drugs-corticosteroids, DM, thyroid Flashcards
corticosteroids are used to establish the endocrine disorder dx of ___
cushings syndrome
mifepristone is a _____ receptor antagonists
glucocorticoid
prednisone is a ____ agonist, fludrocortisone is a a ___ agonist
glucocorticoids
mineralocorticoids
aldosterone and cortisol bind with ___ affinity to the ___ receptor
equal affinity to the MR receptor
what enzyme converts cortisol from active to inactive back to active form? and what is the inert steroid name?
active: cortisol (corticosterone, prednisolone)
- — [11 B-HSD2] —> inactive: cortisone, 11-dehydrocortisone, prednisone—-[11 B-HSD1]—> active form
- 11 B-HSD2 = 11 B-dehydrogenase
- 11-B HSD1 = 11-ketoreductase
therapeutic effects of corticosteroids
immunosupression (transplants, cancer, autoimmune dz)
anti-inflammatory
anti-allergy
pain relief (secondary)
side effects of glucocorticoids
infections osteoporosis hyperglycemia weight gain "cushingoid" appearance HPA insufficiency (adrenal atrophy) HTN neuropsychiatric DO cataracts/glaucoma myopathies skin thinning
factors of corticosteroids that influence therapeutic and adverse affects
- potency
- pharmokinetics
- daily dose
- timing of dose
- difference of metabolism in individuals
- duration of tx
what is the criteria for initiating therapy with corticosteroids
- medical emergencies (high doses for ONLY a few days)
2. chronic therapy (must be evidence foe use)
T/F corticosteroids cannot be given chronically without the risk of adverse affects
true
tx of addisons dz (primary adrenal insufficiency) and CAH
both: hydrocortisone and fludrocortisone
effects of corticosteroids on the immune system
decrease: Prostaglandins , leukotrienes, immune cells, cytokines and receptors, neutrophil and MO migration, cell adhesion molecules
= 1. decreased inflammation and mainfestations
- immune suppression
- decreased allergic and hypersensitivity reactions
corticosteroids affect of carbohydrate metabolism
increase gluconeogenisis increase glucose output increase glycogen synthesis decrease glucose uptake =HYPERGLYCEMIA
what causes inhibition of 11 B HSD2 ? what is the effect/
inhibitors: glycyrrhizin (licorice)
-excessive activation of MR receptor mediated by cortisol [ increase NA and H2O retention, increase K+ loss—>increase BP]
= HTN
corticosteroids drug dosing rules
- lowest dose for shortest time (use short/intermediate acting > long acting)
- reduce distribution (use topical/inhaled vs systemic)
- single daily AM doses or alternate days with pulse tx
- dose-tapering for HPA recovery
____ can tx cancer of the adrenal gland (adrenal cortical carcinoma)
mitotane
“mighty tank”
name short, intermediate and long acting corticosteroids and the duration of action
short: 8-12 hours
- hydrocortisone (cortisol)
- cortisone acetate
intermediate: 12-36 hrs
- prednisone / prednisolone / methylprednisolone
- triamcinolone
long: 36-72 hrs
- dexamethasone
- bethamethosone
*dexamethasone suppression test use to dx cause of Cushings syndrome
pharmokinetics and toxicities of prednisolone
(intermediate acting: 12-36hr ; glucocorticoid agonist)
pharmokinectics: duration of activity is longer than pharmokinectic T 1/2 of drug owing to gene transcription effects
- SE: adrenal suppression
___ is used in dx of adrenal insufficiency (addisons) and occasionally in tx of Cushings (hypercortisolism)
metyrapone
mifepristone MOA, clinical use and SE
- glucocortcoid and progesterone antagonist
- use: medical abortion
- se: vaginal bleeding
two mineralocorticoid receptor antagonists, clinical use, pharmokinetics, and SE
- spironolactone
- tx aldosteronism, hypokalemia from diuretic use, post MI
- kinectics: slow onset and offset (lasts 24-48hrs)
- SE: hyperkalemia, gynecomastia, interaction with other K+ retaining drugs - eplerenone
- tx HTN
- kinectics: cleared by CYP 450 {FYI}
- SE: hyperkalemia, no gynecomastia
ketoconazole MOA, use, SE
MOA: corticosteroids synthesis inhibitor
use: inhibits mammalian steroid hormone synthesis and FUNGAL ERGOSTEROL SYNTHESIS (tx fungal infections)
SE: many drug-drug CYP 450 interactions
what anti-thyroid medication takes weeks for the effects to start ? what is its MOA? and used for tx of? and SE?
radioactive idodine 131 sodium
-MOA: taken up by thyroid, collects in colloid, and creates permanent destruction and damage to thryoid
- tx: graves (hyperthyroidism) ; multi nodular goiter
- SE: AVOID IN PREGANCY ; worsens graves opthalmopathy, will need thyroid replacement following tx
2 types of thioamides? MOA, SE, and tx use
- MOA: decrease TH production/ inhibit hormone synthesis by INHIBITING TPO –> inhibit iodide oxidation organification and coupling
- SE: maculopapular pruritic rash (MC) , lupus like syndrome, agranulocytosis (most dangerous , increases risk of infection) , worsens graves opthalmopathy, hypothyroidism
- PTU (propylthiouracil)
- also inhibits T4–> T3 peripheral conversion by blocking 5 deiodinase
- tx: thyroid storms , used first trimester of pregnancy
- SE: hepatotoxic - methimazole
- perferred thioamide
- used in 2 and 3 trimesters in pregnancy
which anti-thyroid med does not affect heart rate
potassium iodide
Iodide as anti-thyroid medication MOA, use,
potassium iodide
- (wold chaikison effect) high levels of iodine inhibit release of TH, and decrease BF to thyroid
- MOA: inhibit iodide organification, hormone release, and decrease vascularity to hyperplastic thryoid gland
- tx: pre-op reduction of hyperplastic gland, thryoid storm, block thyroid uptake of radioactive isotopes of iodine in radiation emergency/exposure,
- can also treat iodine deficiency in the setting of hypothyroidism
use of beta blockers in thyroid medications
-propranolol (or atenolol has less cerebral affects)
MOA: decreases SNS activity (increased HR, sweating, hyperactivity, anxiety, tremors) ; decrease T4–>T3 conversion
-tx: sx management in graves dz, and thyroid storm adjunct
what can be used to treat inflammation of the eyes in graves ophthalmology
prednisone (glucocorticoid agonist)
what are common pollutants that act as anti-thyroid drugs
anion inhibitors: perchlorate (ClO4-) and thiocyanate (SCN-)
- MOA: block thyroid uptake of iodide by competitive inhibition
- not used clinically often
in setting of graves management:
- ___ is preferred tx for pts > 21yo
- ____ is preferred for young pts with small gland/mild dz
- ____ is used for large glands or multi nodular goiters
- ___, ____, and ____ is the adjunct tx for sx
- radioactive iodine 131 (80% develop hypothyroidism)
- methimazole»_space; PTU
- thyroidectomy
- B-blockers, CCB (diltiazem), and NSAIDs
in the setting of thyroid storm:
- _____ used to block TH synthesis
- ___ is used to block TH release
- ___ is used as arrhythmia control
- ____ is used to block T4–>T3 conversion
- PTU > methiamazole (thioamides)
- potassium iodide
- B-blocker
- IV hydrocortisone
what is the med name for T3 hormone replacement drug, and how does it compare to the T4 type, and what is it used to tx , SE
Liothyronine
- short acting, more potent, rapid affect vs T4
- IV Liothyronine tx emergencies (myxedema coma)
- SE: more severe than T4 (mimic hyperthyroidism) ; contraindicated in heart disease
**sx of myxedema coma: weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, death
what is the med name for T4 hormone replacement drug, and how does it compare to the T3 type, and what is it used to tx , SE
Levothyroxine
- long acting, less potent, slower affect (6-8 weeks)
- SE: less severe than T3, contraindicated in heart dz
- tx: longterm chronic hypothyroidism, pregnancy hypothyroidism
- *drug of choice for replacement/ TH deficiency
- *can be used IV for myxedema coma tx
how to dose T3 and T4 replacement therapy
based on TSH and T4 levels in the blood
___ blocks absorption of levothyroxine
cholestyramine
__ can cause thyrotoxicosis —> thyroid storm because it has 50x iodine levels than recommended value
amniadorone (NL used to tx arrhythmias)
___ is most sensitive screening test for hyperthyroid and primary hypothyroidism
TSH (determines if thyroid is hyperfunctioning)
liotrix vs thyroid dessicated tx
liotrix: 4:1 ratio of T4:T3 hormone replacement
desiccated- mix of T3/T4 derived from pigs but is a variable ratio therefore not great for hormone replacement
what is insulin tx is used for in general and MOA? list rapid/short/intermediate/long acting types onset, duration, and tx?
MOA: insulin receptor activates PI3K pathway to synthesize lipids, glycogen, and cell survival (and MAPK path for growth/gene expression)
TX: T1DM , poor controlled T2DM, GDM, severe hyperkalemia
-rapid: Onset 5-10min ; Last 1-3hr
tx: postprandial hyperglycemia
aspart, glulisine, lispro (GAL)
-short: Onset 30min-1hr ; Last 10 hr
tx: basal insulin, overnight coverage, 45 min B4 meals, IV type for DKA
regular insulin
-intermediate: Onset 1-2 hr; Last 10-12 hr
tx: basal insulin; overnight
NPH-neutral protamine hagerdorn
-long: Onset 3-4hr; Last 24hr
tx: basal insulin
Determir , Glargine
name of the amylin analog used in DM meds? MOA? use? SE?
Pramlintide (amylin is pancreatic hormone made by B cells)
- MOA: increases sensitivity to insulin, inhibits glucagon, decreases gastric emptying/ slows glucose absorption rate/ satiety
- tx: T1DM & poor controlled T2DM taking meal insulin, goes before meals as adjunct to insulin
- SE: GI, hypoglycemia, increase anti-cholinergic drugs in GI (increases constipation) `
what is the breakdown of organization of insulin secretagogues used in DM meds
- incretin mimetics (activate / increase GLP-1 )
- GLP-1 agonists *tied up exes and liars (“-tide”)
- exenatide
- liraglutide
- DPP-4 inhibitors (“-gliptin”)
- sitagliptin -linagliptin -saxagliptin -alogliptin - K-ATP Channel blockers (depolarizes cell –> insulin )
- sulfonylureas
- first generation (“-amide”)
- chloropropamide
- tolbutamide
- tolzamide
- second generation
- glipizide ; glyburide; glimepiride
- meglitinides (“-glinide)
- nateglinide
- repaglinide
weight loss DM drugs ? weight gain DM Drugs?
Loss:
- biguanides (metoformin)
- SGLT2 inhibitors
- DPP-4 inhibitors and GLP-1 agonists (incretin mimetic under insulin secretagogues)
- (alpha glycosides inhibitors?)
gain:
- insulin
- thiazolidineediones
- K+channel blockers (sulfonylureas, meglitinidies)
MOA of K+ channel blockers
(Insulin secretagogue)
-binding to SUR (sulfonylurea receptor) and block K + current through inwardly rectifying K+ channel which depolarizes cell to allow Ca2+ influx and insulin release
tx of hypoglycemia SE from DM drugs
- glucose (juice)
- octreotide (somatostatin agonist– inhibits insulin)
- diazoxide (K+channel opener)
- glucagon
what is the effect of diazoxide
K + channel opener, inhibit insulin release, raise BG
K channel blockers interaction with CYP
sulfonyureas
-decrease in CYP activity will increase hypoglycemia effect
(alcohol decreases CYP activity)
sulfonyureas interaction with ABX
sulfamethazole abx has similar structure to sulfonyureas and both bind to albumin in blood. the abx can displace the DM drug and increase its intended concentration therefore dose should be decreased when combined or it will cause hypoglycemia
what is the first line of tx for T2DM ? why? MOA? contraindicated
biguanides (metformin)
- better glucose lowering, NO hypoglycemia SE, no weight gain SE, and decreases complication seen in DM, and is oral
- MOA: reduce hepatic glucose production by AMP dependent protein Kinase activation (AMPK activation) in liver and decreases intestinal absorption of glucose, and increases insulin sensitivity by increasing peripheral glucose uptake
- contraindicated in HF, COPD, renal failure, alcoholism/cirrhosis
which DM drug takes a 1-3 months to take full effect and lasts a while after stopping (slow on and off)
thiazolidineodiones (“-glitazone”)
-increases glucose uptake and insulin receptors and decreases gluconeogensis
which DM drug should not be used if have hypovolemia
SGLT2 inhibitors ("-liflozin")
*glucose flows in 2 the urinewhich DM do not cause hypoglycemia
biguanidies (metformin)
SGLT2 inhibitors (‘-liflozin” )
alpha glycosides inhibitors (acarbose , miglitol)
thiazolidinediones (“-glitazone”)
