Endocrine Flashcards
Wheezing (asthma symptoms) + diarrhea + facial flushing + mass lesion in appendix area: Diagnosis? Treatment?
Carcinoid syndrome
- -> ultimate treatment = surgery
- -> symptomatic treatment = Octreotide (long-acting somatostatin analog)
Most common adrenal medulla tumor in adults? kids?
adults–> pheochromocytoma (causes HTN)
kids–> neuroblastoma (does not cause HTN)
Aldosterone is secreted from?
zona glomerulosa of adrenal cortex
- -> “salt”
- -> stimulated by Renin-angiotensin
Cortisol (and some sex hormones) secreted from?
zona fasciculata of adrenal cortex
- -> “sugar”
- -> stimulated by ACTH, hypothalamic CRH
Androgens (sex hormones) are secreted from?
zona reticularis of adrenal cortex
- -> “sex”
- -> stimulated by ACTH, hypothalamic CRH
Catecholamines are secreted from?
chromaffin cells of adrenal medulla (neural crest derivative!)
–>stimulated by preganglionic sympathetic fibers
Adrenal gland drainage: Left adrenal? Right adrenal?
Left adrenal –> L adrenal vein –> L renal vein –> IVC
Right adrenal –> R adrenal vein –> IVC
(same as left and right gonadal veins!)
neurohypophysis (post pit) is derived from? adenohypophysis (ant pit)?
- neurohypophysis = neuroectoderm derivative
- adenohypophysis = surface ectoderm derivative (from Rathke’s pouch)!
Rathke’s pouch gives rise to?
Adenohypophysis (ant pit)!
–> Rathke’s pouch = oral ectoderm
hormones secreted from posterior pituitary?
- ADH
- Oxytocin
*made in hypothalamus, then shipped to post pituitary
hormones from anterior pituitary?
- which are acidophils?
- basophils?
“FLAT PiG”
- FSH
- LH
- ACTH
- TSH
- Prolactin
- GH
- Acidophils: GH, Prolactin
- Basophils = “B-FLAT” = FSH, LH, ACTH, TSH
alpha- vs beta-subunit of pituitary hormones:
- alpha = common to TSH, LH, FSH, hCG
- beta = determines hormone specificity; different in all of them!
Hormones produced by alpha, beta, and delta cells of Islets of Langerhans in pancreas?
alpha cells –> glucagon (peripheral)
beta cells –> insulin (central)
delta cells –> somatostatin (interspersed)
- note: somatostatin is also produced by delta cells in gastric mucosa and throughout gut
- insulin inhibits glucagon release by alpha cells!
Does insulin cross the placenta?
nope!
Effects on insulin release of:
- GH
- somatostatin
- Beta-agonists
- alpha-agonists
GH–>increase insulin
Somatostatin–>decreases insulin
Beta-agonists–>stimulate insulin
Alpha-agonists–>inhibit insulin
Cell types that don’t need insulin for glucose uptake?
“BRICK L”
- Brain
- RBCs
- Intestine
- Cornea
- Kidney
- Liver
GLUT-1
- RBCs
- Brain
*tissues with GLUT-1 receptors take up glucose regardless of insulin levels
GLUT-2
- beta islet cells
- liver
- kidney
- small intestine
GLUT-4
- Requires insulin to be activated!
- Adipose tissue
- Skeletal muscle
Anabolic effects of insulin (X6)
1) increases glucose transport into adipose and skeletal muscle
2) increases glycogen synthesis and storage
3) increases TG synthesis and storage
4) increases Na retention in kidneys
5) increases protein synthesis in muscles
6) increases cellular uptake of K and AAs
Glucagon:
- secreted by?
- secreted in response to?
- inhibited by?
- effects?
- secreted by alpha cells of islets of pancreas
- secreted in response to hypoglycemia
- inhibited by: insulin, hyperglycemia, somatostatin
- effects:
- ->glycogenolysis, gluconeogenesis
- ->lipolysis and ketone production
- ->increases glucose production/release so in effect also increases insulin release
Bromocriptin
dopamine agonist
–>inhibits prolactin secretion; so, can be used to treat prolactinomas
Drug types that stimulate prolactin secretion?
- Dopamine antagonists (most antipsychotics)
- Estrogens (OCPs, Pregnancy)
Why is a side effect of anti-psychotic drugs galactorrhea?
- anti-psychotics are dopamine antagonists
- dopamine inhibits prolactin; if decrease dopamine, then increase prolactin
- prolactin stimulate milk production!
Prolactin functions:
- stimulates milk production in breast
- inhibits GnRH –> so decreases LH and FSH –> so inhibits ovulation in females, spermatogenesis in males
Somatotropin = Growth Hormone:
- stimulated by?
- inhibited by?
- when is their increased secretion?
- released in pulses in response to GHRH from hypothalamus
- increased secretion during exercise and sleep
- secretion inhibited by glucose and somatostatin
17-alpha-hydroxylase deficiency:
- what’s increased/decreased?
- symptoms
- increased MCs (aldosterone)
- decreased GCs (cortisol) and androgens
- symptoms:
- ->Hypertension
- ->Hypokalemia
- –>XY: decreased DHT –> pseudohermaphroditism (looks female, but no internal reproductive structures b/c of mullerian inhibiting factor)
- ->XX: looks female, has normal internal sex organs, but lacks secondary sex characteristics)
phenotypic female who lacks internal reproductive structures; has HTN and hypokalemia
17-alpha-hydroxylase deficiency
–>XY pseudohermaphrodite, but decreased DHT; no internal organs b/c of MIF
phenotypic female with normal internal sex organs, but lacks secondary sex characteristics; has HTN and hypokalemia
-XX with 17-alpha-hydroxylase deficiency
21-hydroxylase deficiency:
- what’s increased/decreased?
- symptoms?
- increased androgens
- decreased MCs (aldosterone) and GCs (cortisol)
- symptoms:
- ->masculinization (female pseudohermaphrodite)
- ->hypOtension
- ->hyperkalemia
- ->increased renin activity
***this is the most common form of congenital adrenal hyperplasia
11-beta-hydroxylase deficiency:
- what’s increased/decreased?
- symptoms?
- increased: Androgens and 11-Deoxycorticosterone (not aldosterone though)
- decreased: GCs (cortisol) and Aldosterone
- symptoms:
- ->Hypertension (d/t 11-deoxycorticosterone)
- ->Masculinization
Finasteride
- inhibits 5-alpha-reductase
- ->so: decreased DHT
- ->used to treat male baldness! and BPH
Functions of Cortisol (X5):
“BBIIG”
1) Blood pressure maintenance (stimulates alpha-1 receptors on arterioles)
2) decreased Bone formation (side effect = osteoporosis)
3) anti-Inflammatory/Immunosuppressive
4) increases Insulin resistance (diabetogenic)
5) increases Gluconeogenesis, lipolysis, proteolysis
source of PTH?
-chief cells of parathyroid
PTH functions/effects (X4):
1) increases bone resorption–>increases Ca and P
2) increases kidney reabsorption of Ca (in distal convoluted tubule)
3) decreases kidney reabsorption of phosphate
4) increases vitamin D (calcitriol) production by stimulating kidney 1-alpha-hydroxylase
- **stimulates osteoclasts (and thus bone resorption) by increasing production of M-CSF and RANK-L in osteoblasts, which stimulates osteoclasts
- **low serum Phosphorous stimulates vitamin D conversion to active form –> vitamin D stimulates phosphate release from bone and increases phosphate reabsorption (though PTH causes decreased phosphate reabsorption)
what stimulates PTH secretion?
- decreased serum Ca
- decreased serum Mg
vitamin D3 vs D2?
D3–> from sun
D2–> from plants
*both are converted to 25-OH vitamin D in liver and to 1,25-(OH)2 vitamin D (active form) in kidney
Conversion of vitamin D to active form:
- enzyme?
- what stimulates enzyme?
- where does it happen?
1-alpha-hydroxylase
- PTH stimulates enzyme
- in kidney
functions of vitamin D (X2):
- increase dietary Ca and P absorption
- increase bone resorption of calcium and phosphate (increases osteoclasts)
why is their increases vitamin D and hypercalcemia in sarcoidosis?
-b/c granulomas –> macrophages generate vitamin D (active form)
Source of Calcitonin?
Parafollicular (C) cells of thyroid (neural crest derivative!)
Medullary thyroid carcinoma:
abnormal growth of C-cells (doesn’t really affect Calcium metabolism though; despite that Calcitonin is released from C cells)
hormones that use cAMP signaling pathways:
“FLAT CHAMP + GCG” (all the ant pit hormones, except prolactin and GH)
- FSH
- LH
- ACTH
- TSH
- CRH
- hCG
- ADH (V2 receptor)
- MSH (melanocyte stimulating hormone)
- PTH
- GHRH
- Calcitonin
- Glucagon
hormones that use cGMP signaling pathway:
- Vasodilators:
- ANP
- NO
hormones that use IP3 signaling pathway:
“GOAT + HAG” (post pit hormones!)
- GnRH
- Oxytocin
- ADH (V1 receptor)
- TRH
- Histamine (H1)
- Angiotensin II
- Gastrin
hormones that use cytosolic steroid receptors:
“VET CAP” (adrenal hormones + vitamin D!)
- Vitamin D
- Estrogen
- Testosterone
- Cortisol
- Aldosterone
- Progesterone
hormones that use nuclear steroid receptors:
-Thyroid hormones –> T3, T4
hormones that use intrinsic tyrosine kinase (MAP kinase pathway) signaling pathway:
- growth factors:
- insulin
- IGF-1
- FGF (fibroblast growth factor)
- PDGF (platelet-derived growth factor)
hormones that use receptor-associated tyrosine kinase (JAK/STAT pathway) signaling pathway:
- Prolactin
- GH
- cytokines (IL-2, IL-6, IL-8…)
Which is the active form of hormones: bound or unbound?
-unbound –> free hormone = active hormone
SHBG (sex hormone-binding globulin):
- what happens if increased in men?
- if decreased in women?
- during pregnancy?
- if increased in men–> decreased free testosterone –> gynecomastia
- if decreased in women–> increased free testosterone–> hirsutism
*have increased SHBG levels during pregnancy
Source of T3 vs T4?
T4 is from follicles of thyroid
T3 is formed from T4 conversion in blood
4 main functions of T3:
- 4 B’s:
1) Brain maturation (CNS maturation)
2) Bone growth (synergistic with GH)
3) Beta-adrenergic effects (Beta-1 receptors in heart–> increased CO, HR, SV, contractility)
4) increased BMR (via Na/K-ATPase activity –> so increased O2 consumption, RR, body temp)
*Also: increased glycogenolysis, gluconeogenesis, lipolysis
TBG:
- what is it?
- how is it affected in hepatic failure? pregnancy? OCP use?
thyroxine-binding globulin –> binds most T3/T4 in blood
- ->only free hormone is active
- reduced in hepatic failure
- increased in pregnancy and OCP use (increased estrogen–>increased TBG)
TSI
thyroid-stimulating-immunoglobulin
–>acts like TSH to stimulate follicular cells in Grave’s disease
anti-thyroid peroxidase antibodies
Hashimoto’s
Wolff-Chaikoff effect:
transient decrease in T3/T4 due to ingestion of iodide, which inhibits thyroid peroxidase, and therefore organification
–> hypothyroidism symptoms
Cushing’s syndrome
increased cortisol; causes vary
1 cause of Cushing’s syndrome?
Exogenous/Iatrogenic steroids–> increased cortisol–> decreased ACTH and decreased CRH
Endogenous causes of Cushing’s syndrome: (and ACTH levels)
1) Cushing’s disease –> pituitary adenoma –> increased ACTH secretion
2) Ectopic ACTH: nonpituitary tissue making ACTH (have very high ACTH; ie from Small cell lung cancer, bronchial carcinoids)
3) Adrenal: adenoma, carcinoma, nodular adrenal hyperplasia –> decreased ACTH (very low/undetectable)
Dexamethasone test
test to determine cause of Cushing’s syndrome
Which cause of Cushing’s syndrome is affected by Dexamethasone?
ACTH-Pituitary tumor –> get decreased cortisol levels when give a high dose of dexamethasone
Causes of primary hyperaldosteronism?
- results?
- treatment?
Caused by adrenal hyperplasia or aldosterone-secreting adrenal adenoma (Conn’s syndrome)
- Effects:
- hypertension
- hypokalemia
- LOW plasma renin
- metabolic alkalosis
- Trtmnt:
- surgery to remove tumor
- K-sparing diuretic –> aldosterone antagonist
Causes of secondary hyperaldosteronism?
-results?
- -> have an overactive RAAS system, because the kidney “thinks” that there’s a low intravascular volume
- Causes:
- renal artery stenosis
- chronic renal failure
- CHF
- Cirrhosis
- Nephrotic syndrome
- -> cirrhosis and nephrotic syndrome are low protein states –> so, lose lots of fluid in urine –> so, RAAS kicks in to increase BP
- Effects:
- HIGH plasma renin and high aldosterone
primary vs secondary vs tertiary adrenal insufficiency:
- primary –> level of adrenal gland
- secondary –> level of pituitary (ie no ACTH)
- tertiary –> d/t abrupt withdrawal of GCs (still have aldosterone, so no hyperkalemia)
- **primary–> have hyperpigmentation and hyperkalemia
- **secondary –> no hyperpigmentation, no hyperkalemia (b/c still produce aldosterone, just no cortisol)
Acute primary adrenal insufficiency:
Caused by Waterhouse-Friderichsen syndrome –> adrenal hemorrhage associated with N. meningitidis septicemia, DIC, petechial rash, endotoxic shock
increased urinary VMA
VMA= breakdown product of norepinephrine
- increased in pheochromocytoma
- ->also have increased plasma catecholamines
Symptoms of pheochromocytoma:
- 6 P’s:
- Pressure –> elevated BP
- Pain –> headache
- Perspiration
- Palpitatons –> tachycardia
- Pallor
- Panic attacks
***symptoms occur in “spells” - relapse and remit
Treatment for Pheochromocytoma?
- Alpha-blockers, especially Phenoxybenzamine = nonselective, irreversible alpha-blocker
- then: do surgery to remove tumor
elevated urinary HVA (homovanillic acid)
Neuroblastoma (=most common adrenal medulla tumor in kids)
–>HVA=breakdown product of domapine
T3 uptake in hypothyroidism? hyperthyroidism?
- decreased in hypothyroidism
- increased in hyperthyroidism
antimicrosomal, anti-thyroglobulin antibodies
Hashimoto’s
Hurthle cells
enlarged epithelial cells with excessive eosinophilic granular cytoplasm; found in Hashimoto’s
What cancer is increased risk in Hashimoto’s?
non-Hodgkin’s lymphoma
pot-bellied, pale, puffy-faced child with protruding umbilicus and protuberant tongue:
Cretinism –> d/t severe fetal hypothyroism
- endemic in areas lacking dietary iodine
- sporadic d/t defect in T4 formation or developmental failure in thyroid formation
Very tender thyroid, following a flulike illness; self-limited hypothyroidism
Subacute thyroiditis = de Quervain’s
–>have increased ESR, jaw pain, tender thyroid… may look hyperthyroid early in course
rock-hard, painless goiter
Riedel’s thyroiditis –> type of hypothyroidism
- thyroid replaced by fibrous tissue
- histology: fibrosis, macrophages, eosinophils infiltrate in thyroid
pretibial myxedema
Grave’s disease
Thyroid storm:
- what is it?
- treatment?
- stress-induced catecholamine surge leading to death by arrhythmia
- -> complication of Grave’s and other hyperthyroid syndromes
- ->treat with Beta-blockers (Propranolol)
Focal patches of hyperfunctioning follicular thyroid cells; cells work independently of TSH d/t a mutation in TSH receptor
–>elevated T3 and T4 = hyperthyroid
Toxic multonodular goiter
Jod-Basedow phenomenon
Classic example: pt receives radio-contrast dye with iodine and becomes hyperthyroid from it
–>thyrotoxicosis if a pt with iodine defiency goiter is made iodine replete
Papillary thyroid carcinoma
- most common and excellent prognosis
- Orphan Annie nuclei = “ground glass” nuclei
- psammoma bodies (whorled, look like a rose!)
- increased risk with childhood radiation
thyroid cancer with psammoma bodies and orphan annie nuclei?
Papillary thyroid carcinoma
thryoid cancer associated with childhood irradiaton?
Papillary thryoid carcinoma
Medullary thryoid carcinoma:
- from parafollicular “C” cells of thryoid
- produces calcitonin
- assoc with MEN 2A and 2B
- sheets of cells in ayloid stroma
Renal stones + Bone loss + GI upset/ulcers + psychiatric disorders
Primary hyperparathyroidism
- -> elevated PTH d/t adenoma, usually
- Hypercalcemia
- Hypophosphatemia
- elevated PTH
- elevated ALP
- elevated cAMP in urine
- may be asymptomatic or have weakness and constipation
*initiating problem in primary hyper-PTH = elevated PTH
bone pain and bone spaces filled with brown fibrous tissue
osteitis fibrosa cystica
Cause of and Findings in Secondary Hyperparathyroidism:
- usually d/t chronic renal disease. Why?
- ->renal disease –> can’t convert vitamin D to active form –> decreased Ca absorption in gut –> increased PTH –> increased bone resorption –> increased phosphate and increased ALP from bone resorption –> but, still have hyperphosphatemia b/c kidney failure so can’t excrete it!
- Findings:
- Hypocalcemia
- elevated PTH
- Hyperphosphatemia
- elevated ALP
*initiating problem here is decreased Ca
tap facial nerve –> get contraction of facial muscles
Chovstek’s sign –> sign of hypocalcemia
-get with hypoparathyroidism
BP cuff causes carpal spasm
Trousseau’s sign –> sign of hypocalcemia; see with hypoparathyroidism
Hypocalcemia (pee out calcium) + shortened 4th/5th digits + short stature
Pseudohypoparathyroidism = Albright’s hereditary osteodystrophy
- ->autosomal dominant
- ->kidney is unresponsive to PTH at renal tubule; so have high PTH, but pee out calcium (clinically looks like PTH is low)
Cabergoline
Dopamine agonist
-can be used to treat pituitary adenomas (Bromocriptine is also a dopamine agonist; can be used to treat pit adenoma)
Octreotide
=Somatostatin
- ->used to treat acromegaly (following pit adenoma resection) b/c inhibits GH
- ->also can treat carcinoid, gastrinoma, glucagonoma
How to dx acromegaly?
elevated serum IGF-1
-also failure to suppress serum GH following oral glucose tolerance test
Central vs Nephrogenic DI
Central –> lack ADH
Nephrogenic –>lack renal response to ADH
Demeclocycline
ADH antagonist –> can lead to nephrogenic DI
-Lithium can also cause nephrogenic DI!
Desmopressin
=synthetic ADH
–> can distinguish b/w central and nephrogenic DI
Treatment for nephrogenic DI:
- Hydrochlorothiazide –> concentrates urine
- Indomethacin –> decreased RBF
- Amiloride –> for lithium-induced nephrogenic DI (it’s a K-sparing diuretic)
Demeclocycline
treatment for SIADH
Causes of SIADH:
1) Ectopic ADH (ie small cell lung cancer)
2) CNS disorders/head trauma
3) Pulmonary disease
4) Drugs –> ie cyclophosphamide
***SIADH = Syndrome of Inappropriate ADH secretion
Empty sella syndrome
unexplained atrophy of pituitary –> get hypopituitarism
–>common in obese women
Fatigue + failure to lactate post-partum?
- ->Sheehan’s syndrome = postpartum hypopituitarism
- ->Cause: increased size of ant pituitary during pregnancy, without increased blood supply; so, have increased risk of pituitary infarction. If have lots of bleeding/hemorrhage during delivery or post-partum, then get hypoperfusion/hypotension to pituitary –> ischemic infarction of pituitary –> signs of hypopituitarism
Causes of small and large vessel disease in chronic diabetes:
-NON-enzymatic glycosylation –> glucose gets tacked on to thins
Kimmelstein-Wilson nodules
–>diabetes
What causes cataracts in chronic diabetes?
-sorbitol accumulation leads to osmotic damage
What causes retinopathy and glaucoma in chronic diabetes?
-small vessel disease d/t nonenzymatic glycosylation
HLA’s associated with DM I?
- HLA-D3
- HLA-D4
Histology of DM I vs DM II?
DM I –> Islet leukocytic infiltrate (leukocytes!)
DM II –> Islet amyloid deposit (amyloid!)
Kussmaul respirations
rapid/deep breathing; DKA (try to exhale CO2 to fix acidosis)
labs in DKA
- hyperglycemia
- elevated H+ = decreased pH
- decreased HCO3 (anion gap met acidosis)
- ketonemia
- Hyperkalemia (though depleted intracellar K+; decreased insulin shifts K+ outside cells)
- Hyponatremia
- Leukoctyosis
Treatment of DKA?
- IV fluids
- IV insulin
- K+ (to replete intracellular stores)
- glucose if necessary to prevent hypoglycemia
most common tumor of appendix?
-Carcinoid tumor!
recurrent diarrhea + cutaneous flushing + asthmatic wheezing + right-sided valvular disease + elevated 5-HIAA in urine?
Carcinoid syndrome (5-HIAA = serotonin metabolite)
Treatment for serotonin syndrome?
Octreotide = somatostatin analogue
When may carcinoid syndrome be subclinical?
if limited to GI tract - only
–> because serotonin undergoes first-pass metabolism in liver
Rule of 1/3rds in Carcinoid syndrome:
- 1/3 metastasize
- 1/3 present with 2nd malignancy
- 1/3 multiple
Carcinoid tumors are derived from what kind of cells?
-derived from neuroendocrine cells of GI tract
Zollinger-Ellison syndrome
tumor in pancreas or duodenum that secretes gastrin –> so, get hypersecretion of acid in stomach and rugal thickening
- get recurrent ulcers!
- may be assoc with MEN I (pancreatic endocrine tumors…)
Which thyroid cancer is associated with amiloid deposition?
medullary thyroid carcinoma (MEN 2A and 2B)
Clinical uses for Insulin:
- Type 1 DM
- Type 2 DM, once necessary
- life-threatening hyperkalemia (b/c insulin shifts potassium INTO cells, so can cause HYPOkalemia)
- stress-induced hyperglycemia
Sulfonylureas mechanism of action:
Sulfonylureas:
- 1st gen:
- Tolbutamide
- Chlorpropamide
- 2nd gen:
- Glyburide
- Glimepiride
- Glipizide
- Mechanism:
- Close K+ channels in Beta-cells of pancreas (which is what glucose usually does: glucose–>increased ATP–>closes K+ channels–>depolarizes cell allowing for Calcium influx into cell–>release of insulin into blood)
- ->SO: stimulates release of endogenous insulin (so, must have some functional Beta cells left to work; so, can only be used in DMII, not in DMI)
Glyburide
2nd generation sulfonylurea
–>stimulates release of endogenous insulin
Clinical use of Glyburide?
- ->Diabetes Type II
- stimulates endogenous release of insulin from Beta cells, so must still have some functional islet cells; therefore, it’s useless in type I
Side effects of Glyburide?
Hypoglycemia
Side effects of 1st generation sulfonylureas?
1st gen sulfonylureas = Tolbutamide, Chlorpropramide
- ->Disulfiram-like effects (so, not used much)
- Remember: Disulfiram = Antabuse –> get hangover-like effects
Side effects of 2nd generation sulfonylureas?
2nd gen sulfonylureas = Glyburide, Glimepiride, Glipizide (all the “G—ides”!)
Hypoglycemia
1st line drug for DM II?
Metformin
Metformin mechanism?
unknown exactly; but:
- decreases gluconeogenesis in liver (so, decreased glucose!)
- increased glycolysis (use that glucose up!)
- increase peripheral glucose uptake by whatever insulin that is (so, increased insulin sensitivity)
- **so, overall: decreases glucose in blood!
- **can use in pts without any islet cell function
Mechanism of Exogenous Insulin?
Binds insulin receptor (Tyrosine Kinase activity)
Which diabetes drug is contraindicated in pts with renal failure?
Metformin
–>b/c if renal failure: get reduced clearance of metformin and lactate (which builds up d/t the inhibition of gluconeogenesis, b/c lactate is a substrate for gluconeogenesis); so, increased risk of lactic acidosis
Worst side effect of Metformin?
Lactic acidosis (rare; but its most grave side effect) --> this is why Metformin is contraindicated in pts with kidney failure; b/c decreased clearance of metformin and lactate, and thus increased risk of lactic acidosis
Biguanides
=diabetes drug class –> only drug in it is Metformin!
Glitazones = Thiazolidinediones:
-mechanism?
- Includes: Pioglitazone, Rosiglitazone
- Mechanism:
- increased insulin sensitivity in peripheral tissues; by binding to PPAR-gamma-nuclear transcription regulator (in adipose tissue and skeletal muscle)
4 main side effects of Glitazones? (KNOW!)
1) Weight gain
2) Edema
3) Hepatotoxicity
4) Heart failure (may exacerbate CHF)
Acarbose:
- class?
- mechanism?
- side effects?
alpha-glucosidase inhibitor
(diabetes drug)
–>not used much
- mechanism:
- ->inhibits intestinal brush border alpha-glucosidases –> so, get delayed sugar hydrolysis and glucose absorption –> thus, decreased postprandial hyperglycemia
- side effects:
- GI disturbances
Miglitol:
- class
- mechanism
- side effects
- alpha-glucosidase inhibitor (diabetes drug) (same class as Acarbose)
- ->not used much
- mechanism:
- ->inhibits intestinal brush border alpha-glucosidases –> so, get delayed sugar hydrolysis and glucose absorption –> thus, decreased postprandial hyperglycemia
- side effects:
- GI disturbances
Pramlintide:
- class of drug
- mechanism
- side effects?
- Mimetic (diabetes drug)
- mechanism: decreases glucagon (hormone secreted by pancreas, raises blood glucose; opposite of insulin)
- side effects: hypoglycemia, nausea, diarrhea
Exenatide:
- class of drug?
- source of this drug?
- mechanism?
- side effects?
GLP-1 analog (Glucagon-Like Peptide)
- mechanism: increase insulin, decrease glucagon release
- source = Gila monster saliva! (sort of; it’s a synthetic version of a protein derived from Gila monster)
- Side effects:
- Pancreatitis
- Nausea
- Vomiting
Which diabetes drugs may cause Hypoglycemia?
- Insulin
- Pramlintide (mimetic agent)
- 2nd generation sulfonylureas (glyburide, glimepiride, glipizide)
Which diabetes drug may cause pancreatitis?
Exenatide (GLP-1 analog)
Which diabetes drugs may cause disulfiram-like reactions?
1st gen sulfonylureas (tolbutamide, chlorpropamide)
Which diabetes drug may cause lactic acidosis?
–>Metformin (therefore contraindicated in renal failure pts)
Which diabetes drug may exacerbate CHF?
Glitazones
Which diabetes drugs may cause hepatotoxicity?
Glitazones
Which diabetes drugs may cause weight gain and edema?
Glitazones
Propylthiouracil:
- clinical use?
- mechanism?
- Toxicities?
Treatment for Hyperthyroidism (can be given to pregnant women with hyperthyroidism too)
- Mechanism:
- Blocks Peroxidase, so inhibits organification of iodide and coupling of thyroid hormone
- Also: blocks 5’-deiodinase –> decreased peripheral conversion of T4–>T3
- **Overall: decreased Thyroid hormone
- Toxicities:
- Agruanulocytosis (rare)
- Aplastic anemia
- skin rash
- Hepatotoxicity
5’-Deiodinase
Enzyme that converts T4 to T3 in peripheral tissue
*Propylthiouracil inhibits 5’-deiodinase (so, inhibits peripheral conversion to T3) and also inhibits peroxidase
Methimazole:
- clinical use?
- mechanism?
- toxicities?
- treatment for hyperthyroidism
- Mechanism:
- blocks peroxidase –> so, inhibits organification of iodide and coupling of thyroid hormone synthesis
- toxicities:
- agranulocytosis (rare)
- aplastic anemia
- skin rash
- may be teratogenic (don’t give to pregnant women)
Levothyroxine:
- clinical use?
- mechanism?
- treatment for Hypothyroidism and Myxedema
* Mechanism = Thyroxine (T4) replacement
Triiodothyronine:
- clinical use?
- mechanism?
- treatment for hypothyroidism and myxedema
* mechanism = thryoxine (T4) replacement
Clinical uses of GH?
- GH deficiency
- Turner syndrome (just to promote growth to full adult height)
Clinical uses of Octreotide (Somatostatin)
- Acromegaly
- Gastrinoma
- Carcinoid syndrome
- Glucagonoma
Clinical uses of Oxytocin?
- controls uterine hemorrhage
- stimulates labor and uterine contractions
- milk let-down
clinical use of Desmopressin/ADH?
-Central DI
Domeclocyline:
- mechanism?
- clinical use?
- Toxicities?
- ADH antagonist (it’s a member of the Tetracycline family)
- Treatment of SIADH (syndrome of inappropraite ADH secretion)
*Toxicites:
-Nephrogenic DI
-photosensitivity
-abnormalities of bone and teeth (like tetracycline!)
-
Triamcinolone (what class of drug is it?)
a glucocorticoid
Beclomethasone (what class of drug is it?)
a glucocorticoid
Glucorticoids:
- mechanism?
- clinical uses?
- toxicities?
*Prednisone, Hydrocortisone, Triamcinolone, Dexamethasone, Beclomethasone
- Mechanism:
- decrease production of leukotrienes and prostaglandins, by inhibiting phospholipase A2 and expression of COX-2
- Uses:
- anti-inflmmatory
- Addison’s disease (chronic primary adrenal insufficiency: defiency of cortisol and aldosterone)
- immune suppression
- asthma
- inject directly into keloids
- Toxicities:
- iatrogenic Cushing’s syndrome
- tertiary adrenal insufficiency (when drug is stopped after chronic use)
- also: psychosis, insomnia, gluacoma, acne
