Quiz 6

  1. Thyroid Hormones are the only compounds containing what?
  2. What is the world's most preventable cause of mental retardation?
  3. To avoid iodine deficiency in the US what is done?
    Iodine is added to table salt
  4. Iodine and what are absorbed concurrently?
  5. What drugs can inhibit the uptake of iodine?
    Cardiac glycosides (digoxin, loop-diuretics) because they inhibit the uptake of potassium
  6. How can calorgenesis and oxygen consumpution be measured? What will this tell us?
    • Easily measured by carbon dioxide production
    • The more carbon dioxide the higher the metabolic rate
  7. Hypothyroidism has a connection to what cardiovascular issue?
  8. Lack of iodine in the body can cause what mood changes?
    Crabbiness and Depression
  9. What is the mechanism of action of iodide in the body?
    • Binds to nuclear thyroid hormones receptors (TRalpha and TRbeta)
    • Modulate both regulator/promoter areas of genes leading to transcription of proteins
    • Thyroid hormones are metabolic hormones that upregulate metabolism
  10. QSAR studies are underway for TRbeta1 selective ligands in the hope of discovering agents?
    without cardiac side effects
  11. Bile acids induce energy expenditure by promoting?
    Intracellular thyroid activation
  12. Levels of thryoid hormones are controlled by what type of feedback?
  13. What is TRH?
    Thyrotropin releasing hormone
  14. What is TRH produced by?
  15. TRH travels to where after being produced by the hypothalamus?
    Pituitary gland
  16. A patient thyroid panel includes what?
    • TSH Level
    • T4 or free T4 level
    • T3 or free T3 level
    • Sometimes T3 uptake to calculate FTI (Free T4 Index)
  17. TRH binds to receptors on the pituitary gland stimulating the release of what?
    TSH thyroid stimulating hormone
  18. What are T3 levels capable of blocking?
    The TRH induced release of TSH and the transcription of the alpha and beta subunits of TSH
  19. Thyroid hormones are stored as amino acid residues of a protein called what?
  20. What is resoponsible for the transport of thyroid hormones in the blood?
    • HDL
    • Two Plasma Proteins: Thyroxine binding globulin, Transthyretin
  21. What type of hormone is metabolically active?
  22. What is the percentage of free T4?
  23. What is the percentage of free T3?
  24. What is more active T3 or T4? How much more?
    • T3
    • 5x More active
  25. What are 3 thyroid issues that can occur?
    • 1. Changes in shape and size: goiters
    • 2. Hypothyroid Conditions: myxedema, Gull's disease
    • 3. Hyperthyroidism: Thyrotoxicosis, Graves disease, Exophthalmic goiter
  26. What are goiters?
    Beneign or malignant tumors, euthryoid patients have normal thyroid function
  27. What are the five types of hypothroidism?
    • 1. Primary: poor production in the thyroid of T3/T4
    • 2. Central: Decreased TSH
    • 3. Secondary: Pituitary gland failure no response to TRH no TSH
    • 4. Tertiary: Hypothalamic failure, no TRH
    • 5. Goitrogens: environmental chemicals that suppresses thyroid function
  28. What is the treatment in all cases of hypothyroidism?
    Replacement Therapy
  29. What is hyperthyroidism?
    Excessive release of the hormones from the thyroid gland
  30. Exophthalmic goiter leads to?
    The protusion of the eye balls
  31. What are some symptoms of hyperthyroidism?
    • Increase heart rate
    • Weight Loss
    • Enlargement of gland
    • Nervousness
  32. What are some symptoms of Grave's disease?
    • Palpitations
    • Anxiety
    • Tremor
    • Weight loss
    • T3/T3 3x normal
  33. Graves disease can be treated with what?
    • Propranolol
    • Methimazole
    • Radioiodine
    • Surgury (removal of thyroid)
  34. T4 is converted to what? How much of it is? By what enzyme?
    • T3
    • 41%
    • 5'-deiodinase I
  35. The conversion of T4 is down regulated in what?
  36. In what is T4 excreted?
    The feces
  37. How much enterohepatic recirculation is there in phenolic hydroxyl?
  38. What is the major metabolic route in thyroid hormones?
    • Deiodination in peripheral tissues
    • Three thyroid hormone producs are possible (Regular T3 and two reverse T3)
  39. What role does the liver play in metabolism of thyroid hormones?
    Liver responsible for glucuronide and sulfate formation on the phenolic hydroxyl
  40. Thyroid hormones increase what?
    The catabolism of Vitamin K dependent clotting factor, increasing bleeding time
  41. What drugs interfer with the deioniation reaction to T3?
    Amiodarone, warfarin, dicoumarol, iopanoic acid (radiocontrast agent)
  42. What drugs interfer with T4 binding to plasma transport proteins?
    Sulfonamides and heparin
  43. In diabetic patients receiving thyroid replacement therapy you have to mointor what else?
    Blood glucose levels and increase insulin and hypoglycemic medications
  44. Thyroid drug
    Tablet and injection forms
    • Levothyroxine sodium
    • Liothyronine sodium
  45. Levothyroxine sodium
    • T4
    • L-thyroxine, Levo-T, Levothryroid, Levoxyl, Synthroid, Eltroxin
  46. Liothyronine Sodium
    • T3
    • Cytomel
  47. Soft gel capsule that avoids heating during manufacturing to improve stability and reliable dosing 12.5 to 150 mg?
  48. Liotrix-1-Thyrolar is a 4:1 ration of t4:t3 that is made of?
    Desiccated pig thyroid
  49. 4:3 ratio of T4:T3
    Made of Desiccated pig thyroid
  50. What time of day does Levothyroxine produce benefits?
  51. What do iodine thyroid products do?
    • Supplement and provide iodine for the thyroid to use and make thyroid hormone
    • Additional iodine once the gland is saturated it will no longer be incorperated and this can be used to block uptake of radioactive isotopes
  52. Iodine drug products?
    • Lugols solution
    • Thyro-Block tablets
  53. 5% iodine and 10% potassium iodine
    OTC product
    Oral solution of KI
    approved by the FDA for radiological terrorist attack use
    Lugol's solution, Thyroshield
  54. Indicated for adjunctive therapy in hyperthyroid patients taking an anti-thyroid drug, thryoid block in the case of radiation emergency
    Thyro-block tablets
  55. What are the two options for clincal treatment of hyperthyroidism?
    • Directly prevent the overproduction of excess thyroid hormone or preventing release
    • Ablating the thyroid tissue with surgery or radiation
  56. Disadvantages of clinical approaches in hyperthyroid therapy?
    Longer half-life of the hormone stores prevents return immediately to euthyroid state
  57. Anti-thyroid drugs
    directly prevent the overproduction of excess thyroid hormone or preventing release
    Black box warning for severe liver injury for those who cannot tolerate other treatments
    Indicated: Hyperthyroidism, preparation for thyroidectomy or radioiodine therapy or patients in which surgery is contraindicated
    MOA: Inhibits iodine uptake and hormone biosynthetic iodination and T4 deionization enzyme 5'-deiodinase I, prevents coupling of two dilodetyrosines during synthesis May develop Agranulocytosis as a severe side effect (sore throat and fever)
    Leading drug induced cause of liver transplation
    Watch for unusal bleeding moitor prothrombin
    Neuritis, depression, jaundice, N/V
    Long term therapy may lead to disease remission
    Propylthiouracil (PTu)- Generics
  58. Anti-thyroid drugs
    Directly prevent the overproduction of excess thyroid hormones or preventing release
    Indications: Hyperthryroidism, preperation for thyroidectomy or radioiodine therapy or patients in which surgery is contraindicated
    MOA: Inhibits iodide uptake and hormone biosynthectic iodination and T4 delodination enzyme 5'-deiodinase I
    causes less hepatoxicity
    Methimazole (Tapazole)
  59. Preferred for thyroid storm
    Blocks T4 to T3 conversion peripherally
    Prefered in pregnancy because doesn't cross placenta but not always true
  60. Iodine product that has radioactivity
    Indications: hyperthyroidism and cases of selected thyroid cancer
    Beta and gamma emitter with a half-life of 8 days
    Rapidly absorbed and concentrated in the thyroid, rapid excretion via the kidney
    Contraindicated in pregnancy, preexisting N/V and diarrhea
    May take up to 2 months for effects to become apparent due to signifcant reservoir in carrier proteins
    Avoid any iodine containing product since it will decrease effectiveness of this agent
    Na131I (Iodotope)
  61. Gout Nodulosis presents with elevation levels of what?
    C-reactive protein
  62. Gout Nodulosis lacks what characteristic of other forms of gout?
    Gouty arthritis
  63. Gout often precents where?
    In the big toe, often the joint is totally destroyed
  64. Gout should never be treated with what?
  65. Deforming gout should be treated with what?
    • NSAIDS
    • Low dose colchincine
    • Allopurinol
  66. Acute attack of gout are?
    Inflammtory reactions to the deposition of sodium urate crystals in joint tissue
  67. Uric acid has how many ionized hydroxyl groups?
  68. Uric acid is the end produc of the metabolism of?
    Purines, Adenine and Guanine
  69. Uric acid is higher is which sex?
    Males by 50%
  70. Uricosuric agents are ANIONIC and weak acids
    Indications: prolongation of beta-lactam plasma concentration, gout, gouty arthritis, hyperuricemia
    MOA: Uriscouric activity prevents renal proximal tubular reabsorption of uric acid; penicillins and cephalosporins-prevents tubular excretion
    Can prolong the effect of Tamifulu
    Do not take asprin of salicylates because they will antagonize the effects of this drug, drink lots of water
    Extensive hepatic metabolism followed by renal excretion
    Use with cholchicine
    Probenecid (Generics)
  71. Uricosuric agents are what?
    Anionic drugs
  72. Uricosuric agent
    Indication: Gout, gouty arthritis, anti-platelet agent
    MOA: prevents renal tubular reabsorption of uric acid, also a COX inhibitor, inhibits prostaglandins, decreased inflammatory effect
    Drug interactions with salicylates, inhibits CYP3A4, warfarin, hypoglycemic agents, sulfonylureas
    Not for uses during gouty attack
    inhitis platelet aggregation, watch blood counts
    Sulfinpyrazone, Anturane
  73. Agents to treat gout
    Natural produc isolated from flowering plant seeds and corm, from a member of the lily family
    First used by the Arabs
    Always use together with a uricosuric agent
    ndications: Unique anti-inflammatory agent that is largely effective only in gout, can be used to relieve pain of an acute attack or prophylactically; also unlabled use for MS, cirrhosis and post heart surgery
    MOA: decreases granulocyte phagocytosis and prevents leukocyte migration and lactage production, decreases inflammatory response to deposited crystals, an antimitotic agent, prevents spindle formation. Does not decrease plasma uric acid levels
    Perform periodic blood counts to look for leukopenia, not an analgesic nor uricosuric agent
    Discontinue use at first sign of N/V, diarrhea or stomach pain, causes malabsorption of vitamin B12
    Colchicine (generics)
  74. What are the absorption issues releated with Cholchicine?
    Multiple efflux pumps are involved in the transport of the drug combined effect of P-glycoprotein and Multidrug resistance associated protein 2 leads to less absorption throughout small intestine
  75. Allopurionol is converted to what? By what?
    Alloxanthine by Oxidation
  76. Indications: Management of gout, malignancies, calcium oxalate calculi
    MOA: Inhibits xanthine oxidase which is responsible for the synthesis of urate from xanthine and hypoxanthine
    Has long half-life
    Inhibits liver microsomal enzymes
    Therapy started at low doese and titrated up
    Drink a lot of water
    Allopurinol, Zyloprim
  77. Newest agent for gout in the last 40 years
    For management of gout
    MOA: selective inhibitor of xanthine oxidase which is responsible for the synthesis of urate from xanthine and hypoxanthine
    Febuxostat, Uloric
  78. Drug to be used with patients with gout who have kidney issues?
  79. Gout agent that is injectable
    recombinate DNA technology, biotechnology drug
    For chronic gout in adult patinets refractory to conventional therapies
    Not for asymptomatic hyperuricemia
    Premedicate with corticosteroids and antihistamines, watch for infusion reactions and anaphylaxis
    Admister with a pump over 120 minutes or more, no bolus
    Contraindicated in glucose-6-phosphate dehydrogenase deficiency
    gouty flare occur manage with colchincine and NSAIDS
    Pegloticase, Krystexxa
  80. What is the biggest improvement in respiratory drug therapy the last 10 years?
    Inhalation devices: onset of action is fater, smaller doses and lower risk of systemic effects than with oral drugs
  81. Indications: relief of reversible bronchospasm associated with acute and chronic bronchial asthma, exercise induced bronchspasm emphsema, and other COPD
    Long term Beta2 agonist (Salmeterol) are used in conjunction with anti-inflmamatory agents for long-term control especially nocturnal symptoms
    Short term beta2 agonist (Albuterol, bitolerol, pirbuterol, terbutaline) are the agents of choice for acute attacks and EIB--More than twice weekly also use an inhaled corticosteroid
    Sympathomimetic Bronchodilators
  82. MOA: relative sleactiviy of a particular agent for alpha, beta 1 and beta 2 adrenergic effects determines its usefulness clinicall and predicst and agents side effect that will be observed
    Sympathomimetric Brnchodilators
  83. Sympathetic Bronchodilator
    Tablets, extended release, syrup aerosol, solution, capsules for inhalation
    Racemic mixture
    B1 activity<B2 acitivy PO onset 30 min duration 4-8 hours inhlation onset 5 minutes with duration of 3-6 hours used in ER
    Albuterol, Proventil, Volmax, Ventolin
  84. One enatiomer
    sympathomimetric bronchodilator
    solution for inhlation
    Can be used in pediatrics
    Has less B1 activity than B1 activity
    Levoalbuterol, Xopenex
  85. Sympathomimetric Bronchodilator
    Short acting agent
    B1 activity <B2 activity tablets, aerosol, injections
    Terbutaline sulfate, Brethine, Bricanyl
  86. Sympathomimetic Bronchodilator
    onset 5 minutes duration 5 hours
    Tied with bitolterol for the 5th most potent B2 agent
  87. Prodrug
    Sympathomimetic Bronchodilators
    onset 2-4 minutes duration 5-8 Hours
    Erosol and solutions for inhalation
    Bitolterol Mesylate, Tornalate
  88. Sympathomimetic Bronchodilators
    Short acting agent B1<B2 onset 30 minutes duration 4 hours
    tablets, syrup, solution for inhaltion, aerosol
    Metaproternol Sulfate, Alupent
  89. Sympathomimetic Bronchodilator
    Short acting agent B1=B2 activity, IV onset immediate with duration of 1 hour, inhalation onset 2-5 minutes with duration of 1-3 hours
    2nd most potent B2 agonist abailable
    inhlation, aerosol, injection
    Isoproternol Sulfate, Isuprel
  90. Sympathomimetic Bronchodilators
    Short acting agent B1=B2=alpha
    onset 1-5 minutes duration 1-3 hours subq slower
    Epinephrine, Adrenalin
  91. Capsule
    Sympathomimetic Bronchodilators
    PO onset 15-60 minutes
    capsules and injections
    Natural product
    D-(-)-Ephedrine, Gerneric sulfate salt
  92. Sympathomimetic Bronchodilator
    combo with a corticosteroid fluticason
    B1<B2, onset 20 minutes
    Salmeterol, Serevent, Advair Discus (Combo)
  93. Long acting agents
    Sympathomimetic bronchodilator
    200x higher affinity for B2 receptors over B1 (S,S), 1000x less potent as B2 agonist than (R, R)
    Also an inhbitior of mast cell mediators such as histamine and leukotrienes
    • Bueseonine and formoterol, Symbicort
    • Perforomist
    • Formoterol fumerated, Foradil Aerolizer
Card Set
Quiz 6
Med. Chem Quiz 6, Gout, Thyroid, Respiratory