Pharmacodynamics MBBS-Class 4.pptx

7/27/2019 Pharmacodynamics MBBS-Class 4.pptx

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PharmacodynamicsDr.U.P.Rathnakar

MD.DIH.PGDHM


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Adverse Drug Effects

Any undesirable or unintended consequence of

drug administration

Any response to a drug that is noxious and

unintended and that occurs at doses used in man

for the prophylaxis, diagnosis, or therapy of

disease or for modification of physiological

function WHO

Adverse event: Any untoward event that occurs

during treatment not necessarily with causal

relation ship to treatment


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Adverse Drug Reactions

[ADR]

Drugs used for favorable response

Unfortunately also produce ADR


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ADR: Severity

Minor:

No tt required

Moderate: Requires change in tt, change of drug

Severe:

Potentially life threatening, permanent damage Lethal:

Directly or indirectly contributes to death


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ADR

Type A[Augmented]

Extension of

pharmacological actions

Predictable Dose dependent

High incidence

Low mortality

Dose reduction

Eg. Blurring of vision &

dryness of mouth [atropine]

Hypoglycemia[Glipizide]

Type B [Bizarre]

Immunological/genetic

Not predictable

Qualitative[not dose dependent]

Low incidence

High mortality

Discontinue drug

Eg. Anaphylaxis due to

Penicillin , Hemolysis due to

primaquine


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ADR

Type A[augmented]

Side effects:

Unwanted ,unavoidable pharmacodynamic effects at

therapeutic doses

Eg. Antihistaminics cause sedation Secondary effects:

Indirect consequence of primary action of a drug

Eg. Tetracyclines cause super infection

Toxic effects: Due to overdose or prolonged use

Eg. Respiratory failure by morphine

Coma by barbiturates


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ADR

Type B[Bizarre]

Allergy/hypersensitivity

Idiosyncratic

Type C[Continuous use]

[dependence, organ

toxicity]

Type D[Delayed effect]

Mutagenicity,

carcinogenicity,

teratogenic effect Type E[End of use]

[withdrawal, HPA axis

suppression]


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Intolerance

Low threshold to the action of drug

Eg. EPS with single dose of Metoclopromide


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Idiosyncrasy

A genetically determined reaction

An unusual individual reaction to food or a drug

Eg. Barbiturates cause excitement and mental confusion

Chloramphenicol causes aplastic anemia


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Drug allergy

(drug hypersensitivity)

Immunologically mediated reaction

Types of drug allergy

1. Anaphylactic- -Type I

2. Cytolytic- -Type II

3. Immune complex

mediated[Arthus]: -Type III

4. Delayed

hypersensitivity -Type IV


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Type 1

Eg. Betalactam antimicrobial agents


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Type 1

[Anaphylactic]Exposure to

drugEg.Penicillin

IgE ABFixed tomast cells

Re-exposure

AG+AB

Release of mediators:

Histamine, 5-HT, PGs,LTs, PAF

Anaphylactic shock:

Hypotension,

Bronchospasm, UrticariaEtc.

Treatment:Medical emergency

Inj.Adrenaline[1:1000]

0.3 to 0.5 ml i.m.

Inj.Hydrocortisone

100 mgi.v.Inj.Diphenhydramine

25mg i.v.

Oxygen

i.v. fluids


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Type II[Cytotoxic]

Eg. Sulfa, thiazides, quinidinepuprura, hemolysis


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Type II [Cytolytic]

Exposure to drug

Eg.Quinine

Drug+Tissue=AG

IgG, IgM- ABRe exposure

Tissue+AB

Complement

Cell destruction

Eg. Hemolysis

by Quinine,

Quinidine


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Type III

AG+ABIgG

Complementfixation

Destructive inflammatory response

Eg. Serum sicknes [Fever,urticaria, joint pain,lymphadenopathy]

Penicillin,

SulfaNSAIDs

Deposited on vascular

endothelium


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Type IV[cell mediated, delayed]

Eg.Contact dermatitis by metals, ointments


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Type IV [Delayed]

Inflammatory responseDelayed by 2-3 days

Not AB related

Cell mediated

Eg. Contact dermatitis with LA creams


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Photosensitivity[Pt. taking a drug develops reaction on body parts exposed to light]

Phototoxicity [hyperpigmentation[desquamation]

Sensitization of the skin by drugs

UV radiation Cutaneous reaction-Photosensitivity

Stopped when drug stopped

Photo allergy [eczematous, papular]

Persists even after drug withdrawal

Examples????


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Carcinogenicity & mutagenicity

Ability of the drug to cause cancer and genetic

defects respectively

Eg. Tobacco, anticancer drugs


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Iatrogenic diseases:

iatros = physician

(physician induced diseases):

ParkinsonismPhenothiazines Peptic ulcer Aspirin,corticosteroids

Hepatitis - Isoniazid


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Drugs frequently cause allergic

reactions

Penicillins

Cephalosporin

Sulfonamides

Tetracyclines

Quinolones

Antitubercular drugs

Salicylates

Carbamazapine

ACE inhibitors

Local anesthetics


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Teratogenicity

terataos = monster

Capacity of the drug to cause fetal abnormalities when

administered to pregnant mother

I. Pre-implantation: conception to 17 days-Abortion

ii.Organogenesis: 18-55 days-Deformities

iii.Growth and development: 56 days onwards

ThalidomidePhocomelia

CorticosteroidsCleft lip

TC- Discolouration of teeth, retarded bone growth

PREGNANCY


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PREGNANCY

CATEGORIES

Category A [ANIMALS [-] Humans[-]-------------No riskStudies have failed to demonstrate a risk to the fetus

Category B [ANIMALS [-] Humans[Not known] [ANIMALS [+] Human[none] ---No evidence

of risk

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are

no studies in pregnant women.

Category C [ANIMALS [++] Humans[Not known] [Consider risk benefit before use]

Animal reproduction studies have shown an adverse effect on the fetus and there are no

adequate and well-controlled studies in humans, but potential benefits may warrant use of

the drug in pregnant women despite potential risks.

Category D [Humans risk ++] [Benefit may outweigh risk]There is positive evidence of human fetal risk - but potential benefits may warrant use of

the drug in pregnant women despite potential risks.

Category X [Abnormalities demonstrated] [Not to be used in pregnant women]

Studies in animals or humans have demonstrated fetal abnormalities and/or there is

positive evidence of human fetal risk based on adverse reaction data from investigational

or marketing experience and the risks involved in use of the drug in pregnant womenclearly outweigh potential benefits.


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Organ toxicity

Hepatotoxicity: INH, Rifampicin

Nephrotoxicity: Aminoglycosides

Ototoxicity: Aminoglycosides, Frusemide

Ocular toxicity: Ethambutol, Chloroquine


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Drug dependence

A state of

Psychological or physical dependence

Due to interaction - living organism+Drug

Characterized by behavioral and other responses Always includes a compulsion to take the drug continuously or

periodically

Psychological: Intense desire to take drug and immensesatisfaction later

Physical: Physiological equilibrium is maintained by drug


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Poisoning

Poisons in small doses are the best medicines;

and useful medicines in too large doses are

poisonous

William Withering 1789


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Poisoning

Large enough dose of a drug

Substance which endangers life

Accidental or suicidal


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Poisoning

Principles of treatment

1.Resuscitation and maintenance of vital functions

Airway, BP, Body temp., Blood sugar

2. Termination of exposure

Fresh air, remove wet clothes, wash,

3. Prevention of absorption

Gastric lavage, Activated charcoal,

4. Hastening elimination

Diuresis, Altering urine pH, Hemodialysis

5. Antidotes if available


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Prevention of adverse effects

Right dose, route, frequency

Previous history drug allergy and allergic

diseases

Rule out drug interactions

Correct technique of administration

TDM if appropriate


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Clinical significance of ADR

Common-

3-5% of admissions

Increases duration of

stay

Initially reversible

Awareness-ADR or new

symptoms

Surgeries are avoided

[gynecomastia andspironolactone]

Reduce the no.of drugs


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Pharmacovigilance

Actively look for adverse drug effects

Activities relating to detection, assessment, understanding and prevention

of adverse effects or any other drug related problem

Causality assessment1. Temporal relationship

2. Previous knowledge

3. Dechallenge

4. Rechallenge

Information collected by

Regional centers to

Zonal centers to

National centers to

Uppsala monitoring center (Sweden)

Definite, probable, possible or doubtful

Documents

Pharmacodynamics MBBS-Class 4.pptx