Farmakologi Kortikosteroid

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 Mineralocorticoid Duration of (dose equivalent) effect effect (in hours) SHORT ACTING Cortisone 25mg ++++ 8-12 hours Hydrocortisone 20mg ++++ 8-12 hours

INTERMEDIATE-ACTING Prednisolone 5mg ++ 18-36 hours Triamcinolone 4mg - 18-36 hours Methylprednisolone 4mg - 18-36 hours Fludrocortisone - ++++ 24-36 hours

LONG-ACTING Dexamethasone 750 micrograms - 36-54 hours Betamethasone 750 micrograms - 36-54 hours

HPA AXIS

Pharmacological Actions

1. Carbohydrate

2. Protein

3. Lipid

4. Electrolyte and H2O

5. CVS

6. Skeletal Muscle

7. CNS

8. Stomach

9. Blood

10. Anti-inflammatory

11. Immunosuppressant

12. Respiratory system

13. Growth and Cell

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.

Administer as a single dose after breakfast, but before 9.00 am., with milk or food plus a full glass of water.

Topical applications should avoid the face, and be free of occlusive dressings (including disposable nappies).

Rectal administration may give erratic absorption and cause local pain and bleeding.

If giving intramuscular injections, use each site only once and document.

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 1000 micrograms - 19.5 hours

Budesonide 1000 micrograms - 6.9 hours

Fluticasone 500 micrograms - 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

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).

SE

POTENTIAL PROBLEM


Nutrition

Increase in appetite

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

Potensi masalah

POTENTIAL PROBLEM


Nutrition

Risk of dental caries

Encourage scrupulous dental

hygiene

& low-sugar diet.

Arrange 6 monthly dental

inspections

Consider using a mouthwash

POTENTIAL PROBLEM


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


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


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


Nutrition

Salt and water retention

Limit salt intake.

Fluid balance records and daily

weighing are important during

initiation of therapy

POTENTIAL PROBLEM


Cardiovascular disease

Hyperglycaemia / diabetes

Increased cholesterol and

triglycerides

Congestive heart failure

? increased risks of

thrombosis

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

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


preparations)

Thinning of the skin

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


Skin


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


Gastrointestinal Tract

Irritation of stomach and

oesophagus

Take oral corticosteroids with food or

milk

Observe and test stools for blood loss

POTENTIAL PROBLEM


Bones

Osteoporosis

(see nutrition above)

Growth

Encourage moderate exercise

Bone densiometry assessments

Consider HRT

Plot height and weight on centile

charts at regular intervals.

POTENTIAL PROBLEM


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

Emotional changes such as

moodiness, depression,

euphoria or hallucinations

Steroid abuse/ dependence

Monitor behaviour.

Consider the possibility of steroid

psychosis and refer as necessary.

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

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

Changes in menstrual cycle

Impotence

Offer reassurance

Advise clients of potential problems

POTENTIAL PROBLEM


Adrenal suppression/

insufficiency:

Persists 3 months- years

after discontinuation

Administer medication before 9.00 am.

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


Withdrawal of therapy

Supervise gradual 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.


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.

Lower doses are needed in patients unable to eliminate drugs at the normal rate: hypothyroidism, liver failure, renal failure, elderly.


Pregnancy. The risks of intrauterine growth retardation

with repeated courses of intra-muscular corticosteroids are administered to prevent respiratory distress of the new-born 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.

Breastfeeding: avoid if >40mg prednisolone /day (or equivalent) administered. Doses below those causing systemic side effects are considered safe.

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, intrauterine 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

Documents

Farmakologi Kortikosteroid