Endocrine management Flashcards
Insulin actions
- hormone that catalyzes glucose uptake
- regulates amino acid uptake and protein synthesis
- regulates lipid storage
Alpha glucosidases
-enzyme secreted by the intestine that breaks bond of glucosyl units, like sucrose into glucose
Gluconeogenesis
- synthesis of glucose in the liver from lactate, amino acids, and glycerol
- stimulated during fasting, prolonged exercise, high protein diet, and stress
Insulin stimulation
-released from beta cells, stimulated by meals, high levels of circulating glucagons and amino acids, and CNS stimulation
Patho of Type I DM
- often caused by genetic predisposition, activated by environmental insult
- aggressive antibodies develop against beta cells, eventually killing all beta cells
- pancreas fails to release insulin
- absolute/complete absence of insulin
- body burns fat instead for fuel => ketones and acidosis
Patho of Type II DM
- Hyperglycemia caused by peripheral tissue receptor insensitivity OR decreased beta cell production of insulin
- circulating insulin sufficient to prevent acidosis, but inadequate to prevent hyperglycemia
Patho of Obese Type II DM
- periph. insulin receptors not working properly d/t fat deposits =>intracellular glucose movement does not occur
- beta cell compensate by producing more insulin (hyper insulinemia with normoglycemia for years)
- beta cells burn out from overwork
- body cells perceive hypoglycemia and ramp up liver gluconeogenesis
Non-obese type II DM
- failure of beta cell to respond to insulinogenic stim-
- low normal body weight
- does not respond as well to typical Rx
MODY
Mature onset diabetes of the young
- rare monogenetic disorder
- gene mutation causes decreased beta cell response to glucose
Role of incretin
- intestinal secretion of insulin as GLP-1 or GIP
- GLP-1 is broken down quickly by DPP4
Effects of GLP-1
- slows gastric emptying
- suppresses glucagon secretion
- enhances insulin secretion
- enhances beta cell proliferation and decreases apoptosis
Insulinogenic drugs
Sulfonylureas and meglitinides
- stimulate insulin release by binding to beta cell receptors
- not good very early (beta cells hyperfunctioning) or very late (beta cell burn out) in diagnosis
- risk of hypoglycemia
Sulfonylureas
- insulinogenic drugs for T2DM
- highly effective if beta cells still functioning
- Active metabolite- consider renal function (decreased excretion may cause hypoglycemia)
Meglitinides
- insulinogenic drugs for T2DM
- repaglinide, nateglinide
- insulin release stimulated in glucose-sensitive manner
- fast-acting, rapid metabolism
- good for prandial surges (given before meals)
Non-insulinogenic drugs
* Do not stimulate insulin release from beta cells Metformin Thiazolidinediones Incretin mimetics/DPP4 inhibitors Pramlintide Sodium Glucose Cotransporters Alpha glucosidase inhibitors
Drug of choice for Obese Type 2 DM
Metformin
Metformin
- type 2 DM
- suppresses hepatic glucogenesis
- reduces fasting plasma insulin
- improves insulin sensitivity
What patient should not take Metformin?
- decreased renal function (causes lactic acidosis)
- intolerance of adverse effects (GI intolerance)
Adverse effects of Metformin
GI intolerance (bowel incontinence) Lactic acidosis (from renal impairment)
Thiazolidinediones
- Type 2 DM
- Pioglitazone (Actose), Rosiglitazone (Avandia)
- reduces insulin resistance and improves insulin receptor sensitivity
- reduces glucose, insulin, and FFA
- useful as secondary agent with Metformin or if patient not tolerating metformin
Safety concerns for Thiazolidinediones
- hepatic toxicity
- cardiac disease and CHF
- Actose linked to bladder cancer
Incretin Mimetics
- Type 2 DM
- synthetic GLP-1
- reduces fasting and postprandial glucose concentrations
- stimulates insulin release and inhibits glucagon release
- slows gastric emptying- appetite suppression and wt loss
- Liraglutide (Victoza), Exenatide (Byetta)
Adverse effects of Incretin Mimetics and DPP4 inhibitors
- Nausea (40% drop out rate)
- endocrine malignancies
- pancreatic inflammation
- gastroparesis
contraindications for incretin mimetics
- hx or risk of endocrine cancer
- pancreatitis
DPP4 inhibitors
- Type 2 DM
- blocks DPP4 enzyme from degrading GLP-1 => enhanced GLP-1
- patient must be capable of producing own GLP-1 and have functioning beta cells
- Sitagliptin (Januva), Saxagliptin (Onglyza), Linagliptin (Tradjenta)
Pramlintide
- Type 1 and 2 DM
- amylin analogue
- modulates gastric emptying, prevents post-prandial glucagon
- produces satiety =>decreased intake and wt loss
Adverse effects of Pramlintide
- Nausea (most frequent and severe)
- can cause severe hypoglycemia
Sodium Glucose Cotransporters
- Type 2 DM
- Canagliflozin, Dapaglifozin, Empagliflozin
- facilitates renal exretion of sodium and glucose via renal tubules
- acts on postprandial glucose
Adverse effects of Sodium Glucose Cotransporters
d/t glucose in urine
- urinary sx
- genital fungal infection
Alpha Glucosidase Inhibitors
- Type 2 DM
- prevent hydrolysis of disaccharides in gut
- essential makes patients sucrose intolerant
- Acarbose and miglitol
- used as additive therapy
- GI adverse effects
Hypothyroidism
- most common thyroid disorder
- women > men
- primary (Hashimotos automimmune) or secondary (to drug therapy or therapies for hyperthyroidism)
- body systems/metabolism slows down
Hypothyroidism treatment
Replacement hormones T3 or T4
- T3 (liothyronine) - very metabolically active, so more difficult to manage
- T4 (levothyroxine)- less metobolically active, so used more often
Safety issue with thyroid hormone replacement
potential for overmedication and toxicity
Patient education for thyroid hormone replacement
- take on empty stomach- easily binds to other substances in the gut
- will need to monitor TSH level every 8-12 wks
- elderly may need lower dose (slow metabolism) and children may need higher dose (hypermetabolic)
Thyrotoxicosis
condition of thyroid hormone excess
-d/t hyperfunctioning thyroid gland or inflammation of gland resulting in large release of hormone
Hyperthyroidism
hyperfunctioning thyroid gland => excess hormone production
Grave’s disease
- most common cause of thyrotoxicosis
- autoimmune- thyroid receptor antibodies (TRAb) develop
- severe, will need definitive treatment
Grave’s disease treatment
- for symptoms- noncardioselective beta blocker (Propranol)
- cure- radioactive iodine (RAI) as treatment of choice OR surgery (pregnant women)
- can pretreat with antithyroid drugs (ATDs)- for cardiovascular disease and elderly pts
Autonomous Thyrotoxicosis
- single or multiple nodules on thyroid gland
- slower disease
- Symptoms- primarily cardiovascular, also weakness, muscle wasting, and emotional lability
Treatment for Autonomous Thyrotoxicosis
- observation if clinically euthyroid
- surgical removal of nodule if symptomatic
TMNG
- Toxic multinodular goiter
- many nodules on thyroid gland
- RAI treatment of choice after pretreatment with ATDs
- requires higher dose of iodine and use low iodine diet prior to treatment
Subacute Thyroiditis
- AKA de Quervain thyroiditis
- often virus causes inflammation =>gland dumps a bunch of hormone at once
- s/s last 4-10 weeks and then patient returns to normal
- self-limiting, may need propranolol for symptoms
- no need for curative therapies or ATDs
Beta blockers for hyperthyroidism
- Propranolol and atenolol are drugs of choice
- block CV and SNS symptoms
- no glandular changes
Iodides for hyperthyroidism
- Lugol’s solution (and others)
- inhibit organification and proteolysis (shut down thyroid gland function
- inhibit peripheral deiodination of T4
- works quickly (24 hrs), useful in toxic patients
- also augments RAI
- can use for several months
Antithyroid agents
- Propylthiouracil (PTU) and Methimazole (Tapazle)
- inhibit organification, coupling, and proteolysis
- not drugs of choice
- side effects- agranulocytosis, rashes, dyspepsia
Radioactive iodine (RAI)
- curative treatment for hyperthyroidism
- avoid close contact x 11 days
- avoid pregnancy x 6 mnths
- side effects- nausea, sore throat, edema of salivary glands
Aldosterone
- major mineralocorticoid
- reabsorption of Na in kidney => Na and H2O retention
Cortisol
- major glucocorticoid
- utilization of fuel (fats, carbs, proteins)
- suppression of inflammation
- vasoconstriction
Androgens
- sex hormones
- precursors of testosterone
What is the focus of adrenal pharmacology
-replacing deficient hormones
Fludrocotrisone (Florinef)
- replaces aldosterone => salt retention
- very potent- watch for s/s of na/water retention
s/s of sodium and water retention
HTN, rales, edema, bounding pulse, electrolyte abn (hypernatremia, hyperkalemia)
Hydrocortisone (Prednisone)
- replaces cortisol
- concern for toxicity- HTN, hyperglycemia, lack of inflammation (poor healing)
What group of women may benefit from hormone replacement therapy
Younger, perimenopausal women with no history of CVD
What group of women may be harmed by hormone replacement therapy
- Older, post-menopausal women with CVD history
- women with high risk of cancer (esp breast)
Benefits of hormone replacement therapy
- stabilizes fibrinogen
- elevates HDL and increases LDL uptake
- decreases cardiac workload while increasing contractility
- reduces plasma endothelin levels
- moderates vascular smooth muscle response to catecholamines
- improves osteoblast/decreases osteoclastic
- decreases vaginal dryness
- decreases skin wrinkling
Contraindications to H(R)T
breast neoplasms
liver disease
clotting abnormalities
vaginal bleeding post-menopause
What non-hormonal agents are available for vasomotor symptoms in menopause
Brisdelle (paroxitine with another name)
Venlafaxine (Effexor)
-less effective than hormones
Drug of choice for osteoporosis
Bisphosphonates
Drugs used for osteoporosis
- Bisphosphonates
- SERMS- raloxifene (Evista)
- Calcitonin
