Voorzorgsmaatregelen en controles bij gebruik van systemische corticosteroiden

Orale of parenterale systemische corticosteroiden worden in de dermatologie regelmatig en bij vele indicaties toegepast. In deze richtlijn wordt voornamelijk ingegaan op zinvolle voorzorgsmaatregelen, controles, of laboratoriumbepalingen bij het starten of continueren van systemische therapie met prednison of vergelijkbare corticosteroiden.

De adviezen zijn van toepassing op een dosering waarbij bijwerkingen te verwachten zijn, globaal is dat meer dan 10 mg prednison per dag. Dit is een arbitrair getrokken grens, het wil niet zeggen dat er bij lagere doseringen geen bijwerkingen kunnen optreden, maar we achten het niet noodzakelijk om bij een patient die 10 mg prednison of minder gebruikt, routinematig controles te verrichten.

Voor de hoogte van de dosering wordt verwezen naar de adviezen die bij de afzonderlijke indicaties worden gegeven. Wel opgenomen in deze richtlijn is een omrekentabel voor andere synthetische steroiden en een samenvatting van de meest voorkomende bijwerkingen.

 

Controles voor het starten van prednison:

 

Controles tijdens prednisontherapie:

 

In de poliklinische setting is deze frequentie moeilijker realiseerbaar dan in de kliniek. Eventueel huisarts inschakelen. Advies: controleer bij langdurige prednisontherapie minimaal gedurende de eerste 3 maanden 2 x per maand glucose in urine, gewicht, en Hb, daarna indien stabiel 1 x per 1-3 maanden.


Indicaties voor maagzuursecretieremmers (Pantozol, Losec, of Zantac)

 

Dosering: pantoprazol (Pantozol) 1 dd 20 mg, omeprazol (Losec) 1 dd 20 mg, 's morgens, of ranitidine (Zantac) 2 dd 150 mg, 's morgens en voor het slapen gaan.

 

Voorkomen van osteoporose

 

Aanbevolen calciumintake (NIH, National Institutes of Health Consensus Development Conference on Optimal Calcium Intake, Washington, 1994)

 

0-6 maanden

400 mg

6 maanden - 1 jaar

600 mg

1-10 jaar

800 mg

16-25 jaar

1200-1500 mg

vrouwen

mannen

25-50 jaar: 1000 mg 

25-50 jaar: 800 mg

> 50 met HRT: 1000 mg

51-65 jaar 1000 mg

> 50 zonder HRT: 1500 mg

> 65 jaar 1500 mg

Bij zwangerschap of tijdens borstvoeding 400 mg extra

 


Aanvullende opmerkingen

 

Indicaties en werkzaamheid corticosteroiden

Indicaties: voor immuunsuppresie de glucocorticoiden (methylprednisolon, prednison, prednisolon). Voor substitutietherapie cortisonacetaat en hydrocortison, soms in combinatie met mineralo-corticoiden (fluorhydrocortison). In speciale gevallen (b.v. hersenoedeem) de gefluorideerde corticoiden (betamethason, dexamethason, paramethason, triamcinolon).

 

generische naam corticosteroïd:

relatieve anti-inflammatoire werkzaamheid:

relatieve mineralocorticoide werkzaamheid:

hydrocortison

1

1

cortison 

0.8

0.8

prednison

4

0.6

prednisolon

4

0.6

methylprednisolon

5

0.5

triamcinolon

5

0

paramethason 

10

0

betamethason

25

0

dexamethason 

25

0



Afleveringsvormen: Oraal: Intraveneus:

hydrocortison hydrocortison 20 mg Hydro-Adreson aquosum 100 mg, hydrocortison

100 mg, Solu-Cortef 100 mg

cortison cortison 5/25 mg, -

prednison prednison 5 mg -

prednisolon prednisolon 5 mg Di-Adreson-F aquosum 25 mg,

prednisolonpoeder 25 mg

methylprednisolon - Metypresol 40/125/500/1000 mg,

Solumedrol 40/125/250/500/1000 mg

triamcinolon Kenacort 4 mg,

Ledercort 2/4 mg,

triamcinolon 4 mg

paramethason Dillar 2 mg -

betamethason Betnelan 0.5 mg, Celestone 4 mg/1 ml

Celestone 0.5 mg

dexamethason dexamethason 0.5/1.5 mg, Decadron 4/20/100 mg, Dexamethason

Oradexon 1.5 mg 5/20/100 mg, Oradexon 5 mg

 

Bijwerkingen van systemische therapie

- acute bijnierschorsinsufficiëntie in stress situaties (vooral bij plotseling staken van therapie).

- retentie van water en natrium met als gevolg decompensatio cordis, oedeem en hypertensie (cave ß-blokkers), kaliumverlies, hypokaliëmische alkalose, verhoogde calciumuitscheiding.

- verlaagde koolhydraat tolerantie, glucosurie en/of diabetes met of zonder ketoacidose.

- maagulcera/perforaties, bloeding, pancreatitis, opgezette buik, ulceratieve oesophagitis.

- psychische veranderingen, euforie, slapeloosheid, stemmingswisselingen, karakter-veranderingen, depressie, onevenwichtigheid, psychosen.

- negatieve stikstofbalans, eiwitafbraak.

- osteoporose, compressiefracturen vertebrae, aseptische/avasculaire femurkopnecrose, spontane fracturen, peesruptuur.

- spierzwakte, spieratrofie, proximale steroïdmyopathie.

- menstruatiestoornissen, groeiremming bij kinderen, secundaire remming van hypofyse en bijnierschors (cave Addisonse crisis bij stress).

- Cushing syndroom (bolle gelaatsvorm (moonface), centripetale adipositas, buffalo hump).

- thrombo-embolie, gewichtstoename, toegenomen eetlust, misselijkheid, malaise.

- convulsies, intracraniële drukverhoging, papiloedeem (pseudotumor cerebri), vertigo, hoofdpijn, tremoren (zelden).

- subcapsulair lenscataract, verhoogde oogboldruk, glaucoom (bij oudere patiënten), exophthalmus, secundaire ooginfecties (schimmels, virussen).

- maskering van infekties.

- erytrocytose, granulocytose, lymfopenie, eosinopenie

- koorts, myalgie, artralgie, malaise na staken van langdurig gegeven therapie.



Effecten op de huid:

- gestoorde wondgenezing, dunne broze huid (atrofie van epidermis en dermis), ontstaan van teleangiëctasiën, bloedvatfragiliteit (haematomen, ecchymosen, petechiën), striae (remming collageensynthese).

- maskering infekties gisten, schimmels, bacteriën.

- granuloma gluteale infantum (roodpaarse noduli luiergebied).

- verhoogde transpiratie, soms branderig tintelend gevoel, vooral in perineum.

- acne.

- onderdrukking van epicutane allergische testen.

- soms allergische reacties (toxicodermie, urticaria, angio-oedeem).

- hypopigmentaties en atrofie bij lokale injectie





Corticosteroïd-geïnduceerde bijnierschors insufficiëntie

Symptomen primaire bijnierinsufficiëntie (m. Addison): asthenia, pigmentatie huid en slijmvliezen, gewichtsverlies, anorexia, misselijkheid, overgeven, hypotensie (<110/70), buikklachten, zouthonger, diarrhee, soms constipatie, syncope, associatie met vitiligo. Soms hypoglycemie, ernstige hypotensie (80/50), dehydratie, karakterveranderingen (snel geïrriteerd, rusteloos), verlies schaamhaar en pubishaar. Onderzoek: verlaagd natrium, chloor en bicarbonaat (hyponatriëmie door tekort aan aldosteron, verlaagt extracellulair volume, versterkt hypotensie), verhoogd kalium. Soms hypercalciëmie, normocytaire anemie, relatieve lymfocytose, lichte eosinofilie, ECG/EEG afwijkingen. Aldosteron laag, vasopressine en angiotensine II hoog, onvoldoende cortisol produktie na stimulatie bijnier met ACTH (Synacten).

Therapie: cortison 12.5-50 mg dd (b.v. 's ochtends 25 mg, 's avonds 12.5 mg), of cortisol 30 mg dd, of prednison 7.5 mg dd. Gecombineerd met mineralocorticosteroid, 0.05-0.1 mg 9-alpha-fluorohydrocortison (Florinef of fluorhydrocortison tab à 0.1 mg).

Bij de steroïd-geïnduceerde secundaire vorm ontbreekt de hyperpigmentatie (ACTH is niet verhoogd), en de associatie met vitiligo. De elektrolytafwijkingen zijn meestal minder ernstig. Na langdurige corticosteroïd therapie reageert de bijnier steeds minder goed op ACTH, ook wordt steeds minder ACTH geproduceerd. Nuchter cortisol is ook verlaagd, andere steroïden zijn verlaagd of laag-normaal. Net als bij m. Addison is substitutie therapie nodig met glucocorticosteroiden, de mineralocorticosteroid productie (aldosteron) is meestal nog voldoende.



Acute bijnierschorsinsufficiëntie (Addisonse crisis) kan ontstaan door plotseling relatief te kortschieten in stress situaties (acute infectie, sepsis, ernstige intermitterende ziekte, operatie), ook bij acute destructie (o.a. Waterhouse Friedrichsen syndroom), echter de belangrijkste oorzaak is het te snel staken van systemische steroiden. Symptomen: verergering bovengenoemde symptomen, hoge koorts, lethargie, somnolentie, bloeddrukdaling, hypovolemische shock (na chronisch glucocorticoïd gebruik valt de dehydratie en hypotensie meestal mee). Therapie: glucose 5% in fysiologisch zoutoplossing per infuus, onmiddelijk gecombineerd met 100 mg cortisol i.v., daarna continu 10 mg cortisol per uur. Voor de zekerheid ook direkt 50 mg cortisonacetaat i.m. Correctie van water en elektrolytverlies in overleg met internist. In ernstige gevallen kan dobutamine nodig zijn. Geleidelijk afbouwen naar een onderhoudsdosering, zonodig ook mineralocorticosteroid-suppletie.



Bijnierschorsinsufficiëntie uitsluiten: eerst een nuchter cortisol bepalen. Indien te laag een Synacten test laten doen door endocrinologie.



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