Download - Farmakologi Kortikosteroid
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Kortikosteroid
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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
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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.
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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
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HPA AXIS
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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
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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)
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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
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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)
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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.
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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.
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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.
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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)
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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
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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
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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
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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
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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.
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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.
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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.
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
Nutrition
Salt and water retention
Limit salt intake.
Fluid balance records and daily
weighing are important during
initiation of therapy
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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.
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
Skin
(particularly topical
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.
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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.
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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
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
Bones
Osteoporosis
(see nutrition above)
Growth
Encourage moderate exercise
Bone densiometry assessments
Consider HRT
Plot height and weight on centile
charts at regular intervals.
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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
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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.
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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.
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
Reproductive system
Delayed puberty
Changes in menstrual cycle
Impotence
Offer reassurance
Advise clients of potential problems
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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
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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
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POTENTIAL PROBLEM
SUGGESTED PREVENTION
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'
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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.
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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.
Lower doses are needed in patients unable to eliminate drugs at the normal rate: hypothyroidism, liver failure, renal failure, elderly.
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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 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.
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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
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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