Introduction Def1: Pharmacology is the study of pharmacokinetic and pharmacodynamic studies of...

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Introduction Def1: Pharmacology is the study of

pharmacokinetic and pharmacodynamic studies of drugs.

Def2: Pharmacology is the study of drugs.Def3: Pharmacology is a scientific discipline

that studies about chemical, therapeutic and the side effects of drugs.

What is a Drug?In WHO drug is defined, any substance or

product that is used to explore a physiological systems or pathological states for the benefit of the recipient.

Word of drug derived from French word, drogue meaning dry herb which is used for diagnosis, prevention and cure of a disease.

Dose, it is the quantity of the drug.Dosage, it is the schedule of the dose,

frequency and duration of administration of drugs.

Drug dosageDose is the appropriate amount of a drug

needed to produce a certain degree of response in a patient.

Dose can be classified into:1.Standard dose e.g contraceptives ,

chloroquine 2.Regulated dose e.g anticoagulants, diuretics 3.Target level dose e.g digoxin, lithium 4.Titrated dose e.g anticancer drugs &

levodopa

Rights of Pharmacology Right drugRight dose Right time Right route Right patient

Pharmacokinetics Pharmacokinetic is the study of what actually

happens to a drug from the time it is put into the body until the time all of it and it is metabolites have left the body.

Pharmacokinetic is what body do to the drug.

Pharmacokinetic is the study of absorption, distribution, metabolism and excretion (ADME).

Absorption

• Drug absorption is the processes of incorporating a drug into the body and its various tissues, organs and other biological sites.

• If two medications have the same bioavailability, they are said to be bio-equivalent.

• Bioavailability is the amount of a drug in a particular dosage form that is absorbed into the circulation.

• There are various factors that affecting the rate of drug absorption, these include administration route of a drug, food, and fluids, administered with a drug, the dosage formulation, the status of the absorptive surface, and the acidity of the stomach.

Distribution

Once a drug enters the blood stream (circulation), it is distributed throughout the body.

A drug can be freely distributed to extravascular tissue only if it is not bound to a protein. If a drug is bound in to a protein, it is generally too large to pass into tissues.

The transport of a drug that in the body by the blood stream to its site of action is referred to us distribution.

Continue There are three primary proteins that carry that

bind to and carry drugs throughout the body and they are:

Albumin (most important)Alpha 1 acid glycoproteinCorticosteroid binding globulinDistribution can be classified into two

compartments:Rapid distribution like heart, liver, kidney and

brain.Slow distribution like muscle, skin and fat

continueA theoretical volume, called volume of

distribution, is sometimes used to describe the various areas where drugs may be distributed.

Typically a drug that is highly water soluble will have a small volume of distribution and high blood concentrations.

Fat soluble drugs have a large volume of distribution and low blood concentrations.

MetabolismMetabolism is also referred to as

biotransformation because it involves the biologic transformation of a drug into an inactive metabolite, a more soluble compound or a more potent metabolite.

Biotransformation is the next step after absorption and distribution.

The organ most responsible for the biotransformation or metabolism of drugs is the liver. Other tissues and organs that aid in the metabolism of drugs are the kidney, lungs, plasma, and intestinal mucosa.

Continue Biotransformation means chemical alteration

of the drug in the body.The biotransformation capabilities of the liver

can vary considerably from patient to patient.Hepatic biotransformation involves the use of

an enormous variety of microsomal enzymes.

Assignment Biotransformation reactions can be classified

into:1.non-synthetic or phase I reactions: like

oxidation, reduction, hydrolysis, cyclization, and decyclization.

2.Synthetic reactions: like glucuronide conjugation, acetylation, methylation, sulfate conjugation, Glycine conjugation, glutathione conjugation.

Excretion The elimination of drugs from the body is

referred to as excretion.The primary organ that is responsible for

excretion is kidney.Two other organs that also play an important

role in the excretion of drugs are the liver and the bowel.

The actual act of excretion is accomplished through glomerular filtration, resorption, and tubular

Continue Excretion is the passage out of systemically

absorbed drug.The excretion of drugs by the intestines is

another common route of elimination. This is also referred to as biliary excretion. Drugs that are eliminated by this route are taken up by the liver, released into the bile, and eliminated in the feces.

Half life It is the time it takes for one half of the

original amount of a drug in the body to be removed and is a measure of the rate at which drugs are removed from the body.

E.g tetracycline 500mg, it is first half life is 250mg.

Half life of some representative drugs

Aspirin 4 hours Penicillin G 30 minutes Doxycycline 20 hours Digoxin 40 hours Digitoxin 7 days Phenobarbitone 90 hours

Onset, Peak, Duration The terms onset, peak, and duration are used

to describe drug effects.A drug onset of action is the time it takes

for the drug to elicit a therapeutic response.

The time it takes for a drug to reach it is maximum therapeutic response is its peak effect.

The duration of action of a drug is the time that drug concentration is sufficient to elicit a therapeutic response.

Pharmacodynamics The study of the mechanism of drug actions

in living tissues is called pharmacodynamics.Pharmacodynamics is what drug does to the

body.Pharmacodynamics can be classified into:Therapeutic utility Mechanism of action Receptor interactions

Principles of drug action The principles of drug actions are as the

following:1.Stimulation 2.Depression 3.Irritation 4.Replacement 5.Cytotoxic actions

Stimulation It refers to selective enhancement of the level

of activity of speacilized cells. e.g adrenaline stimulates heart, pilocarpine stimulates salivary glands. However excessive stimulation is often followed by depression of that function, e.g picrotoxin a central nervous system stimulant produces convulsions followed by coma and respiratory depression.

Depression It means selective diminution of activity of

specialized cells. E.g barbitutares depress CNS, quinidine depresses heart. Certain drugs stimulate one type of cells but depress the other. E,g acetylcholine stimulates intestinal smooth muscle but depress sinoatrial node in heart, thus most drugs cannot be simply classed as stimulants or depressants.

Irritation This connotes a nonselective often noxious

effect and is particularly applied to less speacilized cells. Mild irritation may stimulate associated function. E.g bitters increase salivary and gastric secretion, counterirritants increase blood flow to the site, but strong irritation results in inflammation, necrosis, and morphological damage.

Replacement This refers to the use of natural metabolites,

hormones or their congeners in deficiency states. E.g levodopa in parkinsonian, iron in anemia, insulin in diabettes.

Cytotoxic actionSelective Cytotoxic action for invading

parasites or cancer cells, attenuating them with out significantly affecting the host cells is utilized for cure of infections and neoplasm's. E.g. zidovudine, chloroquine, penicillin.

Assignment Describe the therapeutic index concept

including formula and ways of calculation.

Combined effects of drugs When two or more drugs are given

simultaneously or in quick succession, they may be either indifferent to each other or exhibit synergism or antagonism.

The interaction may take place at pharmacokinetic level or at pharmacodynamic level.

Synergism When the action of one drug is facilitated or

increased by other, they are said to be synergistic. In synergistic pair both the drugs can have action in the same direction or given alone one may be inactive but still enhance the action of the other when given together.

Synergism can be:1.Additive 2.Supraadditive

additiveThe effect of the two drugs is in the same

direction and simply adds up. E.g effect of drugs A+B= effect of drug A + effect of drug B.

Examples are the following:Aspirin + paracetamol = analgesic/antipyretic Nitrous oxide + halothane = general anesthesia Amlodipine + atenalol = antihypertensive Glibenclamide + Metformin = hypoglycemic Ephedrine + Theophylline = bronchodilator

Supraadditive The effect of combination is greater than the

individual effects of the components.Effect of drug A + B is greater than effect of

drug A + effect of drug B.Examples are the following:1.Acetylcholine plus physostigmine 2.Levodopa plus carbidopa plus benserazide3.Adrenaline plus cocaine plus desipramine 4.Sulfamethaxazole plus trimethoprim 5.Enalapril plus hydrochlorothiazide

Antagonism When one drug decreases or abolishes the action of

another, they are said to be antagonistic.Effect of drug A + B is less than effect of drug A +

effect of drug B.Antagonism can be classified into:1.Physical antagonism e.g charcoal adsorbs alkaloids2.Chemical antagonism e.g heparin intercts penicillin3.Physiological antagonism e.g glucagon & insulin 4.Receptor antagonism e.g agonist & antagonist drugs

Pharmacotherapeutics Pharmacotherapy is a dynamic process that

should be occurring continuously throughout a patient’s therapy.

The use of a medication to treat a pathologic condition is called Pharmacotherapeutics.

Acute TherapyAcute therapy involves intensive drug

therapy and is typically implemented in the critically ill patient. It is generally needed to sustain life. Examples are the administration of vasopressors to maintain blood pressure and cardiac output after open heart surgery or the use of volume expanders in a patient who is in shock.

Maintenance TherapyMaintenance therapy typically does not

eradicate the problems the patient may have but doesn’t prevent progression of the disease. It is used for the treatment of chronic illnesses such as hypertension.

The drug therapy maintains the patient’s blood pressure within certain limits, which prevents certain end organ damage.

Supplemental TherapySupplemental or replacement therapy

supplies the body with a substance needed to maintain normal function.

This substance may be needed either because it cannot be made or because it is deficient in quantity.

Examples are the administration of insulin to diabetic patients or iron to patients with iron deficiency anemia.

Palliative TherapyThe goal of palliative therapy is to make the

patient as comfortable as possible. It is typically used in the end stages of an illness when all possible therapy has failed.

The use of high dose narcotic analgesics to relieve pain in the final stages of cancer is an example; the use of oxygen in end stage of pulmonary disease is another.

Supportive TherapySupportive therapy maintains the integrity of

the body functions while the patient is recovering. Providing fluids and electrolytes to prevent dehydration in a patient with the flu who is vomiting and has a diarrhea is an example.

Giving fluids, volume expanders or blood products to a patient who has lost blood during surgery is an example.

Prophylactic TherapyProphylactic therapy is drug therapy

provided on the basis of prior practical experience. It is based on scientific knowledge often acquired during years of observation of a disease and it is causes.

Pharmacology Terminology Tolerance Dependance OnsetPeakDuration of actionFirst pass effectEfficacyAgonist and antagonist

Continue Idiosyncrasy Summation Synergism Potentiation

Pregnancy categories Pregnancy categories can be divided into:1.A2.B3.C4.D5.X

Drug Classification Drugs are classified by:1.Chemistry, e.g electrolytes 2.Mechanism, e.g beta-blockers and

benzodiazepines.3.Disease, e.g anti-hypertensive and anti-

emetics

Classification of drugs by legal purposesDrugs are grouped for legal purposes as follows:1.Official drugs: drugs which are included in the

pharmacopeias of that particular country are termed official drugs.

2.Dangerous drugs: this include drugs of addiction. E.g opium and cannabis.

3.Prescription drugs (POM): drugs which are given only by the prescription of the doctor.

4.Over the counter (OTC): drugs which are available by public with out prescription.

Drug Nomenclature A drug generally has three categories of

names:1.Chemical name 2.Non-proprietary name 3.Proprietary name

Chemical name It describes the substance chemically,. E.g 1-

isopropylamino-3-1-naphthyloxy propan 2-ol.This is cumbersome and not suitable for use

in prescribing.

Non-proprietary name It is the name accepted by a competent

scientific body/authority, e.g united states adopted name (USAN) by the council of USAN council.

Similarly, there is the British approved name (BAN) of a drug. The non proprietary names of newer drugs are kept uniform by an agreement to use the recommended international non proprietary name (rINN) in all member countries of W.H.O.

Proprietary (Brand) name It is the name assigned by the manufacturers

and is his property or trade mark.One drug may have multiple proprietary

names.Example: altol, atcardil, atecor, aten,

betacard, lonol, tenormin, tenalol for atenalol from different manufactures.

Brand names are designed to be catchy, short, easy, to remember.

Adverse Drug Reactions1. Side-effects. e.g Atropine: dry mouth

2. Toxic effects: mostly seen with higher doses. E.g Morphine, respiratory depression.

3. Drug tolerance: single dose of streptomycin producing vestibular dysfunction.

4. Idiosyncratic reactions: e.g barbiturates produce CNS stimulation.

5. Allergic reactions: immunologically based adverse reactions to drugs are called allergic reactions which are not related to pharmacological actions of drugs.

Factors modifying the action of drugs

1. Body weight, Clarks rule: dose: body weight in kg times average adult dose divide by 70.

Example A patient whose body weight is 65kg has been

taken paracetamol. If the average adult dose of paractemol is 500mg. Calculate the dose of this patient.

Result: 464.3 mg

Continued Body surface area (BSA): The individual dose

= BSA (m2) / 1.7 times average adult dose.The BSA (m2)= BW(kg) 0.425 times Height

(cm) 0.725 times 0.007184Result: 677.1 mg

Continue 2. Age, Youngest rule: age in years times

adult dose divide by age in years plus 12.Example A patient whose his age is 11 years has been

taken Aspirin 365mg. Calculate the dose of this patient.

Result: 174.56mgDillings Formula: child dose= Age times

adult dose divide by 20.Result: 200.175mg

Continued 3. Sex 4. A species and race 5. Diet and environment

Continue 6. Route of administration. E.g Magnesium

sulphate 7. Genetic factor. E.g G6PD patients causes

hemodialysis.8. Diseases. E.g liver diseases9. Renal dysfunction. E.g kidneys,

streptomycin, Amphotericin B, phenytoin.10. Tolerance: can be grouped into natural and

acquired.

Pregnancy considerations Increased maternal heart rate, cardiac output

and blood volume.Drugs may cross placenta Drugs may cross into a breast milkTeratogens

Pediatric considerations Decrease oral absorption Thinner skin Decrease plasma protein concentration Increase extracellular fluid in neonate Altered metabolic rates Decrease elimination Decrease metabolism

Geriatric considerations Decrease oral absorption Decrease plasma protein concentration Decrease muscle mass Increase fat body Decrease liver/ renal function Multiple drugs Multiple diseases

Pharmaceutical Abbreviations Drug Dosage 1.CC: Cubic Centimeter2.G: Gram 3.Gr: Grain 4.Gtt: Drop5.Lb: Pound6.Ml: Milliliter7.Qs: Quantity Sufficient

Continue 8. ss: One half9. tbsp: Tablespoon 10. tsp: Teaspoon 11. ID: intradermal 12. IM: intramuscular 13. IV: intravenous 14. OD: right eye 15. OS: left eye

Continue 16. OU: both eyes17. PO: by mouth 18. SC: subcutaneous 19. SL: sublingual 20: AA: of each21: Ac: before meals 22. Ad lib: as desired 23. bid: Twice a day

Continue 24. h: hour 25. hs: hour of sleep 26. noct: night 27. pc: after meals28. prn: when needed29. qd: every day 30: qh: every hour 31: qid: four times a day

Continue 32. qod: every other day 33. sos: if necessary 34. stat: immediately 35. tid: three times a day

Essential Drug Concept W.H.O has defined (essential drugs) as those

drugs which satisfy priority health needs of the population.

They are selected with due regard to public health relevance evidence on efficacy, safety and comparative cost effectiveness.

Should be available at all times and adequate amounts.

Routes of Drug AdministrationDrugs may be administered by various

routes:1.Enteral 2.Parentral 3.Topical

Enteral routes Enteral means through gastrointestinal tract.1.Oral route It is the most common route of

administration. GIT has a large surface area and different PH at different parts helps absorption of drugs. At the same time some drugs can be destroyed by the enzymes secreted in gastrointestinal tract.

Advantages Convenient: patients can swallow them selvesEconomical: oral compounds are cheaper. Non-invasive : no technique is required, no

syringes and needles.

Disadvantages Slow onset of action Bitter drugs may cause irritation like nausea

and vomiting.Some drugs are not absorbed. E.g

streptomycin Some are destroyed. E.g insulin Cannot be given to unconcious and

uncooperative patientsSome drugs may undergo extensive first pass

metabolism.

Various oral preparations Powders Tablets Capsules Mixtures Syrups Linctus: syrup with soothing agent.Emulsion

Factors that affects oral route Food interferes with absorption of some

drugs.Milk, calcium can affectDrugs should be swallowed with lot of water

and sitting position.

Parenteral Routes Parenteral routes include:1.Injections 2.Transdermal 3.Inhalation 4.Transmucosal

Injections 1. intradermal: in intradermal injection the

drug is injected into the layers of skin. E.g BCG vaccine.

2. Sub-cutaneous: when the drug is injected below the skin, it is absorbed slowly.

3. Intramuscular: is an injection in to the skeletal muscles.

4. Intravenous: the drug is injected directly into the vein.

Advantages & disadvantages IVAdvantages1.In emergency 2.Unconscious patients 3.When the drug is not suitable for IM or

subcutaneous injections.4.When large volumes are required. E.g NS,

5% Dextrose

Continue Disadvantage s1.Rupture of vein 2.Transmission of diseases through blood

transfusion 3.Should be given only to trained person

Inhalational Administration Some drugs may be given by inhalation

through nose to produce either local action on the respiratory tract or systemic action. They are absorbed through lungs. E.g beclomethasone, salbutamol.

Transdermal Administration Highly lipid soluble drugs can be absorbed

effectively from the skin. The drug is applied the skin in the form of a patch having the drug container which releases the drug at a constant rate.

Advantages 1.Prolonged and slow action 2.Can be removed when it is not required.

Continue Disadvantages 1.Absorption can be variable 2.Slow action 3.Sometimes there will be skin reaction

Transmucosal Administration Sublingual route: A number of drugs can be

absorbed from the thinner portion of oral mucosal. The drug is kept in the form of tablet or powder under the tongue.

Advantages 1.It is rapidly absorbed it bypasses liver and

first pass metabolism.2.Easy procedure 3.Quick action

Continue Disadvantages 1.All drugs cannot be given by this route 2.Sometimes it may cause irritation of mucosa

Rectal administration Rectum can serve as useful site for drug

administration especially in unconscious patients and if nausea and vomiting are severe.

Highly lipid soluble drugs are readily absorbed by rectal route.

Topical It is employed for local action of drugs; the

various preparations for topical use are ointment, creams, lotions and paints, eye drops, ear drops, and nasal drops.

Sources of Drugs Drugs are obtained from different sources.

They are natural and synthetic.1.plants: atropine from atropa belladona,

digoxin from digitalis purpura, morphine from papavarum somniferum, quinine from cinchona bark.

2.Animals: insulin, heparin and gonadotropin 3.Minerals: magnesiun sulphate, iron, lithium.4.Microorganisms: penicillins from penicillium

chrysogenum, cephalosporins.5.5. Human sources: growth hormone, insulin,

chorionic gonadotropins from pregnancy ladys urine.

Pharmacopoias 1. IP: Indian pharmacopoeia 2. BP: British Pharmacopoeia3. USP: United states Pharmacopoeia

Assignments Pharmacovigilance Standard dose Regulated dose Target level dose Titrated dose Loading dose Maintenance dose

Continued

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