Block 4: Thyroid Pharm Flashcards
1
Q
What is the tx for SIADH?
A
Mild to no sx: fluid restriction
Severe: Hypertonic saline must have greater Osm that urine or will make hyponatremia worse
* Increaseing Na too fast can cause Central pontine myelinolysis
2
Q
What are the pharms that can be used for SIADH>
A
- Remove or correct offending cause
- Loop Diuretics
- Demeclocycline (antibiotic (tetracycline derivative) that also antagonizes ADH receptors)
* ADR: Nephrogenic Diabetes Insipidus
3
Q
Conivaptan
Class, Brand, MOA, Form
A
Vaprisol: Non selective vasopressin receptor antagonist
MOA: Blocks ADH-induced increase in cAMP in renal collecting ducts and prevents translocation of aquaporin 2
Form: IV formulation
4
Q
Tolvaptan
Brand, Class, MOA, Form, ADR
A
Samsca: V2 selective Vasopressin Receptor Antagonist
MOA: blocks binding of ADH to the V2 receptor in kindeys
Forms: PO
* Less effect on vasculature (less hypotension) due to lack of V1a receptor antagonism
* Increases serum Na+
ADR: Dry mouth, thirst, constipation, hyperglycemia, urninary frequency
5
Q
What are vasopressin preps?
A
- Synthetic arginine vasopressin (Vasostrict, human form)
- Desmopressin (1-deamino-8-D-arginine vasopressin, DAVP):
* V2 effects > V1
6
Q
What are the clinical uses for vasopressin?
A
Diagnostic to differentiate central vs neprhogenic DI:
* One hour after treatment, urine osmolality should increase >50 % if due to AVP deficiency (or central DI)
Replacement therapy for central DI: use desmopressin due to longer DOA
7
Q
What are GI applications of vasopressin?
A
- Based on V1-mediated contraction of GI smooth muscle, can be used for postoperative ileus and to dispel intestinal gas before abdominal imaging
- Based on V1-mediated contraction of vascular smooth muscle can be used for emergency treatment of bleeding
Not DAVP
8
Q
What are the ADR of V1?
A
- Constriction of blood and coronary vessels
- Stimulation of GI muscle
- Cross-reaction with the oxytocin receptor causing stimulation of uterine smooth muscle
9
Q
What are the ADR of V2?
A
Rare
10
Q
Tx for lithium induced nephrogenic DI?
A
Thiazide diuretics
11
Q
Drug of choice for induction of labor? Monitoring?
A
Oxytocin: Monitor uterine activity, fetal heart rate
12
Q
ADR of oxytocin?
A
- Uterine rupture
- Trauma or death of infant
- Risks minimized by use of conservative protocol
13
Q
Apart from induction of labor what are other uses for oxytocin?
A
- Control of postpartum bleeding by maintain uterine tone
- Increasing milk ejection
- Oxytocin challenge test to measure uteroplacental sufficiency in high risk pregnancies
14
Q
What is the tx for Growth Hormone Dependent (GHD) short stature?
A
Recombinant GH
15
Q
When can Recombinant GH be initiated?
A
Early age, prior to the onset of puberty is associated with a more favorable increase in height
16
Q
Outcomes of hyposecretion of GH?
A
Short stature:
1. Hypopituitary short stature (pituitary dwarfism)
2. Laron syndrome: Failure of GH to stimulate IGF-I production
17
Q
What are the clinical tx for hyposecretion of GH?
A
Somatropin (Humatrope, Norditropin, & others):
* Recombinant human GH (rhGH) for SC & IM
Sustained-release rhGH formulations:
* Nutropin depot
* Skytrofa
* Sogroya
* Ngenla
18
Q
What are the ADRs and DDIs of somatropin and somatrem?
A
ADR: peripheral edema, myalgias, arthralgias, carpal tunnel syndrome
DDI: Increased cytochrome P450 isoforms -> increased clearance of steroids, anticonvulvants, cyclosporine
19
Q
What is increlex?
A
Mecasermin:
Long-term treatment of growth failure in children caused by severe primary IGF-1 deficiency (e.g. Laron syndrome)
20
Q
What is the treatment choice for acromegaly?
A
Trans-sphenoidal surgical resection of the GH-secreting adenoma
21
Q
A
22
Q
What are the pharm tx for acromegaly?
A
- Somatostatin analogs (Somatostatin Receptor Ligands)
- Dopamine agonists
- GH receptor antagonist: Pegvisomant
23
Q
What are the somatostatin analogs?
A
- Octreotide (Sandostatin)
- Lanreotide depot (Somatuline Depot)
- Pasireotide (Signifor)
24
Q
Octreotide
Brand, Indications, MOA, Forms, ADR
A
Sandostatin
Indications: acromegaly
MOA: More potent at inhibiting GH secretion than native SRIF
FormsSustained-release form: Sandostatin LAR
ADR: HA, cardiac conduction changes, GI reactions
25
Lanreotide
| Brand, Form, Indication, ADR
**Somatuline Depot:** Deep SQ Q28D
**Indication:** acromegaly
**ADR:** Reduction of bile production, gallbladder contractility leading to biliary sludge and/or gallstones, GI disturbances
26
Pasireotide
| Brand, Forms, Indication, MOA, ADR
**Signifor**
**Form:** IM Preparation (Signifor LAR)
**Indication:** Cushings and acromegaly
**MOA:** Somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of GH
**ADR:** Hyperglycemia
27
What is the GH analog?
Pegvisomant (Somavert)
28
Describe the structure of Pegvisomant?
1. Recombinant hGH analog that act as a GHR antagonist
2. Polyethylene Glycol derivative of a mutated Growth Hormone
3. The mutated GH, B2036, prevents functional receptor dimerization with reduced binding affinity
4. While pegylation reduces affinity for the GH receptor, requiring a higher dose requirement, pegylation increases half life by up to 6 days
29
What is the most effective tx for acromegaly?
Pegvisomant (Somavert)
30
What is the tx for prolactin hypersecretion?
Dopamine Agonists: Inhibits release of prolactin (inhibiting hormone)
31
What are the types of dopamin agonists?
| Forms, ADRs
Bromocriptine, Cabergoline, Ropinirole*, Pramipexole*
**Form:** PO
**ADR:** NV/DZ, postural hypotension
32
What is the tx for cushings?
Steroidogenic inhibition
33
What are the Steroidogenic inhibititors?
1. Metyrapone
2. Ketoconazole
3. Levoketoconazole (Recorlev)
4. Mitotane (Lysodren)
5. Osilodrostat (Isturisa)
34
MOA of metyrapone?
Inhibits cortisol synthesis by inhibiting 11-beta hydroxylase
35
MOA of ketoconazole?
1. Treatment of fungal infection
2. inhibitor of mitochondrial P450 enzymes systems and 11-hydroxylase
36
Levoketoconazole (Recorlev)
| Clinical use
Cortisol synthesis inhibitor for patients whom surgery is not an option or curative
37
Mitotane
| Brand, MOA, ADR
**Lysodren**
**MOA:** Inhibits 11-hydroxylation of 11-desoxycortisol and 11-desoxycorticosterone and pregnenolone synthesis from cholesterol in adrenal cortex
* Reduces synthesis of cortisol and corticosterone
**ADR:** adrenal crisis in settings of shock or severe trauma, CNS toxicity
38
Osilodrostat
| Brand, Indication, MOA
**Isturisa**
**Indication:** nonsurgical tx of Cushing adults who don't qualify for surgery
**MOA:** Potent cortisol synthesis inhibitor that blocks 11 beta-hydroxylase to interrupt the last step of the cortisol synthesis pathway
39
What is adrenal or addidsonian crisis?
1. Acute adrenocortical insufficiency which represents an endocrine emergency
2. Most common cause of adrenal crisis is HPA-axis suppression brought on by chronic use of exogenous glucocorticoids and abrupt withdrawal
40
What are the tx options for addisons?
Hydrocortisone, Cortisone, Prednisone
* Mimics normal diurnal adrenal rhythm
41
Describe the selectivity of hydrocortisone?
Both glucocorticoid and mineralocorticoid activity
42
What is the tx for hypoaldosteronism? MOA
Fludrocortisone: Acts as a potent mineralocoricoid with weak GCC activity
43
Tx options for hyperaldosteronism?
Spironolactone (Aldactone)
44
Spironolactone
| Brand, MOA, Indication, ADR
**Aldactone**
**MOA:** competitive antagonist of aldosterone and blocks androgen receptors
**Indications:** aldosterone-producing adrenal adenomas, Idiopathic hyperaldosteronism, CHF, hypokalemia, CKD
**ADR:** due to adrogen receptor blocking
* Men: gynecomastia, feminization, sexual dysfunction
* Women: menstrual irregularities, breast tenderness and enlargement
45
What are the prinicples of GCC?
1. Response is a function of the specific receptors that are activated
2. MOA of steroids is complex and not fully understood
3. PK of GCC varies by agent
4. Suppression of HPA-axis is a major concern when systemic steroids are withdrawn due to long-term suppression of the HPA axis
46
**T/F:** Iodine is an ideal thyroid hormone replacement.
**F:** No benefit to giving iodine due to Wolff-Chaikoff effect
47
What are the products for TH replacement?
1. Synthetic Levothyroxine, T4 (Levo-T, Levothroid, Levoxyl, Synthroid, Tirosint, Unithroid)
2. Liothyronine, T3 (Cytomel, Triostat)
3. Combined LT4 / LT3 (Liotrix)
48
Levothyroxine
| Brand, Dosing, Warning
(Synthroid, Levothroid, Levoxyl, Levo-T, Tirosint, Unithroid, others)
**Dosing:** T4 is converted in the body, start with reduced dose in elderly and patients with heart dx
**DDI**
* Inhibition of GI absorption of TH: Ca++, Al++, and Mg++, BASm Iron sulfate, sucralfate
* Increased metabolism of TH: Rifampin, Carbamazepine, Phenytoin, Phenobarbital, Sertraline
**Warning:** Narrow TI requiring titration
49
Liothyronine
| Brand, MOA
Cytomel, Triostat
**MOA:** 10x more potent -> palpitations or cardiac ADRs
* Causes high plasma T3 levels, lower T4 levels (this is not physiologic)
50
Desiccated Thyroid
| Brands, Forms
Nature-Throid, Westhroid, Armour
**Form:** Desiccated powder derived from porcine-thyroid
* Contains both T4 and T3 not necessarily consistent
51
Tx options for hyperthyroidism?
1. Palliative treatment of mild hyperthyroidism may be accomplished by using B-blockers
2. Thyroidectomy
3. Radioactive Iodine (131I)
52
Radioactive Iodine
| Safety, ADR
**Safety:**
* Eliminated in the urine, saliva and feces in the following 4-8 weeks
* No close contact with children and pregnant women for the first 48-72 hours after treatment
**ADR:** Graves ophthalmology can or may worsen (radioactive iodine does nothing for TSI levels)
**CI:** Pregnancy, lactation, active Graves’ ophthalmopathy
53
How do you prevent the development of Graves opthalmology?
Prednisone
54
What is the preferred tx method for hyperthyroidism by most thyroidologists?
Radioactive Iodine
55
Tx for thyroid eye disease?
Tepezza (teprotumumab-trbw) is an insulin-like growth factor-1 receptor inhibitor
56
What are thionamides indicated for?
1. Hyperthyroidism in permanent remission in 40-50% of treated patients
2. treatment of choice in children, pregnant women and young adults with uncomplicated Graves' disease
57
Types of thionamide?
1. Propylthiouracil (PTU)
2. Methimazole (Tapazole)
58
Thionamides
| MOA, Onset
**MOA:** Inhibitors of thyroid peroxidase enzyme (TPO) that is responsible for iodination of tyrosine residues of thyroglobulin
* Prevents TH syntheis
**Onset:** 4-6 week, TSK levels may remain undetectable for months
**ADR:** Dose dependent with Tapazole, idiosyncratic with PTU
* Agranulocytosis: common in PTU
* Hepatoxicity w/ PTU
* Cholestatic jaundice w/ Tapazole (resolves in 2-8 weeks with dc)
59
Propylthiouracil (PTU)
| MOA, Indication, ADR
**MOA:**thionamide action and inhibits the peripheral conversion of T4 to T3 (but not by methimazole)
**Indication:** Thyroid storm
**ADR:** Agranulocytosis, hepatotox, hepatic necrosis
60
Methimazole
| Brand, MOA, ADR
**Tapazole**
**MOA:** Inhibits thyroid peroxidase enzyme, decreasing iodination of tyrosines on thyroglobulin
**ADR:**
* Lower risk of agranulocytosis and hepatotoxicity
* Does NOT inhibit peripheral conversion of T4 to T3
61
Outocmes of using Iodine for hyperthyroidism?
1. Short term inhibitor of thyroid hormone release due to Wolff-Chaikoff effect
2. The effect of iodide is overcome by TSH levels that increase in response to lower plasma levels of free thyroid hormone
3. Not widely used: Occasionally used as preoperative preparation and thyroid storm
62
Functions of beta blockers with hyperthyroidism?
1. Decreases adrenergic activity of TH
2. Blocks peripheral conversion of T4 to T3
**Propranolol** (nonselective) is preferred
Also use in thyroid storm and reduction of T4 conversion
63
Functions of GCC with hyperthyroidism?
1. Reduces effects of TSI in Graves’ Ophthalmopathy
2. Blocks peripheral conversion of T4 to T3
64
Wht is the initial tx for thyroid storm?
Initial stabilization includes airway protection, oxygenation, fluids and cardiac monitoring
65
How is thyroid storm tx divides?
1. General supportive care
1. Inhibition of thyroid hormone synthesis
1. Retardation of thyroid hormone release
1. Blockade of peripheral thyroid hormone effects
1. Identification and treatment of precipitating events
66
What are the pharm tx for thyroid storm?
1. Propylthiouracil or Methimazole: prevents synthesis of the TH hormone
2. Treat cardiac symptoms, fever and hypertension: Propranolol decreases adrenergic hyperactivity and has the additional effect of blocking peripheral conversion of T4 -> T3
3. Glucocorticoids: inhibit thyroid hormone production and decreases peripheral conversion from T4 -> T3.
4. Sodium iodide solution (Lugol’s solution) or lithium: **Do not administer iodine or lithium until the synthetic pathway has been blocked (with PTU or Methimazole)**
67
Drug disease interactions with TH?
1. Diabetes and Hypoglycemic agents
1. Estrogens may increase TBG -> decrease FT4
1. Seizure disorder: TH can decrease seizure threshold
1. Levothyroxine increases the response to oral anticoagulant therapy
1. The therapeutic effects of digitalis glycosides may be reduced by levothyroxine
68
DDI of TH?
1. Drugs which may decrease thyroid hormone synthesis or secretion
2. Drugs that may decrease T4 absorption from GI tract
3. Drugs that may alter T4 and T3 serum transport
4. Phenytoin and carbamazepine when used with levothyroxine can decrease the effects of levothyroxine
69
What thyroid functions are altered with pregnacy?
1. Transient increase in hCG, during the 1st trimester stimulates the TSH-R
2. ) Estradiol increases thyroxine binding globulin (TBG) during the 1st trimester, which is sustained throughout pregnancy: ↓ FT4
3. Iodine def
4. Alterations in immune function
70
How do you prevent hypothyroidism in pregnancy?
Women need more LT4 during pregnancy
* Dose changes based on serum FT4 +TSH
71
RF of Graves in pregnancy?
1. Fetal anomalies
2. spontaneous abortion
3. preterm labor
4. fetal hyperthyroidism
5. thyroid storm in labor
72
Tx of Graves during pregnancy?
1. Antithyroid drugs are still the primary treatment
2. Propylthiouracil preferred 1st trimester
3. Methimazole in 2nd and 3rd trimesters
**ABSOLUTE CONTRAINDICATION…
No RAI while pregnant… Ever…**
73
Causes of postpartum thyroiditis?
Lymphocytic infiltration (Hashimoto’s)
