Endocrinology Pharm Flashcards
what is the HPA axis
hypothalamus -> pituitary gland -> adrenal gland
what is the adrenal gland comprised of
adrenal cortex and adrenal medulla
what is the inner portion and what does it secrete
medulla
- catecholamines
what is the outer portion of the adrenal gland and what does it secrete
- cortex
- adrenal steroids
adrenal cortex produces about _____ different chemicals
50
what are the hormones in the adrenal gland with pharmacologic properties
- mineralocorticoids
- glucocorticoids, cortisol
- androgens
what are the 3 layers within the cortex and what do they produce
- zona glomerulosa: mineralocorticoids
- zona fasciculata: produces glucocorticoids
- zona reticularis: produces sex hormones; mostly androgens and small amount of glucocorticoids
what do mineralocorticoids do
regulate water and electrolyte balance
- sodium, potassium, and fluid balance
- provide important homeostatic functions
what is the main endogenous hormone and what type of hormone is it and what does it do
- aldosterone
- essential for BP regulation and electrolyte and fluid homeostasis- helps to maintain normal blood pressure and electrolyte balance
- acts on the mineralocorticoid receptor
what does the mineralocorticoid receptor
- MR present in kidneys impacts fluid and electrolyte balance
- extra renal MR plays a relevant role in the control of cardiovascular and metabolic funcitons
- overactivation of the MR is implicated in the pathophysiology of aging related to cardiovascular, metabolic and kidney dysfunction and progress of disease
what is the MOA of aldosterone
- increases Na+ reabsorption by distal tubules in kidney with concomitant increased excretion of K+ and H+
-increased BP and blood volume - balance/control the amount of sodium and fluids in the body - work on specific intercellular receptors in kidney
what type of medication is fludrocortisone
mineraliocorticoid
- functionally similar to aldosterone
what is the indication for fludricortisone
replacement therapy for Addisons disease/adrenal insufficiency
- orthostatic hypotension
- septic shock
imbalances in aldosterone and overactivity of the mineralocorticoid receptor contribute to:
HTN, kidney insufficiency, heart failure, and potentially other cardiovascular disease
what is the most and least common imbalances in aldosterone
- most common: idiopathic adrenal hyperactivity
- less common: benign tumor (Conn’s syndrome)
what drugs are antagonists of aldosterone
spironolactone and eplerenone
what is the MOA of spironolactone
- competitive aldosterone antagonist at the mineralocorticoid receptor at distal renal tubules - kidney specific MR
- increases sodium chloride and water excretion while conserving potassium and hydrogen ions - prevents mineralocorticoid effects of adrenal steroids on the renal tubule
- AKA potassium sparing diuretic
- reduces blood volume by decreasing sodium retention in the kidneys
what are the indications for spironolactone and eplerenone
- hyperaldosteronism
- heart failure
- HTN
what are the drugs that inhibit aldosterone (non steroidal
finerenone and glucocorticoids
what is the MOA of finerenone
selectively blocks (antagonist) mineralocorticoid receptor- mediated sodium reabsorption and overactivation of kidney, blood vessel and heart tissues, reducing fibrosis and inflammation
what are the indications for finerenone
chronic kidney disease associated with type 2 diabetes
what is the MOA of glucocorticoids
- work through specific glucocorticoid intracellular receptors to regulate several vital cell activities
- metabolic
- immune function
- widespread actions on intermediate metabolism, affecting carbohydrate, protein, and fat metabolism
- potent regulatory effects on host defense mechanisms including inflammation and immune function
- glucocorticoid receptors up regulate expression of anti inflammatory proteins and down regulate expression of pro inflammatory proteins
what is another name for glucocorticoids
corticosteroids
what is the main endogenous hormone in humans
hydrocortisone (also called cortisol)
describe the secretion of hydrocortisone
- produce 24-30 mg endogenous cortisol
- use up to 300 mg/day in times of significant stress
- secreted in circadian rhythm in healthy humans
- highest concentrations in early morning
describe the parts of the HPA axis pathway
- hypothalamus releases CRH
- adrenocorticotropic hormone (ACTH) released from the anterior pituitary
- adrenals release glucocorticoids
what is the MOA of the HPA axis pathway
negative feedback mechanism to inhibit CRH and ACTH when glucocorticoid concentrations increase in the blood
describe the therapeutic use of corticosteroids
most are used for anti inflammatory and immunosuppressive properties
- addisons
- cancer therapy
- anaphylaxis
- hypersensitivity states
-shock
- SLE
- RA
-IBS
- asthma
- COPD
- respiratory distress in infnats
- suppressing rejection of skin grafts or organ transplants
- acute renal insufficiency
- inflammatory conditions of eyes, ear,s nose, skin
what are the uses of steroids in dentistry/facial indications
- use for anti inflammatory, pain management and auto immune properties
- oral lesions
- restorative dentistry pain management
- bell’s palsy
- post herpetic neuralgia
- TMJ disorder
- temporal arteritis
what are the dental (topical oral) applications
- pastes, ointments, gels, lozenges, intralesional therapy, rinses
- importance of contact time with lesion
- kenalog in orabase / triamcinolone dental paste
- press paste onto area to be treated until it sticks and a smooth slippery film forms. dont spread
- apply 2-3 times per day and at bedtime and following meals
what are the steroid dosing considerations
- consider potency
- weigh pros/cons of topical vs systemic therapy
- topical/other types of administration may cause systemic effects
- use lowest effective dose for shortest duration
- monitor for adverse effects
- if pt on systemic therapy for longer than 14 days, taper dose off
what are the steroid dosing considerations
- take in the morning if taking orally once a day
- take with food if taking orally
- if given for chronic adrenal insufficiency may need to give 2/3 dose in AM and 1/3 dose in PM
what are the dosing considerations for low, moderate and high dose
- low: <10 mg prednisone/day
- moderate: 10-20 mg prednisone/day
- high > 20 mg prednisone/day
describe prednisone dosing
- usually lowest cost oral steroid
- available in wide range of strength for titration
- morning dosing/can split larger doses to BID but give earlier in the day to minimize insomnia and mimic higher endogenous steroid production in the AM
what is an example of a dose pack for medrol
dispense 1 pack
- take as directed (or take all in AM or if cannot tolerate taking all at once, try to take all before evening. take with food)
what is an example of a dose pack for prednisone 5mg
dispense 21 tabs
- with morning meal, take 4 tabs day 1 and 2, take 3 tabs day 3 and 4, take 2 tabs day 5 and 6 , take 1 tab day 7 and 8, take 1/2 tab day 9 and 10
what is the dental use for IV steroids and what is used and what is it for
- IV sedated patient -3rds
- IV dexamethasone 4-8mg or methylprednisone 40mg
- provides anti inflammatory effect (reduces pain and swelling)
- helps reduce post op nausea from the sedation
what happens when providing supraphysiologic doses of corticosteroids (>25-30mg of hydrocortisone/cortisol equivalents) x 14 days or more
HPA Axis suppression
- may take weeks to months to fully recover
- use of chronic exogenous corticosteroids= suppression of adrenal gland = atrophy
- inability of the adrenals to respond to stress can result in adrenal crisis
- pt may develop chronic adrenal insufficiency from various causes
what is primary chronic AI
addisons disease
what is secondary AI
damage/disease of the pituitary or hypothalamus
- also caused from long term use of glucocorticoids
what are the treatments for primary AI
oral hydrocortisone with or without fludrocortisone
- other options include prednisone, dexamethasone
what is acute adrenal crisis, who do we expect to see it in, what are the symptoms and lab findings
- medical emergency - rare
- life threatening condition
- predicated in patients with chronic adrenal insufficiency with increased significant stress such as infection, trauma or surgery
- symptoms: fever, abdominal pain, weakness, hypotension, dehydration, nausea, vomiting, slow,sluggish movement, fatigue, profound weakness, rapid heart rate, rapid RR, confusion, loss of consciouness
- lab findings: low K+, low Na+, acidosis, uremia
what is the management of AI in surgery
- IV fluids
- hydrocortisone
- 10-25mg hydrocortisone po for those at high risk addisons disease undergoing major dental surgery with general anesthesia
what are the acute adverse effects to long term effects of corticosteroids
- CV: tachycardia, HTN
- Derm: acne, delayed wound healing, facial flushing
- endo: hyperglycemia
- GI: abdominal pain, diarrhea, constipation, heartburn, increased appetite, peptic ulcers, and GI bleeds
- infections: suppression of response to infection, opportunisitc ifnections
- neuro: anxiety, insomnia, mood swings, euphoria, hallucinations, depression
- bone: osteoporosis
- muscle: muscle wasting and weakness
- growth inhibition in children
- eyes: glaucoma
- adrenal suppression
- cushing syndrome
what are the drug interactions with corticosteroids
- increased prothrombin time/INR with warfarin
- risk of hypokalemia with potassium depleting diuretics (hydrochlorothiazide)
- increases risk of cardiac toxicity and arrhythmias with cardiac glycosides
- interferes with calcium absorption in food
- absorption of glucocorticoids is decreased in presence of St Johns wort
what are the contraindications for corticosteroids
- severe infections, severe HTN, severe Heart failure, severe renal impairment
what are the dental implications with corticosteroids
- effectiveness in decreasing swelling/inflammation and pain
- altered responses to infection and wound healing
- oral thrush from inhaled steroids
- contribute to tooth decay, periodontal disease, decreased bone density
- patients with chronic adrenal insufficiency: risk of adrenal crisus when placed in stressful situations
what is the purpose of steroids for patients
- relieve discomfort and redness, swelling/inflammation of some mouth and gum problems or during/after dental procedures
- useful for pain
- timeframe for expected improvement
what are the dose/frequency/ dosing instructions for patients with steroids
- take in AM for systemic administration
- length of therapy
- specific instructions for dental paste/topical application
- do not use more often or for a longer time than your medical doctor or dentist ordered
what are the common short term side effects of steroids
- insomnia
- agitation/changes in mood/irritability
- weight gain
- leg swelling
- risk of increased blood glucose
- risk of increase BP
what medications impact the effects of aldosterone
- mineralocorticoid effects- fludrocortisone
- aldosterone antagonists: spironolactone and eplerenone and finerenone
when are steroids for adrenal crisis in patients with adrenal insufficiency indicated
only needed for patients undergoing major dental surgery
what 3 hormones does the thyroid gland secrete
- thyroxine (T4) - large storage, high serum concentrations in body
- tri-idothyronine (T3)- small storage - low serum concentrations in body (fast turnover rate)
- calcitonin
_____ of T3 daily production is a result of peripheral conversion of T4-> T3
80%
where is T3 converted from T4
primarily in the liver and kidney but also in many other tissues
what are T3 and T4 used for
- normal growth and development in children
- control energy/metabolism
- involved in normal functioning of almost every organ system including the brain, heart, liver and muscles
what does calcitonin do
control of plasma calcium
what are the 2 major effects of thyroid hormones
- effects on metabolism
- effects on growth and development
describe the effects of thyroid hormones on metabolism
increased metabolism on carbohydrates, fats and proteins
T3 is ________ active than T4
3-5x more
what are the effects of thyroid hormones on growth and development
- direct action and indirectly influences growth hormone
- skeletal development
- growth and. maturation of CNS
what are the types of hyperthyroidism
- diffuse toxic goiter (Graves disease): autoimmune disease (Autoantibodies to TSH receptor) and protruding eyeballs
- toxic nodular goiter: benign neoplasm or adenoma
what are the symptoms of hyperthyroidism
- overactive thyroid- gas , increased sympathetic activity
- nervousness or irritability
- fatigue
- muscle weakness
- trouble tolerating heat
- trouble sleeping
- tremor, usually in your hands
- rapid or irregular heartbeat
- frequent bower movements and/or diarrhea
- weight loss
- mood swings
- goiter, an enlarged thyroid
what are the treatments for hyperthyroidism
- surgery
- radioactive iodine
- drug therapy: propylthiouracil, methimazole, beta blockers (propanolol) - symptomatic relief only, glucocorticoids for exopthalmos in graves disease
what is the MOA and ADRs with methimazole
- MOA: inhibit biosynthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine (T4) and T3, does not inactive circulating T4 and T3
- ADRs: neutropenia, agranulocytosis, aplastic anemia, liver toxicity
what is the general definition of hypothyroidism
free T4 is sub normal/low (normal range 0.8-2.8mg/dl) and TSH is usually elevated/ high (normal range 0.45 mIU/L 4.12mIU/L
- myxedema- term used for severe hypothyroidism: dermatologic changes that can occur, coma that can occur as an extreme complication
what is subclinical hypothyroidism
- early hypothyroidism
- free thyroxine (t4) is normal
- thyroid stimulating hormone TSH is elevated/high
- mild to no symptoms of hypothyroidism
what is overt hypothryoidism
free T4 is sub-normal/low
- thyroid stimulating hormone is usually elevated (normally > 10 U/ml)
what is the worldwide cause of hypothyroidism causes
iodine deficiency
what are the iodine sufficient countries
chronic autoimmune thyroiditis (AITD/Hashimotos)
- reaction against thyroglobulin or other thyroid tissue
- women > men
- age
- other autoimmune disorders
- goiter may or may not be present
what are the subjective symptoms of hypothyroidism
- low metabolic rate- increased parasympathetic activity
- dry skin
- cold sensitivity/intolerance
- fatigue
- muscle cramps
- voice changes
- slow speech
- constipation
- weight gain
- thickened skin
what is the goal of thyroid disorder therapy
- restore euthyroid state
- TSH usually 0.45 mIU/L - 4.12 mIU/L
- alleviate symptoms
- reduction in size of goiter
- avoidance of overtreatment
what is the drug therapy for hypothyroidism
- levothyroxine/Synthroid (synthetic T4)- most common therapy: usual dose 50-100mcg
- lower doses in patients with coronary artery disease
- liothyronine, triostat (synthetic T3)
- liotrix (4:1 ratio of synthetic T4:T3)
- thyroid dessication/ armour thyroid
- dosing dependent on age, sex, body size
- onset of action 1-2 weeks, full effects 4-6 week
- take on empty stomach 30-60 minutes before meals (in morning) and before other medications
- recommended to a consistent product to minimize variability
- dangers of using thyroid supplementation for weight loss in euthyroid patients
what are the adverse effects of thyroid treatments
- too much or too little supplementation/thyroid hormone
what are the drug interactions with thyroid supplementation
- interference with absorption: bile acid sequestrans, PPIs, oral bisphosphonates, iron and calcium supplements, orlistat
- decreased hormone production/secretion: amiodarone, lithium
- peripheral metabolism of T4: glucocorticoids, amiodarone
- altered secretion of TSH: dopamine, glucocorticoids, amphetamine
- increased clearance of T4: many antiepileptics, quetiapine
what are narrow therapeutic index drugs
- small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life threatening or result in persistent or significant disability or incapacity
which thyroid medication has a narrow therapeutic index
levothyroxine
what is the recommendation of levothyroxine
on an empty stomach usually in the morning, 30-60 minutes before food or other medication intake to avoid erratic absorption
what is oral manifestation of uncontrolled hyperthyroidism
- increased susceptibility to caries
- periodontal disease
- ageusia (loss of taste)
- burning mouth syndrome
- mandibular and/or maxillary osteoporosis
- difficulty swallowing (if goiter)
- increased anxiety or stress
- macroglossia
- sialadenitis
- dysguesia
- poor periodontal health
- enamel hypoplasia
- burning mouth syndrome
- xerostomia
- effect on bone health
- malocclusion
- swollen lips and face
- difficulty swallowing
what are the dental implications to hyperthyroidism
- increased sensitivity to sympathomimetic drugs/vasopressors such as epinephrine
- decrease effectiveness of/increaed tolerance to sedative/CNS depressants
- symptoms mistaken for anxiety
- CV symptoms - increased heart rate, BP
what are the dental implications to hypothyroidism
- increased respiratory and cardiac depression with sedatives/CNS depressants such as benzodiazepines, barbituates, and opioid analgesics
- possible bradycardia and decreased heart rate/cardiac output, increased peripheal resistance = more stress on CV system
- delayed wound healing due to decreased metabolic activity in fibroblasts
if euthyroid what do you do
manage normally during dental interventions/treatments/procedures
what are the hyperthyroid symptoms
- consider decreasing or avoiding sympathomimetics/vasopressors due to increased sensitivity
- may require higher doses of sedative/ CNS depressants
what are the dental implications of hypothyroid symptoms
- consider decreasing or avoiding CNS depressants due to increased sensitivity
- caution with sympathomimetics/vasopressors due to more stress on CV system
what are the dental implications of severe/uncontrolled hyper/hypo thyroid condition
consider postpoing dental treatment until consultation from provider or condition better managed (may take weeks to months)
what are adverse effects on propylthiouracil or methimazole for hyperthyroidism
- bleeding from agranulocytosis
- risk of infection from neutropenia
