ADRs for Nurse

7/31/2019 ADRs for Nurse

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Adverse Drug Reactions(ADRs)

PathamaPathama LeewanichLeewanichDepartment of PharmacologyDepartment of Pharmacology

Faculty of MedicineFaculty of Medicine

SrinakharinwirotSrinakharinwirot

UniversityUniversity


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Define adverse drug reactions

Classification of ADRs Drug allergy

Prevention

Objectives/ Contents


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Therapeutic EffectTherapeutic Effect

Desired EffectDesired Effect

Adverse ReactionsAdverse Reactions

Undesired EffectUndesired Effect
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Adverse Drug Reactions

Noxious, unintended and undesired

effects that occur at normal drugdoses

Exclude overdose

drug abuse noncompliance therapeutic failures


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Onset of event

Severity of reaction

Type of reaction

Classification

CriteriaCriteria


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Acute : within 60 minutes:- ampicillin

Sub-acute : 1 to 24 hours

Latent (chronic) : > 2 days

:- chloramphenicol--> aplastic anemia

Classification - Onset


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Mild

bothersome but requires no change intherapy

Moderate

requires change in therapy, additionaltreatment, hospitalization

Severe

disabling or life-threatening

Classification - Severity


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Type A

extension of pharmacologic effect

often predictable and dose dependent

responsible for at least two-thirds ofADRs

:- propranolol and heart block,

anticholinergics and dry mouth

Classification - TypeType


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Type B

idiosyncratic (genetic predisposition)

or immunologic reactions

rare and unpredictable

:- chloramphenicol and aplastic anemia



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Type C

associated with long-term use

involves dose accumulation

:- phenacetin and interstitial nephritis or

antimalarials and ocular toxicity



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Type D

Delayed effects, dose independent Carcinogenicity

:- immunosuppressants

Teratogenicity (birth defect)

:- fetal hydantoin syndrome



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( I mmunologic Drug React ions)

Drug allergy

Drug hypersensitivity

or

Urticaria/Hives (left) and delayed reaction to penicillin (right)


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Who is more likely to suffer drug

allergy ?


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Drug allergies are no more likely to occur inpeople w ith other allergies (such as hay fever, asthma oreczema) than anyone else.

While there are reports of some families who have manypeople with drug allergies, most drug allergies are notinherited.


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tuberculin test,

poison ivy,

granuloma

SLE, farmer's

lung disease

erythroblastosis

fetalis,

Goodpasture'snephritis

allergic asthma,

hay fever

Examples

T-cellsantibodyantibodyantibodyTransferredwith

monocytes and

lymphocytes

complement

and neutrophils

antibody and

complement

basophils and

eosinophilHistology

erythema and

induration

erythema and

edema,necrosis

lysis and

necrosisweal & flareAppearance

48-72 hours3-8 hoursminutes-hours15-30 minutesResponse time

tissues &organs

solublecell surfaceexogenousAntigen

NoneIgG, IgMIgG, IgMIgEAntibody

Type-IV(delayed type)

Type-III(immunecomplex)

Type-II(cytotoxic)

Type-I(anaphylactic)

Characteristics

Comparison of Different Types of hypersensitivity

S ifi D H iti it C d


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Causativedrug Syndrome Hydralazine(anti HT)Procainamide(antiarrhythmia)

Lupus-like syndrome

Carbamazepine(Anticonvulsant)

Phenytoin

(Anticonvulsant)

Anticonvulsant hypersensitivitysyndrome

SulfonamidesAnticonvulsants

Stevens-Johnson syndrome

Specific Drug Hypersensitivity Causedby Non-IgE Immune Mechanisms


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Antibiotics Antineoplastics*

Anticoagulants Cardiovascular drugs*

Hypoglycemics

Antihypertensives

NSAIDs / analgesics

Diagnostic agents

CNS drugs*

*high incidence of fatal ADRs

Common Causes of ADRs


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Age (children and elderly)

Multiple medications

Multiple co-morbid conditions

Inappropriate medication prescribing,

use, or monitoring End-organ dysfunction: liver, kidney

Altered physiology

Prior history of ADRs

Extent (dose) and duration of exposure

Genetic predisposition

ADRs Risk Factors


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Subjective report

Patient complaint

History of the symptoms

Objective report:Direct observation of event

Abnormal findings physical exam

laboratory test

diagnostic procedure

ADRs Detection


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Ways to minimize ADRs

Avoid harmful drugs

Monitor for signs & symptoms

Educate Clinical testing


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ADRs 1. ADRs ?2. ADRs onset ?3. ADRs ?4. ADRs ?5. ADRs6. ?7. ?8. ?9. ADRs ?10. ADRs ?11. ADRs ?


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Drug Interactions(DIs)

PathamaPathama LeewanichLeewanichDepartment of PharmacologyDepartment of Pharmacology

Faculty of MedicineFaculty of Medicine

SrinakharinwirotSrinakharinwirot UniversityUniversity


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Define drug interactions

Classification of drug interactions Prevention

Objectives/ Contents


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Drug Interactions

Taking other drugs, herbs or even

food can cause large changes in t heamount of a medicat ion in your

bloodstream.

I t is ser ious because t oo mucht oo much of t he drug

in your bloodst ream can cause ser ious sideeffect s, and t oo l it t le can mean t hat t he drugw i ll not w ork.


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Drug Interactions

Drug-drug interaction

Drug-food interaction

Drug-herb interaction

D D I t ti


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Drug-Drug Interaction

a phenomenon which occurs when theeffects of one drug are modified by theprior or concurrent administration ofanother drug(s)

increase with the number of drugs usedincrease with the number of drugs used

and are associated with an increased riskand are associated with an increased risk

of adverse drug eventsof adverse drug events

Consequences of DDIConsequences of DDI


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1)Intensif icationIntensif icationof ef fect s

I ncreased t herapeut ic ef fect s I ncreased adverse ef fect s

Consequences of DDIConsequences of DDI

2) ReductionReductionof ef fect s

Reduced therapeut ic effect s Reduced adverse effect s

3) CreationCreationof unique response

: - alcohol

+

disulfiram

unpleasant,dangerous response


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1. Chemical / physical interaction

2. Pharmacokinetic interaction

3. Pharmacodynamic interaction

MechanismMechanismss


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Inact ivat ion:- penici l lin G + dext rose

nit roplusside + light

Precipitation:- kanamycin + methicil l in

Chemical / physical interaction

Pharmacokinetic interaction


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Alt ered Absorpt ion

By elevat ing gast r ic pH : - antacids

Accelerate drugs passage t hrough intest ine

: - laxat ives

Depress per ist alsis : - morphine, at ropine I nduce vomit t ing

Adsorb other drugs :- cholest yramine,

adsorbent drugs

Reduce regional blood f low : - epinephr ine

Pharmacokinetic interaction


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Altered Distribution

Compet it ion for protein binding

increase free drugincrease ef fect s

Alterat ion of ext racel lular pH

ionization


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Altered Metabolismliver

Consequences of Drug Metabolism

Inactive products

Active metabolites

Similar to parent drug

More active than parent

New action

Toxic metabolites

Cytochrome P450 Isoforms


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Cytochrome P450 Isoforms

CYP3ACYP2D6

CYP2C

CYP1A2CYP2E1

Relative Importance ofP450s in Drug Metabolism

Al d M b li li


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Altered Metabolismliver

Induct ionof drug-met abolizing enzymes

Enzyme I nducer : - phenobarbit al

increase drug metabolism

decrease free drug

Inhibi t ionof drug-met abolizing enzymes

Enzyme I nhibit or : - cimet idine

decrease drug met abolism

increase free drug


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CYP3A Inhibitors CYP3A Inducers

Ketoconazole

Itraconazole

Fluconazole Cimetidine

Clarithromycin Erythromycin

Troleandomycin

Grapefruit juice

Carbamazepine

Rifampin

Rifabutin Ritonavir

St. Johns wort


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Enzyme I nducer

AA Enzyme AEnzyme A AA

Drug inactiveDrug inactive


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AA

BB

Enzyme AEnzyme A

Enzyme BEnzyme B

AA

BB



Enzyme I nducer


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Enzyme I nducer

AA

BB

Enzyme AEnzyme A

Enzyme BEnzyme B

+AA

BB

+


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AA

BB

Enzyme AEnzyme A

Enzyme BEnzyme B

+AA

BB

Drug B is an enzyme inducer.Drug B is an enzyme inducer.

+

Enzyme I nducer


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Enzyme .

AA

BB

Enzyme AEnzyme A

Enzyme BEnzyme B

-AA

BB

+


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Enzyme I nhibit or

AA

BB

Enzyme AEnzyme A

Enzyme BEnzyme B

-AA

BB

+

Alt d R l E ti


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Altered Renal Excretion

Reduced cardiac out put renal blood f low

glomerular

f i l t rat ionrate

Alt ered ur inary pH ionizationpassive tubularreabsorption

Compet ed t ubular secretion

Pharmacodynamic interaction


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Act ions at t he samesite:

agonist -antagonist int eract ions inhibit ion:- morphine + naloxone

Act ions at separatesites:

physiologic int eract ions potent iat ion

inhibit ion: - morphine + diazepam

yAt receptorAt receptor


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Drug-Drug Interactions ?

Risk Factors

DrugDrug--FoodFood InteractionInteraction


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Consequences

Alt er absorpt ion : onset/ intensityof ef fect: - calcium-containing foods + tet racycl ine

Affect drug met abolism

: - grapefruit j u ice inhibit cyt P-450

I npact on drug tox icit y

: - t yramine-r ich foods + MAO inhibi tors

hypertension

DrugDrug-FoodFood InteractionInteraction

HerbHerb--DrugDrug InteractionInteraction


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HerbHerb DrugDrug InteractionInteraction

St. JohnSt. Johnss wortwort andand digoxindigoxin,,

indinavirindinavir,, cyclosporincyclosporin, others, others

Garlic can reduce blood levels ofGarlic can reduce blood levels of

antianti--HIV drugsHIV drugs..


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DIs 1. DIs ?2. DIs ?3. DIs ?4. DIs ?5. enzyme inducer enzyme inhibitor ?6. DIs ?7. DIs ?


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ADRs for Nurse