{"id":6538,"date":"2024-11-16T11:28:10","date_gmt":"2024-11-16T11:28:10","guid":{"rendered":"https:\/\/workhouse.sweetdishy.com\/?p=6538"},"modified":"2024-11-16T11:41:39","modified_gmt":"2024-11-16T11:41:39","slug":"drug-safety-and-effectiveness","status":"publish","type":"post","link":"https:\/\/workhouse.sweetdishy.com\/index.php\/2024\/11\/16\/drug-safety-and-effectiveness\/","title":{"rendered":"Drug safety and effectiveness"},"content":{"rendered":"\n

A. Factors modifying the dosage and action of drugs :
<\/strong>Individuals differ both in the degree and the character of the response that a drug may elicit and
therefore the optimum dose of a drug which produces the desired therapeutic effect varies from
person to person. The important factors which influence the effect of a drug are:<\/p>\n\n\n\n

Drug intolerance:<\/strong> It is a quantitative deviation from the anticipated response to a given dose
of a drug. Thus drug intolerance is inability of the individual to tolerate a drug. It is also
called as hypersusceptibility.<\/p>\n\n\n\n

    \n
  1. Sex difference:<\/strong> Special care should be exercised when drugs are administrated during
    menstruation, pregnancy and lactation.
    a) Menstruation: Drugs producing pelvic congestion should be avoided during menstruation
    e.g. drastic purgatives.
    b) Pregnancy:<\/strong> During pregnancy, the use of all drugs except those essential to maintain
    pregnancy should be used with caution. Drugs which may stimulate the uterine smooth
    muscle, are contraindicated during pregnancy. Further, many drugs administered to
    mother are capable of crossing the placenta and affecting the foetus. Most of drugs can
    produce teratogenicity when they are used in pregnancy. Teratogenicity means
    congenital malformation i) Drugs known to produce teratogenicity e.g thalidomide,
    cyclophosphamide, methotexate, tetracyclines, phenytoin, carbamazepine and
    progestogens. ii) drugs may be teratogenic e.g Warfarin, lithium, quinine, primaquine,
    trimethoprim, rifampicin, anaesthetic agents.
    c) Breast feeding:<\/strong> Nearly all agents received by mother are likely to be found in her milk
    and could theoretically harm the infant. Most of the lipid soluble drugs get into breast
    milk. Therefore the drugs, which are excreted in the milk and harm the infant health
    should be, avoided by breast-feeding mothers e.g. sulphonamides, tetracyclines,
    nalidixic acid, isoniazid, diazepam, lithium, Indomethacin, aspirin, etc.<\/li>\n\n\n\n
  2. Body Weight:<\/strong> The average dose is mentioned either in terms of mg per kg body weight or as
    the total single dose for an adult weighing between 50-100kg. However, dose expressed in
    this fashion may not apply in cases of excessively obese individuals or those suffering from
    edema, or dehydration nutritional factors can sometimes alter drug metabolizing capacity
    and this should be kept in mind in malnourished patients.<\/li>\n\n\n\n
  3. Age:<\/strong> The pharmacokinetics of maany drugs changes with age. Thus gastric emptying is<\/li>\n\n\n\n
  4. prolonged and the gastric pH fluctuates in neonates and infant, further the liver capacity to<\/li>\n\n\n\n
  5. metabolize drugs is low, renal function is less developed and the proportion of body water is<\/li>\n\n\n\n
  6. higher in the newborn and the neonates. Hence children may not react to all drugs in the<\/li>\n\n\n\n
  7. same fashion as young adults. With a few exceptions, drugs are more active and more toxic<\/li>\n\n\n\n
  8. in the new born than the adults.<\/li>\n<\/ol>\n\n\n\n

    The paediatric doses are expressed in terms of body weight (mg\/kg per dose or day) or in terms
    of body surface area (mg\/m2
    per day). The body surface area can be calculated from the height
    and weight of the child.
    Like children, old people also present problems in dosage adjustment and this may vary widely
    with different people. The metabolism of drugs may diminish in the elderly and the renal function
    declines with age. Elderly are sensitive to the drugs like hypnotics, tranquilizers,
    phenylbutazone, diazepam, pethidine, etc.
    i) Dose adjustment on the basis of age (young\u2019s formula)
    Age in years____ x adult dose
    Age in years + 12
    ii) Dose adjustment on the basis of body weight (Clark s formula) (1 Kg=2.2 pounds)
    Weight of child in pound x Adult dose
    150
    e.g. A 3 year old child having body weight of 30 pound requires to administer drug X.
    The adult dose is 100mg. So
    a) Using age of the child the dose will be
    3 x 10 = 3 x100 = 20mg
    3+12 15
    b) Using body weight of the child it will be
    30 x 100 = 1 x 100 = 20mg
    150 5<\/p>\n\n\n\n

      \n
    1. Disease state<\/strong>: Some antimicrobial agents penetrate the cerebrospinal fluid well across the
      normal meninges while other antimicrobials penetrate well only when the meninges are
      inflammed (meningitis) e.g. sulphonamides, metronidazole, chloramphenicol, isoniazid and
      rifampicin penetrate well through the normal meninges and other antimicrobial agents like
      benzyl penicillin, ampicillin, tettetracycline, streptomycin, gentamicin and cephalosporin<\/li>\n\n\n\n
    2. penetrate only when the meninges are inflammed.<\/li>\n\n\n\n
    3. Acute or chronic liver diseases markedly modify the rate and extent of biotransformation of<\/li>\n\n\n\n
    4. drugs. The t1\/2 of chlordiazepoxide and diazepam in patients with liver cirrhosis is greatly<\/li>\n\n\n\n
    5. increased with corresponding prolongation of their effects.<\/li>\n\n\n\n
    6. Cardiac disease by limiting blood flow to the liver may impair disposition of those drugs whose<\/li>\n\n\n\n
    7. biotransformation is flow limited e.g. imipramine, isoniazid, lignocaine, morphine and<\/li>\n\n\n\n
    8. propranolol.<\/li>\n\n\n\n
    9. Similarly renal and pulmonary diseases may modify the biotransformation of drugs like insulin or<\/li>\n\n\n\n
    10. isoprenaline. Excretion of drug is impaired in chronic renal disease.<\/li>\n\n\n\n
    11. Pharmacogenetics<\/strong>: The science pharmacogenetics is concerned with the geneticallymediated variations in drug responses. Some examples of genetically mediated variations
      are:
      Acetylation and hydroxylation of drugs: The rate of acetylation of INH, dapsone, hydralazine
      procainamide and some sulfonamides is controlled by an autosomal recessive gene and the
      dosage of these drugs depends up on the acetylator status of individuals.
      7) Drug interactions:<\/strong>
      It is usual for patients to receive a number of drugs at the same time.
      It is a phenomenon which occurs when the effects of one drug are modified by the prior or
      concurrent administration of another drug(s). A drug interaction may result in beneficial or
      harmful effects and may be classified into:
      a) Pharmaceutical drug interactions:<\/strong>
      Serious loss of potency can occur from incompatibility between an infusion fluid and a drug that
      is added to it.
      For example diazepam if added to infusion fluid there will be a precipitate formation \u2192 loss of
      therapeutic effect.
      b) Pharmacokinetic drug interactions:<\/strong>
      1) Interaction during absorption: Drugs may interact in the gastrointestinal tract resulting in<\/li>\n\n\n\n
    12. either decreased or increased absorption.<\/li>\n\n\n\n
    13. e.g. Tetracycline + Calcium \u2192 Decreased absorption of tetracycline.<\/li>\n\n\n\n
    14. 2) Interaction during distribution: A drug which is extensively bound to plasma protein can be<\/li>\n\n\n\n
    15. displaced from its binding sites by another drug or displacement from other tissue binding<\/li>\n\n\n\n
    16. sites.<\/li>\n\n\n\n
    17. e.g. (i) Sulfonamide can be displaced by salicylates from plasma proteins and it leads to<\/li>\n\n\n\n
    18. sulfonamide toxicity.<\/li>\n\n\n\n
    19. (ii) Quinidine displaces digoxin from binding sites in tissues and plasma and leads to<\/li>\n\n\n\n
    20. digoxin toxicity<\/li>\n<\/ol>\n\n\n\n

      ) Interactions during biotransformation:<\/strong> This can be explained by two mechanisms:
      (i) Enzyme induction.
      (ii) Enzyme inhibition.
      (i) Enzyme induction: By this the biotransformation of drugs is accelerated and is a cause of
      therapeutic failure. If the drug A is metabolized by the microsomal enzymes, then concurrent
      administration with a microsomal inducer (drug B) will result in enhanced metabolism of drug
      A.
      e.g. Warfarin (anticoagulant) + Barbiturate (enzyme inducer) \u2192 decreased anticoagulation.
      Enzyme inducers<\/strong>: Rifampicine, phenytoin, sulfonamides, etc.
      (ii) Enzyme inhibition: By this the biotransformation of drugs is delayed and is a cause of
      increased intensity, duration of action and some times toxicity.
      e.g. Warfarin + Metronidazole (enzyme inhibitor) \u2192 Haemorrhage.
      Enzyme inhibitors<\/strong>: Disulfiram, isoniazid, allopurinol, cimetidine, etc.
      e) Interactions during excretion: Some drugs interacts with others at the site of excretion i.e.
      in kidneys.
      e.g. Penicillin (antibiotic) + Probenecid (antigout drug) \u2192 Increases the duration of action of
      penicillin (Both drugs excreted throug<\/p>\n\n\n\n

      C. Pharmacodynamic interactions:<\/strong>
      (i) Drug Synergism: When the therapeutic effect of two drugs are greater than the effect of
      individual drugs, it is said to be drug synergism.It is of two types.
      (a) Additive effect: When the total pharmacological action of two or more drugs administered
      together is equivalent to the summation of their individual pharmacological actions is called
      additive effect.
      i.e A + B = AB
      e.g. Combination of ephedrine and aminophyllin in the treatment of bronchial asthma.
      (b) Potentiation effect<\/strong>: When the net effect of two drugs used together is greater than the sum of
      individual effects, the drugs are said to have potentiation effect.
      i.e AB > A + B
      e.g. Trimethoprim+sulfamethoxazole<\/p>\n\n\n\n

      <\/p>\n\n\n\n

      ) Drug Antagonism:<\/strong> The phenomenon of opposing actions of two drugs on the same
      physiological system is called drug antagonism.
      a) Chemical antagonism:<\/strong> In this the biological activity of a drug can be reduced or
      abolished by a chemical reaction with another agent.
      e.g. Antagonism between acids and alkalis.
      b) Competitive or reversible antagonism<\/strong>: In this the agonist and antagonist compete for the
      same receptors and the extent to which the antagonist opposes the pharmacological
      action of the agonist. Competitive antagonism can be overcome by increasing the
      concentration of the agonist at the receptor site.
      e.g. Acetylcholine and atropine antagonism at muscarinic receptors.
      c) Non competitive antagonism<\/strong>: In this type of the antagonism an antagonist inactivates the
      receptor (R) so that the effective complex with the agonist cannot be formed, irrespective
      of the agonist cocentration.<\/p>\n\n\n\n

      ) Physiological antagonism: <\/strong>When the physiological effect of a drug is antagonized by
      another drug by acting on two different types of receptors
      e.g. Acetyl choline causes constriction where as adrenaline causes dilatation of pupil.
      Importance of drug antagonism<\/strong>
      (i) Correcting adverse effects of drugs
      (ii) Treating drug poisoning.
      e.g. Morphine with naloxone, organophosphate compounds with atropine.
      (iii) Predicting drug combinations which would reduce drug efficacy.
      8) Repeated administration and drug cumulation:<\/strong>
      If a drug is excreted slowly, its administration may build up a sufficiently high concentration in
      the body to produce toxicity. e.g. digitalis, emetine.
      To avoid cumulation. a) One must know if a drug is eliminated slowly or rapidly, b) Stop the drug
      administration at the appearance of the first warning symptoms c) Carefully select the form in
      which the drug is to be administered.<\/p>\n\n\n\n

      Drug tolerance:<\/strong>
      When an unusually large dose of a drug is required to elicit an effect ordinarily produced by the
      normal therapeutic dose of the drug, the phenomenon is termed as drug tolerance.
      Tachyphylaxis: Rapid development of tolerance on repeated administration is called
      tachyphylaxis
      e.g. Ephedrine, amphetamine and nitroglycerine which produce tachyphylaxis on repeated
      administration.
      10) Emotional factors.<\/strong>
      eg. Placebo response.
      Placebo:<\/strong> It is a Latin word meaning\u201d I shall please\u201d and it is a tablet looking exactly like the
      active treatment but containing no active component. It refers originally to substances merely to
      please the patient when no specific treatment was available.
      B. Adverse drug reactions:<\/strong>
      The drugs that produce useful therapeutic effect may also produce unwanted or toxic effects. It
      has been estimated that about 0.5% of patients who die in hospitals do so as a result of their
      treatment rather than the condition for which they were treated. Serious systemic drug toxicity
      may result from overdoses. If is always an exaggeration of its pharmacological actions and
      some times it is predictable.<\/p>\n\n\n\n

      e.g. Hypotension following antihypertensive drugs. Hypoglycaemia following insulin.
      An adverse drug reaction is defined as any response to a drug that is noxious and unintended
      and that occurs at doses used in man for prophylaxis, diagnosis or therapy (WHO).
      The adverse effects are 1)Side effects 2)untoward effects 3)allergic reactions 4)idiosyncratic
      reactions and 5)teratogenic effects.
      1) Side effects:<\/strong> Side effects are infact pharmacological effects produced with therapeutic dose
      of the drug.
      e.g: Dryness of mouth with atropine which is troublesome in peptic ulcer patients and useful
      when used as a preanaesthetic medication.<\/p>\n\n\n\n

      2) Untoward effects:<\/strong> Untoward effects develop with therapeutic dose of a drug. They are
      undesirable and if very severe, may necessitate the cessation of treatment.
      e.g: Diarrhoea with ampicillin and potassium loss with diuretics.
      3) Allergic reactions<\/strong>: Most of the drugs and sera used in therapeutics are capable of causing
      allergic or hypersensitive reactions. These reactions may be mild or very severe like
      anaphylaxis. When an individual has been sensitized to an antigen (allergen) further contact
      with that antigen can some times lead to tissue damaging reactions. These allergic reactions
      are 4 types.<\/p>\n\n\n\n

        \n
      • Type-I reactions or anaphylactic reactions (Immediate hypersensitive reaction).<\/li>\n\n\n\n
      • Type-II reactions or cytotoxic reactions.<\/li>\n\n\n\n
      • Type-III reactions or immune complex mediated reactions.<\/li>\n\n\n\n
      • Type-IV reactions or cell mediated reactions (Delayed hypersensitive reactions).
        4) Idiosyncratic reactions:<\/strong> The term idiosyncrasy means one\u2019s peculiar response to drugs.
        With the increasing knowledge of pharmacogenetics, many idiosyncratic reactions have
        been found to be genetically determined.
        e.g: Drugs like primaquine, sulfonamides and dapsone may cause haemolysis in patients with
        glucose -6 phosphate dehydrogenase defeciency.
        5) Teratogenic effect:<\/strong> Some drugs given in the first three months of pregnancy may cause
        congenital abnormalities and are said to be teratogenic. The best known example is
        thalidomide which results in early easily recognizable abnormalities such as absent or
        grossly abnormal limbs.
        Other drugs with teratogenic potential are androgens, steroids, anti convulsants, anti neoplastic<\/li>\n\n\n\n
      • drugs, cortisone, lithium, pencillamine, tricyclic antidepressants and warfarin<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

        A. Factors modifying the dosage and action of drugs :Individuals differ both in the degree and the character of the response that a drug may elicit andtherefore the optimum dose of a drug which produces the desired therapeutic effect varies fromperson to person. The important factors which influence the effect of a drug are: Drug […]<\/p>\n","protected":false},"author":1,"featured_media":6501,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[689],"tags":[],"class_list":["post-6538","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-general-pharmacology"],"jetpack_featured_media_url":"https:\/\/workhouse.sweetdishy.com\/wp-content\/uploads\/2024\/11\/pharmacology-2.png","_links":{"self":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6538","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/comments?post=6538"}],"version-history":[{"count":2,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6538\/revisions"}],"predecessor-version":[{"id":6541,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6538\/revisions\/6541"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/media\/6501"}],"wp:attachment":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/media?parent=6538"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/categories?post=6538"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/tags?post=6538"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}