Anda berpenyakit lelah?

Are you asthmatic?

Do you know your medicine?

Drugs (Kumpulan ubat yang diguna dalam rawatan lelah)

1. Symptomimetic agents
2. Methylxanthine drugs
3. Antimuscarinic agents
4. Corticosteroids
5. Cromolyn & Nedocromil
6. Leukotriene pathway inhibitors


Asthma

Bagaimana lelah terjadi:
• Chronic inflammatory disorder of the airways (Radang)
– Clinical - Bouts of coughing, SOB, Chest tightness, wheezing
– Physiological - Widespread narrowing bronchial airways, increased bronchial responsiveness to inhaled stimuli (Alahan)
– Pathological - Remodelling of bronchial mucosa, deposition of collagen beneath basement membrane, hyperplasia of the cells of all structural elements.

Histopathological changes (Perubahan patologi yang berlaku)
• Cells infiltration: eosinophils, T-lymphocytes, mast cells; Plasma exudation; Oedema; Smooth muscle hypertrophy; Mucus plugging; Epithelial changes;
•
Patogenesis
• Genetic – Atopy - Masalah keturunan
• Airway hyperesponsiveness - Kerengsaan
• Common allergens - Terdapat beberapa bahan penyebab alergi seperti debunga, habuk
• Non specific precipitants - Bersenam juga boleh menyebabkan lelah
• Occupational

Ubatan mengikut kumpulan:

1. Sympathomimetic agents

1. Adrenaline
2. Ephedrine
3. Isoproterenol
4. Albuterol (Salbutamol)
5. Terbutaline
6. Salmeterol
7. Metaproterenol
8. Isoetharine

Mechanisms - Bagaimanakah ia bertindak:
• Relax airway smooth muscle.
• Inhibit release of some bronchoconstricting mediators from mast cells.
• Inhibit microvascular leakage
• Increase mucociliary transport by increase in ciliary activity.
• Stimulates adenyl cyclase and catalyze the formation of cAMP in air way tissue

β2 Agonists – most widely used anti asthmatic today. Less side effects from of β1 stimulation.

• Short-acting β2 Agonists. Albuterol (=salbutamol), Terbutaline, Metaproterenol. Route: MDI, nebuliser, oral: bronchodilation achieved within 15-30 minutes. Last 3-4 hours. SC injection: terbutaline:for severe asthma for emergency treatment. Caution: cumulative effect from longer t ½

• Long-acting β2 Agonists. Salmeterol, Formoterol. Long acting (≥ 12 hours) because of high lipid solubility

2. Methylxanthine drugs

Mechanism of action

 Inhibit PDE enzymes. PDE hydrolyzes the cAMP. cAMP. PDE4 inhibition  reduce release of cytokine/chemokine
 Inhibit receptors for adenosine that modulate adenyl cylase activity. Adenosine causes contraction of isolated airway smooth muscle and enhance histamine release

Kesan Sampingan:

1. Theophylline – requires TDMbecause therapeutic and toxic effects - related to plasma concentration
2. Narrow Therapeutic index (TI), requires monitoring. Active plasma conc = 5-20 mg/ L
3. At 15mg/L - anorexia, nausea, vomiting, abdominal discomfort, headaches, anxiety
4. At > 40 mg/L –seizures, arrhythmia.
5. IV injection: do it slowly (over 30 minutes) - because rapid injection cause transient toxic plasma levels with the risk of seizure or cardiac arrhythmia
6. Metabolism in the liver – liver disease  decreased clearance. Enzyme induction eg. Smoking  increased clearance
7. Clearance vary with age
8. Overdose: Death
9. Lost its importance in asthma treatment due to narrow TI.

3. Antimuscarinic agents

1. Atropin
2. Ipratropium bromide

Mechanism of action
• Competitive inhibitor of acetylcholine at muscarinic receptors
• Block the contraction of airway smooth muscle and the increase in the secretion of mucus that occurs in response to vagal activity
• Response to treatment varies: Involvement of parasympathetic on bronchospasm vary between individuals

4. Corticosteroids

Mechanism of action
– Broad anti-inflammatory effect of airways. Inhibit lymphocytes, eosinophils.
– reduce bronchial reactivity/asthma exacerbation.
– Contraction of engorged vessel.

Clinical use
– Reduce severity of symptoms, increase airway calibre, reduce bronchial reactivity, reduce exacerbations, improve quality of life.
– Indications: those need urgent treatment (oral or IV ), or worsening symptoms.usually discontinued after a week or ten days.
– Route: Oral/ IV/aerosol = inhalation
– Reduce dose as symptoms improve, discontinue 7-10 days treatment. Adrenal suppression may occur based on the dose.
– Aerosol treatment – decrease systemic adverse effects

• Chronic use – effective reduce symptoms
• Improve pulmonary function
• Eliminate need for oral steroid in severe disease
• Reduce bronchial activityNow routinely prescribed for patients who require more than occasional sympathomimetic agent. Continue to 12 week. Evaluate. ? Prolong treatment needed.

Adverse effects (Kesan sampingan)

• oropharyngeal candidiasis,
• hoarseness of voice,
• ? Osteoporosis and cataract
• Reduce growth in children ? transient
• Catarract, Muscle weakness, Glaucoma, Glucose intolerance, Depression, hypertension

5. Cromolyn and Nedocromil (Ubatan profilaksis)
– Prophylactic drugs. Not effective in reversing asthmatic bronchospasm and no effects on smooth muscle
– Inhibit antigen and exercise induced asthma
– Route: aerosol (extremely insoluble salt)

Mechanism of actions
• Alter function of delayed chloride channels in the cell membrane.Thus inhibit cell activation.
• Nerve cell Inhibits cough
• Mast cellinhibit response to antigen challenge
• Eosinophilsinhibit late response. Effective even after mast cell degranulation

Cromolyn indication
• Asthma – use before eg exercise, occupational related cause (aerosol inhalation)
• Allergic rhinoconjunctivitis. (Spray)

6.Leukotriene pathway inhibitor

Mechanism of drug actions
Interrupt leukotriene pathway
– inhibit 5-lipoxygenase prevent the synthesis of leukotriene (Zileuton).
– inhibit binding of leukotriene D4 to its receptor (Zafirlukast, Montelukast).Role in aspirin induced asthma