Systemic Steroids and Autoimmune Conditions Flashcards
Why are steroids used in adrenal insufficiency?
to replace endogenous steroids that adrenal gland is not producing enough of
which endogenous steroids requirement replacement in adrenal insufficiency?
Cortisol -> replaced by any steroids
Aldosterone -> replaced by fludrocortisone
what does aldosterone/fludrocortisone do?
it has mineralocorticoid activity
AKA maintains the balance of water and electrolytes to keep blood pressure stable
what are the indications for fludrocortisone?
FDA: Addison’s
Non-FDA: orthostatic hypotension
What does glucocorticoid activity entail?
anti-inflammatory effects
What can systemic steroids with glucocorticoid activity cause the adrenal gland to do?
stop producing cortisol due to feedback inhibition
HPA axis suppression!
Why is it important to taper off steroids?
so the adrenal gland has time to resume cortisol production
Explain the HPA axis
Hypothalamus produces CRH (cortisol releasing hormone) which stimulates the pituitary gland to release ACTH (adrenocrticotropic hormone) which stimulates the adrenal glands to produce cortisol. Cortisol suppresses ACTH and CRH produces vai negative feedback
how does Cushing’s develop?
adrenal gland produces too much cortisol or exogenous drugs are taken in high doses
How does Addison’s develop?
opposite of Cushing’s! it’s when the adrenal gland is not making enough cortisol or if exogenous steroids are stopped suddenly (Addison’s crisis) = fatal!
Adverse effects of cushing’s
Psychiatric chcanges acnes glaucoma moon face/buffalo hump stretch marks muscle wasting impaired wound healing diabetes irregular periods/hirsutism poor bone health gi bleeding/ulcers
ways to reduce the adverse effect of steroids
alternate day dosing
use localized therapy (inhaltion for lungs, injection for joints)
lowest possible dose for shortest amount of time
which steroid has low systemic absorption?
budesonide
Steroids least to most potent and dose equivalence
Cortisone 25mg Hydrocortisone 20mg Prednisone 5 mg Prednisolone 5 mg Methylprednisolone 4 mg Triamcinolone 4 mg Dexamethasone 0.75 mg Betamethasone 0.6 mg "Cute Hot Pharmacists and Physicians Marry Together and Deliver Babies"
Contraindications for systemic steroids
Live vaccines, serious systemic infections
prodrug of cortisol
cortisone
prodrug of prednisolone
prednisone
which steroid is typically used in children?
prednisolone (liquid form)
At what dose and time period is a patient on steroids considered immunosuppressed
> 2mg/kg/day for > 2 weeks
lab tests that can detect inflammation in autoimmune disorders
ESR
CRP
RF
ANA (anti-nuclear antibody)
Why is a high dose given intially then tapered down?
to prevent Addison’s crisis AND
quickly reduce inflammation then treat remaining inflammation while preventing a rebound attack
what conditions does the use of strong immunosuppressants increase the risk of?
re-activating TB/HepB and C : test and treat before starting
live vaccine virus : vaccinate before starting immunosuppressants
Lymphoma/skin cancers
fungal/bacterial infections - monitor CBC
RA presents bilaterally/symmetrically or unilaterally?
bilaterally/symmetrically
OA presents bilaterally/symmetrically or unilaterally
unilaterally
Symptoms of RA
systemic! fever, weakness, loss of appetite, worsening stiffness after rest (morning stiffness) joint swelling bone deformity edema redness
does OA cause prolonged stiffness?
NO!
how to diagnosis RA
test for ACPA (anti-citrullinated peptide antibdoy) and RF
if later in disease state will see joint erosion and rheumatoid nodules
what should a patient be started on if symptomatic despite severity level?
DMARD
how do DMARDs work?
slow disease progression and prevent further joint damage
Preferred initial therapy in most patients?
Methotrexate
What is preferred therapy in patients with mod-severe RA
combo of DMARD or TNF inhibitor biologic or a non-TNF biologic with/without MTX
What should never be done with RA drug treatment
using 2 biologics together!
Risk of serious infections!
when can you use a low dose steroid in RA patients/
when starting a DMARD in a moderate or severe patient to provide some relief while waiting for the DMARD to work
or in patients with hx of dmard failure
MOA of MTX
inhibis dihydrofolate reductase inhbiting folate causing immune modulator and anti-inflammatory activity
RA dosing for MTX
7.5 - 20 mg once WEEKLY!
daily dosing in RA leads to liver damage and intestinal bleeding
monitoring with MTX use
cbc
lfts
chest x-ray
hep B and C serologies
what can be given with MTX to decrease Gi and hepatic side effects
folate
Warnings with hydroxychloroquine
irreversible retinopathy - eye exam needed!
counseling note with sulfasalazine
yellow-orange color of skin/urine
MOA of leflunomide (Arava) f
inhibits pyrimidine synthesis causing anti-proliferative and anti-inflammatory effects
which traditional DMARDs are teratogenic?
MTX and Leflunomide
Warnings with leflunomide
DNU in pregnancy
hepatotoxicity
SJS risk
Accelerated drug elimination process needed upon d/c to lower levels of teriflunomide (active metabolite)
what DMARD requires accelerated drug elimination?
leflunomide
what are the two accelerate drug elimination options with lefluomide?
- cholestyramine 8 g tid for 11 days
2. activated charcoal suspension 50 g q 12 h 11 days
how long must a patient wait if wanting to get pregnant after using leflunomide?
2 years or use accelerated drug elimination procedure
List of Janus Kinase Inhibitors (JAK)
Tofacitinib (Xeljanz)
Baricitinib (Olumiant)
Upadacitinib (Rinvoq)
JAK inibitor MOA
Inhibit the enzyme janus kinase which stimulates immune cells
Boxed warnings with JAK inhibitors
serious infections
malignancy risk increase
thrombosis risk
Special warning with Xeljanz (tofacitinib)
increased mortality in patient >50 years old with 1 or more CV risk and taking higher dose
Interactions with MTX
alcohol - liver tox NSAIDs/beta lactams/probenecid - renal tox sulfonamides and topical tacrolimus loops cyclosporines
List of Anti-TNF (tumor necrosis factor) alpha inhibitors
etanercept (Enbrel) adalimumab (Humira) infliximab (Remicadde) certolizumab pegol (Cimzia) golimumab (Simponi)
Etanercept (enbrel) dosing schedule
50 mg sc WEEKLY
Adalimumab (humira) dosing schedule
40 mg sc EVERY OTHER week
without MTX: weekly
Infliximab dosing (Remicade)
3 mg/kg IV weeks 0,2,6 then every 8 weeks
can do 10mg/kg or every 4 weeks but increased infection risk
Remicade preparation
filter needed
only stable in Normal saline
what’s something unique about hypersensitivity reactions with Remicade?
delayed (3-12 days) after administartion
Simponi (golimumab) dosing
50 m gmonthy for sc
2mg/kg IV at week 0,4 then every 8
Which anti-TNF biologic DMARDs require filters?
Simponi (golimumab) and Remicade (infliximab)
CI specific for infliximab
doses >5 mg/kg in mod-severe heart failure
CI specific for etanercept
sepsis
role of anti-TNF biologics
add-on therapy with MTX unless the presentation is severe, then can be started as initial therapy with or without MTX
