Introduction of Pharmacology_1 - Copy

7/27/2019 Introduction of Pharmacology_1 - Copy

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INTRODUCTION OF

PHARMACOLOGYEdy Ramdhani, dr


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WHATS PHARMACOLOGY?

Pharmacology is the body ofknowledge concerned with the actionof chemicals on biologic systems


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THE NATURE OF DRUGS

Drugs in common use :

- inorganic ions

- nonpeptide organic molecules

- small peptides and proteins- nucleic acids

- lipids

- carbohydrates They are found in animals or plants and

synthetics of these


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THE MOVEMENT OF DRUGS IN

THE BODY

Permeation (the movement of drugmolecules into and within thebiologic environment), involves

several processes :

1. Aqueous diffusion

2. lipid diffusion

3. transport by special carriers

4. Endocytosis, pinocytosis


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ABSORPTION OF DRUGS

Routes of administration:To enter the bloodstream, a drug must be absorbed from itssite of administration

1. Oral (swallowed)2. Intravenous3. Intramuscular4. Subcutaneous5. Buccal and lingual6. Rectal (suppositoria)

7. Inhalation8. Topical9. transdermal


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DISTRIBUTION OF DRUGS

Distribution of drugs to the tissuesdepends on :

1. Size of the organ

2. Blood flow

3. Solubility

4. Binding of the drug tomacromolecules in the blood


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METABOLISM OF DRUGS

Drug metabolism occurs primarily in the liver

Drug metabolism as a mechanism oftermination of drug actionthe action of many drugs is terminated before they are

excreted because they are metabolized to biologicallyinactive derivatives

Drug metabolism as a mechanism of drugactivationprodrugs are inactive as administered and must be

metabolized to become active

Drug elimination without metabolismsome drugs are not modified by the body, theycontinue to act until they are excreted


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ELIMINATION OF DRUGS

Dissapearance of the activemolecules from the bloodstream orbody

Drug elimination is not the same asdrug excretion

The excretion of most drugs and

metabolites is primarily by way ofthe kidney, except anesthetics gases(excreted by the lungs)


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ELIMINATION OF DRUGS

First-Order Elimination: the rate of elimination isproportionate to the concentration.The drugs concentration in plasma decreasesexponentially with time.

Most drugs in clinical use demonstrate first-orderkinetics Zero-order Elimination : the rate of elimination is

constant regardless of concentration.The concentrations of these drugs in plasma

decrease in a linear fashion over time.Ethanol and phenytoin & aspirin (at hightherapeutic or toxic concentration) show thiselimination


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PHARMACODYNAMICS

Effects of drugs on biologic systems The most important principles in

Pharmacodynamic concepts :Receptorsare the spesific molecules in abiologic system with which drugs interactto produce changes in the funtion of thesystemEfectorsare molecules that translate the

drug-receptor interaction into a change incellular activity (ex; enzymes such asadenylyl cyclase


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PHARMACODYNAMICS

Graded dose-response relationshipsWhen the response of particular receptor-effector system is measuredagainst increasing concentrations of a drugThe graph of the response vs drug concentration (dose)Gradded dose-response curve. The Efficacy (Emax) and potency (EC50) parameters arederived from these data.The smaller the EC50 , the greater the potency of the drug

Graded dose-drug binding relationshipmeasure the fraction of receptors bound by a drug, and by plotting thisfraction against the log of the concentration of the drugThe concentration of drug required to bind 50% of the receptor = Kd. Thesmaller the Kd, the greater the affinity of the drug for its receptor

Quantal dose-response relationshipswhen the minimum dose required to produce a specified response is

determined in each member of population.The median Effective (ED50), median toxic(TD50), and median lethal(LD50)


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PHARMACODYNAMICS

Efficacyis the maximal effect (Emax)an agonist can produce if the dose istaken to very high levels.

It can be measured with a gradeddose-response curve.

Potencyis the amount of drugneeded to produce a given effect


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PHARMACODYNAMICS

Agonist and Partial Agonist

Agonist a drug capable fullyactivating the effector system whenit binds to the receptor

Partial Agonist produces less thanthe full effect, even when it hassaturated the receptor


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PHARMACODYNAMICS

Antagonists

Competitive & Irreversible PharmacologicAntagonists

Competitive Antagonists are drugs that binds to

the receptor in a reversible way withoutactivating the effector system for that receptor

the log dose-curve is shift to the higher dosesbut the same max effect is reached

An irreversible antagonist causes a downwardshift of the max, with no shift of the curve on thedose axis unles spare receptors are present


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PHARMACODYNAMICS

Physiologic Antagonists

Physiologic antagonistis a drug that binds to adifferent receptor, producing an effect opposite tothat produced by the drug it is antagonizing.

Differs from a pharmacologic antagonist, whichinteracts with the same receptor as the drug it isinhibiting

Chemical Antagonists

A chemical antagonist is a drug that interactsdirectly with the drug being antagonized toremove it or to prevent it from reaching its target


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PHARMACODYNAMICS

Therapeutic Indexis the ratio of theTD50 (or LD50) to the ED50,determined from quantal dose-

response curves

represent an estimate of thesafety of a drug


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PHARMACOKINETICS

Def : the effects of biologic systems ondrugs

Effective drug concentration is theconcentration of a drug at the receptor

site The plasma concentration is a function of

the rate of input of the drug (byabsorption) into the plasma, the rate of

distribution to the peripheral tissues, & therate of elimination or loss from the body well described by 2 parameters :volume of distribution and clearance


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PHARMACOKINETICS

Bioavailability of a drug is thefraction (F) of the edministered dosethat reaches the systemic circulation

After administration, bioavailability isgenerally reduced by incompleteabsorption, first-pass metabolism, &any distribution into other tissuesbefore the drug enters the systemiccirculation. (except: IV adm=100%)


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PHARMACOKINETICS

Maintenance Dosage :

dosage/min = CL x Plasma conc.

Bioavailability

daily dose = dose/min x 60min/h x 24h/day

Loading dose :

If the therapeutic concentration must be achieved rapidlyand the volume of distribution is large. A large loading dose

may be needed at the onset of therapyLoading doose = Vd x plasma concentration

bioavalability


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DRUG METABOLISM

Types of Metabolic ReactionsA. Phase I Reaction

include : oxydation (especially by theCytochrome P450 group of enzymes),reduction, deamination, & hydrolysis

B. Phase II ReactionSynthetic reactions that involve addition(conugation) of subgroups to OH, -NH,

and SH functions on the drug molecules(glucoronate, acetate, glutathione,sulfate, & methyl groups)


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DRUG METABOLISM

Sites of Drug Metabolism

Most important organ : Liver

Kidney play an important role in themetabolism of some drugs


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CYP (ISOFORM P450)

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Introduction of Pharmacology_1 - Copy

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