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By: Dr. Vahid Nikoui

Email: nikoui@razi.tums.ac.ir
   Dependent to Vitamin D Rachitisme Type II

 Resistance to Anderogens:
 Complete testicular feminization (Recessive X-linked)

 Incomplete testicular feminization (Recessive X-linked)

 5-α- Reductase deficiency (Recessive Autosomal)

 Infertility in men (Recessive X-linked)

 Male Pseudohermaphroditism (Recessive X-linked)
   Cystic fibrosis:
   Unusual response to α-Adrenergics,
    β-Adrenergics and Cholinergics

   Down syndrome:
   More sensitive to Atropine and β-Adrenergics

   Riley-Day syndrome:
   More sensitive to Norepinephrine
   Resistant to oral Vitamin B12
   Dihydrofolate reductase deficiency syndrome
   Methylene tetrahydrofolate reductase
    deficiency syndrome
   Tetrahydrofolate methyl transferase deficiency
    syndrome

   Unusual responses to Folate, Cobalamine and
    Methotrexate
   Increased Succinylcholine esterase activity
   6 fold increased activity
   Increased Acetaldehide
   Pharmacoethnic differences

   Deceased activity in Indians and Eastern people


   Disulfiram like reaction
   Hepatic and Erythropoietic
   Congenital and Acquired
   Neurologic disorders and Photosensitivity
   Increased δ-amino levulinic acid synthase activity
    and Heme biosynthesis
   Erythropoeitic protoporphyria: Ferrochelatase
    deficiency
   Congenital Erythropoeitic porphyria:
    Uroporphyrinogen III cosynthase deficiency
   Acute intermittent porphyria: decreased
    Porphobilinogen deaminase
   Hexachlorobenzene and TCDD
   Increased Aryl hydrocarbon hydroxylase P450
   Production of toxic, motagen, teratogen and
    carcinogen products
   P1 450 and P3 450
   Relationship between AHH induction and
    bronchogenic carcinoma risk in smokers
   Relationship between low AHH induction and
    Leukemia and Aplastic anemia
   Relationship between Pharmacologic disorders
    and cancer:


   Low Isoniaside Acetylator labor in chemical
    colors companies: Increased risk of bladder
    cancer

   High Debrisoquine metabolizers: Increased risk
    of hepatic and alimentary cancer and lung
    cancer in smokers

   High AHH inducers: Increased risk of
    bronchogenic carcinoma in smokers
   Albumin , Pre albumin and TBG

   Increased TBG capacity: Dominant Autosomal
   Decreased TBG capacity: X-linked
   Primary idiopathic hemochromatosis:
   Two fold increase in Ferrum and occupation
   Not change in total Transferrin and tendency

   Hereditory hemochromatosis:
   Recessive Autosomal
   Hepatolenticular degeneration
   Decreased Ceruloplasmin
   Normal amount of Tyrosinase and
    Erythrocuprein
   Treatement with Penicillamine
   5 % of American people
   Recessive Autosomal
   Ocular products
   Hypermetabolic state of skeletal muscles
   Tachycardia, Arrhythmia, Hyperpyrexia and
    Rigidity
   Idiopathic increased of sarcoplasm Ca
   Three fold increased O2 consumption during
    general anesthesia
   Inhalation halogens and Succinylcholine
   Muscle sample diagnostic test (in-vitro),
    sensitivity to Caffeine and Halothane
   Recessive Autosomal
   Dose dependent and rarely dose independent
   Anaerobically reduction by P450 II
   Last oxidative metabolite is a suicide substrate
    and make a covalent bound to P450.
   Dose dependent and reversible

   Dose independent:
   Aplasia, A Pharmacogenetic disorder
   Oxamyl chloride, covalent binding
   Gingiva hyperplasia due to Phenytoin
   More thromboembolic disorders in A, B and
    AB blood groups
   Effects of genetic differences on acute response
    to drugs

   Effects of genetic differences on chronic
    response to drugs

   Natural selection of different genes by
    environmental changes
   Clinical observations
   Familiar studies
   Animal studies
   Relationship between cancer and acetylation
    differences
   Relationship between cancer and Lupus
    erythematosus and Hemolytic anemia
   Relationship between Debrisoquine and Ah
    locus
   Relationship between neurotoxicity and
    acetylation differences

   Labor sensitivity
   Ethnopharmacology
   The reason of quantitative differences in drugs
    metabolism between different population

   Sickle shape anemia:
   Hemoglobin S heterozygotes are resistant to
    malaria
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Pharmacogenetics

  • 1. By: Dr. Vahid Nikoui Email: nikoui@razi.tums.ac.ir
  • 2. Dependent to Vitamin D Rachitisme Type II  Resistance to Anderogens:  Complete testicular feminization (Recessive X-linked)  Incomplete testicular feminization (Recessive X-linked)  5-α- Reductase deficiency (Recessive Autosomal)  Infertility in men (Recessive X-linked)  Male Pseudohermaphroditism (Recessive X-linked)
  • 3. Cystic fibrosis:  Unusual response to α-Adrenergics, β-Adrenergics and Cholinergics  Down syndrome:  More sensitive to Atropine and β-Adrenergics  Riley-Day syndrome:  More sensitive to Norepinephrine
  • 4.
  • 5. Resistant to oral Vitamin B12
  • 6. Dihydrofolate reductase deficiency syndrome  Methylene tetrahydrofolate reductase deficiency syndrome  Tetrahydrofolate methyl transferase deficiency syndrome  Unusual responses to Folate, Cobalamine and Methotrexate
  • 7.
  • 8. Increased Succinylcholine esterase activity
  • 9. 6 fold increased activity  Increased Acetaldehide
  • 10. Pharmacoethnic differences  Deceased activity in Indians and Eastern people  Disulfiram like reaction
  • 11.
  • 12. Hepatic and Erythropoietic  Congenital and Acquired  Neurologic disorders and Photosensitivity  Increased δ-amino levulinic acid synthase activity and Heme biosynthesis  Erythropoeitic protoporphyria: Ferrochelatase deficiency  Congenital Erythropoeitic porphyria: Uroporphyrinogen III cosynthase deficiency  Acute intermittent porphyria: decreased Porphobilinogen deaminase  Hexachlorobenzene and TCDD
  • 13. Increased Aryl hydrocarbon hydroxylase P450  Production of toxic, motagen, teratogen and carcinogen products  P1 450 and P3 450  Relationship between AHH induction and bronchogenic carcinoma risk in smokers  Relationship between low AHH induction and Leukemia and Aplastic anemia
  • 14. Relationship between Pharmacologic disorders and cancer:  Low Isoniaside Acetylator labor in chemical colors companies: Increased risk of bladder cancer  High Debrisoquine metabolizers: Increased risk of hepatic and alimentary cancer and lung cancer in smokers  High AHH inducers: Increased risk of bronchogenic carcinoma in smokers
  • 15.
  • 16. Albumin , Pre albumin and TBG  Increased TBG capacity: Dominant Autosomal  Decreased TBG capacity: X-linked
  • 17. Primary idiopathic hemochromatosis:  Two fold increase in Ferrum and occupation  Not change in total Transferrin and tendency  Hereditory hemochromatosis:  Recessive Autosomal
  • 18. Hepatolenticular degeneration  Decreased Ceruloplasmin  Normal amount of Tyrosinase and Erythrocuprein  Treatement with Penicillamine
  • 19.
  • 20. 5 % of American people  Recessive Autosomal  Ocular products
  • 21. Hypermetabolic state of skeletal muscles  Tachycardia, Arrhythmia, Hyperpyrexia and Rigidity  Idiopathic increased of sarcoplasm Ca  Three fold increased O2 consumption during general anesthesia  Inhalation halogens and Succinylcholine  Muscle sample diagnostic test (in-vitro), sensitivity to Caffeine and Halothane  Recessive Autosomal
  • 22. Dose dependent and rarely dose independent  Anaerobically reduction by P450 II  Last oxidative metabolite is a suicide substrate and make a covalent bound to P450.
  • 23. Dose dependent and reversible  Dose independent:  Aplasia, A Pharmacogenetic disorder  Oxamyl chloride, covalent binding
  • 24. Gingiva hyperplasia due to Phenytoin  More thromboembolic disorders in A, B and AB blood groups
  • 25.
  • 26. Effects of genetic differences on acute response to drugs  Effects of genetic differences on chronic response to drugs  Natural selection of different genes by environmental changes
  • 27. Clinical observations  Familiar studies  Animal studies
  • 28. Relationship between cancer and acetylation differences  Relationship between cancer and Lupus erythematosus and Hemolytic anemia  Relationship between Debrisoquine and Ah locus  Relationship between neurotoxicity and acetylation differences  Labor sensitivity
  • 29. Ethnopharmacology  The reason of quantitative differences in drugs metabolism between different population  Sickle shape anemia:  Hemoglobin S heterozygotes are resistant to malaria