Pharmacodynamics - 3

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    PharmacodynamicsDr.U.P.Rathnakar

    MD.DIH.PGDHM

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    Factors modifying fuel efficiency???

    Factors modifying drug action

    New

    Driver

    Mfr.defect

    Bad road

    Over loaded

    Engine problem

    Traffic congestion

    [Age?]

    [M or F]

    [Genetic?]

    [Envn.]

    [Obesity?]

    [Patho.states]

    [DI, polypharmacy]

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    Factors modifying drug action

    Quantitative changes-plasma concentration

    and the action of drug is altered. This can be

    corrected by altering the dose-COMMON

    Qualitative-UNCOMMON-Allergy,

    idiosyncrasy[response is altered]-drug may

    have to be discontinued

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    Factors Modifying Drug Action

    Age

    Body size

    Sex[Gender]

    Species & race

    Genetics

    Route

    Environment

    Psychological

    Diseases[Pathological state]

    Other drugs

    Cumulation

    Tolerance

    Drug resistance

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    Factors Modifying Drug Action:

    1. Route

    Quantitative- Oral dose more than i.v. dose

    Qualitative

    Mgso4 Locally- Reduces edema

    Mgso4 orally - Purgative

    Mgso4 i.v. - CNS depressant

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    Presence of other drugs

    Combined effect-synergism or antagonism

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    Cumulation:

    When elimination is slower- may accumulate

    and produce toxic effect- Digoxin

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    Factors Modifying Drug Action:

    Age:

    Infants & Children: not just small adults!

    Low GFR and immature tubular transport

    Penicillin G is given BID Inadequate hepatic metabolizing system

    Chloramphenicolgray baby syndrome

    Blood brain barrier is more permeable -kernicterus

    Skin is more permeable

    Rectal absorption is faster

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    Factors Modifying Drug Action:Children

    Tablets & aerosols difficult to administer

    Tetracyclines get deposited in teeth

    Drug metabolism may be faster in children-higher dose of digoxin

    Children are definitely not Miniature adults

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    Factors Modifying Drug Action:

    Children

    Youngs formula

    Child's Dose = Adult Dose X Age

    Age+12 Dillings formula

    Child's Dose Adult Dose X Age

    20

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    Factors Modifying Drug Action:

    Elderly:

    - decline in renal function

    -reduced hepatic activity

    -reduced intestinal motility

    -altered volume of distribution

    -drug interactions

    -prostatic hypertrophy - urinary retention

    ADE [Adverse effects] more

    Dose to be lowered- Eg.Aminoglycosides

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    Body Wt. And Surface Area

    Body weight:

    Individual = Body weight (kg) X Adult dose

    Dose 70

    BSA

    Individual = BSA x Adult doseDose 1.7

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    7. Sex[gender]

    Females-smaller size

    Androgens[Females] & estrogens[Males]

    Betablockers-affect sexual function only in males

    Ketaconozloe-libido in men, gynecomastia

    Pregnancy:

    GI motility low-delayed absorption

    Renal blood flow increases-Fast elimination of drugs

    Terratogenic

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    Environment and time of

    administration

    Environment:

    Pollutants like DDT, Cigarette smoke,

    Insecticides, Alcohol-Enzyme inducers- Eg.

    Oral Contarceptive Pills

    Hypnotics more effective at night

    Glucocorticoids given in mornings-Least HPAaxis

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    Genetic factors

    Pharmacogenetics- Study of genetic basis for

    variability of drug response

    Pharmacogenomics- Use of this information

    for the choice of drugs in an individual

    INH [Isoniazid]-Fast and slow acetylators Succinylcholine-Apnoea [Atypical

    pseudocholinesterase]

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    Emotional factors

    Placebo [I will please] [Nocebo-I will harm]

    Dummy medicine without Pharmacological effect [Psychodynamiceffect]

    Some may have endogenous activity [Naloxone blocks analgesic effect of

    placebo] Placebo reactors

    Uses

    1. Relief of subjective symptoms- Eg .Anxiety

    2. In Clinical trials to reduce bias Factors affecting placebo action

    Pt factors-With neurotic symptoms

    Drug factor-Injection, Capsules, colored tablets

    Doctor factor-Personality, Fame, Dr - Pt relationship

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    Pathological states

    Gastrointestinal diseases:

    Malabsorption syndrome:

    Achlorhydria: Decreases aspirin absorption

    Liver disease:

    First pass metabolism

    B.A of Lidocaine, Propranalol

    Kidney disease

    Clearance of drugs that are excreted in unchanged

    form.

    Aminoglycosides

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    Kidney disease[Aminoglycosides, Digoxin, Phenobarbitone]

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    Tolerance

    Tolerance occurs when the person no longer

    responds to the drug in the way that person

    initially responded.

    A state in which higher dose is required to

    achieve the same effect

    Eg.

    Nitrates in Angina

    Morphine in pain relief

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    Types of Tolerance

    AcquiredToleranceNatural

    SPECIES

    Rabbits

    are

    resistant toAtropine

    RACE

    In Afro

    Carribeans

    blockers

    Less

    effective

    On

    repeated

    exposure

    May be

    only tosome

    effects of

    a drug

    Morphine

    Not to

    Constipation

    and

    Miotic actions

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    Tolerance: Mechanism

    Pharmacokinetic:

    Increased Metabolism, reduced absorption

    [Barbiturates]

    Pharmacodynamic

    Cells of the target organ become less sensitive

    Morphine, Barbiturates, Nitrates,Alcohol

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    Tachyphylaxis

    (acute tolerance)

    Rapid development of tolerance, can not be overcome

    by increasing the dose

    Ephedrine, Amphetamine, Nicotine

    Cross tolerance:

    Development of tolerance to pharmacologically

    related drugs

    Eg. Alcohol and Barbiturates

    Morphine and Barbiturates

    Morphine and Pethidine

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    Others

    Antipyeretics lower body temp.-Fever

    Thiazides marked diuresis-Edema

    Myesthenics-sensitive to curare Hypnotics in a pt. with pain-mental confusion

    and delirium

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    12. Drug interactions

    When the action of one drug is affected by another

    Drug interactions may be defined as an

    Alteration in duration and/or onset of action or

    effect

    Of one drug produced by another drug.

    Beneficial or harmful

    Polypharmacy may be a necessity!

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    Drug interactions may be

    unavoidable Hypertension Congestive cardiac failure

    Multiple diseases

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    Drug interactions classification

    Pharmacokinetic,which occur at the level of

    Absorption,

    Distribution,

    Metabolism and

    Excretion of one drug by another. Pharmacodynamic:

    Response of a drug target is modified by asecond drug

    Eg. NSAIDs and ACE inhibitorsNitrates and Sildenafil

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    PD interactions

    The direct pharmacodynamic interactions Antagonism or synergism

    The indirect pharmacodynamic interactions

    Digoxin and spironolactone

    Salicylates and warfarin

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    Drug interactions

    Beneficial or harmful [Make a listfrom text book]

    Common with drugs exhibiting

    Steep DRC Low TIEnzyme induction / inhibition

    Zero order kineticsSeverely ill patientsImpaired renal / liver function