if the metabolites are not water soluble it undergoes phase II reactions.

2.phase II (Synthetic reaction) : in this reactions water soluble substance present in the body like glucuronicacid,sulfuric acid or an aminoacid combine with the drug to form a highly polar compounds it excreted by the kidneys.large molecules are excreted through the bile.

Excretion The major organs of excretion are the kidneys,intestine,biliary

systemand the lungs.Drugs are small amounts are excreted in

saliva,sweat ,and milk.

Renal excretion

Kidney is the most important organ of drug excretion.highly

lipid soluble drugs are reabsorbed in in the renal tubules ,so

their excretion is slow.

Unabsorbed portion of the orally administered drugs are

eliminated through the feces.large water soluble conjugates are

excreted in the bile.

The lungs are the main route of elimination for gases and

liquids, e.g. GA , Alcohol.

Plasma half-life (t1/2) is the time taken for the plasma

concentration of a drug to be reduced to half its value.

Minimum dose is the smallest dose required to produce a

desired therapeutic effect of the drug.

Maximum dose is the largest dose of the drug that can be

safely given to a patient without producing harmful effect.

Toxic dose is the dose of the drug which produce

undesirable effects in majority of the patients

Lethal dose is the dose of the drug which can cause

death.e.g lethal dose of phenobarbitone is 6-10gm.

PHARMACODYNAMICS

PHARMACODYNAMICS Pharmacodynamics is the study of actions of the drugs on

the body and their mechanism of action, i.e to know what

drugs do and how they do it.

Drugs produce their effects by interacting with the

physiological system of the organisms. By such

interaction drugs can only modify the rate of function of

various systems.

e.g drugs may es or es the secretions.but they cannot

change the basic funtion of any physiological system.

Thus drugs act by :

1. stimulation

2.Depression

3.Irritation

4.Replacement

5.Anti-infective or cytotoxic action

6.Modification of the immune status

Stimulation is thees in activity of the specialized cells, e.g adrenaline stimulates the heart.

Depression is the es in activity of the specialized cells, e.gquinidine depresses the heart.

Irritation : This can occur on all types of tissues in the body and may result in inflammation, corrosion and necrosis of cells.

Replacement : drugs may be used for replacement when there is deficiency of natural subatances like hormones ,metabolites or nutrients ,e.g insulin in diabetes, iron in anemia ,vit C in scurvy.

Anti –infective and cytotoxic action: drugs may act by specifically destroying infective organism,e.g penicillin ,cytotoxic effect on cancer cells.

Modification of immune status:

vaccines and sera act by improving our immunity while immunosuppressants act by depressing immunity,e.g glucocorticoids.

Sites and mechanism of drug action

Sites :drugs may produce their effects by locally or systematically.

Local : drugs may act at the site of application.e.gantibiotics,antifungal agent.

Drugs may act by one or more complex mechanism of

action. funtamental mechanism of drug action may be:

Through receptor

Through enzymes and pumps

Through ion channel

By physical action

By chemical interaction

By altering metabolic processes

Through receptor

Drugs may interact specific receptor in the body.

Through enzymes and pumps

Drugs may act by inhibition of various enzymes,thus altering

the enzyme –mediated reaction ,e.g . Allopurinal inhibits the

enzyme xanthine oxidase ; acetazolamide inhibit carbonic

anhydrase.

Through ion channel

Drugs may interfere with the movement of ions across specific

channels, e.g . Ca channel blocker , K channel blocker.

Physical action

The action of drug could result from its physical properties. E.g .absorption –activated charcoal in poisoning.

Chemical interaction

Drugs may act by chemical reaction.

Antacids - Neutralize gastric acids

Oxidising agents - kmno4 (germicidal)

Alternating metabolic processes

drugs like antimicrobial alter the metabolic pathway in the micro organism resulting destruction of MO.e.gsulfonamides interfere with bacterial folic acid synthesis.

Receptor

A receptor is a site on the cell with which an agonist binds to bring about a change. Receptor are proteins.they may be present in the cytoplasm or on the nucleus.

Funtions of receptors

The receptor has to identify the compound, and when the compound binds to the receptor ,it has convey the message to bring about a response.

Agonist :An agonist is a substance that binds to the receptor and produce a response.

Antagonist :An antagonist is a substance that binds to the receptor and prevents the action of agonist on the receptor.

Partial agonist :It binds to the receptor but has low intrinsic activity that is , produce partial response.

Drug synergism and antagonism When two or more drugs are given concurrently ,the effect may

be additive, synergistic or antagonistic.

Additive effect : the effect of two or more drugs get added up

and the total effect is equal to the sum of their individual

actions.e.g . Ephedrine with theophylline in bronchial asthma.

Synergism : when action of one drug is enhanced or facilitated

by another drug the combination is synergistic.here the total

effect of the combonation is greater than the sum of their

independent effect.it is often called ‘potentiation’ or supra-

additive effect.e.g acetylcholine + physostigmine.

Antagonism : one drug opposing or inhibiting the action of another drug is antagonism.based on the mechanism antagonism may be

Chemical antagonism ,

physiological antagonism ,

Antagonism at the receptor level

-Reversible (competitive)

-Irreversible

Non- competitive antagonism

Chemical antagonism: Two subtaces chemically interact

to result in inactivation of the effect,e.g . Antacid like

aluminium hydroxide netralize gastric acids.

Physiological antagonism : Two drugs act at different

sites to produce opposing effect. E.g . Insulin and

glucogan have opposite effects on the blood sugar level.

Antagonism at the receptor level

The antagonist inhibits the binding of the agonist to the

receptor .such antagonism may be reversible or

irreversible.

Reversible competitive antagonism : The agonist and

antagonist compete for the same receptor . By incresing the

concentration of the agonist,the antagonism can be overcome.it is

thus reversible antagonism.Ach and atropine compete at

muscarnic receptor .the antagonism can be overcome by

incresing the concentration of Ach at the receptor.

Irreversible antagonism : The antagonist binds so firmly by

covalent bonds to the receptor that it dissociate slowly not at

all.it block the agonist the blockade cannot be overcome by

increase the dose of agonist hence it is irreversible

antagonism,e.g. Adrenaline and phenoxybenzamine at -

adrenergic receptor.

Factors modifying the drug action Various factor modifying the drug action.they are

1.body weight : The recommented dose is calculated for medium and built persons.for the obese and underweight persons,the dose has to be calculated individually.

Dose = body wt (kg)/70 x average adult dose

2. Age : In the new born ,the liver and kidney are not fully mature to handle the drugs,e.g barbiturates which produce sedation in adults may produce excitation in children.

Youngs formula, childs dose = age (years) x adult dose

age +12

3.Sex : The hormonal effects and smaller body size may influence drug response in women.special care is necessary while prescribing for pregnant and lactating women during menstruation.

4.species and race : response to drug may vary with species and race.e.g. Rabbits are resistant to atropine need more dose to produce mydriasis.

5.Diet and environment : food interfere with the absorption of the drugs. e.g.tetracycline form complexes with Ca present in the food and are poorly absorbed.

6.Route of administration : route of administration may modify the pharmacodynamic response.e.g. Mgso4 given orally it is a purgative,in IV it causes CNS depression and has anticonvulsion effects.applied topically it reduce local edema.

7.Genetic factor : the enzyme production are genetically controlled. The responce of the drugs differ according to the metabolizing enzymes.

A. Acetylation of drugs : the rate of drug acetylationdiffers among individuals people may be fast or slow acetylators.e.g. INH,sulfonamides and hydralazine.

B.G6PD deficiency : primaquine,sulphones and quinolonescan cause hemolysis in such people.

8.Dose : it is interesting to know the response of the drug, the dose is increased the response also increased till the maximum reached .incase some drugs further increased the drug response is lowered.e.g. Myasthenia gravis ,neostigmine enhance the muscle power in therapeutic doses in higher the dose it produce muscle paralysis.

9.Diseases : presence of certain disease can influence drug responses,e.g . Malabsorption –drugs are poorly absorbed ,liver diseases-rate of metabolism reduced.

10.Repeated dosing :Can result in

cumulation,tolerance,tachyphylaxis.

Cumulation : Drugs like digoxin which are slowly eliminated

may cumulate resulting in toxicity.

Tolerance :Tolerance is defined as the capacity of the body to

become less responsive to a substance.

Lethal dose of Morphine is 250 mg, addict can tolerate

morphine in gm.

Trachy phylaxis : is the rapid development of tolerance.when

some drugs are administered repeadly at short interval

,tolerance develops rapidly and is known as tachyphylaxis or

acute tolerance.

11.Psychological factor : the docter patient relationship as

well as the nursing care influence the response to a large extent

by acting on the patient psychology .The patients confidence in

the doctor may itself be sufficient to relieve a suffering

,particularly the psychomatic disorder.placebo is the inert

dosage form with no biological activity but only resembles the

actual preparation in appearance.

12.presence of other drugs :

The concurrent use of two or more drugs can

influence the response of each other.