Respiratory Drugs Flashcards
What are the signs of infectious exacerbations of COPD?
Increasing dyspnoea
Increased sputum purulence
Increased sputum volume/viscosity
How is type 2 respiratory failure characterised?
Hypercapnic respiratory failure - PaCO2 higher than 50mmHg
- hypoxaemia is common
What are the groups of treatments which someone with infective COPD exacerbation, Type 2 respiratory failure and a right sided chest infection need?
Oxygen Nebulisers Antibiotics Steroids Bronchodilators - if needed
How asthma managed during an acute attack?
High flow oxygen Nebulised bronchodilators IV magnesium IV salbutamol/aminophylline Steroids Consider ventilation - if PaCO2 is normal or increased
How is an acute exacerbation of COPD managed?
Tailored oxygen after ABG results - be careful because oxygen can kill COPD patients Nebulised bronchodilators IV salbutamol/aminophylline Steroids Consider ventilation (non-invasive)
What antibiotics should be given to an infective COPD exacerbation and a right sides lung infection?
IV Amoxicillin - 500mg every 8 hours for 5 days
Oral Clarithromycin - 500mg every 12 hours for 5 days
- inhibits CYP450, so has many drug interactions
Oral Doxycycline - 200mg daily for 5 days
Co-trimoxazole (trimethoprim and sulphamethoxazole)
What drug interactions can occur with Clarithromycin?
This inhibits the CYP450 pathway in the liver, meaning the following drugs are inhibited
- Theophylline warfarin
- Carbamazepine
- Digoxin
- Phenytoin
- Simvastatin
What methods of action and excretion of doxycycline mean you have to be careful of drug interactions and dosage?
Renal and hepatic elimination - can cause hypersensitivity to this drug
Can take when someone has renal impairment - just adjust interval between doses
Chelates iron and calcium, which means there is decreased absorption by antacids
What are the common side effects of co-trimoxazole?
Rash, SJS, fever, cough, aching, toxic epidermal necrolysis and blood dyscrasias
Which steroids are used when treating infectious COPD exacerbations?
Oral prednisolone - 30-50mg daily for 7 days
OR
IV hydrocortisone - 50-100mg every 8 hours until the patient can swallow
What is the mechanism of action, and the associated effects of prednisolone?
Interact with glucocorticoid receptor and nuclear DNA
- alters gene transcription so there is decreased synthesis and activation of prostaglandins, cytokines, leukotrines, T-lymphocytes, macrophages, eosinophils and airway epithelial cells
Reducation in mucosal oedema
Improved responsiveness to beta2-agonists by upregulating adrenoceptors
What are the classes of bronchodilators?
Beta-2 agonists
Anti-muscarinics
Theophylline
Describe the mechanism of action of salbutamol.
Mimics adrenaline, but with low affinity for cardiac beta-1 receptors
G proteins stimulate adenyl cyclase to increase intracellular cAMP - relaxation of the bronchial smooth muscle
What are the side effects of beta-2 agonist administration?
Tremor - stimulates skeletal muscle beta-2 receptors
Vasodilation - flushing, reflex tachycardia
High doses
- beta-2 hypokalaemia, hyperglycaemia, hypomagnesaemia
- beta-1 tachycardia, arrhythmias
How are anti-muscarinics administered?
Ipratropium bromide 500mg four times daily via an air driven nebuliser
- use a mouthpiece, not a mask, as this reduces risk of acute angle glaucoma
What is the difference between the anti-muscarinic agents ipratropium bromide be given over trotropium?
Inhaled ipratropium bromide reduces the risk of anti-cholinergic side-effects
Ipratropium bromide is short acting (3-6 hours)
Triotropium bromide is long acting (over 24 hours)
When would the bronchodilator theophylline be used?
If the patient has no response to nebulised salbutamol and ipratropium
What is the mechanism of action of theophylline?
Inhibits phosphodiesterase type 4 enzyme (PDE4)
- increases mucociliary clearance
What are the adverse effects of theophylline?
Over 15-20mg/l - GI irritation - Tachycardia - CNS stimulation Serious toxicity (over 30-40mg/l) - hypokalaemia - VT - VF - seizures
Why is theophylline difficult to use?
Dose varies with age, weight, height, hepatic disease, smoking, enzyme inducers (Rifampicin) and inhibitors (clarithromycin, ciprofloxacin)
Beware of drug interactions - CYP 1A2
What is the definition of type 1 respiratory failure?
Ventilation/perfusion inequality
- low PaO2 (less than 8kPa)
- normal or low PaCO2 - respiratory failure occurs because having a high PaCO2 normally drives respiratory rate
What is the definition of type 2 respiratory failure?
Ventilation failure caused by lung damage (emphysema)
- low PaO2 (less than 8kPa)
- raised PaCO2 (greater than 6kPa)
Because the PaCO2 is raised all the time, the patient relies on the low PaO2 to drive respiration
- so giving pink puffers too much oxygen is dangerous as the patient stops breathing
When someone has respiratory failure, what PaO2 and saturation that is being aimed for?
7.5-10kPa
94-98% (unless the person retains CO2 -> 88-92%)
If the person can no longer breathe by themselves though a mask, what can be done?
Never use a nasal cannula
Consider nasal intermittent positive pressure ventilation (NIPPV) or intubation and mechanical ventilation
What is the mechanism of action of inhaled anti-muscarinics?
Blockage of the parasympathetic nervous system (stimulation of cholinergic M2, M3 muscarinic receptors, intracellular calcium release and bronchoconstriction)
What are the side effects of ipratropium bromide?
Blurred vision
Dry mouth
Decrease gut motility
When would the anti-muscarinic agent tiotropium bromide be used?
Chronic conditions (not an acute bronchospasm) - long action due to dissociate half life from the M3 receptor
What are the side effects of tiotropium bromide?
Dry mouth
Difficulty in micturition
Why are anti-muscarinics used in COPD?
Evidence of increased resting cholinergic tone in COPD - so anti-muscarinic agents are logical
Clinical evidence suggests long acting beta-agonists are as effective or more effective
- effect is enhanced when combined with a beta-agonist
When someone is admitted with an acute COPD exacerbation, what drugs need to be stopped/changed?
Tiotropium - stop only if they are being put on ipratropium
Salbutamol - stop while on the nebuliser
Secretive - stop while on the nebuliser
Simvastatin - stop while on Clarithromycin
Clarithromycin 250mg - increase to 500mg
Name and describe two long-acting beta agonists.
Salmetrol
- partial agonist, almost irreversibly binding to the beta-2 receptor
- lasts for over 12 hours
Formoterol
- full agonist, lipophilic
- quick onset and long duration of action
Why are long acting beta agonist used?
Gives continuous bronchodilators and improves symptoms if inhaled steroids and short acting beta-2 agonist are inadequate
What drug must long acting beta agonist be combined with?
Steroids
- combination inhalers aid compliance
- seretide (fluticasone and salmeterol)
- symbicort (budesonide and formoterol)
What is the mechanism of action of Leukotriene receptor inhibitors (used in asthma)?
Block cysteinyl leukotriene receptor in smooth muscle and macrophages
This inhibits eicosanoids LTC4, LTD4 and LTE4 (released from mast cells) and eosinophils
Used for prophylaxis of exercise induced asthma
Name some Leukotriene receptor inhibitors.
Montelukast
Zafirlukast
Name a mucolytic and its mechanism of action.
Carbocysteine
- may facilitate expectoration by reducing the viscosity of the sputum
- may reduce COPD exacerbations
