Fundamental Pharmaceutical Training-1

FUNDAMENTAL PHARMACEUTICAL TRAINING CLINICAL PHARMACOLOGY

To calculate the precise effect that a drug will have in the body, Clinical Pharmacology has three components

♦ Pharmacokinetics Absorption Distribution Metabolism Exceretion

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Pharmacodynamics Clinical effects Mechanism of action

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Drug delivery system Drug form Drug formulation route of administration

Oral cavity

Mouth

Pharynx

Tongue Salivary glands

Esophagus Liver

Stomach

Pyloric sphincter Stomach

Gallbladder Pancreas

Small intestine Large intestine

Rectum

Anus

Pharmacokinetics is the study of distribution and movement of a drug to the various compartments of the body after absorption and its metabolism and excretion ▼ Bioavailability of a medicinal product may be regarded as the quantity of administered dose which arrive in a therapeutic form at the site where it will exert its biological action’ ▼ Bioavailability of active ingredient of medicinal product is dependent on it Absorption, Distribution, Metabolism, and Excretion.

Bioavailability is often expressed in %age of oral Vs IV & IV =100%) ▼

Absorption may be influenced by the drug formulation or factors as acidity alkalinity and gut movement.

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▼ Metabolism the drug may

Distribution drug vary

then be chemically changed by the body into other, usually smaller, molecules, or metabolites before excretion. Sometimes these metabolites are active in their own right.

in speed in which they ▼ Excretion most drugs are excreted in the urine, usually as penetrate cells and in the extent to which they bind metabolites. Some however, may be eliminated in the bile, from to blood proteins. Some are the gut wall, or, in the case of more concentrated in some anesthetics from lungs certain tissues.

Bile

Liver

Stomach

Gallbladder Bile

Duodenum of small intestine

Acid chyme

Pancreas

FIRST PASS EFFECT ▼

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the first pass effect can be influence a drug’s bioavailability. when a drug is absorbed orally the greater part is first carried to the liver via portal circulation. if the drug is one that is normally broken down in the liver, by the time it reaches the systemic circulation the amount available at the site of action is considerably less than that absorbed. This is known as (first pass) effect and must be taken into account when considering relative dosage. With highly bioavailable drug, a good amount of administered dose reaches the blood, increasing the chance of an optimum therapeutic effect. The peak serum drug concentration is the maximum amount of drug achieved in the blood and must reach therapeutic levels to have an effect. In chronic conditions the aim of dosing regimes is to achieve a steady state concentration maintaining serum drug concentrations at a therapeutic level

T½ ▼

HALF - LIFE

The half-life of a drug is the time taken for the concentration to fall by 50% from peak values. It is a resultant of distribution , metabolism and excretion and may be complex.

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Half –life time required for one half of the concentration of drug in the blood to be eliminated from the body. Precise knowledge of bioavailability and pharmacokinetics may be critically important for antibiotics used in the treatment of lifethreatening infections but it is of less consequence for mild analgesics used for symptomatic relief of pain. It is particularly important in designing dosage schedules and avoiding unnecessary peaks ad troughs in blood concentrations

PHARMACODYNAMICS ▼

It is the study of the activity of a drug both in nature and size of response once it reaches the site of action.

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Plasma monitoring of drug levels is critical for products with narrow therapeutic index. Many drugs are thought to produce their effects by combining with some enzymes, cell membranes or other cell components. this interaction is thought to alter the function of the cell, thereby starting a series of biochemical and physiological changes by which the drug is characterized. The initial interaction is the action of drug, the subsequent events are correctly termed the drug’s effects.

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MODE OF ACTION OF DRUGS ▼

DRUG STRUCTURE AND ACTIVITY: The actions of drugs are closely tied up with their molecular structure, very often slight molecular changes result in major changes in the drug’s properties. Research into variations in the drug structures has often lead to valuable new drugs.

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RECEPTORS: the part of cell on which the drug acts is known as receptor. amongst the best known are the alpha and betaadrenergic receptors. Receptors may not necessarily be present on the surface of cell; they may well be an internal component.

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SITE OF ACTION: some drugs act only on certain cells, tissues or organs and their effect is localized. others act on most cells of the body in a general way. this can be explained by selective distribution through out the body, but this is by no means always the reason. drugs can act extracellularly, at the surface cell , or intracellularly. drugs may produce their effect indirectly by blocking the action of another substance. drugs can act directly on effectors cells. for example, blood pressure may be lowered directly by inhibition of vascular smooth muscle.

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BIOCHEMISTRY OF DRUG ACTION:

The detailed biochemical action of many drugs is not known. in some however it is. Antibiotics and chemotherapeutic agents act by selectively toxic to bacteria. In infectious diseases the cause is invasion of the body by microorganisms. Fortunately the biochemistry of the microbial cell is sufficiently different drugs to be given which destroy the invader, but don’t harm the host. The use of drugs with a selective action on abnormal rapidly dividing cells offers an approach to the problem of alleviating the malignant disease. These are sometime referred to as cytotoxic drugs. Drugs presently available tends to attack normal growing cells as well as cancerous cells. Their scope is therefore limited as toxic effect (death to normal cell) limits their therapeutic use.

MEASURING THE DRUG EFFECTS ▼

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A SPECFIC DRUG’S EFFECT CAN BE MEASURED BY PLOTTING A DOSE-RESPONSE CURVE. THIS ILLUSTRATES THE INTENSITY OF EFFECT, OR EFFICACY, AT DIFFERENT DOSES AND ALSO IDENTIFIES THE POTENCY OF A DRUG – THE REALTIVE AMOUNT IS REQUIRED TO PRODUCE A SPECFIC EFFECT. THE MINIMUM EFFCETIVE DOSE IS THE LOWEST DOSE THAT WILL PRODUCE AN APPRECIABLE EFFECT. THE MINIMUM EFFECTIVE DOSE IS REACHED WHEN INCREASING THE DOSE FAILS TO INCREASE THE CLINICAL EFFCET. DOSE RESPONSE CURVE PROVIDE A USEFUL BASIS FOR COMAPRING DRUGS WITH SIMILSR EFFECTS TO ASSESS RELATIVE POTENCY AND EFFICACY.

ADVERSE REACTIONS ▼

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The choice of appropriate pharmacological therapy is based on drug efficacy and drug safety. Drugs exert their beneficial effects by altering biological processes within the body. this can lead to unwanted, or non-therapeutic effects. Side effects of drug other than those required for therapeutic purposes which occur in normal dosage range. toxic effects are usually dangerous which normally occur outside the normal therapeutic range. The therapeutic index or therapeutic ratio is used to describe the relative safety vs. efficacy of a drug.

Following are the examples of factors , which may cause adverse reaction ▼

Variation in therapeutic response Body weight Individuals at the extreme of age (infants, elderly)

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Extreme susceptibility to drugs salicylates

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Abnormally in patient causing relative over dosage, either from physiological change, or enhancement of effect. Normal but unpleasant pharmacological effects. Undesirable local effects Secondary effects: these occur as an indirect consequence of the activity of the drug. hypersensitivity and allergy genetic abnormalities. direct toxic effects e.g. hepatotxicity and nephrotoxicity: because drugs are concentrated in the liver and the kidney.

Teratogenic effects are those which cause adverse effects to the developing fetus in a drug which crosses from the maternal to fetus circulation. ▼ Other toxic effects on the foetus and the new born. ▼ Drug interaction resulting from the introduction of more powerful drugs and increasing use of combining therapy. When two drugs are given together, the action of one drug upon the other may lead to an increase, reduction or modification of effect, sometime with more serious results. These interactions may cause by alterations to the absorption, metabolism or excretion of one or both drugs ▼