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Clinical Pharmacokinetics. Clinical Pharmacodynamics. Drugs’ Interaction. Adverse Effects of Drugs

Clinical Pharmacokinetics. Clinical Pharmacodynamics. Drugs’ Interaction. Adverse Effects of Drugs

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Clinical Pharmacokinetics. Clinical Pharmacodynamics. Drugs’ Interaction.

Adverse Effects of Drugs

DRUG NAMES

The genericname often indicates the drug group (eg, drugs with genericnames ending in “cillin” are penicillins). The trade name isdesignated and patented by the manufacturer. For example,amoxicillin is manufactured by several pharmaceutical companies,some of which assign a specific trade name (eg,Amoxil, Trimox) and several of which use only the genericname.

Amoxicillin

Metronidazole

Ranitidin

. ENTRY AND MOVEMENT OF DRUG MOLECULES

THROUGH THE BODYTO SITES OF ACTION, METABOLISM, AND

EXCRETION

ABSORPTION is the process that occurs from the time a drug entersthe body to the time it enters the bloodstream to be circulated.Onset of drug action is largely determined by the rateof absorption; intensity is determined by the extent of absorption.

Dosage formis a major determinant of a drug’s bioavailability (the portionof a dose that reaches the systemic circulation and is availableto act on body cells). An intravenous drug is virtually100% bioavailable; an oral drug is virtually always less than100% bioavailable because some is not absorbed from the GItract and some goes to the liver and is partially metabolizedbefore reaching the systemic circulation.

Most oral drugs must be swallowed, dissolved in gastric

fluid, and delivered to the small intestine (which has a large

surface area for absorption of nutrients and drugs) before they

are absorbed. Liquid medications are absorbed faster than

tablets or capsules because they need not be dissolved.

Sustained blood levels

The size and frequency of dosing is determined by the pharmacodynamic and pharmacokinetic properties of the drug. The slower the rate of absorption, the less the blood concentrations fluctuate within a dosing interval. This enables higher doses to be given less frequently. For drugs with relatively short half-lives, the use of extended-release products may maintain therapeutic concentrations over prolonged periods

Drug transport pathways. Drug molecules cross cellmembranes to move into and out of body cells by directly

penetratingthe lipid layer, diffusing through open or gated channels,

or attaching to carrier proteins.

Plasma proteins, mainly albumin (A), act as carriers for

drug molecules (D). Bound drug (A–D) stays in bloodstream and is

pharmacologically inactive. Free drug (D) can leave the bloodstreamand act on body cells.

Half-life of a drug

Elimination of a hypothetical drug with a half-life of 5 hours.

The drug concentration decreases by 50% every 5 hours

(i.e., T1/2 5 hours). The slope of the line is the elimination rate (Ke).

THE LIVER IS THE PRINCIPAL ORGAN OF DRUG

METABOLISM. Other tissues that display considerable activity include the gastrointestinal tract, the lungs, the skin, and the kidneys. Following oral administration, many drugs (eg, isoproterenol, meperidine, pentazocine, morphine) are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism. This process has been called a first-pass effect.

Pharmacodynamic Variables

Clearance is the single most important factor determining drug concentrations.

Clearance is readily estimated from the dosing rate and mean steady-state concentration. Blood samples should be appropriately timed to estimate steady-state concentration.

Вioavailability is defined as the fraction of a given drug dose that reaches the circulation in unchanged form and becomes available for systemic distribution. The larger the

presystemic elimination, the smaller is the bioavailability of an orally administered

drug.

Сеll membrane contains receptors for physiologic substances

such as hormones (H) and neurotransmitters (NT). These substances

stimulate or inhibit cellular function. Drug molecules (Da and Db)

also interact with receptors to stimulate or inhibit cellular function

Presystemic eliminationPresystemic elimination

Factors that influence on drug metabolismFactors that influence on drug metabolismFactor Reaction type

Age (newborns, children, elderly)

Decreasing of metabolism speed

Pregnancy Increasing of metabolism speed Genetic factor Various reactions Liver pathology Decreasing of excreation speed of drugs, depending on their kinetics, type

and stage of liver disease, increasing of bioavailability and decreasing of excretion speed of orally administered drugs with high hepatic clearence

GI pathology Changes in metabolism in GI epithelium

Nutrition character

Increasing of metabolism speed of certain drugs in case of diet with dominance of proteins and carbohydrates Decreasing of metabolism speed in case of heavy digestive disorders linked with starvation (total or protein)

Environment Increasing of metabolism speed if in contact with chlorine insecticides

Alcohol — one time consumption

Depressing of enzymes that metabolise drugs

— chronic consumption

Induction of enzyme system

Smoking Increasing of metabolism of certain drugs (i.e. theophyllin)

Way of excretion

Metabolism in liver before entering system circulation (first going-through effect) after peroral administration of drugs

Time of introduction of drugs

Circade changes in drugs metabolism

Interaction of drugs

Stimulation and depression of enzyme reaction

Client-Related VariablesAgeBody WeightGenetic and Ethnic CharacteristicsGender (еxcept during pregnancy and

lactation, gender has been considered a minor influence on drug action).

Pathologic ConditionsPsychological Considerations

TOLERANCE AND CROSS-TOLERANCEDrug tolerance occurs when the body becomes accustomed

to a particular drug over time so that larger doses must be

given to produce the same effects. Tolerance may be acquired

to the pharmacologic action of many drugs, especially opioid

analgesics, alcohol, and other CNS depressants. Tolerance to

pharmacologically related drugs is called cross-tolerance.

For example, a person who regularly drinks large amounts of

alcohol becomes able to ingest even larger amounts before

becoming intoxicated—this is tolerance to alcohol. If the person

is then given sedative-type drugs or a general anesthetic,

larger-than-usual doses are required to produce a pharmacologic

effect—this is cross-tolerance.

Tolerance and cross-tolerance are usually attributed to activation

of drug-metabolizing enzymes in the liver, which accelerates

drug metabolism and excretion. They also are attributed

to decreased sensitivity or numbers of receptor sites.

1. Drug-drug interaction

2. Drug-food interaction

1. Drug-others(herbs, supplements and DNA)

Fixed drug eruptions

Erythema nodosum

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