systemic steroids and RA

systemic steroids

used for a variety of conditions, such as inflammatory conditions

can also be used to treat adrenal insufficiency

hydrocortisone, cortisone, and prednisolone are commonly used as adrenal hormone replacement therapy. --> these have more GC (anti-inflammatory) effects than fludrocortisone, which has MC activity (helps with water and electrolyte balance)

fludrocortisone mimics aldosterone and is used to treat Addison's disease and sometimes orthostatic hypotension

systemic steroids can cause the adrenal gland to stop producing cortisol --> this is called suppression of the hypothalamic-pituitary-adrenal axis

when long term steroids are discontinued, they need to be tapered off to give the adrenal gland time to resume cortisol production

cushing's syndrome

can develop when the adrenal gland produces too much cortisol, or if exogenous steroids are taken in doses higher than the normal amount of exogenous cortisol

addison's disease is the opposite --> not making enough cortisol --> can be fatal

long-term effects of steroids

psychiatric changes

acne

GI bleeding/esophagitis/ulcers

diabetes

poor bone health

infection, impaired wound healing

growth retardation, muscle wasting

pink-purple stretch marks on abdomen, thighs, breasts, and arms

thin skin that bruises easily

fat deposits in face, abdomen, upper back

glaucoma, cataracts

women only --> hair growth on face and body, irregular or absent periods

ways to reduce systemic steroid risks

use every other day dosing

for joint inflammation, use intra-articular injections

for GI conditions, use a steroids with low systemic absorption

for treatment of asthma, use inhaled steroids that mainly stay in the lungs

for conditions that require long-term steroids, use the lowest effective dose for the shortest time possible

systemic steroid dosing/potency

short acting

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cortisone 25mg

hydrocortisone 20mg

intermediate acting

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prednisone 5mg

prednisolone 5mg

methylprednisolone 4mg

triamcinolone 4mg

long-acting and highest potency

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dexamethasone 0.75mg

betamethasone 0.6mg

steroids: least potent to most potent

** remember

Cute Helpful Pharmacists and Physicians Marry Together & Deliver Babies

GC (systemic steroids) drugs

dexamethasone (decadron)

hydrocortisone (solu-cortef)

methylprednisolone (medrol, solu-medrol)

prednisone

prednisolone (millipred, orapred ODT)

triamcinolone (kenalog)

betamethasone

cortisone

GC dosing

take oral doses with food to decrease GI upset

GC warnings

adrenal suppression --> if taking longer than 14 days, must taper slowly

GC side effects

short-term SEs (used <1 month) -->

fluid retention

stomach upset

emotional instability

insomnia

increased appetite

weight gain

acute increase in blood glucose/pressure

GC notes

cortisone is a prodrug of coritsol

prednisone is a prodrug of prednisolone

methylprednisolone is available as a therapy pack and an injection

immunosuppression from steroids

a patient is immunocompromised when using 2 or more mg/kg/day or 20 or more mg/day of prednisone or prednisone equivalent for >2 weeks

for these patients --> avoid live vaccines and taper when DC steroids due to HPA axis suppression

there are many ways to taper steroids; one method is to reduce the dose by ~10-20% every few days. taper lengths vary depending on the condition being treated

treating acute inflammation with steroids

give a high dose initially, then taper the dose down to treat the remaining inflammation while preventing a rebound attack

the medrol therapy pack provides a convenient taper kit, with 21 x 4mg tablets (will not be appropriate for all patients; may need a longer taper or higher starting dose)

day 1 --> 2 before breakfast, 1 at lunch, 1 at dinner, 2 at bedtime

day 2 --> 1, 1, 1, 2

day 3 --> 1, 1, 1, 1

day 4 --> 1, 1, 0, 1

day 5 --> 1, 0, 0, 1

day 6 --> 1

autoimmune conditions

common symptoms include fatigue, weakness, and pain

non-specific inflammatory markers can be useful in detecting inflammation --> ESR, CRP, RF, ANA

the use of strong immunosuppressants can increase the risk of certain conditions, including:

reactivation of tuberculosis or hepatitis (B or C) --> testing and treatment must be done prior to starting immunosuppressant drugs

viruses --> live vaccines should be given prior to starting immunosuppressant drugs

lymphomas and certain skin cancers --> these conditions are normally suppressed by a competent immune system

infections

rheumatoid arthritis

a chronic, progressive disorder that effects the joints

RA clinical presentaiton

bilateral, symmetrical inflammation with pain --> RA diagnosis

stiffness and pain are worse after rest, which is why morning stiffness is a common complaint --> in contrast, OA does not cause prolonged stiffness

anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) are useful lab tests for diagnosing RA

classic articular symptoms of RA

joint swelling

pain

stiffness

bone deformity

weakness

difficult to move

edema

redness

RA drug treatment

patients with symptomatic RA should be started on a disease modifying antirheumatic drug (DMARD), regardless of the severity of the disease

DMARDs work to slow the disease process and help prevent further joint damage

methotrexate (MTX) is the preferred initial therapy for most patients

never use 2 biologic DMARDs in combination

steroids are commonly used in RA flares and should be used at the lowest dose and for the shortest duration possible

DMARDs drugs

methotrexate (trexall)

hydroxychloroquine (plaquenil)

salfasalazine

leflunomide

JAKi --> tofacitinib, baricitinib, upadacitinib

methotrexate details

trexall is an oral tablet

other brands are SC auto-injections --> otrexup, rasuvo

irreversibly binds and inhibits dihydrofolate reductase, inhibiting folate

methotrexate dosing

7.5-20mg once weekly (PO, SC, IM)

low weekly doses are used for RA; to avoid error, it is safest to take as a single dose

never dose daily for RA --> can lead to liver damage

methotrexate BBW

hepatotoxicity

myelosuppression

mucositis/stomatitis

pregnancy

methotrexate monitoring

CBC

LFTs

chest X-ray

hepatitis B and C serologies

methotrexate notes

folate can be given to decrease hematological, GI, and hepatic side effects

hydroxychloroquine warnings

irreversible retinopathy

QT prolongation

hydroxychloroquine side effects

vision changes (dose-related)

hydroxychloroquine monitoring

eye exam

sulfasalazine CIs

sulfa or salicylate allergy

sulfasalazine ntoes

can cause yellow-orange coloration of the skin/urine

leflunomide details

inhibits pyrimidine synthesis

leflunomide BBW

do not use in pregnancy

hepatotoxicity

leflunomide CIs

pregnancy

leflunomide notes

accelerated drug elimination options:

- cholestyramine 8g PO TID x 11 days

- activated charcoal suspension 50g PO Q12h x 11 days

must have negative pregnancy test prior and use 2 forms of birth control during treatment --> if pregnancy is desired, must wait 2 years after DC or use an accelerated drug elimination process

JAKi BBW

serious infections

malignancy

thrombosis

JAKi notes

do NOT use with biologic DMARDs or potent immunosuppressants

methotrexate drug interactions

alcohol

renal elimination is decreased by aspirin/NSAIDs

anti-TNF biologic DMARDs

each drug has a pregnancy registry for tracking potential risks to the fetus

anti-TNF biologic DMARDs drugs

etanercept (enbrel) +/- MTX

adalimumab (humira) +/- MTX

infliximab (remicade) + MTX

certolizumab pegol (cimzia) +/- MTX

golimumab (simponi) + MTX

etanercept details

SC weekly

adalimumab details

SC every other week

infliximab details

IV

stable in NS only

infusion reactions

delayed HSR 3-12 days after admin

certolizumab pegol details

SC every other week

golimumab details

SC monthly

IV requires a filter

anti-TNF BBW

serious infections --> screen for latent TB (and treat if needed) prior to therapy

malignancies

anti-TNF warnings

can cause -->

demyelinating disease

hep B reactivation

HF

hepatotoxicity

lupus-like syndrome

** do NOT use with other biologic DMARDs or live vaccines

anti-TNF monitoring

prior to initiation --> TB test and treat if positive; test for HBV

signs of infection

anti-TNF notes

do not shake or freeze --> requires refrigeration

MTX is used 1st line and anti-TNFs are add-on therapy --> however, if initial presentation is severe, they can be started as initial therapy (+/- MTX)

other biologic DMARDs (non-TNFi) drugs

rituximab (rituxan) + MTX

anakinra

abatacept

tocilizumab

sarilumab

rituximab details

depletes CD20 B cells

IV

premedicate with a steroid, APAP, and an antihistamine

rituximab BBW

infusion-related reactions

HBV reactivation --> screen high risk groups for HBV and HCV prior to initiating therapy

rituximab warnings

do not give with other biological DMARDs or live vaccines

anakinra warnings

malignancies and serious infections

tocilizumab and sarilumab BBW

infections

screen for TB prior to initiating therapy

tocilizumab and sarilumab warnings

do not give with other biologic DMARDs or live vaccines

MTX counseling

dosed once a week for RA and psoriasis --> do not use daily or double up doses. choose a day of the week to take your medication that you can remember

can cause --> liver damage, infection, mouth sores, and stomach bleeding when used with aspirin/NSAIDs

avoid in pregnancy

avoid alcohol

take folic acid to decrease side effects

rasuvo and otrexup singe use auto-injector counseling

administer by SC injection into the abdomen or upper thigh --> do NOT inject into the arms

pinch the skin and inject at a 90 degree angle. press firmly until you hear a click. hold 3 seconds for otrexup and 5 seconds for rasuvo

needles are included

adalimumab, etanercept, and golimumab counseling

administer by SC injection

can cause --> injection site reactions, infection, liver damage, and HF

store the medication in the refrigerator with protection from light and sources of heat --> etanercept and adalimumab can be stored at room temp for 14 days

for adalimumab --> inject SC into the abdomen or thigh

for etanercept --> inject into the abdomen, thigh, or upper arm

for golimumab --> inject into the abdomen, thigh, or upper arm

needles are included