Endocrine System Flashcards
thyroid and parathyroid glands
TH
thyroglobulin
PTH
Pancreas
exocrine: trypinogen, chymotrypsin, amylase, lipase
endocrine: insulin, glucagon
adrenal
- cortisol
- aldosterone
- estrogens
- androgens
bone formation
PTH: calcium, phosphorous
growth formation
estrogens, androgens: testosterone
-growth hormone releasing hormone-GH (somatropin)
metabolic rate control
TSH
TH
CHO metabolism
insulin
glucagon
blood pressure control
cortisol
aldosterone
ADH
bisphosphanates
- used for osteoporosis and Paget’s disease
- alendronate (fosomax), etidronate (Didronell), pamidronate (Aredia), risedronate (Actonel), tiludronate (Skelid)
- alendronate, risedronate, ibendronate are used mostly for prevention
- rational drug selection: high risk: white, Asian, hx of eating disorders
- correct preexisting vit. D deficiency, hypocalcemia b/4 starting bisphonates
pharmacodynamics of bisphosphanates
-inhibits osteoclastic activity and bone resorption thus increases bone density
-bone density mass increases rapidly in first year and plateau’s after 2-3 yrs
ADRs: diarrhea, constipation, n/v, hypocalcemia, hypophosphatemia, dyspenia, esophageal ulcers, arthragia, myalgia, HA, rash, afib
-pathologic fx for tx >3 months
-osteonecrosis (jaw)
-muscular skeletal pain
-caution with patients with renal impairment, hrt failure, liver dz, active GI problems
-drug and food interactions: ranitidine doubles alendronate bioavailability, calcium supplements, antacids
pharmacokinetics of bisphonates
- must be taken with 8 oz of water and fasting
- pt. must remain upright for 30 minutes or one hour with ibandronate
- onset 3-6 wks peak 3-6 months
- half life ten years
- metabolism-none
- excretion: urine, feces (unabsorbed drug)
- most pregnancy category C except pamidronate category D
Human growth hormone
- stimulates growth and metabolism of every cell in body
- used for short stature men
pharmacodynamics of human growth horomone
- initial insulin-like effect
- simulates growth of linear bones, skeletal muscles and organs
- simulates erythropoietin
pharmacokinetic human growth hormone
IM and SQ well absorbed -bioavailability 75% SQ -metabolism: hepatic renal 90% excretion: renal ADRs: antibody development, hyperglycemia, edema, hypothyroidism, arthralgia, ha, dizziness, flu-like sx's
pancreatic enzymes
-used for cystic fibrosis and pancreatitis
-monitoring: CF-lifetime
pancreatitis-contraindicated during times of acute illness
hypersensitivity-may need products from vegetable sources
steatorrhea: needs monitoring
pharmacodynamics of pancreatic enzymes
- inactivated by pH values
- pancreatin (Ku-zyme) pancrealipase (Pancreas)
- subsititute for pancreatic enzymes
pharmacokinetic of pancreatic enzymes
-taken immediately before of with meal
-absorption: none, because it acts locally in GI tract
-excretion: feces
-pancrelipase made from pork, pancreatin is made from pork, cow, or vegetable source-not good for people with gout or renal impairment
-antacids decrease effectiveness, decreases absorption of oral iron
ADRs: skin irritation, rashes, GI: n/v, stomatitis, hyperuicosuria, hyperuricemia
pharmacodynamics of inulin
- total number of receptor sites can be decreased by obesity and long standing hyperglycemia
- binds at insulin receptor sites on cell membrane allowing glucose to enter cells
- acts on liver to increase storage of glucose as glycogen, decreases production of urea, catabolic activity and cAMP,
- promotes protein synthesis on muscle cells
- reduces circulation of free fatty acids and promotes storage of triglycerides in adipose tissue
types of inslin
rapid-acting: Lispro (Humalog), apart (Novolog), or glulisine (Apidra), onset about 5 minutes, peaks in one hour, duration 4-5 hours SQ
short-acting: humulin insulins, sometime used around mealtime; takes 30-45 minutes before eating, peaks in 3-4 hrs. duration 4-ten hours, can give IM off label use
intermediate-acting: NPH is mixed with protamine delaying absorption insulin looks cloudy and has to be mixed before its injected; onset half to hour peak 4 to ten duration twelve 24 hours
long-acting: glargine (Lantus), detemir (levemir) insulin onset 2-4 hours, duration 24 hours with little or no peak
ultra long lasting: Degludec, 42 hour duration
hypothalmic-pituitary system
- thyrotropin-releasing hormone creates TSH
- GnRh-leads to FSH, LH
- prolactin releasing hormone-prolactin
- oxytocin
- antidiuretic hormone (ADH)
etidronate (Didronel)
- bisphosphanate
- reduces both bone resorption and formation (coupled together)
- reduce vertebral fractures
pamidronate and risedronate (Aredia and Actonel)
- bisphosphonate
- inhibits resorption without inhibiting formation or mineralization
- pamidronate only available in parenteral form
- both reduce vertebral fractures
- risedronate reduces non-vertebral fractures
alendronate (Fosamax)
- bisphosphonate
- 100-500x more potent then other drugs
- highly selective inhibitor
- inhibits osteoclastic activities without interfering with osteoclast recruitment or attachment
- reduces both vertebral and nonvertebral fractures
tiludronate (Skelid)
- bisphosphonate
- inhibits osteclastic activity by interfering with osteoclasts attachment to bone surface and inhibiting osteclastic proton pump
- decreases vertebral fractures
zoledronic acid (Zometa)
- bisphosphonate
- inhibits osteoclast activities and induces apoptosis
- only IV
- reduces vertbral fractures
ibandronate (Boniva)
- bisphosphonate
- inhibits osteoclastic activity and reduces bone resorption
- reduces vertebral fractures
- can be given IV every 3 months if po untolerated or unwilling
monitoring on bisphosponate
- electrolytes-especially serum calcium
- alkaline phosphatase-increasing positive for paget’s dz
somatrem and somatropin
-for GH depression
-given to stimulate synthesis of somatomedins in growth plate cartilage resulting in increased linear, organ and skeletal growth and increased protein synthesis
-insulin-like effect
-contraindicated for patients with closed epiphyses, or active tumor growth
-close monitoring is needed for patient with thyroid disorders
-insulin resistance can occur–cautious with diabetic patients
ADRs: hyperglycemia, hypothyroidism, edema to secondary Na+ retention
pancreas
- exocrine and endocrine glad
- 2 major dz: CF and pancreatitis
- both leads to obstruction of ducts resulting in activated digestive enzymes within pancreas and failure of releasing enzymes into duodenum to digest–malabsorption
diabetes
type one: destruction of beta cells to produce insulin
type 2: insulin resistant
-either one-disequilibrium between excess production of glucagon and lack of insulin
pharmacokinetics of insulin
-absorption dependent on type, injection site, and volume injected
-abdominal absorbs 50% more
-metabolism: induces CYP1A2
-excretion: urine
ADRs: hypoglycemia, diabetic ketoacidosis,
ETOH increases hypoglycemia
-drug interactions: beta blks increase insulin resistance and masks hypoglycemic symptoms
average dosing for insulin
0.6-0.8 U/kg
monitoring for diabetes
- routine glycohemoglobin, renal function and CBC
- A1C test x2/yr when under control; once quarterly if tx goals not reached
- goal usually is A1C
type 2 diabetes
- insulin resistance
- 4 primary alterations: insufficient production of endogenous insulin by beta cells, tissue insensitivity to insulin, impaired response of beta cells to BG levels, excessive production of glucose secondary to increased glucagon levels
- liver and incretin hormone system is the major organ
sulfonyureas
- helps with insufficient production of endogenous insulin by stimulating release from beta cells
- improve insulin binding or increase # of receptors but does not improve insulin utilization
- second line drug
- not used as monotherapy
- all potentiate effects of antidiuretic hormone
- glipizide (Glucotrol), glyburide (Diabeta), glimeride (Amaryl)-
pharmacokinetics of sulfonylureas
- metabolism: liver CYP2C9
- absorption: all with most
- protein binding: >95%
- excretion: urine and feces
pharmacotherapeutics of sulfonylureas
-precautions/contraindications: cross sensitivity with sulfonamides and thiazide diuretics
-pregnancy C
-older adults more sensitive
-pediatric use for 10-18 yrs old but off label
ADRs: hypoglycemia, GI, derm rashes, SIDH, hemolytic anemia, leukopenia, thrombocytopenia, wt. gain
clinical use/dosing for sulfonyureas
- for type 2
- use either first or second generation–first generation more hypoglycemia, wt. gain, and reduction of efficacy overtime
- dose on individual response-titrate every 4-7 days
- for neurogenic diabetes insipidus–chlorpropamide off label use
rational drug selection/dosing for sulfonylureas
- age: avoid using chlorpropamide and glyburide in older adults–use short acting glipizide
- low cost-generic available
- with comorbidities: renal impairment use glipizide/tolbutamide or glyburide
- concurrent with insulin-only glimepiride by FDA, most 2nd generation
monitoring of sulfonylureas
-HbA1C baseline every 6 months if meeting therapy goals or every 3 months if adjusting
CBC on onset and every8-ten months
-can be taken food except glipizide must be taken 30 minutes prior to meal
biguanides
- oral antihyperglycemic drug
- first line drug for adults and children over age ten
- metformin (glucophage)
- monotherapy-lacks hypoglycemic effects, weight neutral, and decreased CVD events
pharmacodynamics biguanides
- decreases glucose in liver
- decreases GI glucose absorption and improves insulin sensitivity by increasing peripheral glucose uptake and utilization
- does not stimulate insulin from beta cells
- inhibits platelet aggregation and reduces blood viscosity
pharmacokinetics of biguanides
- absorption: 50-60% after po dose; food decreases and delays absorption
- no hepatic metabolism
- excreted by kidneys
- ETOH potentiates drug’s effect on lactate metabolism
pharmacotherapies for biguanides-
precautions/contraindications
- renal dz/dysfunction
- metabolic acidosis
- hepatic dz
- withhold 48 hrs prior to test with iodine contrast
- monitor pt. with b 12 deficiency
- category B-not recommended
- not for use of children
rational drug selection/dosing of biguanides
- IR v. ER-can safely switch btwn both.-just monitor glucose
- start 500 mg BID with max of 2550 mg/day
- if pts not responded after 4 weeks consider adding other oral agents like sulfonylurea
- part of metabolic syndrome treatment protocol
- monitoring: renal function, ketones, and HbA1C
Alpha-glucosdiase inhibitors
- acarbose (Precose)
- migitrol (glyset)
- NOT monotherapy *can be for pre-diabetes
pharmacodynamics of alpha-glucosidase inhibitors
- inhibits absorption of CHO from GI tract high lowers BG after meals
- no hypoglycemia effect
pharmacokinetics of alpha-glucosidase inhibitors
-
Pharmacotherapies of alpha-glucosidase inhibitors
Precautions/contraindications
-not given to patients with IBS, possible bowel obstruction or renal impairment
-not for pregnant patients
ADRs: flatulance, diarrhea, abdominal pain
-drug interactions: acarbose and digoxin and miglitol and propanolol and ratadine
Clinical use/dosing of alpha-glucosidase inhibitors
- initial dose 25 mg TID titration 4-8 weeks
- take with first bite of meal
pharmacodynamics of thiazolidinediones
- pioglitazone (Actos), rosiglitazone (Avandia)
- improves target cell response to insulin
- increases utilization of insulin by liver and muscle cells
- reduces liver glucose production
- modest impact on lipids
- no hypoglycemic effects
- higher risk of bladder ca
- increased risk of of HF
- weight gain
pharmacokinetics of thiazolidinediones
- rapidly absorbed after po dose
- metabolized by liver CYP2C8 and 3A4
- 99% protein bound
- excrete through urine and feces as metabolites
pharmacotherapies of thiazolidinediones
precautions/contraindications
-chronic liver dz-increased concentrations of metabolites
-fluid retention-exacerbates HF
-restriction of use of rosiglitizone d/t increased risk of MI
ADRs: edema, URI, headache, fatigue
drug interactions: oral contraceptives need higher doses;
-any drug metabolized by CYP3A4-corticosteroids, ketoconazole
meglitinides
- short acting insulin secretagogues
- add-on therapy
- repalinide (Prandin), nateglinide (Starlix)
- used in place of sulfonylurea
- expensive
pharmacodynamics of meglitinides
- increases insulin release from beta cells by closing K+ channels leading to opening of Ca+ channels which then releases insulin
- short time in plasm
pharmacokinetics of meglitinides
- absorbed rapidly and completely
- metabolized in liver by CYP3A4 and CYP2C8
- excreted within 96 hours; mostly in feces some in urine
pharmacotherapies of meglitinides
precautions/contraindications
-liver impairment-higher concentrations of substrate
-pregnancy cat C
-not approved for pediatrics
ADRs: hypoglycemia
drug interactions: any drugs metabolized by CYP 3A4 or CYP 2C9
-antifungals and antimicrobials inhibit metabolism–increasing risk of hypoglycemia
dosing for meglitinides
- patient’s with HbAC 8 initial one mg before each meal
- titrate every 2 weeks for maximum of sixteen mg/24 hours
dipeptidyl peptidase-4 inhibitors
- “gliptins”
- newest class of antidiabetic agents
- sitagliptin (Januvia) and saxaglipin (Onglyza)
- different mechanism of action: works on incretin hormone system
- add-on therapy-*can be used as monotherapy but more effective in combination
- once a day
pharmacodynamics of dipeptidyl peptidase-4 inhibitors
- inhibits DPP-4 which breaksdown GLP and GIP which are released in response to meals
- increases secretion of insulin
- suppresses release of glucagon from pancreas
- promotes pre/post prandial glucose
- slows gastric emptying
- promotes weight loss
- well tolerated
pharmacotherapies for dipeptidyl peptidase-4 inhibitors
precautions/contraindications
-renal dysfunction-dependence on renal system for elimination
-pregnancy cat B
-not approved for pediatrics
ADRs: GI, headaches
drug interactions: ace inhibitors-increased risk for angioedema
glucagon-like peptide 1 agonists
- new drug of antidiabetic agents
- exenatide (Byetta)
- SQ injection twice daily; can be given weekly
- given 60 minutes before meals
- dose 6 hours apart
- very expensive
- add on therapy
pharmacodynamics of glucagon-like peptide-1 agonists
- promotes insulin release from beta cells when glucose level rises
- decreases glucagon secretion
- increases satiety
pharmacotherapies of glucagon-like peptide agonists
Precautions/contraindications -severe GI dz-colitis, crohns -pregnancy cat C -renal dz ADRs: n/v/d, pancreatitis drug interactions: increased INR if given with warfarin, digoxin
amylin agonists
- pramlintide (Symlin)
- adjunct therapy for type one and type 2
- co-administered with insulin
- lowers glucose by acting on glucagon secretion and slowing gastric emptying
- via SQ injections
pharmacodynamics of amylin
- slows gastric emptying
- suppresses glucagon secretion leading to decreased endogenous glucose
- centrally mediated modulation of appetite–potential weight loss
pharmacotherapies of amylin
precautions/contraindications
-high risk of hypoglycemia since administer with insulin
-pregnancy cat C
ADRs: GI
drug reactions: acetaminophen pharmacokinetics altered–must administer separately
glucagon
- considered antidote: used for diabetic patients who have hypoglycemia d/t insulin overdose
- SQ, IM, IV
pharmacodynamics of glucagon
- stimulates hepatic gluconeogensis and glycogenolysis leading to increased BG
- BG rises within ten minutes of injection with maximal effect after 30 minutes
- hepatic stores necessary for glucagon to produce antihypoglycemic effect
pharmacotherapies of glucagon
precautions/contraindications
-pregnancy cat B
-use caution with pt suspected having phenochromocytoma or insulinoma
ADRs: n/v
drug interactions: increased anticoagulant effects of po anticoagulants
patient education on glucagon
- educate family members/roommates on to administer IM
- pt given supplemental CHO when awake and can swallow
- lifestyle management
thyroid hormones
- levothyroin (T4), liothyronine (T3), liotrix (mixture of T3 and T4)
- hypothalamus-pituitary-thyroid-hormone begins with secretion of TRH from hypotalamus in response to cold, stress, decreased levels of T4
- TRH leads to secretion of TSH which: releases stored thyroid hormone, increases iodine uptake and utilization, increases synthesis of T3 and T4, increases synthesis of prostaglandins
- create negative feedback loop to inhibit TRH and TSH
- synthetic hormones produces feedback loop to stop secretion of TSH
- levothyroxine drug of choice d/t longer half life
pharmacokinetics of thyroid hormones
- absorption is erratic with po and decreases with age, food, health of GI tract
- majority is protein bound
- excreted by bile/feces
pharmacotherapies of thyroid hormones
precautions/contraindication
-contraindicated after acute MI or thyrotoxiocosis
-pregnancy cat A
-may need higher doses when pregnant
ADRs: symptoms of hyperthyroidism, long term use associated with decreased bone density in hips/spine
drug interactions: bile-acid sequestrants, iron salts, antacid decrease absorption; estrogen decrease response; warfarin, digoxin, and beta blockers may decrease action
hypothyroidism
- tx indicated with TSH>ten or btwn 5-ten if goiter or anit-thyroid peroxidase
- thyroxin replacement is lifelong
- levothyroxine drug of choice
levothyroxine dosing
pts with CV: initial dose 50 mcg/day 2-4 wks may titrate
-average full replacement one hundred -one hundred twenty five mcg/day
pt>50 with CV or lifelong disease: initial dose twelve.5 to 25 mcg/day, titrate monthly
antithyroid agents
-propylthiouracil (PTU), methimazole (Tapazole)
pharmacodynamics:
-blocks synthesis of thyroxine and trilodothyronine
-does not treat underlying pathology in hyperthyroidism
pharmacokinetics of antithyroid agents
-rapidly absorbed after po dosing peaking within one hour
75-80% protein bound–except methimazole is NOT protein bound
-short half life
-excreted through urine
pharmacotherapies of antithyroid agents
precautions/contraindications -pregnancy cat D -high concentrations in breast milk -PTU not recommended for children ADRs: agranulocytosis, drowsiness, headache, alopecia, skin rashes, renal/hepatic failure drug reaction: lithium, warfarin
