I. Introduction -basic Pharmacology.pdf 4k3a34

PHARMACOLOGY – Dela Rosa Edition INTRODUCTION :BASIC PHARMACOLOGY PHARMACOLOGY • Science of drug interactions between living systems & moleculess introduced from outside the system • Study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. GOAL OF PHARMACOLOGY • To understand the mechanism by which drugs interact with the biologic systems in the diagnosis & treatment of disease DRUG • An agent intended for use in the diagnosis , mitigation , treatment ent ,cure, or prevention of disease in man or in animal • A natural product ,chemical substance, or pharmaceutical preparation to be used in the diagnosis or treatment of a disease • Varies in of o Molecular size o Shape o Chemical nature DRUG NAMES : Chemical name

Chemical

N-acetyl-

structure of the

paminophenol

drug Non proprietary

Generic name

acetaminophen

Trade name or

Tylenol

1. Pharmacy • involved in the compounding, preparation, collection, standardization and dispensing of the drug. 2. Pharmacognosy • recognize the drugs (description, sources, chemical composition, nature of doing, etc) • study of the physical and chemical properties of the drugs with the description and identification of their sources and nature.) 3. Biochemorphology • (structure activity relationship or SAR) • how the chemical structure of the drug is related to physiological, biological and biochemical effects. endogenous catecholamines • synthesized in the body • (epinephrine, norepinephrine, dopamine, tyrosine) synthetic (exogenous) catecholamines • from outside given to the body • (isoproterenol) ephedrine acting sympathomimetic symp agent; CNS • mixed-acting stimulation; not a catecholamine but its effects on bronchi and other smooth muscles are quantitatively similar to those of epinephrine amphetamine acts indirectly by releasing norepinephrine; also a • CNS stimulant; depresses the appetite by affecting the feeding center in the lateral hypothalamus Norepinephrine – affects α1, α2 and β1 Epinephrine – affects α1, α2, β1 and β2

name Proprietary name

brand name BRANCHES OF PHARMACY

4. Toxicology - study of the harmful effects of drugs and other chemicals on human, animals and plants 5. Posology - deals with the dosage of the drug required to produce a therapeutic response 6. Molecular Pharmacology studies the mechanism of enzymatic level (gene therapy; engineering)

action of a drug at genetic

7. Developmental Pharmacology - deals w// drug given to mother as it affects the fetus during natal, prenatal, perinatal & neonatal periods. 8. Pharmacogenetics - studies the influence of heredity on the pharmacokinetic and pharmacodynamic response of the drug. 9. Pharmacogenomic - describes the use of genetic information to guide the choice of drug therapy on an individual basis

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discovers which specific gene variations are associated with a good or poor therapeutic response to a particular drug

10. Pharmacoepidemiology

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studies the response in population at a given time and space of the pharmacologic events, whether they are adverse or beneficial with the use of measures of epidemiology

PHASES OF A CLINICAL DRUG INVESTIGATION PHASE I II III IV

PURPOSE establish safety Establish efficacy and dose efficacy and detect ADR’S Obtain additional data following approval

PHASES OF DRUG MANUFACTURE 11. Pharmacoeconomics

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studies the cost effectiveness of drug treatment

deals with the interethnic differences in response to or metabolism of chemical substances, and the presence and absence of enzymes in different regions of the Phil. or of different races.

I ANIMAL TESTING Pre-clinical testing

13. Clinical Pharmacology

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tested in at least 2 rodent & 1 non rodent species 1 to 3 yrs. (ave. 18 months) here you determine for the: o Acute toxicity - observation of animal 7-14 days using a simple dosage of the drug being tested. o Subacute toxicity - 2 weeks to 3 months. o Chronic toxicity - 6 months to 2 years. -

12. Ethnopharmacology

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PHASE

Deals w/ rational development of drugs, their safe & effective use, and other proper evaluation of drugs in humans for the prevention, diagnosis, treatment, alleviation or cure of a disease. refers to the rational use of criteria)

drugs (ESSC

II FDA III CLINICAL TESTING

Efficacy – considers pharmacodynamics, pharmacokinetics, of the different drug groups; ability of drug to accomplish what it is intended to do. Safety – side effects, toxicity, frequency and severity

30 days safety review –Includes humans (healthy adult males) –2-10 yrs (average 5-6 yrs) –the lowest effective dose given to man because humans can react differently to the drug –pediatric patients not included in the testing because some drugs can have adverse effects on the development of the patient. –Short term –Long term (chronic toxicity, reproduction, teratogenicity) Phase I

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Suitability – convenience, compliance, practicality, contraindications and possible interactions.

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Cost

involves normal healthy adult male to measure the initial drug safety, biological effects, metabolism, kinetics done by the clinical pharmacologist

Phase II • involves selected patients, needing the treatment • to measure therapeutic efficacy, dosage range, metabolism, kinetics • done by clinical pharmacologist

14. Pharmacokinetics (kinetic=bodydrug) - “what the body does to the to the drug” - movement of the drug in the body and how the body acts on the drug - fate of drug in the body Involves four processes (E)

Phase III

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● Absorption ● Distribution ● Metabolism (biotransformation) ● Excretion 15. Pharmacodynamics (dynamic = drugbody) - “what the drug does to the body” - biochemical and physiological effects of drugs and their mechanism of action (includes enzymatic or molecular level and also toxicological or adverse effects.)

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involves large sample of selected patients to measure the safety and efficacy ● done by clinical investigators

IV New Drug Application (NDA)

- Review (BFAD) - Marketing approval

V. Post Marketing Surveillance (PMS)

-to look for chronic effects Phase IV – drug is available commercially – Involves patient given the drug treatment – to look for adverse reactions, patterns of drug utilization, additional indications discovered. – Done by all physicians.

PHASES OF PRODUCT DEVELOPMENT – –

It takes 12 years on average for an experimental drug to travel from lab to medicine chest. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.

SYSTEMIC- produces a systemic effect even if you just apply it on your on your skin; sprayed or injected ACTIONS IN RELATION TO SPECIFIC EFFECTS Cathartic Laxative Hypnotic Diuretic

increases bowel movement for constipated patients induces sleep increases urination

AntacidVasodilator

has buffering actions; neutralizes HCl relaxed vascular smooth muscles (Ca 2+ blocker)

VARIABLES INVOLVED IN DRUG ACTIVITY Dose of drug istered ↓ Pharmaceutical phase (bioavailability) (disintegration and dissolution) ↓ Pharmacokinetic Phase (E) ↓ Pharmacodynamic phase (drug-cell, drug-receptor, drug-drug interactions; individual sensitivity; pathological conditions) ↓ Placebo – “ I shall please” ● Used to achieve blindness and subjective bias ● Response may involve objective, physiologic and biochemical changes as well as change in subject’s complaints associated with the disease. ● Two types: 1. do not contain pharmacologically active ingredients (used for negative control) 2. contain some compound with pharmacological activity different from the test drug (used for positive control) FUNDAMENTAL TYPES OF DRUG ACTION STIMULATION – enhances the specialized tissues DEPRESSION – diminished functional activity of specialized tissues IRRITATION – either stimulate or depress non-specialized tissues OTHER DRUG ACTIONS REPLACEMENT THERAPY- replaces what is sufficient and deficient ANTI-INFECTIVE- entails the use of anti-microbial agents LOCAL- Topically applied, and action is just on the area itself

Effects (toxic, therapeutic, subtherapeutic)

PHARMACEUTICAL PHASE – involves disintegration of dosage form (generally water soluble) & dissolution of active ingredients (lipid soluble) ● Bioavailability – fraction of unchanged drug reaching the systemic circulation following istration by any route PHARMACODYNAMIC PHASE •Drug-drug interaction – simultaneous intake of two different drugs, one drug may displace another for Its binding site – another may reduce the metabolism of the other •Individual sensitivity – interpatient variability (for hyperactive and hypoactive people. •Pathological conditions – renal, cardiac, hepatic dysfunctions, malnutrition

DEFINITION OF : DIDACTIC STUDY GUIDE PHARMACOLOGY

Science of drug interactions between living systems & molecules introduced from outside the system

DRUG ACTION AND EFFECT PHARMACOKINETICS BIOAVAILABILITY

what the body does to the to the drug” movement of the drug in the body and how the body acts on the drug fraction of unchanged drug reaching the systemic circulation following istration by any route

FIRST ORDER KINETICS ZERO ORDER KINTICS VOLUME OF DISTRIBUTION CLEARANCE STEADY STATE CONCENTRATION HALF LIFE

The measure of the apparent space in the body available to contain the drug . The measure of ability of the body to eliminate the drug

Is the time required to change the amount of drug in the body by one half during elimination -t1/2

LOADING DOSE MAINTENANCE DOSE PEAK AND THROUGH LEVEL OF DRUGS PHARMACODYNAMIC

-“what the drug does to the body” -biochemical and physiological effects

of drugs and their mechanism of action

EFFICACY POTENCY AFFINITY AGONIST PARTIAL AGONIST MEDIAN EFECTIVE DOSE THERAPEUTIC INDEX RECEPTOR/SPARE RECEPTOR TOLERANCE TACHYPHYLAXIS OVERSHOOT OR REBOUND PHENOMENOM UP/DOWN REGULATION IDIOSYNCRASY PLACEBO/PLACEBO RESPONSE CLINICAL PHARMACOLOGY

XENOBIOTICX PHARCOEGENOMICS

Used to achieve blindness and subjective bias Asses drug interaction • To produce its characteristic effect, a drug must be present in an appropriate concentration at its site of action (bioavailable amount). The effect may be subtherapeutic (lacking); while too much would cause toxicity. Substances that are absorbed across the lungs or skin or more commonly ingested either unintentionally Is the study of the genetic variation that cause differences in drug response among individuals or populations