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Thyroid Hormones are the only compounds containing what?
What is the world's most preventable cause of mental retardation?
To avoid iodine deficiency in the US what is done?
Iodine is added to table salt
Iodine and what are absorbed concurrently?
What drugs can inhibit the uptake of iodine?
Cardiac glycosides (digoxin, loop-diuretics) because they inhibit the uptake of potassium
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
Hypothyroidism has a connection to what cardiovascular issue?
Lack of iodine in the body can cause what mood changes?
Crabbiness and Depression
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
QSAR studies are underway for TRbeta1 selective ligands in the hope of discovering agents?
without cardiac side effects
Bile acids induce energy expenditure by promoting?
Intracellular thyroid activation
Levels of thryoid hormones are controlled by what type of feedback?
What is TRH?
Thyrotropin releasing hormone
What is TRH produced by?
TRH travels to where after being produced by the hypothalamus?
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)
TRH binds to receptors on the pituitary gland stimulating the release of what?
TSH thyroid stimulating hormone
What are T3 levels capable of blocking?
The TRH induced release of TSH and the transcription of the alpha and beta subunits of TSH
Thyroid hormones are stored as amino acid residues of a protein called what?
What is resoponsible for the transport of thyroid hormones in the blood?
- Two Plasma Proteins: Thyroxine binding globulin, Transthyretin
What type of hormone is metabolically active?
What is the percentage of free T4?
What is the percentage of free T3?
What is more active T3 or T4? How much more?
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
What are goiters?
Beneign or malignant tumors, euthryoid patients have normal thyroid function
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
What is the treatment in all cases of hypothyroidism?
What is hyperthyroidism?
Excessive release of the hormones from the thyroid gland
Exophthalmic goiter leads to?
The protusion of the eye balls
What are some symptoms of hyperthyroidism?
- Increase heart rate
- Weight Loss
- Enlargement of gland
What are some symptoms of Grave's disease?
- Weight loss
- T3/T3 3x normal
Graves disease can be treated with what?
- Surgury (removal of thyroid)
T4 is converted to what? How much of it is? By what enzyme?
The conversion of T4 is down regulated in what?
In what is T4 excreted?
How much enterohepatic recirculation is there in phenolic hydroxyl?
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)
What role does the liver play in metabolism of thyroid hormones?
Liver responsible for glucuronide and sulfate formation on the phenolic hydroxyl
Thyroid hormones increase what?
The catabolism of Vitamin K dependent clotting factor, increasing bleeding time
What drugs interfer with the deioniation reaction to T3?
Amiodarone, warfarin, dicoumarol, iopanoic acid (radiocontrast agent)
What drugs interfer with T4 binding to plasma transport proteins?
Sulfonamides and heparin
In diabetic patients receiving thyroid replacement therapy you have to mointor what else?
Blood glucose levels and increase insulin and hypoglycemic medications
Tablet and injection forms
- Levothyroxine sodium
- Liothyronine sodium
- L-thyroxine, Levo-T, Levothryroid, Levoxyl, Synthroid, Eltroxin
Soft gel capsule that avoids heating during manufacturing to improve stability and reliable dosing 12.5 to 150 mg?
Liotrix-1-Thyrolar is a 4:1 ration of t4:t3 that is made of?
Desiccated pig thyroid
4:3 ratio of T4:T3
Made of Desiccated pig thyroid
What time of day does Levothyroxine produce benefits?
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
Iodine drug products?
- Lugols solution
- Thyro-Block tablets
5% iodine and 10% potassium iodine
Oral solution of KI
approved by the FDA for radiological terrorist attack use
Lugol's solution, Thyroshield
Indicated for adjunctive therapy in hyperthyroid patients taking an anti-thyroid drug, thryoid block in the case of radiation emergency
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
Disadvantages of clinical approaches in hyperthyroid therapy?
Longer half-life of the hormone stores prevents return immediately to euthyroid state
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
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
Preferred for thyroid storm
Blocks T4 to T3 conversion peripherally
Prefered in pregnancy because doesn't cross placenta but not always true
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
Gout Nodulosis presents with elevation levels of what?
Gout Nodulosis lacks what characteristic of other forms of gout?
Gout often precents where?
In the big toe, often the joint is totally destroyed
Gout should never be treated with what?
Deforming gout should be treated with what?
- Low dose colchincine
Acute attack of gout are?
Inflammtory reactions to the deposition of sodium urate crystals in joint tissue
Uric acid has how many ionized hydroxyl groups?
Uric acid is the end produc of the metabolism of?
Purines, Adenine and Guanine
Uric acid is higher is which sex?
Males by 50%
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
SHOULD NOT BE USED DURING GOUT ATTACK!
Use with cholchicine
Uricosuric agents are what?
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
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
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
Allopurionol is converted to what? By what?
Alloxanthine by Oxidation
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
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
Drug to be used with patients with gout who have kidney issues?
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
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
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
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
Tablets, extended release, syrup aerosol, solution, capsules for inhalation
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
solution for inhlation
Can be used in pediatrics
Has less B1 activity than B1 activity
Short acting agent
B1 activity <B2 activity tablets, aerosol, injections
Terbutaline sulfate, Brethine, Bricanyl
onset 5 minutes duration 5 hours
Tied with bitolterol for the 5th most potent B2 agent
onset 2-4 minutes duration 5-8 Hours
Erosol and solutions for inhalation
Bitolterol Mesylate, Tornalate
Short acting agent B1<B2 onset 30 minutes duration 4 hours
tablets, syrup, solution for inhaltion, aerosol
Metaproternol Sulfate, Alupent
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
Short acting agent B1=B2=alpha
onset 1-5 minutes duration 1-3 hours subq slower
PO onset 15-60 minutes
capsules and injections
D-(-)-Ephedrine, Gerneric sulfate salt
combo with a corticosteroid fluticason
B1<B2, onset 20 minutes
Salmeterol, Serevent, Advair Discus (Combo)
Long acting agents
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
- Formoterol fumerated, Foradil Aerolizer
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