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Kortikosteroid

Kortikosteroid
Bentuk sintetik dari hormon yang disekresi oleh kortek

adrenal. Esensial: Maintenan beberapa sistem terutama sistem kardiovaskular Berperan pada respon tubuh thd stress
Mekanisme

Supresi proses inflamasi, alergi dan sistem imun Dapat untuk prevensi dan tx asma dan artritis rematoid

Actions of corticosteroids are grouped:


Glucocorticoid effects, including metabolic changes

and anti-inflammatory actions.


Mineralocorticoid effects, mainly retention of salt

and water, together with loss of potassium and hydrogen ions.

Classification of Corticosteroids ORAL CORTICOSTEROIDS


Glucocorticoid Effect

(dose equivalent)
SHORT ACTING Cortisone Hydrocortisone

Mineralocorticoid effect ++++ ++++

Duration of effect (in hours 8-12 hours 8-12 hours

25mg 20mg

INTERMEDIATE-ACTING Prednisolone 5mg Triamcinolone 4mg Methylprednisolone 4mg Fludrocortisone 750 micrograms 750 micrograms

++ ++++
-

18-36 hours 18-36 hours 18-36 hours 24-36 hours


36-54 hours 36-54 hours

LONG-ACTING Dexamethasone Betamethasone

HPA AXIS

Pharmacological Actions
1. Carbohydrate 8. Stomach 9.

2. Protein
3. Lipid 4. Electrolyte and H2O

Blood

10. Anti-inflammatory 11. Immunosuppressant 12. Respiratory system 13. Growth and Cell

5. CVS
6. Skeletal Muscle 7. CNS

Division
14. Calcium metabolism

Indikasi kortikosteroid:
Kontrol gejala: Asthma, allergic rhinitis, rheumatoid arthritis and related connective tissue disorders, temporal arteritis, inflammatory bowel disease, inflammatory skin conditions, emesis following chemotherapy, chronic pain, anaphylactic shock Prevensi: Transplant rejection, respiratory distress in the newborn, cerebral oedema Treatment: Certain tumours, hypercalcaemia, some blood disorders, nephrotic syndrome Replacement therapy in Addisons disease (under-activity of

the adrenal cortex)

Efek samping
Dosis tinggi jangka pendek --- ES < dosis rendah jangka

panjang Efek samping jangka panjang:

Redistribusi lemak

Hipertensi
Intoleransi glukosa Gangguan penyembuhan luka

Osteoporosis (bisa dicegah dg bifosfonat)


Katarak Tukak lambung (Omeprazol, misoprostol) resiko infeksi Efek SSP, psikosis Hambatan pertumbuhan pada anak

Cushings syndrome

Indikasi kortikosteroid:
Kontrol simtom: Asthma, allergic rhinitis, rheumatoid arthritis and related connective tissue disorders, temporal arteritis, inflammatory bowel disease, inflammatory skin conditions, emesis following chemotherapy, chronic pain, anaphylactic shock Prevensi: Transplant rejection, respiratory distress in the newborn, cerebral oedema Treatment: Certain tumours, hypercalcaemia, some blood disorders, nephrotic syndrome Replacement therapy in Addisons disease (under-activity of

the adrenal cortex)

Doses and Administration


Regular medication reviews are needed to ensure doses are kept to the minimum necessary to manage the underlying condition. Inhaled beclomethasone, budesonide daily doses >800 mcg (adult)

>400mcg (child) are associated with systemic (general) side effects. Side effects are seen at half these doses for fluticasone. Some high dose regimens include daily doses up to 2 mg and 1mg (fluticasone). Advice to patients should include:

Keep to the same spacer device. Mouth rinsing may reduce candidiasis and systemic absorption.

Pre-treatment with bronchodilator may reduce cough.

Doses and Administration


Oral prednisolone. Side effects appear if daily dose >7.5 mg.

Maintenance doses usually 2.5-15mg/ day. Severe disease may necessitate much higher doses. milk or food plus a full glass of water.

Administer as a single dose after breakfast, but before 9.00 am., with

Topical applications should avoid the face, and be free of occlusive

dressings (including disposable nappies).


and bleeding. document.

Rectal administration may give erratic absorption and cause local pain

If giving intramuscular injections, use each site only once and

Managing the Common Adverse Effects of Corticosteroids


Short courses at high dosage for emergencies appear

to cause fewer adverse effects than prolonged courses using lower doses.
Many adverse effects, for example, those related to

nutrition, only arise with long-term therapy.

INHALED CORTICOSTEROIDS
(dose equivalent Time in circulation for adverse effects)

Beclometasone Budesonide Fluticasone

1000 micrograms 1000 micrograms 500 micrograms

19.5 hours 6.9 hours 43.2 hours

propionate *calculated as 3 times the terminal half life.

(Karch 2000, BNF 2002, Cave et al. 1999, Lipworth 1999)

Corticosteroids may affect:


inflammatory and immune responses metabolic pathways: the starvation response + redistribution

skin gastrointestinal tract bones muscles

cardiovascular system central nervous system eyes reproductive system adrenal glands

SE

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Increased risk of infections

Teach good hand washing techniques Monitor body temperature at 5-6 p.m. daily Avoid exposure to infectious disease Contact doctor on exposure to chickenpox or measles. Caution with immunisations: avoid live vaccines (also for 6 months after discontinuation).

Potensi masalah
POTENTIAL PROBLEM SUGGESTED PREVENTION Encourage a well balanced, low calorie diet. Ask dietician to provide diet plan Monitor intake by asking patient to record intake for 24-hour periods. Weigh patient weekly Measure waist circumference regularly

Nutrition Increase in appetite

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Nutrition

Risk of dental caries

Encourage scrupulous dental hygiene & low-sugar diet. Arrange 6 monthly dental inspections Consider using a mouthwash

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Nutrition

Risk of hypertension

Foods rich in salt should be avoided, except with replacement regimens. Condiments and processed foods are high in sodium. Avoid salt-containing medicines e.g. some antacids. Avoid liquorice. Monitor blood pressure regularly.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Nutrition Risk of osteoporosis

Encourage patient to eat foods high in calcium. Low fat dairy products are suggested. Suggest vitamin D supplementation, together with monitoring for vitamin D intoxication.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Nutrition Loss of potassium, causing muscle weakness, depression, constipation, cardiac complications. Venous blood samples to monitor electrolytes Encourage foods that are high in potassium e.g. raisins, bananas, meat.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Nutrition

Limit salt intake. Fluid balance records and daily weighing are important during initiation of therapy

Salt and water retention

POTENTIAL PROBLEM Cardiovascular disease Hyperglycaemia / diabetes Increased cholesterol and triglycerides Congestive heart failure ? increased risks of thrombosis

SUGGESTED PREVENTION

Monitor blood glucose concentrations regularly and if thrush appears on the skin Monitor lipid profile Observe for breathlessness. Monitor fluid retention. Minimise salt intake. Monitor full blood count

POTENTIAL PROBLEM
Skin (particularly topical preparations) Increase in body hair and acne Poor wound healing

SUGGESTED PREVENTION

Provide advice on managing acne

Consult podiatrist regarding foot-care.


Anticipate poor healing and contact wound care specialists promptly.

Take swabs if healing delayed.

POTENTIAL PROBLEM Skin (particularly topical preparations) Thinning of the skin

SUGGESTED PREVENTION

Increased vigilance of pressure areas. Evaluate pressure damage risk score regularly Avoid friction and shearing forces on the skin, for example, teach patients in the correct use of moving and handling aids (glide sheets) when moving along the bed/chair.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Skin (particularly topical preparations) Thinning of the skin

Allow extra time for procedures involving tissue handling, such as transfer to hoist, care of infusion sites. Ensure good communication within the multidisciplinary team: for example, orthopaedic surgeons, and plaster technicians, or nurses applying plaster casts, need to be aware that the patient is prescribed corticosteroids, and adjust treatment, if possible.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Gastrointestinal Tract Irritation of stomach and oesophagus

Take oral corticosteroids with food or milk Observe and test stools for blood loss

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Bones Osteoporosis (see nutrition above)

Encourage moderate exercise Bone densiometry assessments Consider HRT

Growth Plot height and weight on centile charts at regular intervals.

POTENTIAL PROBLEM

SUGGESTED PREVENTION

Muscles Muscle weakness Cramps

Routine exercise may help to prevent or decrease muscle weakness. Assess activities such as rising from a chair Monitor respiratory function Check electrolytes if cramps occur

POTENTIAL PROBLEM Mental health

SUGGESTED PREVENTION

Monitor behaviour. Emotional changes such as moodiness, depression, euphoria or hallucinations

Consider the possibility of steroid psychosis and refer as necessary.

Steroid abuse/ dependence Refer patients who resist dose reductions.

POTENTIAL PROBLEM
Eyes (particularly eye drops or if creams applied close to eyes) Increased intraocular pressure and glaucoma Cataracts or clouding of vision Infections

SUGGESTED PREVENTION

Regular eye examinations are important to detect changes before permanent eye damage occurs. Arrange appointments on initiation of therapy, after 6 months, then at least yearly.

POTENTIAL PROBLEM Reproductive system Delayed puberty

SUGGESTED PREVENTION

Offer reassurance Changes in menstrual cycle Advise clients of potential problems Impotence

POTENTIAL PROBLEM

SUGGESTED PREVENTION Administer medication before 9.00 am.

Adrenal suppression/ insufficiency: Persists 3 months- years after discontinuation

Monitor pulse, blood pressure, electrolytes and glucose regularly. Repeat checks if bruises appear. After 1 weeks use, advise against sudden discontinuation of therapy. Advise wearing a medical-alert bracelet to inform emergency workers of medication

Control of Glucocorticoid Secretion (The hypothalamic/pituitary/adrenal (HPA) axis)

Corticosteroids administered as medications constantly inhibit CRH & ACTH secretion. The adrenal cortex eventually shrinks and may fail to synthesise any hormones, even in response to extreme stress, such as surgery or infection.

In health, when there is not stress, cortisol suppresses secretion of CRH and ACTH by a negative feedback mechanism

POTENTIAL PROBLEM

SUGGESTED PREVENTION Supervise gradual withdrawal of therapy

Withdrawal of therapy

Supervise transition from oral to inhaled administration and conversion to alternate day therapy.
Continue to monitor patients for possible adrenal insufficiency for a year after discontinuation. Ensure that patient always carries a 'steroid card'

Cautions and contra-indications


When administering corticosteroids, caution is needed in some circumstances: Presence of infections. Infections may 'flare up', including HIV/AIDS,

previous TB, wound infection, Herpes simplex.

Conditions which will be exacerbated: hypertension, diabetes, heart

failure, osteoporosis, glaucoma, epilepsy, mood disorders, pressure sores.

Conditions where potassium loss will prove dangerous: liver failure. Situations where muscle weakening could be problematic: Recent

myocardial infarction, muscle wasting, elderly, bedridden.

Cautions and contra-indications


Masking of serious symptoms: peptic ulcer,

inflammatory bowel disease, pneumonia

Corticosteroids worsen cardiovascular risk factors.

Their long-term use should be carefully evaluated in patients already at high risk of stroke or heart attack. eliminate drugs at the normal rate:

Lower doses are needed in patients unable to

hypothyroidism, liver failure, renal failure, elderly.

Cautions and contra-indications


Pregnancy. The risks of intrauterine growth retardation

with repeated courses of intra-muscular corticosteroids are administered to prevent respiratory distress of the newborn are currently under investigation. When cortIcosteroids are administered for severe maternal disease, the benefits are likely to outweigh any risks. Most prednisolone (unlike dexamethasone) is inactivated by the placenta.
equivalent) administered. Doses below those causing systemic side effects are considered safe.

Breastfeeding: avoid if >40mg prednisolone /day (or

Interactions (Not a complete list)


Corticosteroids interact with many other drugs. Some drugs intensify the adverse reactions of

corticosteroids:

Increased risk of gastro-intestinal bleeding: alcohol,

anticoagulants, aspirin, NSAIDs Increased fluid retention and hypertension: beta2 agonists, NSAIDs, sodium-containing preparations, oestrogens, liquorice, ginseng, some Asian herbal mixtures Increased potassium depletion: beta2 agonists, diuretics, digoxin, laxatives

Interactions (Not a complete list)


The effects of some drugs and appliances are antagonised: anti epileptics, anti-diabetics, anti-hypertensives, growth hormone, intra uterine contraceptive devices. The dose of corticosteroids is effectively reduced by: co-administration with antacids, within 2 hours carbamazepine, phenytoin, rifampicin, theophylline The dose of corticosteroids is effectively increased by: erythromycin, ketoconazole, itraconazole, ciclosporin, some anti-virals