final ICH ppt (2)(1)

DONE BY: SHAHINBANU GHORI

INHALED CORTICOSTEROIDS:

Inhaled corticosteroids are the most effective long term control asthma

medicines.

Inhaled corticosteroids act locally in the lungs to inhibit the inflammatory

process, which causes asthma. They are potent anti-inflammatory agents and

effectively reduce asthma symptoms.

INHALED CORTICOSTEROIDS USES:

Inhaled

corticosteroids:

Asthma

COPD

Inflammation in the

airways in lungs

INHALED CORTICOSTEROIDS EXAMPLES:

Fluticasonepropionate

Budesonide Beclomethasonedipropionate

Flunisolide Triamcinolone Mometasone Ciclesonide

MECHANISM OF ACTION:

Anti inflammatory effect by--

Inhibition of the synthesis of other

cytokines like interferon and tumor necrosis

factor-a.

Interference with synthesis of interleukin 1

in macrophages and interleukin 2 in T-

lymphocytes.

Reduction of prostaglandin synthesis

due to inhibition of cyclooxygenase-2 (cox-

2) induction.

Improvement of airways

hyperresponsivness

The British Thoracic Society/Scottish Intercollegiate

Guidelines Network (BTS/SIGN) and Global Initiative for

Asthma (GINA) guidelines recommend the use of ICSs to reduce

symptoms, improve lung function, reduce the frequency of severe

exacerbations, including hospital and ICU admissions, and

decrease the risk of mortality.

Patients with asthma who do not use an ICS regularly have

poorer outcomes. A national review of asthma deaths in the UK

in 2014 found that patients with asthma who did not use an ICS

were at significantly greater risk of death.

INHALED CORTICOSTEROIDS:place in therapy

EPIDEMIOLOGY:

A systemic review and meta analysis of 13 studies shows

long-term use of high-dose ICS therapy has potential to cause

side effects—impaired growth in children, decreased bone mineral

density, skin thinning and bruising, and cataracts.

SIDE EFFECTS:

INHALED CORTICOSTEROIDS

SYSTEMIC SIDE EFFECTS

LOCAL SIDE EFFECTS

SYSTEMIC SIDE EFFECTS:

Adrenal suppression

Growth suppression

Bruising

Osteoporosis Cataracts Glaucoma

LOCAL SIDE EFFECTS:

Dysphonia Hoarseness Oropharyngealcandidiasis

Cough Pneumonia (COPD patients)

Why this side effects occur?????

CAUSES OF SIDE EFEECTS:There are several case reports of adverse systemic effects of

ICS, and these may be idiosyncratic reactions, which may be

due to……..

1• Abnormal pharmacokinetic

2• Over long periods therapy

3• High dose

4• The site of delivery (gastrointestinal

tract and lung)

5• Individual differences in the patient's

response to the corticosteroid.

6• The amount of drug absorbed into the

systemic circulation.

Comparison between ICS Several ICS are currently on the market for use in asthma, although their

availability varies between countries.

There have been relatively few studies comparing efficacy of the differentICS.

These studies conclude that Fluticasone propionate, Budesonide,Beclomethasone dipropionate, Flunisolide are causes more systemic sideeffects as compare to Ciclesonide.

Ciclesonide a nonhalogenated ICS, possesses key pharmacokinetic andpharmacodynamic characteristics that yield high efficacy and low risk forsystemic exposure.

Because ciclesonide does not cause significant cortisol suppression, it isunlikely that ciclesonide poses a risk for other systemic side effects that arethought to be related to HPA-axis suppression.

However, no data for ciclesonide are available for other systemic sideeffects such as skin thinning, bruising, and fracture.

MANAGEMENT :

High-dose inhaled corticosteroids safety card:

Patients who are using high-dose ICS should be advised to inform the healthcare team responsible for their treatment if they fall ill for any reason, as this may affect the dose required.

Patients who require prolonged high-dose ICS are at risk

of side effects so should be issued with a corticosteroid

treatment card.

Doses of ICS that require a corticosteroid card in adults

High-dose ICS safety card

Dose optimization: The main strategy to minimize the risk of ICS-induced

side effects is dose optimization.

In most patients with asthma, there is limited evidence that increasing the dose of ICS above 800mcg BDP equivalent per day improves asthma control, although high doses are associated with an increased risk of adverse events.

The BTS/SIGN guidelines recommend that the dose of any ICS should be reduced by 25–50% in patients with good asthma control (i.e. no exacerbations for three months), to the lowest dose that controls symptoms.

Before increasing the dose of an ICS, it is important to check the patient’s adherence to therapy, and to improve ICS delivery to the lungs. This can be done by optimizing the patient’s inhaler technique, or by using a metered dose inhaler (MDI) with a spacer device, which can improve lung deposition.

Individual management of side effects:

Adrenal suppression Adrenal suppression is a condition in which the

adrenal glands do not produce adequate amount of steroid hormones, cortisol, ACTH, CRH, and aldosterone(a mineralcorticoid).

Use of high-dose steroids for more than a week begins to produce suppressionof the patient's adrenal glands because the exogenous glucocorticoids suppresshypothalamic corticotropin-releasing hormone (CRH) and pituitaryadrenocorticotropic hormone (ACTH). With prolonged suppression, theadrenal glands atrophy (physically shrink), and can take months to recover fullfunction after discontinuation of the exogenous glucocorticoid. During thisrecovery time, the patient is vulnerable to adrenal insufficiency during times ofstress, such as illness.

Adrenal suppressionDiagnosis: ACTH stimulation test.(CRH, ACTH, cortisol,

aldosterone, Na, and K level)

Management:

Addison’s disease - Adrenal crisis o Intravenous fluidso Infusion of isotonic sodium chloride solution to correct hypotension.

o Intravenous steroid ( hydrocortisone sodium succinate 250-300 mg in 24 hrs, after 2- 3 days 100-150mg/day and then after 4-5 days 72- 75 mg/day.

o later start oral hydrocortisone therapy – 30- 50mg/day or prednisone 20- 40 mg/day.

o Rest

Adrenal suppression Congenital adrenal hyperplasia – Cortisol deficiencyo Infusion of isotonic sodium chloride solution to correct hypotension.

o first line : Hydrocortisone IV 100 – 250mg /day then patient is stabilized 50mg/day.

or

o Prednisone: 20- 40mg/day

Mineralocorticoid deficiency (low aldosterone)o Fludrocortisone Acetate: 0.1mg/day PO. o If hypertension occurs: 0.05mg/day PO.

(To balance sodium, potassium and increase water retention)

Growth suppression Growth suppression is a medical condition in which

the body dose not produce enough growth hormone (GH).

ICH may suppress growth in the first year of treatment in children. It is more common in children as compare to adult by ICH.

Growth suppression Diagnosis:

Auxologic criteria (defined by body measurements)

Indirect hormonal criteria (IGF levels from a single blood sample)

Direct hormonal criteria (measurement of GH in multiple blood samples)

Management: Children and some adults with growth hormone deficiency will benefit from growth hormone therapy. In some countries this therapy is not licensed for use.

The goals of treatment are to increase growth in children and restore energy, metabolism, and body composition.

The doctor may prescribe growth hormone, also called somatropin(Humatrope, Genotropin). The drug is given as shots a few times a week that is injected underneath the fat of the patient’s skin.

Bruising A bruise is a common skin injury that results in a discoloration of the skin. Blood

from damaged blood cells deep beneath the skin collects near the surface of the skin,

resulting in what we think of as a black and blue mark.

Inhaled corticosteroids high dose cause thinning of the skin, telangiectasiae and

easy bruising, probably as a result of loss of extracellular ground substance

within the dermis, due to an inhibitory effect on dermal fibroblasts.

BruisingManagement:

A cold compress such as an ice pack or a bag of frozen vegetables should be applied to the affected area for 20-30 minutes in order to speed healing and reduce swelling. Do not apply ice directly to the skin. Wrap the ice pack in a towel.

If the bruise takes up a large area of the leg or foot, the leg should be kept elevated as much as possible during the first 24 hours after the injury.

For pain start Acetaminophen 500mg po bd.

Osteoporosis Osteoporosis, or thinning bones, can result in painful

fractures.

Inhaled Corticosteroids lead to a reduction in bone mass by direct

effects on bone formation and resorption and indirectly by suppression

of the pituitary-gonadal and HPA axes, effects on intestinal calcium

absorption, renal tubular calcium reabsorption and secondary

hyperparathyroidism.

Diagnosis: bone mineral density testManagement: calcium and vitamin D supplementsNon pharmacological treatment: bone-healthy lifestyle changes, diet, smoking

cessation, exercise, fall prevention.

Severe osteoporosis: Bisphosphonates 5 mg daily. (Bisphosphonates that bind to bone hydroxyapatite and inhibit osteoclast – mediated bone resorption .)

Cataracts Long-term treatment with inhaled corticosteroids increase the risk of posterior

subcapsular cataracts. In this condition vision is cloudy and blurry.

Diagnosis by eye examination Management: Eyeglasses Eye surgery

The main postulated mechanism is gene transcription induced by glucocorticoidsin the lens epithelium, though other indirect mechanisms acting on growthfactors affecting lens development and homeostasis are suggested. Also suggestedis fluid build up in the lens fibers and lens protein agglutination as a result ofinhibition of the sodium-potassium pump at the lens epithelium is postulated tobe the relevant mechanism via which corticosteroids exert their cataract formingeffect .

Glaucoma Glaucoma is condition that causes damage of eye’s optic

nerve and increase intraocular pressure.

Diagnosis : physical examination of eyes

Management:

eye drops:

β- blocker {betaxolo(0.5%), timolol(0.5%), carteolol(1%)} one drop twice daily.

prostaglandin{ latanoprost(0.005%), bimatoprost(0.01%), travoprost(0.004%) } – one drop daily.

laser surgery

microsurgery

Dysphonia and hoareseness Dysphonia means worsening of voice

Hoareseness that describes abnormal voice changes.

Management:

patients using ICS should be advised to rinse out their mouth with water (spitting out the rinse)

brush their teeth after using their device, which will reduce the risk of developing a sore throat or hoarseness

voice therapy – voice training and voice modification

Oropharyngeal candidiasis oropharyngeal candidiasis that occurs in the mouth. That

is, oral candidiasis is a mycosis (yeast/fungal infection) of Candida species on the mucous membranes of the mouth.

Management: Oropharyngeal candidiasis (OPC) can be treated with

either topical antifungal agents (eg, nystatin, clotrimazole)

or systemic oral azoleso fluconazole 200mg po day- 1then 100mg qdayo itraconazole 200mg po for 3- 4 days then 100mg qdayo posaconazole 100mg po bid on day 1 then 100mg po qday.

Pneumonia (COPD patients) Patients with COPD are at a higher risk of developing pneumonia than

people who do not have COPD, and this risk appears to be further amplified in patients using ICS particularly at high doses.

Diagnosis : chest x- ray, mucus test –( sputum culture)

Management: start empirical therapy till result of culture.

Meropenem 1 g IV q8h or

Ceftriaxone 2 g IV q24h or

Levofloxacin 750mg IV or PO q24h.

After sputum culture shows which Bactria is present then check sensitivity test of antibiotic if given antibiotic is sensitive continue same treatment otherwise according to sensitivity prescribe other antibiotic.

MEASURES TO MINIMIZE SYSTEMIC

SIDE EFFECTSStep down treatment to the lowest possible dose of ICS

that maintains symptom control.

Increase medication frequency while decreasing

daily dose

Optimize compliance

Optimize delivery (use spacer in adults, spacer and

facemask in children)

Evaluate and treat for complicating features of

asthma

Maximize nonpharmacologic

treatment

Inhaled corticosteroids in pregnancy: Inhaled corticosteroids are commonly used for asthma treatment, but their

safety during pregnancy has not been established.

Previous studies suggest that corticosteroids taken by mouth (which give a

much stronger dose than when inhaled) may slow fetal growth.

Based on extensive clinical experience ICS appear to be safe in pregnancy,

although no controlled studies have been performed. There is no evidence

for any adverse effects of ICS on the pregnancy, the delivery or on the fetus.

It is important to recognize that poorly controlled asthma may increase the

incidence of prenatal mortality and retard intra-uterine growth, so that more

effective control of asthma with ICS may reduce these problems.

Budesonide has received a Pregnancy Category B rating from the FDA and

all other ICS approved for asthma treatment are rated Pregnancy Category

C.

PATIENT COUNSELLING : Encourage patients to use appropriate breathing techniques

according to inhaler device e.g.: ’slow and steady’ for an aerosol inhaler, “quick and deep” for a dry powder inhaler.

All patients taking ICS who have never had chickenpox should be advised to avoid people with chickenpox or shingles, and to see a doctor if they come in contact with someone with either illness and then feel unwell.

If patient suffering with COPD, to prevent pneumonia take annual pneumonia vaccine.

Every 6 moths go for whole body checkup. Stop smoking Exercise regularly. Eat a healthy diet.

REFERENCES: www.webmd.com

www.uptodate.com

www.medscape.com

www.pharmaceutical-journal.com

www.ncbi.nlm.nih.gov/pubmed.