endocrine Flashcards
HPA axis diagrammed
Adrenal Gland
Comprised of adrenal cortex and adrenal medulla
◦ Inner – medulla
secretes catecholamines
◦ Outer – cortex
secretes adrenal steroids
Adrenal cortex produces about 50 different chemicals
adrenal products with pharmacologic properties:
Mineralocorticoids
Glucocorticoids, cortisol
Androgens
Adrenal Cortex layers
3 layers within cortex
◦ zona glomerulosa: produces mineralocorticoids
◦ zona fasciculata produces glucocorticoids
◦ zona reticularis: produces sex hormones, mostly androgens and small amount of glucocorticoid
Mineralocorticoids function
(produced in zona glomerulosa)
Regulate water and electrolyte balance
◦ Sodium (Na +), Potassium (K+) and fluid balance
◦ Provide important homeostatic functions
main mineralcorticoid and its function
Aldosterone – main endogenous hormone
◦ essential for blood pressure regulation and electrolyte and fluid homeostasis - helps to maintain normal blood pressure and electrolyte balance
◦ acts on the Mineralocorticoid Receptor (MR
Mineralocorticoid Receptor roles:
MR renal
Extra-renal MR plays a relevant role in?
Overactivation of the MR is implicated in?
MR present in kidneys impacts fluid and electrolyte balance
Extra-renal MR plays a relevant role in the control of cardiovascular and metabolic functions
Overactivation of the MR is implicated in the pathophysiology of aging related to cardiovascular, metabolic and kidney dysfunction and progress of diseas
Aldosterone Basics
Aldosterone Basics
Increases Na+ reabsorption by distal tubules in kidney
with concomitant increased excretion of K + and H +
Increases BP and blood volume – balance/control the
amount of sodium and fluids in the body
Work on specific intercellular receptors in kidney
Pharmacotherapeutic use of medications involving
mineralocorticoid effects
Replacement therapy Addison’s Disease/Adrenal Insufficiency
◦ Addison’s Disease (autoimmune disease)/Adrenal Insufficiency –
adrenal do not produce enough of the steroid hormones, cortisol
and aldosterone
Fludrocortisone (Florinef)
class?
Functionally similar to?
Most effect of all available roids?
Other steroids have much smaller amounts of? or no?
Other indications:
mineralocorticoid
Functionally similar to aldosterone
Most mineralocorticoid effect of available steroids
Other steroids have much smaller amounts of mineralocorticoid effects
(example: hydrocortisone, prednisone) or no mineralocorticoid effects
(example: dexamethasone, methylprednisolone)
Other indications: orthostatic hypotension, septic shock
Drugs that Inhibit Aldosterone:
imbalances of aldo and its results?
Imbalances in aldosterone and overactivity of the mineralocorticoid receptor contribute to hypertension, kidney insufficiency, heart failure and potentially other cardiovascular disease
◦ Due to idiopathic adrenal hyperactivity (most common) or benign tumor (Conn’s
syndrome)
Spironolactone (Aldactone) and Eplerenone (Inspra)
with steroidal structure
competitive aldosterone antagonist at receptor sites in distal renal tubules (block higher
concentration of kidney-specific MR), increasing sodium chloride and water excretion while conserving potassium and hydrogen ions – prevents mineralocorticoid effects of adrenal steroids on the renal tubule
Steroidal structure
Also known as a potassium sparing diuretics
Spironolactone (Aldactone) and Eplerenone (Inspra) indications
Hyperaldosteronism (secondary cause of hypertension and causes low potassium)
Heart failure
Hypertension
Drugs that Inhibit Aldosterone (Non-steroidal)
Finerenone (Kerendia)
Finerenone moa
◦ Blocks Mineralocorticoid receptor (MR) in kidney and heart
◦ Selectively blocks (antagonist) mineralocorticoid receptor-mediated sodium reabsorption and overactivation of kidney, blood vessel, and heart tissues, reducing fibrosis and inflammation
◦ MR overactivation is an important factor associated with CV events and Chronic Kidney Disease (CKD) progression (similar to SGLT2 inhib)
Glucocorticoids:
(endogenously produced in?
Mechanism of action –
* Widespread actions on?
* Potent regulatory effects on?
◦ Glucocorticoid receptors up regulate expression of? and down regulate expression of?
(endogenously produced in zona fasciculata)
Mechanism of action – complex: work through specific glucocorticoid intracellular receptors to regulate several vital cell activities
◦ Metabolic
◦ Immune function
* Widespread actions on intermediate metabolism, affecting carbohydrate (glucose), 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
main endogenous hormone of humans
Main endogenous hormone in humans – hydrocortisone
(also called cortisol)
◦ Produce 24-30 mg endogenous hydrocortisone/cortisol
◦ Use up to 300 mg/day in times of significant stress
how is cortisol secreted/when is it highest?
circadian rhythm, highest early in morning
HPA axis pathway
◦ Hypothalamus releases Corticotrophin-Releasing Hormone [CRH]
◦ Adrenocorticotropic hormone [ACTH] released from the anterior Pituitary
◦ Adrenals release glucocorticoids
◦ Negative feedback mechanism to inhibit CRH and ACTH when glucocorticoid concentrations increase in the blood
Therapeutic Use of Corticosteroids
- Many have partial mineralocorticoid and glucocorticoid properties
- Most are used for anti-inflammatory and immunosuppressive properties
common indications of corticosteroids
◦ Addison’s disease/Adrenal Insufficiency
◦ Cancer therapy (reduce ADE)
◦ Anaphylaxis
◦ Hypersensitivity states
◦ Shock
◦ Autoimmune disease
◦ Asthma (inhaled)
◦ Chronic obstructive pulmonary disease
◦ Respiratory distress syndrome in infants
◦ Suppressing rejection
◦ Acute renal insufficiency
◦ Inflammatory conditions of eyes, ears, nose or skin /rashes of the skin
Use of Steroids in Dentistry
Use for anti-inflammatory, pain management and auto-immune properties
Oral lesions
◦ Aphthous ulcers/stomatitis
◦ Oral lichen planus
◦ Erythema multiforme
◦ Behcet’s disease
◦ Pemphigus
◦ Bullous pemphigoid
◦ Systemic lupus erythematosus
Restorative dentistry/pain management
Bell’s palsy
Post herpetic neuralgia
Temporomandibular joint disorder
Temporal arteritis
Formulations of Corticosteroids for dentistry (topical)
◦ Importance of ?
◦ Example of commercially available product:
Dental (topical oral) applications
◦ Pastes, ointments/orabase, gels, lozenges, intralesional therapy, rinses – commercially
available or compounded
◦ Importance of contact time with lesion
◦ Example of commercially available product:
Kenalog® in Orabase® / Triamcinolone Dental Paste
pt education for corticosteroids used in dentistry
- Using a cotton swab, press (do not rub) a small amount of paste onto the area to be treated until the paste sticks and a smooth, slippery film forms. Do not try to spread the medicine because it will become crumbly and gritty.
- (Usually applied 2-3 times per day – see dosing information of the product). Apply the paste at bedtime so the medicine can work overnight. The other applications of the paste should be made following meals.
Other Formulations of Corticosteroids
Systemic
◦ Oral/IM/IV
◦ Pulse dosing/bursts
◦ Life-long replacement for adrenal suppression
Others
◦ Topical/external (creams/ointments) – skin/joints
◦ Intra-articular – joints
◦ Inhalation – asthma/COPD
Steroid Dosing Consideration
Consider the?
Weigh?
Topical/other types of administration may cause?
◦ Depends on?
Use lwhat doses/durations?
Monitor for ?
If patient on systemic therapy longer than? how do they stop?
Consult with?
with Addison’s Disease?
Consider the potency of steroids and formulations
Weigh pros/cons of oral topical vs. systemic therapy
Topical/other types of administration may cause systemic effects
◦ Depends on potency, amount, surface area covered, absorption,
permeability of tissue, dosing frequency, site treated, etc.
Use lowest effective dose for shortest duration
Monitor for adverse events
If patient on systemic therapy longer than 14 days, taper dose off.
DO NOT STOP ABRUPTLY – use taper
Consult with the patient’s provider for management of patients
with Addison’s Disease, chronic steroid use or steroid tapering
plans, when needed.
Relative Potencies and Equivalent Doses of
Common Corticosteroids
```
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taking systemic steroids
* Take when?
* Take with?
* If given for chronic adrenal insufficiency, may need to?
- 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
potnetcy with topical steroids
many products available can start high and go low or go from low and titrate up
Steroid Dosing
Systemic considerations
◦ Low dose
◦ Moderate dose
◦ High dose
◦ Low dose < 10 mg prednisone/day
◦ Moderate dose 10-20 mg prednisone/day
◦ High dose > 20 mg prednisone/day
Prednisone
◦ cost?
◦ Available in ?
◦ 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
Methylprednisolone (Medrol) Dose Pack dosing
could see insomnia with bedtime doses
Examples of Steroids/Dosing Used in Dental
Practice
how to write these Rx’s
Use of IV Steroids
Intra-operative administration
◦ Example: 3rd molar extractions with IV sedated patient
IV dexamethasone or IV methylprednisolone
◦ Provides anti-inflammatory effect (reduces pain and swelling)
◦ Helps reduce post-op nausea from the sedation
HPA Axis Suppression/Adrenal Suppression with use of corticosteroids
- When providing supraphysiologic doses of corticosteroids (> 25-30 mg of hydrocortisone/cortisol equivalents) X 14 days or more = HPA Axis SUPPRESSION
- May take weeks to months to fully recover function
- Use of chronic exogenous corticosteroids = suppression of adrenal gland = atrophy
- Inability of the adrenals to respond to stress can result in adrenal crisis
- Patient may develop chronic adrenal insufficiency (AI) from various causes
Chronic Adrenal Insufficiency (AI) causes
Primary Chronic AI – Addison’s Disease (autoimmune)
Secondary AI – damage/disease of the pituitary or hypothalamus
◦ Also caused from long-term use of glucocorticoids
chromnic primary AI tx regimens
- Treatment for chronic primary AI often includes oral hydrocortisone +/- fludrocortisone
- Other options for treatment of AI – prednisone, dexamethasone
Adrenal crisis prophylaxis
Acute adrenal crisis =
◦ Life-threatening?
◦ Predicated in?
◦ Symptoms
◦ Laboratory findings
Acute adrenal crisis = medical emergency (rare)
◦ Life-threatening condition
◦ Predicated in patients with chronic adrenal insufficiency (AI) with increased significant stress such as from infection, trauma or surgery
◦ Symptoms –fever, abdominal pain, weakness, hypotension, dehydration, nausea, vomiting, slow, sluggish movement, fatigue, profound weakness, rapid heart rate, rapid respiratory rate, confusion, loss of consciousness/coma
◦ Laboratory findings – low K + , low Na + , acidosis, uremia
Management of Acute Adrenal Insufficiency (AI) in Surgery – Steroid Cover
- IV fluids (5% dextrose in Normal Saline)
- Hydrocortisone
◦ 20-25 mg/day- Primary AI (Addison’s Disease – idiopathic, most commonly auto-immune)
◦ 15-20 mg/day – Secondary AI (exogenous corticosteroids or disease/disorders of hypothalamus or pituitary)
Secondary AI selectively causes glucocorticoid deficiency; therefore, mineralocorticoid function is better maintained
Adrenal crisis less likely than in primary AI - Hydrocortisone – IV initially then change to oral when patient is stable
Current evidence shows that routine dental care and minor oral surgical
procedures under local anesthesia, including uncomplicated dental extractions,
do not?
Current evidence shows that routine dental care and minor oral surgical
procedures under local anesthesia, including uncomplicated dental extractions,
do not increase stress levels enough to precipitate an adrenal crisis
Addisons dx undergoing major sx with general anesthesia prophy?
Consider 10 mg-25 mg hydrocortisone equivalents orally(po) stress dose cover for
those at highest risk (Addison’s Disease) undergoing major dental surgery with general
anesthesia (steroid cover)
Acute Adverse Effects to Long-term Effects of steroid use at diff systems
corticosteroids Interactions:
* warfarin?
* diuretics
* cardiac effects?
* Interferes withwhat absorption in food?
* Absorption of glucocorticoids is decreased in presence of?
- Increased prothrombin time/INR with warfarin
- Risk of hypokalemia with potassium-depleting diuretics (hydrochlorothiazide, others)
- Increased risk of cardiac toxicity and arrhythmias with cardiac glycosides (digoxin)
- Interferes with calcium absorption in food
- Absorption of glucocorticoids is decreased in presence of St. John’s wort
Contraindications to corticosteroids
- Severe infections,
- severe hypertension,
- severe heart failure,
- severe renal impairment
Corticosteroids: dental implications summary
Effective in?
◦ Alternative to?
Altered responses to ?
Oral thrush?
Contribute to ?
Patients with chronic adrenal insufficiency (AI): risk of developing?
- Effective in decreasing swelling/inflammation and pain
◦ Alternative to NSAIDS or opioids for pain in some cases or may decrease need for opioids - Altered responses to infection and wound healing
- Oral thrush from inhaled steroids (advise patients to rinse mouth after each inhaler use)
- Contribute to tooth decay, periodontal disease, decreased bone density (long-
term) - Patients with chronic adrenal insufficiency (AI): risk of developing acute adrenal
crisis when placed in a stressful situation such as major dental procedures
General Considerations for dental corticosteroid use
◦ dose/duratrion?
◦ abx?
◦ For inhaled steroids?
◦ Anxiety control?
◦ Increased administration of glucocorticoids (steroid cover)?
◦ Pulse steroid/lowest effective dose/shortest duration
◦ Systemic antibiotic therapy – if indicated
◦ For inhaled steroids - rinse/spit and spacers
◦ Anxiety control – for all patients, especially those with AI
◦ Increased administration of glucocorticoids (steroid cover)? - only in patients with AI at high risk/major dental procedures/surgery
Patient Education for Steroid Use
Purpose of steroids:
Purpose:
◦ Relieve the discomfort and redness, swelling/inflammation of some mouth and gum
problems or during/after dental procedures
◦ Useful for pain
◦ Timeframe for expected improvement
Dose/frequency/dosing instructions for steroids
◦ for systemic?
Adjustment if patient to receive?
If taper is involved?
◦ Length of ?
◦ Specific instructions for ?
◦ Do not use more often or for a longer time than?
◦ Take in AM for systemic administration
Adjustment if patient to receive steroid prescription (Medrol) in the afternoon to get all tablets in the first day
If taper is involved, specifics of taper, what dose to take each day
◦ 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
Common (short-term) side effects of steroids
◦ sleep?
how to reduce?
◦ mood
◦ Legs
◦ Weight
◦ blood sugar?
◦ bp?
◦ Insomnia/difficulty sleeping (one of the most common complaints)
Taking all in AM may help
Use of sleep agent for 1-2 nights? (risk vs. benefit)
◦ Agitation/changes in mood/irritability
◦ Leg swelling
◦ Weight gain (more with long-term use)
◦ Risk of increased blood glucose (especially in diabetics)
◦ Risk of increased blood pressure (especially if already elevated)
hypothal-pit-thyroid axis diagrammed
thyroid hormones
forms?
coversion?
◦ thyroxine (T4) – large storage – high serum concentrations in body
◦ tri-iodothyronine (T3) – small storage – low serum concentrations in body (fast
turnover rate)
80% of T3 daily production is a result of peripheral conversion of T4 →T3
T4 is converted to T3 primarily in the liver and kidney but also in many other tissues
◦ calcitonin
thyroid hormone functions
T3 and T4 (combined are referred to as thyroid hormone)
◦ normal growth and development in children (brain and body)
◦ control energy/metabolism
◦ involved in normal functioning of almost every organ system including the brain, heart, liver, and muscles
Calcitonin
◦ control of plasma calcium (Ca2+
Basics of Regulation of Thyroid Function
- Thyrotrophin releasing hormone (TRH) stimulated from hypothalamus
- Thyroid stimulating hormone (TSH) from anterior pituitary
- Thyroid hormone synthesi resulting in release of T3 and T4
- Negative feedback on anterior pituitary with T3 more active than T4 ( increased thyroid hormone = decreased TSH)
- Plasma iodine also impacts thyroid hormone production (decrease of iodine = decreased hormone production and decreased TSH)
Actions of Thyroid Hormones: metabolism and growth/development
Effects on metabolism
◦ increased metabolism on carbohydrates, fats and protein (most effects in conjunction with other hormones)
◦ T3 3-5X more active than T4
Effects on growth and development
◦ direct action and indirectly influences growth hormone
skeletal development
growth and maturation of CNS
HYPERthyroidism (Thyrotoxicosis)
Diffuse toxic goiter (Graves Disease/exopthalmic goiter)
◦ autoimmune disease (autoantibodies to TSH receptor)
◦ protruding eyeballs (exophthalmos)
Toxic nodular goiter
◦ benign neoplasm or adenoma
HYPERthyroidism Symptom
HYPERthyroidism treatments
Surgery
Radioactive Iodine (RAI)- 131 I (destroys thyroid follicles)
◦ hypothyroidism usually results from surgery or RAI
Drug Therapy (oral)
◦ Propylthiouracil (PTU)
◦ Methimazole (MMI)s
◦ Beta Blockers (propranolol): symptomatic relief only!
◦ Glucocorticoids for exophthalmos in Graves Disease
◦ Propylthiouracil (PTU) and Methimazole (MMU) moa
MOA → inhibit biosynthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine (T 4) and triiodothyronine (T 3); does not inactivate circulating T 4 and T 3
PTU and MMU ADRs
neutropenia, agranulocytosis, aplastic anemia, liver toxicity
HYPOthyroidism General Definition:
◦ Myxedema?
◦ Free thyroxine (fT4) is: sub-normal/low (normal range 0.8 – 2.8 mg/dl) and Thyroid-
Stimulating Hormone (TSH) is usually elevated/high (normal range 0.45 mIU/L - 4.12
mIU/L-varies depending on lab)
◦ Myxedema – term used for severe hypothyroidism
dermatologic changes that can occur (swelling in legs/eyes)
coma that can occur as an extreme complication
Subclinical Hypothyroidism (early hypothyroidism)
◦ Free thyroxine (fT4) ?
◦ Thyroid-Stimulating Hormone (TSH) ?
◦ s/s?
◦ Free thyroxine (fT4) is: normal
◦ Thyroid-Stimulating Hormone (TSH) is: elevated/high
◦ Mild to no symptoms of hypothyroidism
Overt Hypothyroidism
◦ Free thyroxine (fT4)?
◦ Thyroid-Stimulating Hormone (TSH) ? /
◦ Free thyroxine (fT4) is: sub-normal/low
◦ Thyroid-Stimulating Hormone (TSH) is usually: elevated (normally > 10 U/ml)
HYPOthyroidism Causes
worldwide vs US
Worldwide:
◦ Iodine deficiency
Iodine sufficient countries:
◦ Chronic Autoimmune Thyroiditis (AITD/Hashimoto’s)
hashimotos
risk factors
reaction against thyroglobulin or other thyroid tissue
Women > Men
Age
Other autoimmune disorders
Goiter may or may not be presen
hypothyroid s/s
Goal of therapy for hypothy
Restore ?
TSH?
Reduction in?
Avoidance of ?
Restore euthyroid state
TSH – usually 0.45 mIU/L - 4.12 mIU/L for reference population
Alleviate symptoms
Reduction in size of goiter (if present)
Avoidance of overtreatment (iatrogenic thyrotoxicosis)
Drug Therapy for hypothy
Levothyroxine/Synthroid (synthetic T4 ) – most common therapy
◦ usual dose 50-100 mcg
* ◦ lower doses in patients with coronary artery disease
* other options:
Liothyronine/Cytomel, Triostat (synthetic T3 )
Liotrix / Thyrolar (4:1 ratio of synthtic T4 :T3 )
Thyroid desiccated /Armour Thyroid (“natural” – pig - T4 +T3
Clinical Pearls for hypothyroid rx’s
◦ Dosing dependent on?
◦ Onset of action/ full affects?
◦ Take on an?
◦ Recommended to?
◦ Dangers of using thyroid supplementation for?
◦ Dosing dependent on age, sex and body size
◦ Onset of action 1-2 weeks, full effects 4-6 week
◦ Take on an empty stomach 30-60 minutes before meals (in morning) and before other medications!
◦ Recommended to a consistent product to minimize variability! (narrow therapeutic index)
◦ Dangers of using thyroid supplementation for weight loss in euthyroid patients
Adverse Effects of thyroid treatments
- Too much or too little supplementation/thyroid hormone, could essnetially overcorrect to opposite dx
Drug Interactions with Thyroid Supplementation
- Interference with absorption
- Decreased hormone production/secretion
- Peripheral metabolism of T4
- Altered secretion of TSH
- Increased clearance of T4
Interference with absorption with thyroid supplementing rx
◦ Bile acid sequestrants
◦ PPIs
◦ Oral bisphosphonates
◦ Iron and calcium supplements
◦ Orlistat
Decreased hormone production/secretion with thyroid supplementing rx
◦ Amiodarone (can also cause hyperthyroidism - iodine rich)
◦ Lithium
Peripheral metabolism of T4 ddi with thyroid supplementation
◦ Glucocorticoids, amiodarone
altered secretion of TSH with thryoid supps
◦ Dopamine (and dopaminergic agonists)
◦ Glucocorticoids
◦ Octreotide
◦ St John’s Wort
◦ Amphetamine
Increased clearance of T4 ddi for thyroid supps
◦ Many antiepileptics
◦ Quetiapine
levothyroxine therapeutic index
Narrow therapeutic index (NTI) 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
Evidence from studies hasn’t showing any clinical difference in brand, generic or switching generic manufacturers
when should levothyroxine be taken?
Because absorption can be decreased by other vitamins, minerals and/or medications, it’s recommended to be taken on an empty stomach (usually in the morning), 30-60 minutes before food or other medication intake to avoid erratic absorption
Undiagnosed thyroid dx in pt
Undiagnosed – be aware of hyper/hypo-thyroid symptoms and refer to provider
◦ identification of enlarged thyroid/goiter
Hyperthyroidism implications in dentistry
◦ increased sensitivity to ?
◦ decrease effectiveness of ?
◦ symptoms mistaken for?
◦ increased sensitivity to sympathomimetic drugs/vasopressors such as epinephrine - hypertensive crisis, tachycardia, and/or dysrhythmia
◦ decrease effectiveness of CNS depressants
◦ symptoms mistaken for anxiety
Hypothyroidism implications in dentistry
◦ increased respiratory and cardiac depression with?
◦ Over supplementation could result in?
◦ increased respiratory and cardiac depression with benzodiazepines (diazepam,
alprazolam), barbiturates (sodium thiopental), and opioid analgesics (hydrocodone)
◦ Over supplementation could result in cardiovascular symptoms seen in hyperthyroidism
Dental Implications
* If euthyroid (treated thyroid disorders)?
* Hyper/hypo-thyroid symptoms - consider decreasing or avoiding:
* Severe/uncontrolled hyper/hypo-thyroid condition:
If euthyroid (treated thyroid disorders) – manage normally during dental interventions /treatment /procedures
Hyper/hypo-thyroid symptoms - consider decreasing or avoiding:
◦ sympathomimetics/ vasopressors in symptomatic hyperthyroidism
◦ CNS depressants in symptomatic hypothyroidism
Severe/uncontrolled hyper/hypo-thyroid condition – consider postponing dental treatment until consultation from provider or condition better managed (may take weeks to months)
Dental Implications
* On Propylthiouracil (PTU) or Methimazole (MMI) for hyperthyroidism- caution with? r patients on thyroid supplementation?
On Propylthiouracil (PTU) or Methimazole (MMI) for hyperthyroidism- caution with bleeding from agranulocytosis or risk of infection from neutropenia
Absorption issues or other drug interactions for patients on thyroid supplementation
Steroids for adrenal crisis in patients with Adrenal Insufficiency
only needed for?
Steroids for adrenal crisis in patients with Adrenal Insufficiency
only needed for patients undergoing major dental surgery
which aldo antagonist works at both the kidneys and heart
Finerenone
mineralocorticoid
Functionally similar to aldosterone
Most mineralocorticoid effect of available steroids
Other steroids have much smaller amounts of mineralocorticoid effects
(example: hydrocortisone, prednisone) or no mineralocorticoid effects
(example: dexamethasone, methylprednisolone)
Other indications: orthostatic hypotension, septic shock
Fludrocortisone (Florinef)
class?
Functionally similar to?
Most effect of all available roids?
Other steroids have much smaller amounts of? or no?
Other indications:
competitive aldosterone antagonist at receptor sites in distal renal tubules (block higher
concentration of kidney-specific MR), increasing sodium chloride and water excretion while conserving potassium and hydrogen ions – prevents mineralocorticoid effects of adrenal steroids on the renal tubule
Steroidal structure
Also known as a potassium sparing diuretics
Spironolactone (Aldactone) and Eplerenone (Inspra)
with steroidal structure
◦ Blocks Mineralocorticoid receptor (MR) in kidney and heart
◦ Selectively blocks (antagonist) mineralocorticoid receptor-mediated sodium reabsorption and overactivation of kidney, blood vessel, and heart tissues, reducing fibrosis and inflammation
◦ MR overactivation is an important factor associated with CV events and Chronic Kidney Disease (CKD) progression (similar to SGLT2 inhib)
Finerenone moa
- Severe infections,
- severe hypertension,
- severe heart failure,
- severe renal impairment
Contraindications to corticosteroids
MOA → inhibit biosynthesis of thyroid hormones by blocking the oxidation of
iodine in the thyroid gland; blocks synthesis of thyroxine (T 4) and triiodothyronine
(T 3); does not inactivate circulating T 4 and T 3
◦ Propylthiouracil (PTU) and Methimazole (MMU) moa
neutropenia, agranulocytosis, aplastic anemia, liver toxicity
PTU and MMU ADRs
