steroid_p4.pptx
TRANSCRIPT
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