Corticosteroids Flashcards
Adrenal Gland Anatomy
Overview
Adrenal glands: sit on top of the kidneys & made of the cortex and the medulla (cortex = 90% of the mass)
Cortex: 3 layers
- Glomerulosa: alosterone secreted from here: to alter Na+ retention and K+ secretion
- Fasciculata: Cortisol & Androgens (cortisol > androgens) secreted here
- Reticularis: Androgens & Cortisol ( androgens > cortisol) secreted here
Medulla
- catecholamines (epi and norepi) secreted here
what are the effects of cortisol within the body
- anti-inflammatory properties & immunosuppressive : this is what steroid medications aim to mimic
- increase plasma volume & peripheral vasoconstriction
- retain sodium
- increase fatty acid release from adipose tissue
- release stored glucose
- decrease LDL uptake
- decrease muscle uptake of glucose
Cortisol Diural Rhythm
- highest cortisol peaks early in the AM - 8am
- production of cortisol in the body can change about 5-10 mg/daily
- when you draw labs matters
What is the HPA Axis
Hypothalmus-pituitary-adrenal axis (HPA)
- hypothalmus = secretes CRH (cortisol releasing hormone)
- travels to the pituitary to trigger pituitary
- pituitary = releases adrenocorticotropic (ACTH)
- ACTH travels to the adrenal glands and triggers
- adrenal glands release cortisol
HPA functions through a negative feedback mechanism
- increased levels of cortisol will trigger a downregulation in the production of ACTH and CRH
- decreased levels of cortisol will trigger an upregulation in production of ACTH and CRH
Hypercortisolemia (Cushing’s Syndrome)
- difference between syndrome and disease
- Excess ACTH released from the pituitary gland = cushings disease (a pituitary tumor)
- Excess Cortisol released from the adrenals = ACTH-independent mechanism & usually due to an adrenal tumor
an additiona way in which increased cortisol can be found within the body is due to exogenous steroid use
Adrenal Insufficiency
hypocortiosolemia
Primary: lack of cortisol release from the adrenal glands themselves
Secondary: lack of ACTH from the pituitary therefore a lack of cortisol from the adrenals
the high levels of CRH and ACTH in primary adrenal insuffiency show the lack of cortisol
Types of Corticosteroids
two classes
names under each
Corticosteroids
Glucocorticoids (mimic the actions of cortisol within the body)
- prednisone
- methylprednisolone
- dextamethasone
others include
- betamethasone
- budesonide
- hydrocortisone
- prednisolone
- trimcinolone
Mineralocorticoids (mimic the actions of aldosterone)
- Fludrocortisone
the difference comes to who binds to what receptor. Normally, cortisol will act on its own receptors, but also will act slightly on the mineralocorticoid receptors. This is true of the glucocorticoids as well, they will have some overlap at the mineralocorticoi recepotrs. The mineralocortioid meds will NOT act on cortisol receptors; they dont cross over
MOA of Corticosteroids (exogenous)
anti-inflammatory effects : supress the migrating leukocytes & decrease the ability to have an inflammatory response & reduce capillary permeability
immunosuppressive: reduce activity and ability of the lymphatic system to function (can be a downside of steroid use: more succeptible to infections)
The MOA effects of anti-inflammatory/immunosuppressive are due to transcriptional effects of the glucocorticoid receptor: alters the genes in leukocytes: repressing the ability to reproduce pro-inflammatory cytokins/chemokines
When are Corticosteroids used
acute v chronic use
Acute Use for Steroids
- urticaria (hives)
- asthma & COPD exacerbation
- atopic eczema
- inflammaed joints: OA, gout, etc.
Chronic Use for Steroids
- use lower doses if you are using them longer term
- psoriasis, allergic rhinitis
- asthma/COPD maintenace
Pharmacokinetics of Corticosteroids
bioavalibility
hepatic metablism
obesity consideration
Bioavalibility
- 60-100%
- IV = to oral absorbtion
Hepatic Metabolism
- mostly inactive metabolites after breakdown
- prednisone = has active metabolites so need to be ware in kids and in those with liver disease
- a good thing: meaning those with bad kidneys can still take steroids!
Obese Individuals
- use ideal body weight for weight-base dosing to avoid overdose
- use normal adult dosing if the medication is not a “weight based” dosing form
Contraindications of Corticosteroids
Warnings/Precautions
Contraindications
- systemic fungal infections: do not use; will onyl spread it further
- administeration fo live or live attenuated vaccies should not be done with pt. is on a immunosuppressive dose of prednisone
Warnings
- renal impairment pts = watch fluid retention (because action on the aldosterone receptors)
- hypertension/heart failure pt = watch fluid retention & BP increase (because of aldosterne receptors)
- hepatic impairment = steroids are metabolized here
- seizure disorder = potential risk of seizures
- peptic ulcer pt = risk of GI perforation
Other adverse effects of Steroid use
Psych
- sleep issue
- mood disturbances
- psychosis
Skin
- oedema (fluid bukdup in skin)
CVD
- HTN
MSK
- osteoporosis
Endocrine
- DM
- adrenal axis suppression
Optho
- catarcts
- narrow-angle glacoma
Developmental
- growth retardation
Drug-Drug Interactions of corticosteroids
what CYP
effect of antacids
effect of vaccines
action at the CYP 3A4 enzyme
- thus: CYP 3A4 inducers will decrease level of steroid in body
- CYP 3A4 inhibitors: will increase the level of steroid within the body
Antacids
- can decrease the bioavalibilty of the steroid
- separate dose by 2 hours
Vaccines
- can be less effective when on steroids (since immune system is blunted)
- administer vaccine 2 weeks before giving steroids
co-administration of steroids with other immunosuppressive drugs will increase immunosuppressive activity
Which doses of each corticosteroids are equlivent
where do the drugs act (sodium retentions (aldos.) v not)
Fludracortisone
- ONLY acts at the mineralocoorticoid receptors: NO action at the cortisol receptors
Dextamethasone, Triamcinolone & Methylprednisolone
- ONLY act the the cortisol receptor; NO action on the mineralocoritcoids
- DTM= Dont Touch Mineralocorticoid!!!
Cortisone, Hydrocortison, Prednisolone, Prednisone
- MAINLY act at the cortisol receptors; have MILD effect at the mineralocorticoid receptors
EQUAL DOSING = conversion
- Prednisone = 5 mg
- Cortisone = 25
- HCT = 20
- Methylpred. =4
- Dextamethasone = 0.75
highes to lowest dosing
Cortisone
Hct
Prednisone
Methylpred.
Dexameth.
Effect of exogenous steroid use on the HPA axis
taking large amoutns of corticosteroids for longer periods of time will lead to HPA axis suppression
- essentially: it turns off because you no longer need it, youre getting the cortisol effects from elsewhere
This is why tapering corticosteroids is necessary
- generally: the longer youve been on the med, the longer the taper needs to be
Cushing’s Syndrome
- approach for treatment (labs first)
- clincal presentation of cushings
first, understanding if its disease (coming from the pituitary): excess ACTH = excess cortisol
if its not coming from the pituitary: hypercortisolemia from oversecretion of adrenal gland (adrenal tumor)
how do you tell?
- get excess cortisol reading first : via 24 hour urine cortisol, midnight/late-night plasma/salivary (when its lowest) or dextamethasone suppression test (dex doesnt get picked)
- determine cause: serum ACTH levels & get CT/MRI for pituitary or adrenal tumor
Presentation
- weight gain + central adiposity
- CNS
- hirsutism: increased testosterone (because increased cortisol)
- skin thinning
- osteoporosis
- elevatedBP, glucose and cholesterol
