RESPIRATORY SYSTEM DRUGS

RESPIRATORY SYSTEM DRUGS

ß2 adrenoceptor agonists 
EXAMPLES 

• Short-acting – salbutamol, terbutaline; 
• Long-acting – salmeterol, formoterol.

MECHANISM OF ACTION 

• Selective b2 adrenoceptor agonists in the smooth muscle of upper airways that increase intracellular cAMP.This leads to smooth muscle relaxation and bronchodilation.

INDICATIONS

• Acute asthma (short-acting) . 
• Chronic asthma/COPD (long-acting) . 
• Premature labour

CAUTIONS AND CONTRA-INDICATIONS

• Hypersensitivity

SIDE-EFFECTS 

• Fine tremor .
• Hypokalaemia (if high doses are given).
• Tachycardia.
• Headache 

MONITORING 

• Monitor Kþ levels if high doses of salbutamol given (especially in acute asthma).

DRUG INTERACTIONS 

• Should not be given with non-selective b2 blockers, due to opposing actions. 
• In the management of acute asthma, hypokalaemia may be potentiated by hypoxia and the use of theophylline, steroids and diuretics

IMPORTANT POINTS

• Salbutamol can be administered by inhaler, nebuliser or IV in the management of acute asthma. Salbutamol can be used in the immediate management of hyperkalaemia (increased uptake of Kþ into cells). 
• BTS guidelines recommend a stepwise approach to the management of chronic asthma. First-line therapy involves the use of short-acting ß2 agonists; if symptoms are uncontrolled this is supplemented with inhaled corticosteroids and then long-acting ß2 agonists. 
• ß2 agonists salbutamol and terbutaline can be used to delay uncomplicated premature labour (24–33 weeks gestation) by at least 48h, by inhibition of uterine contractions

Histamine type 1 receptor antagonists 
EXAMPLES 

• Cetirizine, chlorphenamine, desloratadine, fexofenadine

MECHANISM OF ACTION 

• Competitive inhibition at H1 receptors, blocking the acute inflammatory effects of histamine (i.e. vasodilatation, increased vascular permeability and pain). 
• Some also have antimuscarinic effects resulting in drowsiness and contributing to an anti-emetic effect.

INDICATIONS 

• Symptomatic relief of allergy (e.g. seasonal allergic rhinitis).
• Pruritus. 
• Urticaria. 
• Emergency treatment of anaphylaxis and angioedema (chlorphenamine)

CAUTIONS AND CONTRA-INDICATIONS. 

• Prostatic hypertrophy. 
• Urinary retention. 
• Susceptibility to closed-angle glaucoma
• SIDE-EFFECTS. 
• Sedation (particularly chlorphenamine and hydroxyzine). 
• Rarely paradoxical excitation in children and the elderly. 
• Antimuscarinic effects (urinary retention, dry mouth, blurred vision and GI disturbance)

MONITORING 

• No specific drug monitoring required.

DRUG INTERACTIONS 

• Concurrent use of hypnotics, anxiolytics or alcohol may exacerbate drowsiness. 
• Increased antimuscarinic effects when given with MAOIs or TCAs.

IMPORTANT POINTS

• Antihistamines are broadly divided into sedating (e.g. chlorphenamine) and non-sedating agents (e.g. cetirizine, desloratadine, fexofenadine). 
• Drowsiness frequently diminishes after the first few days of treatment but patients should be advised of this adverse effect as it may affect their ability to perform tasks, including driving. 

Inhaled antimuscarinics 
EXAMPLES

•  Ipratropium bromide, tiotropium

MECHANISM OF ACTION 

• Competitive antagonists of acetylcholine in bronchial smooth muscle. 
• Inhaled antimuscarinics bind to and block muscarinic (M3) receptors, thereby preventing smooth muscle contraction and consequent airway constriction.

INDICATIONS

• Asthma (ipratropium bromide only). 
• COPD

CAUTIONS AND CONTRA-INDICATIONS

• Caution in patients susceptible to closed-angle glaucoma

SIDE-EFFECTS

• Dry mouth. 
• Nausea. 
• Headache. 
• Other systemic side-effects may occur but are rare.

MONITORING 

• No specific drug monitoring required.

DRUG INTERACTIONS

• Increased risk of adverse effects if coadministered with other anticholinergic agents

IMPORTANT POINTS 

• Ipratropium bromide is used predominantly in COPD but can be used in a nebulised form with salbutamol for acute asthma not responsive to standard therapy.
• The maximal effect of ipratropium bromide is achieved 30–60min after administration and the duration of action is 3–6h. 
• Tiotropium is a long-acting agent that isn't suitable for the treatment of acute bronchospasm

Leukotriene receptor antagonists 
EXAMPLES 

• Montelukast, zafirlukast

MECHANISM OF ACTION 

• Blocks the action of cysteinyl leukotrienes (pro-inflammatory eicosanoids released from mast cells and eosinophils) in the smooth muscle of the airways, thereby inhibiting the inflammation responsible for symptomatic asthma and rhinitis.

INDICATIONS

• Prophylaxis of asthma. 
• Seasonal allergic rhinitis

CAUTIONS AND CONTRA-INDICATIONS. 

• Hypersensitivity. 
• Hepatic impairment (zafirlukast)

SIDE-EFFECTS

• Abdominal pain. 
• GI disturbance. 
• Headache

MONITORING

•  No specific drug monitoring required.

DRUG INTERACTIONS

• Caution in patients taking liver enzyme-inducing drugs: phenytoin and rifampicin.
• Plasma levels reduced co-administration with phenobarbital.

IMPORTANT POINTS

• Leukotriene receptor antagonists can be used as a single therapy or with an inhaled steroid (their effects are additive). 
• Leukotriene receptor antagonists may be of benefit in exercise-induced asthma. 
• Montelukast is given as a once-daily oral preparation whilst zafirlukast is given as a twice-daily dose

Oxygen
MECHANISM OF ACTION 

• Oxygen is the terminal electron acceptor in the oxidative phosphorylation pathway and is thus an essential component of the electron transport chains that produce ATP. 
• In the absence of oxygen, pyruvate produced from glycolysis is converted into lactate.

INDICATIONS

• Hypoxaemia (oxygen should be titrated to achieve a target saturation of 94–98% for most acutely ill patients and 88–92% for those at risk of hypercapnic respiratory failure pending blood gas results).

CAUTIONS AND CONTRA-INDICATIONS

• Caution in patients at risk of hypercapnic respiratory failure (although oxygen should not be withheld from acutely hypoxaemic patients).

SIDE-EFFECTS

• Respiratory depression in patients reliant upon hypoxic drive. 
• Coronary and cerebral vasoconstriction . 
• Oxygen toxicity from free radicals. 
• Rebound hypoxaemia following sudden cessation of oxygen therapy

MONITORING 

• Pulse oximetry monitoring is required supplemented by blood gas analysis. 
• Oxygen flow rates and delivery system should be adjusted to maintain oxygen saturation within the target range.

DRUG INTERACTIONS 

• Potentiates lung injury due to paraquat poisoning, ingestion of acids or damage due to bleomycin therapy.

IMPORTANT POINTS

• Oxygen should be prescribed in a patient’s drug chart. 
• Low-flow systems (dependent on flow rate and respiratory pattern)

Nasal prongs: FiO2 up to 40%
Face mask: FiO2 up to 60%
Face mask with reservoir bag: FiO2 up to 100%.

• High-flow systems (fixed-flow rate and independent of the respiratory pattern) 

Venturi mask: FiO2 24–60%

Theophylline 
MECHANISM OF ACTION 

• A methylxanthine that inhibits phosphodiesterase isoenzymes resulting in increased cAMP levels and smooth muscle relaxation hence has a bronchodilatory effect on the airways. 
• Theophylline also acts as a respiratory stimulant through the CNS.

INDICATIONS

• Acute severe asthma. 
• Chronic asthma. 
• Moderate to severe COPD

CAUTIONS AND CONTRA-INDICATIONS. 

• Porphyria. 
• Concomitant use of ephedrine in children. 
• Caution should be exercised in cardiac or liver failure and poorly controlled epilepsy (consider dose reduction)

SIDE-EFFECTS

• Hypokalaemia. 
• Tachycardia, palpitations and arrhythmias. 
• Headache and insomnia.
•  GI disturbances (especially nausea). 
• Convulsions, especially if given rapidly by IV injection

MONITORING 

• Levels are measured 4–6 hours after a dose and should be checked within 5 days after starting treatment.
• Narrow therapeutic index. Monitor Kþ levels. 
• Cardiac monitoring recommended for IV doses.

DRUG INTERACTIONS

• Metabolised extensively via Cytochrome P450 and thus multiple drug interactions. 
• Theophylline levels increased with CCBs, cimetidine, quinolones, macrolides and some antifungals (e.g. ketoconazole and fluconazole). 
• Theophylline levels are decreased in smokers, chronic alcohol intake and by drugs that induce liver metabolisms, such as antiepileptics and rifampicin.

IMPORTANT POINTS

• Toxicity may be delayed with modified release preparations. Clinical features include vomiting and agitation. 
• Haematemesis, cardiac arrhythmias and convulsions are potentially life-threatening.
• In overdose, patients need continuous cardiac monitoring and regular blood monitoring (hypokalaemia is potentiated by ß2 agonists and hyperglycaemia). 
• Aminophylline is a combination of theophylline and ethylenediamine; the latter confers water-soluble properties and hence aminophylline is used as an IV preparation