Podcast
Questions and Answers
Which iodine-containing compound is formed by the condensation of two DIT molecules?
Which iodine-containing compound is formed by the condensation of two DIT molecules?
What role does the hypothalamic-pituitary-thyroid axis play in thyroid hormone synthesis?
What role does the hypothalamic-pituitary-thyroid axis play in thyroid hormone synthesis?
Which thyroid hormone is considered more active?
Which thyroid hormone is considered more active?
What is a characteristic of the chemical structure of T3?
What is a characteristic of the chemical structure of T3?
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Levothyroxine is primarily used for which purpose?
Levothyroxine is primarily used for which purpose?
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What is the mechanism of action for anti-thyroid drugs?
What is the mechanism of action for anti-thyroid drugs?
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What is the primary action of ezetimibe in the body?
What is the primary action of ezetimibe in the body?
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Which of the following hyperlipidemias is ezetimibe useful for?
Which of the following hyperlipidemias is ezetimibe useful for?
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Which condition may necessitate the use of anti-thyroid drugs prior to surgery?
Which condition may necessitate the use of anti-thyroid drugs prior to surgery?
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What role do thyroid hormones play in metabolism?
What role do thyroid hormones play in metabolism?
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What is a common effect of thyroid hormones on metabolism?
What is a common effect of thyroid hormones on metabolism?
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Which mineral is essential for the synthesis of thyroid hormones?
Which mineral is essential for the synthesis of thyroid hormones?
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What is the initial step in the production of iodinated amino acids within thyrocytes?
What is the initial step in the production of iodinated amino acids within thyrocytes?
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Which reaction is catalyzed by thyroperoxidase during thyroid hormone synthesis?
Which reaction is catalyzed by thyroperoxidase during thyroid hormone synthesis?
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How do thyroid hormones affect carbohydrate metabolism?
How do thyroid hormones affect carbohydrate metabolism?
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What effect do thyroid hormones have on the cardiovascular system?
What effect do thyroid hormones have on the cardiovascular system?
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What is the primary function of α-glucosidase inhibitors?
What is the primary function of α-glucosidase inhibitors?
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What side effects can result from the use of α-glucosidase inhibitors?
What side effects can result from the use of α-glucosidase inhibitors?
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How do incretins function in the body?
How do incretins function in the body?
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What characterizes meglitinides compared to sulfonylureas?
What characterizes meglitinides compared to sulfonylureas?
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What is the primary mechanism through which diuretics achieve their effect?
What is the primary mechanism through which diuretics achieve their effect?
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What role does α-glucosidase play in carbohydrate digestion?
What role does α-glucosidase play in carbohydrate digestion?
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Why should patients using α-glucosidase inhibitors avoid glucose intake?
Why should patients using α-glucosidase inhibitors avoid glucose intake?
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What is a potential outcome of increased saccharides in the colon due to α-glucosidase inhibitors?
What is a potential outcome of increased saccharides in the colon due to α-glucosidase inhibitors?
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What is primarily lost during acidosis?
What is primarily lost during acidosis?
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Which compound is considered the prototype for heterocyclic sulfonamides?
Which compound is considered the prototype for heterocyclic sulfonamides?
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What characteristic is essential for the diuretic activity of sulfonamides?
What characteristic is essential for the diuretic activity of sulfonamides?
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How does substitution of a methyl group on one of acetazolamide's ring nitrogens affect its activity?
How does substitution of a methyl group on one of acetazolamide's ring nitrogens affect its activity?
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Which of the following is not capable of inhibiting carbonic anhydrase?
Which of the following is not capable of inhibiting carbonic anhydrase?
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What is the significance of the sulfamoyl nitrogen atom remaining unsubstituted?
What is the significance of the sulfamoyl nitrogen atom remaining unsubstituted?
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Which property of sulfonamide derivatives is related to the carbonic anhydrase inhibitory and diuretic activity?
Which property of sulfonamide derivatives is related to the carbonic anhydrase inhibitory and diuretic activity?
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Which characteristic must be present in the moiety to which the sulfamoyl group is attached?
Which characteristic must be present in the moiety to which the sulfamoyl group is attached?
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Which diuretic is NOT included in the site 3 diuretics list?
Which diuretic is NOT included in the site 3 diuretics list?
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What is the significance of position 3 in the structure activity relationship of diuretics?
What is the significance of position 3 in the structure activity relationship of diuretics?
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Which functional group is associated with the acryloyl group that forms an adduct with sodium/potassium ATPase?
Which functional group is associated with the acryloyl group that forms an adduct with sodium/potassium ATPase?
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What type of structural modification can position 2 tolerate according to the structure activity relationship?
What type of structural modification can position 2 tolerate according to the structure activity relationship?
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Which of the following is a characteristic feature of site 3 diuretics?
Which of the following is a characteristic feature of site 3 diuretics?
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Which compound is used in the synthesis of ethacrynic acid and involves AlCl3?
Which compound is used in the synthesis of ethacrynic acid and involves AlCl3?
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What is the role of the sodium/potassium ATPase system in the loop of Henle?
What is the role of the sodium/potassium ATPase system in the loop of Henle?
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Which of the following compounds is a thiazide-like diuretic?
Which of the following compounds is a thiazide-like diuretic?
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Study Notes
Ezetimibe
- Approved in 2002
- Reduces LDL, total cholesterol, and triglycerides
- Increases HDL
- Prevents cholesterol absorption from diet
- Useful in hyperlipidemias (type IIa, IIb, III, IV, and V)
Thyroid Hormones
- Crucial for growth and development
- Stimulates metabolism in most tissues (except adult brain)
Thyroid Hormone Function
- Increases mitochondrial oxidative phosphorylation
- Maintains amino acid and electrolyte transport into cells
- Increases calorigenesis and oxygen consumption
- Stimulates protein synthesis (structural & enzymatic)
- Regulates carbohydrate metabolism (accelerates insulin degradation & increases gluconeogenesis)
- Stimulates lipid metabolism (reduces plasma cholesterol)
- Increases cardiovascular and nervous system sensitivity to catecholamines (leading to increased heart rate, cardiac output, and arousal)
Thyroid Hormone Synthesis Requirements
- Requires tyrosine (amino acid) and iodine (trace mineral)
- Begins with thyroglobulin synthesis, which is post-translationally modified in unique biochemical reactions
Thyroid Hormone Biosynthesis Process
- Iodide is oxidized to iodine by thyroperoxidase (TPO) in the presence of hydrogen peroxide (H2O2)
- Iodine binds to the 3' position in the tyrosyl ring, forming 3-monoiodotyrosine (MIT)
- Another iodine binds to the 5' position of MIT, creating 3,5-diiodotyrosine (DIT)
- T4 is formed by the condensation of two DIT molecules
- T3 and reverse T3 (rT3) are formed by the condensation of DIT and MIT
- These biosynthetic processes are controlled by the hypothalamic-pituitary-thyroid axis feedback mechanism
Thyroid Hormone Drugs
- Used as replacement therapy in thyroid gland deficiency
- T3: L-3,3,5-triiodothyronine
- T4: L-3,5,3,5-tetraiodothyronine (thyroxine)
Thyroid Hormone Drug Structure-Activity Relationships
- Contain two aromatic molecules (A & B) linked via a heteroatom (O or S)
- Ring B contains an amino acid side chain with at least three carbons
- Ring A must be perpendicular to ring B with a 120° angle
- Ring B must be substituted at positions 3 and 5 with halogen (lipophilic group) (iodine is most active)
- Ring A must be substituted at position 3 with halogen
- T3 (3 iodines) is less active than T4 (4 iodines)
- Ring A must contain phenolic OH for receptor binding
Levothyroxine Sodium
- Obtained from domesticated animal thyroid glands
- Also prepared synthetically
- Treats decreased thyroid function
Liothyronine Sodium
- Same uses as levothyroxine, including:
- Hypothyroidism treatment
- Male infertility
- Certain gynecological disorders
Anti-Thyroid Drugs
- Used for hyperthyroidism (excess thyroid hormone production)
- Preparation for surgery
- Thiourea and related compounds are toxic
- Useful drugs include 2-thiouracil derivatives and 2-thioimidazole derivatives
- These drugs prevent iodine incorporation into thyroxine and triiodothyronine precursors
α-Glucosidase Inhibitors
- Acarbose inhibits the breakdown of complex saccharides in the intestine by α-glucosidase
- Mimics sugar structure and binds to the enzyme with higher affinity than the natural substrate
- Decreases monosaccharide absorption and postprandial blood glucose peaks
- Useful for postprandial hyperglycemia
- Avoid consuming glucose
- Can cause colonic distress (diarrhea, flatulence, and cramping)
Meglitinides
- Similar mechanism of action to sulfonylureas, but without toxicities
Incretins
- Gastrointestinal hormones that increase insulin release from pancreatic beta cells after eating
- Inhibit glucagon release from alpha cells
Diuretics
- Increase urine formation
- Inhibit sodium reabsorption in the kidney
- Acidosis occurs due to loss of bicarbonate (HCO3-)
Heterocyclic Sulfonamides
- Examples include acetazolamide (Diamox) and methazolamide (Neptazane)
Diuretic Structure-Activity Relationships
- Acetazolamide is the prototype
- Higher lipid/water partition coefficient and lower pKa lead to greater carbonic anhydrase inhibition and diuretic activity
- Sulfamoyl group is essential for activity
- Sulfamoyl nitrogen must remain unsubstituted
- Methyl substitution on one of the ring nitrogens increases potency
- Sulfamoyl group must be attached to an aromatic moiety
Ethacrynic Acid Synthesis
- Involves a series of reactions including Friedel-Crafts acylation and amination with methylamine
Site 3 Diuretics: Thiazide and Thiazide-like Diuretics
- Include chlorothiazide, hydrochlorothiazide (HCTZ), benzthiazide, cyclothiazide, indapamide, chlorthalidone, bendroflumethizide, metolazone, etc.
Thiazide Structure-Activity Relationships
- Position 2 tolerates small alkyl groups (e.g., CH3)
- Position 3 is critical for potency and duration of action
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Description
This quiz covers essential details about Ezetimibe, a medication approved in 2002 for managing cholesterol levels, as well as thyroid hormones and their crucial functions in metabolism. Explore how these hormones affect growth, energy consumption, and overall cardiovascular health. Additionally, understand the synthesis requirements for thyroid hormones.
