Corticosteroids Flashcards
(27 cards)
Describe the corticosteroid stress response and how it can be triggered.
Stressful situations can override the negative feedback of cortisol at the hypothalamus and anterior pituitary leading to elevated levels of cortisol. Increased levels of cortisol are closely associated with immune suppression.
Possible triggers include pain, fear, cold, major surgery, trauma, injury, hemorrhage, hypoglycemia, and severe infection.
What is meant when corticosteroids are described as pleiotropic and permissive in their actions?
Corticosteroids have action at widespread locations including: metabolism, fluid balance, CV, skeletal, immune, renal, endocrine, and nervous systems.
The permissive action of corticosteroids means it modifies tissues responsiveness to other hormones.
How is mineralocorticoid specificity preserved?
MR is localized to certain tissues, such as kidney, colon, salivary glands, sweat glands, and hippocampus. Also, these tissue express 11Beta-hydroxysteroid dehydrogenase, an enzyme which inactivates cortisol by converting it to cortisone. Aldosterone is resistant to this enzyme.
Describe the effects of cortisol on metabolism of carbs, proteins, and lipids.
Corticosteroids produce an anti-insulin effect and stimulate proteinolysis, lipolysis, and gluconeogenesis.
Redistribution of fat occurs as central adipocity: decreased peripheral fat with abdominal deposition, buffalo hump, and moon face.
Describe the effects of mineralocorticoids and glucocorticoids, individually, on electrolyte/fluid balance and the cardiovascular system.
Mineralocorticoids
Induce sodium retention and potassium and hydrogen secretion at the collecting duct and tubules. This can result in hypertension, hypokalemia, and alkalosis. Mineralocorticoid-induced hypertension can result in atherosclerosis, cerebral hemorrhage, CVA, or cardiomyopathy. Control HTN with monitored dietary Na intake.
Glucocorticoids
Their effect on electrolyte and fluid balance is more passive by stimulating the secretion of Ca in the kidneys and preventing absorption in the gut. Glucocorticoids also have a permissive effect on adrenergic receptors of the cardiovascular system.
What are the effects of corticosteroids on skin and muscle?
Thinning of the skin and muscle wasting
What are the effects of corticosteroids on the CNS?
Aside from the support provided by the indirect effects, glucocorticoids can cause elevation of mood, insomnia, restlessness, and euphoria. A small percentage may experience anxiety, depression, and overt psychosis.
Describe how corticosteroids interact with the formed elements of the blood and the immune system. How does the immune system normally interact with the HPA axis?
Formed elements of blood
Corticosteroids cause the peripheral redistribution of monocytes, eosinophils, basophils, and lymphocytes. PMNs, platelets, and RBCs are increased.
Immune system
Corticosteroids inhibit the formation of many cytokines which play key roles in the immune response: PGs, LKTs, ILs, TNFalpha, Intrerferon, and GM-CSF. In the normal immune response IL-1 triggers CRH and ACTH production at the hypothalamus and anterior pituitary to prevent full blown inflammation.
Describe the relative potency of glucocorticoids with respect to effects on metabolism, inflammation, and sodium retention.
Those with potency in sodium retention, have a direct correlation to their ability to sustain life in adrenalectomized patients.
Those with metabolic effects closely parallel those with anti-inflammatory effects
What are the short-acting glucocorticoids?
Cortisol (hydrocortisone) and cortisone
What are the intermediate acting glucocorticoids?
Prednisone, Prednisolone, and Methylprednisolone
What are the long-acting glucocorticoids?
Dexamethasone
What are the two categories of toxic effects from corticosteroid therapy?
Withdrawal toxicities and supraphysiologic dose toxicities
What are the withdrawal effects?
The most frequent problem is flare-up.
The most severe problem is too rapid withdrawal leading to HPA suppression and acute adrenal insufficiency. Recovery from suppression takes weeks to a year.
Any individual with supraphysiologic doses for two weeks within the past year should be considered HPA suppressed in acute stress situations.
Less severe withdrawal - fever, myalgias, arthalgias, and malaise
What are the toxic effects of corticosteroids with respect to the HPA axis, fluid/electrolyte balance, Immunity, and gastric mucosa?
HPA axis suppression can cause life-threatening susceptibility to stress
Fluid/electrolyte balance - hypertension, hypokalemia, alkalosis, and edema
Immunity - increased susceptibility to infections
Gastric mucosa - Pt.s taking NSAIDs are increased risk for peptic ulcers
Describe the toxic effects of corticosteroids with respect to MSK, growth, behavior, and eyes.
MSK
Myopathy occurs in proximal muscles and manifests as weakness. Recovery is slow and partial. Osteoporosis occurs due to the effects on calcium secretion and absorption, as well as the inhibitory effects on osteoblasts. Low calcium activates osteoclasts leading to osteoporosis and veretebral compression fractures. Osteonecrosis can also occur, and manifests as joint pain or stiffness. Osteonecrosis ultimately requires joint replacement.
Growth is retarded in children who take repeated low doses
Behavior - changes in mood, insomnia, anxiety, and possibly overt psychosis
Eyes - cataracts, which are dose and duration dependent, will develop and may not resolve with discontinuation
What two situations would not warrant consideration of harmful effects linked with corticosteroids?
- A single dose, even very large, is without ADRs
2. A short course of therapy, up to one week and in the absence of CIs, is typically not harmful.
When is corticosteroid therapy constituted curative and palliative?
The only situation in which corticosteroids are curative are replacement therapies for deficiency syndromes. All other situations are considered palliative.
Describe a general approach to dosing corticosteroids.
In symptomatic situations which are mild: initial doses should be low and increased gradually until symptoms are minimally tolerable.
In situation of symptomatic life-threatening disease: Doses should be high at first to control the crisis then gradually lowered. If a high dose is not effective, consider doubling or tripling the dose.
Describe the two available therapeutic regimens and the situations in which they are used.
Alternate-day regimen - used for long-term therapy
Pulse-regimen - used for fulminant disorders
Describe the effects of corticosteroids on the immune system.
Peripheral redistribution of eosinophils, basophils, monocytes, and lymphocytes Increased circulating PMNs Inhibition of recruitment Inhibiton of APCs Inhibition of IL-2R expression
What are the methods and effets of glucocorticoids in the treatment of systemic AI diseases, rheumatoid arthritis, osteoarthritis, and vasculitis?
Systemic AI disease - mainstay of Tx; give high doses to control disease, then gradually taper.
Rheumatoid Arthritis - used to Tx flare-ups, pt.s who failed physiotherapy and NSAIDs, and gap Tx until Au salts or methotrexate kick in.
Osteoarthritis - can be injected into joints; limit frequency to prevent painless joint destruction
Vasculitis - combined with cyclophosphamide
Describe the glucocorticoid Tx of asthma, renal disease, allergic disease, or infectious disease.
Asthma - prophylaxis of asthma and inflammatory COPD; can be used for asthma requiring hospitalizations
Renal Disease - SLE and nephrotic syndrome
Allergic disease - delayed action, often combined with epinephrine
Infectious Disease - P. jirovecii in AIDS pt.s and H. influenzae type B meningitis
Describe the role of glucocorticoids in ocular disease
Applied topically to reduce inflammation. May cause posterior cataracts.
CIs = glaucoma, herpes simplex (dendritic keratitis), and mechanical injury (poor wound healing)
