Exam 4: Endocrine Pharmacology Flashcards
Role of thyroid in infants:
Development of nervous system, growth
Thyroid gland secretes:
T3, T4, calcitonin
Thyroid hormones are made up of:
Two tyrosine molecules, iodinated, joined by ester linkage
More active form of thyroid hormone:
T3
Pathway to thyroid hormones:
Hypothalamus releases TRH → anterior pituitary releases TSH → thyroid secretes T4 > T3 → conversion in periphery
Causes of hyperthyroidism:
Graves’: IgG antibody activates TSH receptor
Toxic multinodular goiter
Iatrogenic (overdose)
Pit tumor, thyroid cancer, testicular cancer (βhCG release)
Examples of thioamides/thioureylenes:
Propylthiouracil
Methimazole (Tapazole)
Indications for thioamides/thioureylenes:
Graves’
Hyperthyroidism
Only useful in overproduction situations
MoA of thioamides/thioureylenes:
Competes with thyroglobulin for iodide and reduces thyroid hormone synthesis
Onset of thioamides/thioureylenes:
1-2 weeks due to thyroid gland stores
A/E of thioamides/thioureylenes:
Goiter d/t ↑ TSH stimulating thyroid hypertrophy Pruritic rash Arthralgias Agranulocytosis Hepatotoxicity Vasculitis/drug-induced lupus
Preferred agent for hyperthyroidism and why:
Methimazole d/t longer half-life, once daily dosing, more potent, less serious A/E
Considerations for PTU:
Inhibits conversion of T4 to T3 in periphery
TID dosing
Preferred in pregnancy and thyroid storm
No IV formulation
A/E of PTU:
Depletes prothrombin so ↑ bleeding time
Additional hyperthyroid therapy beyond thioamides/thioureylenes:
I131 Surgical resection β blockers Corticosteroids Iodide salts (Lugol's)
β blockers for hyperthyroid:
Blocks peripheral conversion of T4 to T3, blocks adrenergic effects
Corticosteroids for hyperthyroid:
Blocks peripheral conversion of T4 to T3, suppresses antibodies and inflammation
Iodide salts for hyperthyroid:
Blocks peripheral conversion of T4 to T3, decreases vascularity of thyroid gland, temporarily blocks TH release due to gland being occupied with iodide uptake
Causes of hypothyroidism:
Hashimoto’s: antibodies against thyroid gland proteins
Thyroid ablation/surgery
Iodine-containing drugs
Pit tumor
PO synthroid:
Synthesized T4
Long half-life (7 days)
Monitor TSH, T4
A/E of synthroid:
Allergic rash
Indications for T3 vs. T4:
Myxedema coma
Drugs that increase levothyroxine metabolism:
Phenobarbital
Phenytoin
Rifampin
Carbamazepine
Drugs that decrease T4 to T3 conversion:
PTU
β blockers
Amiodarone
Glucocorticoids
Drugs that decrease absorption of levothyroxine from the gut:
Cholestyramine FeSO4 Aluminum hydroxide Sucralfate Kayexalate
Drugs that ↑ thyroid binding globulin and bind T4/T3:
Pregnancy
Estrogen
Amiodarone and thyroid status:
Structurally resembles TH, can make hypo or hyperthyroid
Lithium and thyroid status:
Actively concentrates in thyroid gland and can inhibit TH synthesis → hypothyroid
Reglan and thyroid status:
↑ TSH production/release
Natural forms of corticosteroids:
Cortisol, cortisone, aldosterone
Synthetic forms of corticosteroids:
Prednisolone, prednisone, methylprednisone, dexamethasone
Mineralocorticoid effects:
AKA aldosterone
Reabsorption of Na+ and excretion of K+ in distal tubule
Glucocorticoid effects:
AKA cortisol
Antiinflammatory
Augmentation of sustained SNS activity during periods of emotional or physical stress
MoA of corticosteroids:
Enter cells, bind to steroid receptors in cytoplasm, enter nucleus, influence protein synthesis (mostly metabolic/inflammatory)
Mineralocorticoid receptors found:
Organs of excretion
Colon, glands, kidney, hippocampus
Glucocorticoid receptors found:
Everywhere
Metabolic effects of corticosteroids:
↑ BG, amino acids, TGs
Inflammation effects of corticosteroids:
Inhibition of phospholipase A2 → decreased arachidonic acid formation
Endogenous cortisol secretion:
By circadian pattern
Avg 10-20 mg/day
50-150 mg/day under extreme stress
PK of cortisol:
90% protein bound
70% metabolized in liver
E1/2t: 1.5 - 3 hrs
Methylprednisolone highlights:
Intensely glucocorticoid, IV/intraarticular, used as replacement for insufficiency
Betamethasone highlights:
PO/IV; lacks mineralocorticoid effects
Dexamethasone highlights:
PO/IV; good for cerebral edema, antiemesis, airway edema
Triamcinolone highlights:
PO, IV, intraarticular; LBP epidural injections
Prednisolone highlights:
PO/IV; mineralocorticoid and glucocorticoid effects
Indications for corticosteroids:
Replacement tx Antiinflammatory Adrenal insufficiency Allergy/asthma Antiemetic
Chronic adrenal insufficiency dosing:
Cortisone PO
25mg Q AM
12.5 MG Q PM
Usually add fludrocortisone
Acute adrenal insufficiency dosing:
Cortisol
100mg Q8hr
Timeline for corticosteroid effects in acute allergy/asthma:
1 hr to β-agonist enhancement (aka makes epi work better)
4-6 hrs to antiinflammatory effects
Considerations for chronic allergy/asthma management with corticosteroids:
80-90% MDI dose swallowed, can lead to dysphonia
Generally no HPA axis problems until daily doses > 1500mcg adult/400mcg peds
Best corticosteroid to use as antiemetic:
Dexamethasone 8-10mg IV; E1/2t is 3 hrs, antiemetic effect lasts up to 24
Corticosteroids for lumbar disc herniation:
Triamcinolone 25-50mg or methylprednisolone 40-80mg for epidural injection
HPA axis suppression for 1-3 months
Intra-op sequelae of HPA axis suppression:
CV collapse
Synthesis of glucagon:
Produced by α cells of pancreas in response to hypoglycemia or ↑ plasma proteins
MoA of glucagon:
NON-ADRENERGIC enhancement of cAMP formation
Effects of glucagon:
↑ myocardial contractility/HR ↑ renal blood flow ↑ insulin secretion ↑ gluconeogenesis/glycogenolysis ↑ catecholamine release
↓ gastric motility
Relaxation of smooth muscle/vasodilator
Indications for glucagon:
↑ CO in β overblockade Biliary dilation Improves low CO, CHF Enhanced AV node conduction in dig toxicity Dx of pheo
Really only good for acute situations
Dosage of glucagon:
1-5mg IV or 5mcg/kg/min
A/E of glucagon:
Hyperglycemia (or paradoxical hypoglycemia)
Hypokalemia
N/V
Abrupt ↑ in HR in afib
MoA of octreotide/somatostatin:
Inhibit hormone release from GI tract/pancreas (GH, insulin, glucagon, VIP)
Indications for octreotide/somatostatin:
Carcinoid crisis
Hepatorenal syndrome
Esophageal varices
Half-time of somatostatin vs. octreotide:
Somatostatin: 3 min
Octreotide: 2.5 hours
ADH action at V2:
Collecting ducts in nephron - ↑ water permeability back into circulation
ADH action at V1:
Arterial smooth muscle vasoconstriction (takes large doses)
Half-time of vasopressin:
10-20 min
Indications for vasopressin:
DI
Esophageal varices (gets blood out of splanchnic circ)
Hemorrhagic/septic shock
ACLS
A/E of vasopressin:
↑ BP
Coronary vasoconstriction
GI hyperperistalsis
DDAVP vs. vasopressin:
DDAVP = vasopressin analogue with longer half-time (2.5 - 4.4 hrs), more selective for V2 vs. V1, better choice for DI
DDAVP effects on endothelial cells:
Stimulates secretion of vWF, tissue plasminogen activator, prostaglandins
Labor induction dose of oxytocin:
1-2 mU/min, increase 15-30 min by 1-2 mU/min until contractions 2-3 min apart
Uterine atony dose of oxytocin:
Up to 40 mU/min
Anesthetic consideration for oxytocin:
Blunted compensatory responses can see hypotension with oxytocin
MoA of estrogen and progesterone:
Estrogen: prevents FSH release
Progesterone: prevents LH release
A/E of ovarian hormones:
Thromboembolism
MI/stroke risk
HTN risk
