Drugs used in asthma

Asthma is defined as a syndrome in which there is (are):

1 T recurrent reversible obstruction of the airways
1 T intermittent attacks of dyspnoea, wheezing , and cough
1 T disorders in breathing in
1 T disorders in breathing out
1 F recurrent irreversible obstruction of the airways in response to stimuli
Asthma is defined as a syndrome in which there is recurrent reversible obstruction of the airways. The patient has intermittent
attacks of dyspnoea, wheezing, and cough and disorder of breathing.

The characteristic features of asthma is (are):

1 F purely a Type I hypersensitivity reactions
1 T bronchial hyper-responsiveness and inflammatory changes in the airways
1 T the immediate and the late phase
1 F involving only the interaction of allergen with mast-cell-fixed IgE
1 F occurrence only in adults
The characteristic features of asthma are bronchial hyperresponsiveness and inflammatory changes in the airways. Asthma
consists of the immediate and the late phases. 60-80% asthma is due to allergy, elements other than the interaction of allergen
with mast-cell-fixed IgE are involved. Asthma occurs at any age.

The term bronchial hyper-responsiveness refers to abnormal sensitivity to:

1 T allergens (in sensitized individuals)
1 T exercise (the stimulus may be cold air)
1 T respiratory infections
1 T atmospheric pollutants such as sulphur dioxide, cigarette smoke
1 T genetic dispositions
The term bronchial hyper- responsiveness (hyperactivity) refers fo abnormal sensitivity to allergens (in sensitized individuals),
exercise, respiratory infections, atmospheric pollutants such as suplhur dioxide, cigarette smoke. The hyper-responsiveness can
be also due to genetic disposition.

The immediate (early) phase:

1 T occurs abruptly
1 T the cells involved in this phase are predominantly mast cells
1 T can be reversed by bronchodilators (glucocorticoids, cromoglycate)
1 F can be reversed by anti-inflammatory agents
1 F can be reversed by sedatives and hypnotics
The immediate phase occurs abruptly. The cells involved in this phase are predominantly mast cells (activated to release
histamine, and other mediators). Bronchodilators are effective in reversing this response. Sedatives and hypnotics are
absolutely contraindicated.

Bronchodilators are:
1 F beta 2 antagonists
1 F beta 1 agonists
1 T beta 2 agonists
1 T antimuscarinic drugs
1 T methylxanthines
Bronchodilators are: beta 2 agonists, muscarinic receptor antagonists and methylxanthines

Short acting beta 2 mimetics (for an acute attack management) :

1 T are administered via inhalation if possible
1 F only orally
1 T i.v.
1 T s.c.
1 T parenterally
Short acting beta 2 mimetics are administered via inhalation if possible. They can be administered also i.v. or s.c.

Inhalation method(s) is (are):

1 F Intranasal administration for systemic absorption
2 T Metered dose inhaler-aerosol
2 T Aerosol administered via a nebulizer
2 T As a dry power (Turbohaler or Diskhaler)
1 F Intranasal administration for the local effects on nasal mucosa
Inhalation methods are: metered dose inhaler- aerosol , aerosol administered via a nebulizer, as a dry powder (Turbohaler of
Diskhaler)

Using metered dose inhaler -aerosol the dose of........ /puff is administered:
3 F 1ug
3 F 10 ug
3 T 100ug
1 F 1mg
1 F 10 mg
Using metered dose inhaler-aerosol the dose of 100 ug/puff is administered

The increase in FEV-1 after inhalation of 200 ug of salbutamol:

1 F begins within 2 minutes
1 T begins within 15 min
1 T peaks at 1 hour
1 F peaks at 3 hours
1 F persists for 10-12 hours
The increase in FRV-1 after inhalation of 200 ug of salbutamol begins within 15 min, peaks at 1 hours and ¨persists for 4-6
hours.

Pharmacological effects of beta 2 agonists are:

3 F relaxation of skeletal muscle
1 T relaxation of bronchial smooth muscle
1 T relaxation of uterine smooth muscle
1 F decrease in heart rate, force of mycardial contraction, speed of impulse conduction
1 T increase in ectopic foci in the myocardium and automaticity in pacemaker tissue
Pharmacological effects of beta agonists are: relaxation of bronchial muscle, relaxation of uterine smooth muscle, increase in
heart rate, force of myocardial contraction, speed of imupulse condution, increase in ectopic foci in the myocardium and
automaticity in pacemaker tissue. The effects on the heart are reduced if compared to nonspecific (beta 1,2) mimetics.
Nevertheless, they could be severe after i.v. drug administration.The tonus of the skeletal muscle is increased- muscle tremor
occurs.

Adverse effects of beta 2 agonists are:

3 T Muscle tremor, headache and insomnia
1 T Tachycardia, flushing, palpitations and cardiac arrhythmias
2 T The risk of precipitating or exacerbating angina in patients with ischemic heart disease
2 F Acute urinary retention in patients with prostatic hypertrophy
4 F Hyperkalemia.
Adverse effects of beta 2 agonists are: tachycardia, flushing, palpitations and cardiac arrhythmias. The risk of precipitating or
exacerbating angina in patients with ischemic heart disease. Metabolic: hypokalemia.

Muscarinic receptor antagonists (used for the treatment of asthma) involve:

1 F Fenoterol
1 T Ipratropium
1 T Berodual
1 T Atrovent
1 F Atropin
The muscarinic receptor antagonist for asthma treatment is ipratropium (Atrovent) which is combined with fenoterol (the beta
2 mimetic drug) to make Berodual. Atropin is not used. Its bronchodilator effect is low and followed by many adverse effects.
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Ipratropium:
1 F is administered orally .
2 F is more effective than salbutamol
3 T could precipitate acute glaucoma
1 T is used for patients with heart disease
1 F but cannot be used for patients with thyreotoxicosis
Ipratropium is short acting drug administred by inhalation (absorption from GIT is low). The degree and rate of onset of
bronchodilatation is less than that of salbutamol. The drug can precipitate glaucoma if nebulized doses are given via a
facemask. Ipratropium is used for patients with heart disease or thyreotoxicosis in whom beta agonists are unsuitable.

Methylxanthines used for the treatment of asthma are:

1 T theophyllin
2 F oxyphyllin
1 T aminophyllin
3 F pentoxiphyllin
1 F caffeine
In common therapeutic use for asthma there are used: theophyllin, aminophyllin ( a mixture of 80% theophylline and 20%
ethylene diamine). Pentoxiphylline is a vasodilatator. Caffeine stimulates among other CNS.

Theophylline and/or aminophylline in the form of sustained release preparation:

1 F is administered orally 4times/day
1 T is administered orally once or twice a day
1 F is administered i.v. once a day
2 T is not dependent on food
1 T has a reduced incidence of gastrointestinal adverse effects
Methylxantines in the form of sustained release preparation are administered orally once or twice a day. Absorption is not
dependent on food. Adverse effects on GIT are reduced because of slow release rate.

Aminophylline is:
1 T used i.v.( injections)
1 T used orally
1 T used orally in the form of sustained release preparations
1 F by inhalation
1 T used i.v. (infusions)
Aminophylline is used i.v. (by slow injection and/or infusion.) in patients with severe asthma and is used orally in less
severe cases or to reduce symptoms, especially at night. Oral theophylline preparations are widely used in the form of sustained
release preparations

Adverse effects of theophylline:

1 T are generally related to its plasma concentration
1 T include tachycardia, cardiac arrhythmias
1 F do not comprise insomnia, headache, anxiety
1 T include nauzea and vomiting
1 T theophylline can induce anxiety and seizures
Adverse effects of theophylline are related to its plasma concentrations. Theophylline induces nauzea and vomiting even in 15
ug/ml ; tachycardia, cardiac arrhythmias at plasma concentrations of 20-40 ug/ml; insomnia, anxiety, agitation and ultimately
seizures (>40 ug/ml).

Theophylline produces bronchodilating effects by means of:

1 T inhibition of mediator release from mast cells
1 T antagonism of adenosine at A 2 receptors
1 T anti-inflammatory activity on T lymphocytes
1 T central stimulation of respiration
1 F stimulation of beta 2 receptors
Theophylline is a relaxant of smooth muscle and inhibits mediator release from mast cells. It increases intracellular cAMP
concentrations by inhibiting phosphodiesterase. Antagonism of adenosine at A 2 receptors is probably a further mechanism of
bronchodilatation. Anti-inflammatory activity on T-lymphocytes is induced by reducing release of platelet activating factor
(PAF). Aminophylline stimulates the center of respiration.

The therapeutic range of theophylline in plasma is:

2 T 5-15 ug/ml in children
2 T 8-15 ug/ml in adults
2 F 20-40 ug/ml in adults
2 F 0.5 - 5 ug/ml in children
2 F 0.1 - 1 ug/ml in children
The therapeutic range of theophylline in plasma is 5-15 ug/ml in children and 8-15 ug/ml in adults.

Pharmacokinetics of theophylline. Theophylline is:

1 F not metabolised in the liver
1 F excreted predominantly in non-changed form by the urine
1 F used in patients with liver disease without caution
2 T not used in patients with congestive heart failure
1 T used in higher doses in heavy cigarrete smokers
Theophylline is largely metabolised (85-90% ) in the liver. In the paternal form the drug is excreted by the kidneys in 10%.
Theophylline clearance is reduced by an average of 40-60% in patients with liver disease (cirrhosis). In this case the patients
should be dosed with extreme caution. Decreases in clearance of theohyllin have been observed in patients with congestive
heart failure and viral infections as well. On the other hand, renal clearance of theophylline is a small component of total body
clearance (except neonates), thus renal disease has no significant effect on clearance. Clearance of theophylline is increased in
cigarrete smokers (enzyme induction) by 40-80%. Thus the doses have to be increased.

The half-life of theophylline is:

3 F decreased by erythromycin
3 T increased by cimetidine
3 T increased by oral contraceptives
3 F increased by phenytoin
3 T decreased by carbamazepin
The half-life of theophylline is increased by erythromycin, cimetidine (but not ranitidine), ciprofloxacin, oral contraceptives.
This value is decreased by phenytoin, carbamazepine, rifampicin, phenobarbital.

Glucocorticoids are:
1 F bronchodilators with a large effect on early-phase response
1 T not bronchodilators, are not effective in the treatment of the early response to the eliciting agent
1 T administered by inhalation they are extremely powerful anti-inflammatory drugs.
1 T considered as first-line drugs in asthma prophylaxis, for all but the mildest cases
1 T for severe asthma an oral glucocorticoid is indicated
Glucocorticoids are not bronchodilators, they are not effective in the treatment of the early-phase response.Glucocortiocoids
given by inhalation are able to control the disease without causing adverse systemic effects or adrenal suppression. They are
considered first-line drugs in asthma prophylaxis. For severe asthma an oral glucocorticoid is indicated.

Glucocorticoids given by inhalation:

2 T can cause oropharyngeal candidiasis
2 F in low doses cause adrenal suppression
2 T are administered 2-4times daily
1 T involve budesonide, beclomethasone
1 F involve hydrocortisone, prednisolone , methylprednisolone
Glucocorticoids cause candidiasis of the pharynx (13% of pateints) or larynx (5%). The incidence is reduced by administering
the inhaled steroid via a spacer device. Higher doses (800-1600 ug) produce more prolonged suppression of adrenal function.
At the lowest recommended daily dose of 400 ug there is no prolonged suppression of the hypothalamic-pituitary-adrenal axis.
Glucocorticoids are administered twice a day to help compliance and minimize adverse effects. Inhaled corticosteroids are:
beclomethasone, budesonide, fluticasone. Hydrocortisone, prednisolone and methylprednisolone are systemic corticosteroids.