Pharmaco Vig Gi Lance

7/30/2019 Pharmaco Vig Gi Lance

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dr. Prajogo Wibowo, M. Kes


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The phases of drug delivery

1. Drug administration phase

Enteral, Parenteral, etc.

2. Pharmacokinetic phase

Absorption, Distribution, Metabolism,

Excretion

3. Pharmacodynamic phase


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Time of drug administration is determined by

properties of drug 1. Sensitive againts gastric pH/ gastric irritating

drug (e.g. NSAIDs)

2. The absorption interfered by food (e.g.

ampicillin)

3. Modify gastrointestinal physiology (e.g.

atropine)

4. Possibility of drug interaction (e.g.paracetamol with phenobarbital)

5. Fluctuation of gastrointestinal tract

secretion (e.g. antacide with tetracycline)


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Pharmacokinetics describes actions of thebody on drugs, including the principles of

drug absorption, distribution, biotransformation

(metabolism), and excretion.

Pharmacodynamics deals with the study of the

biochemical and physiological effects of

drugs on the body and their mechanisms of

action, includes the principles of receptor

interactions, mechanisms of therapeutics and

toxic action, and close-response relationships.


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Absorption is movement of drug from its

site of administration to systemic

circulation.


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The rate and efficacy of absorption depend on

Route of administration-The intravenous route is

most effective

Blood flow-Highly vascularized organs such as the

small intestine have the the greates absorbing ability

Surface area available-Absorption of a drug is directly

proportional to the surface area available

Solubility of a drug-The ratio of hydrophilic to

lipophilic properties (partition coefficient) that a drug

has will determine whether the drug can permeate cell

membranes.

Drug-drug interactions-When given in combination,

drug can either enhance or inhibit one anothers

absorption

pH-A drugs acidity or alkalinity affects its charge, which

affects absorption.


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Most drugs are weak acids or bases that

are present in solution as both the

nonionized and ionized species. The

nonionized molecules usually are morelipid-soluble and can diffuse readily

across the cell membrane. In contrast,

the ionized molecules usually are unableto penetrate the lipid membrane

because of their low lipid solubility.


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The site of absorption for oral administration is in small intestine,

(except alcohol is in stomach)

Factors affecting gastrointestinal absorption 1. Gastrointestinal motility has a large effect (e.g. loperamid: decrease,

metoclopramide: increase)

2. Gastrointestinal contain-A meal is often slowly absorbed, but there

are some exceptions.

3. Drug formulated-Particle size and formulation have major effects on

absorption. Therapeutic drugs are formulated pharmaceutically to produce

desired absorption characteristic. There are many drug forms (tablet,

capsule, matrix tablet, enteric coated tablet, coated tablet with delayed

release, drops, mixture, effervescent, solution, and suspension)

4. Physicochemical factors-drug interaction affect drug absorption.

Tetracyclin binds strongly to calcium therefore milk prevent its absorption.

Colestyramine binds several drugs.

5. Charateristic of drugs-Aminoglycoside (Streptomycin) is very poorly

absorbed because water soluble.


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Distribution:

The process by which a drug leaves the

bloodstream and enters the interstitium

or the cells of the tissues.


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Factors affecting drug distribution: 1. Circulation (blood flow)

2. Capillary structure (barrier)

- Central Nervous System (Blood BrainBarrier)

- Placenta barrier

- Testis barrier 3. Chemical structure of the drugs


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Metabolism can be defined as thealteration of the chemical structure of

the drug by enzyme.

The liveris the principal organ of drug

metabolism. Other tissues that display

considerably activity include the

gastrointestinal tract, the lungs, the skin,

and the kidneys.


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Factors affecting drug metabolism

Genetic factor-influence enzyme levels

Age & sex-The ability to metabolize drugs is lower in

neonatus and elderly patient.

Liver function-Alcoholic hepatitis, cirrhosis, acut viral,

hemochemochromatosis, and drug induced hepatitis may

impair drug metabolism

Diet & environmental factors-Charcoal-broiled food

(inducer), grape juice (inhibitor), cigarette smokers (inducer),

pesticide may induce or inhibit other drug metabolism

Drug interaction

drug inhibitor, reduced metabolism of other drugs

drug inducer, induced metabolism of other drugs or its own

metabolism


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1st pass metabolism

a condition in which the metabolism of

drug occurs before reaching the Site Of

Action (systemic circulation).


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Excretion

The procces by which a drug or metabolite is removed fromthe body

The routes of excretion

Renal urine is one ofthe most common routes ofexcretion

Fecal

Lung/respiration-primarily for anesthetic gases and vapors

Breast milk

Skin

Hair(e.g. arsen)


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TERMINOLOGY

Adverse Reaction

Unintended and unwanted effect occursat the doses normally given in man for

prophylactic, diagnostic, or therapeuticpurposes

Adverse Drug Reaction Monitoring

The systematic reporting, recording andevaluation of certain or all adversereaction to drug


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POST MARKETING SURVEILLANCE

(PMS)

ADR monitoring is only part of the

totally of post-marketing

surveillance which may providedata both on efficacy and safety


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NATIONAL MONITORING

CENTRE

The national centre for ADR monitoring is a

government agency or body to which

reports of suspected or proven ADRs can

be sent. The Centre evaluates the reportsin the light of all published and unpublished

data available to it and feeds back its

conclusions to the reporters and to health

professionals


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MONITOR

A monitor is a physician, pharmacist

or other designated health

professional who has agreed toundertake certain task in connection

with the reporting of original data to

the National Centre


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Classification of ADRs

(Etiological Basis)Reaction due to inherent anomalies

Acquired patient abnormalities

Anomalies of drug presentation andadministration

Drug interaction


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Classification of ADRs (Etiological Basis)

A. Reactions due to inherent

anomalies1. Drug allergy (hypersensitivity)

- Immunological mechanism

- Characteristic :

a. uncorrelated with the knownpharmacological properties

b. Predictable

c. Repeated exposure will cause

recurrences ofthe reactions

Included : skin rash, angioneurotic edema,serum sickness, and anaphylaxis or asthma


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A. Reactions due to inherent anomalies

2. Genetically determined ADRs :Reaction due to altered :

a. Pharmacokinetic handling of thedrug

b. Tissue responsiveness


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B. Acquired patient abnormalities

Due to the presence of intecurrent illness

which may unmask pharmacological effect

that are not apparent in normal

individuals, exp. : Hemorrhage of perforation in peptic

ulcers due to aspirin or corticosteroid

Hypoglycemia due to oral anti diabetes


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C. Anomalies of drug presentation

and administration Excessive response, alteration in

bioavailability or an inappropriate method of

administration

Potential sources of ADRs :

abnormalities of the drug : decomposition of

its active. Solubilizers, stabilizers, colourizers

in pharmaceutical preparations


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D. Drug Interaction

> 1 drug given at the same time

DI : unwanted effects and certain benefits


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The mechanism and

predisposing factors of ADRs :

Onset of reaction

Age

Pathophysiological

condition

Amount of drug

administered

Sex

Previous history of

allergy

Multiple drug

therapy

Racial or genetic

factors


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Mechanisms of Interaction

Direct physical or chemical interaction ofmore than one drug given concomitantly

Altered GI absorption, competition for proteinbinding sites or receptors

or metabolism of a drug by induction,activation, or inhibition of drug metabolismenzyme

Alteration of acid-base equilibrium, therebyinfluencing drug distribution and renalclearance

Alteration of hemodynamics or renal functionthat influences rates of renal excretion


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Reaction should be reported

ADRs previously unknown to the reporters

Serious or life-threatening ADRs

Cases of suspected dependence

Cases of suspected due to drug

interaction


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Methods of ADRs Monitoring

Incidental reporting

Systematic voluntary reporting

Intensive hospital monitoring

Record linkage

Mandatory or compulsory Monitoring

Limited Monitoring Release

Methods of


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Methods of

ADRsMSpontaneou

sR.

Simple & chip

Largepopulations

Rare & delayed

ADR

Incomplete

reportedFrequency

cant be

evaluated

Systematic

Valuntary

R.

Chip

Large

populations All

drugs

Early warning

Spread easily

Early warning

Is doubt

Low

Participate-on

Of health

professions


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Methods of ADRsM

IntensiveHospital

M.

Determine TheIncidence of

ADR

And risk factors

Large of costLimited population

Delayed ADR cant

be findRecord

linkage

May find chronic,

congenital, and

malignancy

ADRs

The tremendous

amount of data

Not identical

terminology

incomplete record

Methods of


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Methods of

ADRsM

Mandatory/Compulsor

y

M.

The reportexsist

(Rules)

Ideal for the

hospital

Accurate report isdoubted

Limited

Monitoring

Release

Frequency of

ADR can bedetermined

Limited of drug

and period/time

ALGORITM OF CAUSAL RELATIONSHIP


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ALGORITM OF CAUSAL RELATIONSHIPBETWEEN DRUGS AND ADRS

Onset of ADRs

afterAppropriate drug

use

Yes

DECHALLENGE

Yes

ADRs decrease

No Causal relationship

REMOTE

Causal relationship

REMOTE

No

NoCausal relationship

POSSIBLE

PROBABLE


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Yes

RECHALLENGE

Yes

ADRs

Appearing again

Yes

Causal Relationship

HIGHLY PROBABLE

PROBABLE

No

ADRs could not happened

because of clinical situation

Yes

Causal relationship

POSSIBLE

No

No

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