steroid_p4.pptx

FARMAKOLOGI KLINIK OBAT

KHUSUSKORTIKOSTEROID

Ndaru Setyaningrum

TOPIK KORTIKOSTEROID Apa itu steroid? Mekanisme regulasi dan sekresi? Klasifikasi steroid? Fungsi steroid? Efek samping steroid? Withdrawal? Tappering off? Peran farmasis?

DEFINISI Kortikosteroid :

Senyawa kimia termasuk hormon steroid yang secara alami diproduksi oleh korteks adrenal dan analognya dapat disintesis digunakan baik sebagai penegakan diagnosis dan pengobatan gangguan fungsi adrenal

FISIOLOGI KORTEKS RENAL

Glomerulosa (mineralokortiko

id) Fasikulata

(glukokortikoid)

Retikularis (DHEA :

Androgen dehidroepiando

steron)

REGULASI SEKRESI HORMON ADRENAL

Adrenals

Kidney

Posterior Pituitary Gland

Hypothalamus

AnteriorPituitary Gland

ACTH

Stress Circadian

rhythm

CRH

(-)

Glucocorticoids, Catecholamines, etc..

Glucocorticoids, Catecholamines, etc..

Muscle: Net loss of aminoAcids (glucose)

Liver: Deamination of

proteins into amino acids,

gluconeogenesis (glucose)

Fat Cells: Free fatty

acid mobilization

Heart rate: Increased

Immune system: altered

Negative Feedback??

STRESS AND THE ADRENAL GLANDS

FUNGSI KORTIKOSTEROIDrespon terhadap stress, imunitas, regulasi peradangan, metabolisme KH, protein, lipidkadar elektrolit, perilaku

KLASIFIKASI BERDASARKAN AKTIVITAS / FUNGSI

Glucocorticoids (kortisol)mengendalikan metabolisme KH,

protein, dan lemak,efek anti inflamasi melalui

penghambatan pelepasan fosfolipase,menurunkan aksi eosinophil

Mineralcorticoids (aldosterone)mengatur kadar air dan elektrolit

terutama melalui proses retensi Na di ginjal

Cholesterol

Pregnenolone

Progesterone

Corticosterone

11-Desoxy-corticosterone

18-Hydroxy- corticosterone

ALDOSTERONE

17-α- Hydroxy pregnenolone

11- Desoxy- cortisol

17- Hydroxy progesterone

21,β hydroxylase

CORTISOL

11,β hydroxylase

Dehydro-epi androsterone

Andro-stenedione Oestrone

Oestriol

TESTOSTERONE OESTRADIOL

ACTH

KLASIFIKASI BERDASARKAN STRUKTUR KIMIA

"Coopman classification“Group A – hydrocortisone typeGroup B – acetonides (and related substances)

Group C – betamethasone typeGroup D - esters

Group A (short- to medium-acting glucocorticoids) Group B

hydrocortisone, hydrocortisone

acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, prednisone

triamcinolone acetonide,

triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, halcinonide

Group C Group D

betamethasone, betamethasone

sodium phosphate, dexamethasone, dexamethasone

sodium phosphate, fluocortolone.

D1 (Halogenated, less labil) hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate and

pivalate, and fluprednidene acetate

D2 (Labile prodrug esters) hydrocortisone-17-butyrate, 17-aceponate, 17-buteprate, and prednicarbate

INDIKASI TERAPEUTIK GLUKOKORTIKOID Glucocorticoids may be used in low doses

in adrenal insufficiency.Dose is approximately 6–12 mg/m²/day (m² refers BSA)

In much higher doses, oral or inhaled glucocorticoids are used to:Suppress various allergic ImunosuppressionAnti inflammatory

Glucocorticoids can be used in the management of familial hyperaldosteronism type 1

IMMUNOSUPPRESSION

ANTI INFLAMMATO

RY

RESISTANCE 25% of cases of severe asthma may

be unresponsive to steroids, causes :genetic predisposition, ongoing exposure to the cause of the

inflammation (such as allergens), immunological phenomena that bypass

glucocorticoids, and pharmacokinetic disturbances

MINERALKORTIKOID SINTETIS An example of a synthetic

mineralocorticoid is fludrocortisone.

Important mineralocorticoid inhibitors are spironolactone and eplerenone

ABNORMALITAS KADAR MINERALKORTIKOID

Hyperaldosteronism Hypoaldosteronism

Generally results from adrenal cancers.

The two main resulting problems: Hypertension and edema

due to excessive Na+ and water retention.

Accelerated excretion of potassium ions (K+). With extreme K+ loss there is muscle weakness and eventually paralysis.

Underproduction, or, leads to the salt-wasting state associated with Addison's disease, although classical congenital adrenal hyperplasia and other disease states may also cause this situation.

Efek kortikosteroi

d??

EFEK SAMPING KORTIKOSTEROID Corticosteroid withdrawal syndrome

(rebound effect) is a frequently seen occurrence, also called "Red Skin Syndrome". Total cessation of the steroid is mandatory and, while reversible, it can be a prolonged and difficult process to overcome.

Side effects such as cutaneous addiction with the development of uncomfortable and unsightly dermatoses, can occur with just one 15 mg tube of moderate steroid over a period of one year

CON’T ... Use of corticosteroids has several severe

side-effects as for example: hyperglycemia, insulin resistance, DM, osteoporosis, cataract, anxiety, depression, colitis, hypertension, ictus, erectile dysfunction, hypogonadism, hypothyroidism, amenorrhoea, and retinopathy.

While the evidence for corticosteroids causing peptic ulceration is relatively poor except for high doses taken for over a month,the majority of doctors as of 2010 still believe this is the case, and would consider protective prophylaxis measures.

CON’T.. Immunodeficiency

Glucocorticoids cause immunosuppression,This suppression, if large enough, can cause manifestations of immunodeficiency, including T cell deficiency, humoral immune deficiency and neutropenia

Hyperglycemia increased gluconeogenesis, insulin resistance, and impaired glucose tolerance ("steroid diabetes") caution in DM

CON’T ... Increased skin fragility, easy bruising

negative calcium balance due to reduced intestinal calcium absorption

Steroid-induced osteoporosis: reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)

weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation

CON’T ...` adrenal insufficiency (if used for long time

and stopped suddenly without a taper)

muscle breakdown (proteolysis), weakness, reduced muscle mass and repair

expansion of malar fat pads and dilation of small blood vessels in skin

anovulation, irregularity of menstrual periods

growth failure, delayed puberty

CON’T ... increased plasma amino acids,

increased urea formation, negative nitrogen balance

excitatory effect on central nervous system (euphoria, psychosis)

glaucoma due to increased cranial pressure

cataracts

WITHDRAWAL High-dose steroid (> a week) :

suppression of adrenal glands Prolonged suppression atrophy

adrenal glands

STRATEGI TAPPERING OFF Daily high doses ≤5 days, they can be abruptly

stopped (or reduced to physiologic replacement if patients are adrenal-deficient). Full adrenal recovery can be assumed to occur by a week afterward.

If high doses were used 6 - 10 days, reduce to replacement dose immediately and tapering off four more days. Adrenal recovery can be assumed to occur within two to four weeks of completion of steroids.

If high doses were used 11 – 30 days, cut immediately to twice replacement, and then by 25% every four days. Stop entirely when dose is less than half of replacement. Full adrenal recovery should occur within one to three months of completion of withdrawal.

STRATEGI TAPPERING OFF If high doses ≥ 30 days, cut dose immediately to

twice replacement, and reduce by 25% each week until replacement is reached. Then change to oral hydrocortisone or cortisone as a single morning dose, and gradually decrease by 2.5 mg each week. When the morning dose is less than replacement, the return of normal basal adrenal function may be documented by checking 0800 cortisol levels prior to the morning dose; stop drugs when 0800 cortisol is 10 μg/dl. Predicting the time to full adrenal recovery after prolonged suppressive exogenous steroids is difficult; some people may take nearly a year.’

Flare-up of the underlying condition for which steroids are given may require a more gradual taper than outlined above.

PERAN FARMASIS Memastikan penggunaan sesuai dgn indikasi pasien Memastikan bentuk sediaan, dosis KS yang diberikan

sesuai Merekomendasikan pengelolaan efek samping yang

tidak diharapkan pada penggunaan KS Merekomendasikan pengelolaan IO yang diperlukan

pada penggunaan KS Memastikan pasien dapat menggunakan sediaan KS

sesuai petunjuk (misal: salep, tetes / salep mata, tetes telinga, inhaler)

Memastikan pasien akan menjalani terapi tappering off pada penggunaan KS (bila diperlukan)

Memonitoring efektivitas, ESO, IO, kepatuhan penggunaan KS

Mem follow up kondisi pasien dan data obyektif terkait selama penggunaan KS KS : kortikosteroid