Respiratory pharmacology Flashcards
What is a cough?
Cough = a protective mechanism that prevents the lungs from aspiration (entry of foreign material) and a common symptom of respiratory disease.
What are useless coughs? What conditions cause this? Should it be suppressed?
- Persistent and unproductive- dry cough
- Asthma, oesophageal reflux, sinusitis, psychogenic (cough when you over think about coughing)
- Should it be supressed- yes- cough suppressants are called antitussives- remember to treat underlying cause
What are useful coughs? What is an example of this? Should it be suppressed?
- Persistent and unproductive- dry cough
- Asthma, oesophageal reflux, sinusitis, psychogenic (cough when you over think about coughing)
- Should it be supressed- yes- cough suppressants are called antitussives- remember to treat underlying cause
What is the mechanism of a cough?
Cough receptors or lung irritant receptors to cough centre in medulla to vagal simulation leading to cough
What is a linctus?
A cough preparation that gently soothes and relieves your child’s cough
What are dry cough suppressants?
Afferent side- reduce stimuli
Efferent side- medullary cough centre
Where is the afferent side?
- Above larynx: Linctuses (demulscents)
* Below larynx: Steam inhalation- nebulised local anaesthetics (numb efferent receptors in larynx or trachea)
Where is the efferent side?
- Opiods (codeine, methadone, pholcodeine)- side effects making people sleepy, can cause overdose
- Non opiods (dextromethorphan, noscapine)
- Sedatives: diphenhydramine, chlorpheniramine
What do expectorants do?
A medication that helps bring up mucus and other material from the lungs, bronchi, and trachea.
How do expectorants work? What are these drugs?
Increase volume of secretion- making them R more
-Guaiphenesin, ipecacuanha, oils
What do mucolytics do?
Medication that thins mucous
How do mucolytics work and what are these drugs? What is an example of a disease that patient need mucolytics for?
- Decrease the viscosity- provide more fluidity
- Acetyl cysteine, carbocystine, mecysteine
- Recombinant human DNAse
- Cystic fibrosis
What are the most common obstructive pulmonary diseases?
Upper airways cough syndrome (post nasal drip)
- Bronchial asthma
- Chronic Obstructive Pulmonary Disease (COPD)
- Gastroesophageal reflux disease
What are the four types of bronchial asthma?
- Asthma associated with allergic reactions- IgE mediated
- Asthma not associated with specific allergen- intrinsic asthma
- Exercise induced asthma
- Asthma associated with COPD- due to obstructive of elastic tissues in the airways
How does bronchoconstriction occur ?
When exposed to antigen, lymphocyte system is activated, T cells stimulate B cells and make lots of IgE’s. IgE’s bind to mast cells and then become activated. Release mediators which activate pathways which secrete substances. They then cause inflammation of mucosa, swelling of the mucosa layer and constriction of smooth muscle leading to bronchoconstriction.
How to treat asthma?
• Prevention of Ag:Ab reaction
• Non-specific reduction of bronchial hyperactivity:
-Nonpharmacological: Stop smoking, weight reduction
-Pharmacological: Corticosteroids
• Dilatation of narrowed bronchi:
-Mimicking dilator neurotransmitter: Sympathomimetics
-Direct acting bronchodilators: Methylxanthines
-Blockade of constrictor transmitter: Anticholinergics
• Prevention of release of transmitter
-Mast cell stabilisers
• Antagonism of released transmitter:
-Leukotriene receptor antagonists
Prevention of Ag:Ab reaction- how does it work?
• Avoidance of allergen:
-Difficult to find
-Insufficient evidence
• Avoidance of tobacco and weight reduction
Non-specific reduction of bronchial hyperactivity- how does it work?
• Corticosteroids
- Anti-inflammatory
- Inhibition of influx of inflammatory cells after exposure
- Reduced micro-vascular leakage: decreased oedema
- Inhibit release of mediators i.e. cytokines
- Inhibition of cyclooxygenase enzyme
• Reduced bronchial reactivity:
- Reduce asthma exacerbations
- Don’t relax bronchial smooth muscle
What are corticosteroids?- Inhaled and exhaled
• Inhaled corticosteroids (ICS): Brown inhaler -Beclomethasone, Budesonide -Fluticasone, Flunisolide, Triamcinolone -First line regular therapy (mild to mod Asthma) • Oral corticosteroids -Prednisone, Methylprednisolone -Betamethasone and Triamcinolone -Severe asthma (status asthmaticus)
What are corticosteroid adverse effects?
• Iatrogenic: Cushing’s syndrome
-Diabetes, hypertension, Peptic ulcer, psychosis, delayed puberty
• Inhibition of hypothalamic pituitary axis
• Other side effects
-Oropharyngeal candidiasis
-Hoarseness: direct effect vocal cords
What risks are minimised from corticosteroids?
• Inhalational route
• Administration in early morning
• Gargle and spit after every treatment- reduce oropharyngeal candidiasis and reduce hoarseness
• Newer drugs- cyclesonide- prodrug- activated in bronchial epithelium
- When absorbed in circulation very tightly bound to proteins and thus little effect on glucocorticoid receptors elsewhere
What are mast cell stabilisers?
• Cromolyn sodium, Nedocromil sodium
• Inhibit release of mast cell mediators
• Administered by inhalation and very poorly absorbed
• No effect on bronchial smooth muscle
-No use in acute bronchospasm
• Only valuable if taken prophylactically
-Main uses: Allergic rhinitis, allergic conjunctivitis
-Side effects: Throat irritation, cough, dermatitis, myositis, gastroenteritis
What inhibits leukotriene synthesis?
- Inhibit 5-lipoxygenase
- Zileuton (discontinued) – liver toxicity
What are the inhibitors of leukotriene receptors?
Inhibitors of leukotriene receptors
-Inhibit binding of leukotriene to receptor- Montelukast, zafirlukast
What are leukotriene receptor antagonist uses?
- Allergen induced asthma, Exercise induced asthma
- Reduce frequency of exacerbations
What are leukotriene receptor antagonist adverse effects and what are they not effective in?
• Not effective in acute asthma
• Minor adverse effects :
-Headache, Gastritis, Flu-like symptoms, CS syndrome
What are sympathomimetic agents? What are short acting and long acting drugs?
• Act via β2 adrenoceptors : Blue inhaler
• Selective β2 agonist agents:
- Short acting (3-6 hours) SABA -Albuterol- Salbutamol, terbutaline, fenoterol, metaproterenol
• Long acting (12 -24 hours) LABA- Salmetrol, formetrol
Sympathomimetic agents-albuterol
• Albuterol ( Salbutamol)
- Most commonly used
- Inhalation*, nebulisation, oral or intravenous
Sympathomimetic agents-salmetrol
• Salmetrol
-Longer lasting (12 hrs)
When is adrenaline used?
• Adrenaline
- Used in emergency
- As subcutaneous injection or micro-aerosol
What are selective B2 agonists? What are the side effects?
• Metered dose inhalers or nebulisation- can give 5 to ten puffs
• Onset- immediate, Peak-15-30 min, Duration-3-4 hrs
• 1st line of therapy
• Side effects: Due to β2 receptors in heart, muscle and other tissues
-Heart- Palpitation, tachycardia, cardiac arrhythmias
-Muscle- Tremor
-Others - Restlessness, nervousness, hypokalemia
What are methylxanthines?
Used in treatment of airways obstruction
How are methylxanthines administered?
Administered oral or i.v..
What are the adverse effects of methylxanthines?
- Palpitations, cardiac arrhythmia,hypotension
- Gastrointestinal irritation (increased acid production)
- Diuresis, hypokalemia
- Anxiety, headache, seizures
What are examples of methyxanthines?
• Theophylline
- Oral : rapid and complete absorption
- 90 % metabolised, saturable metabolism
-Adjuvant therapy in Asthma
-SR Theophylline
• Aminophylline
-Intravenous
-Used in severe asthma
-Loading dose infusion
What are anticholinergic agents? What are examples of them?
Act via inhibiting muscarinic receptors (M3)
• Selective muscarinic antagonist agents:
-Ipratropium, tiotropium, oxitropium
• Tiotropium – longer acting
-OD dose 18 mcg (24 hours)
-LAMA: Long Acting Muscarinic Antagonists
• Inhibit effects of vagus nerve stimulation- vagus is the parasympathetic nerve
How are anticholinergics administered? What are the adverse effects?
• Admistered via inhalation • Adjuvant therapy in acute severe asthma, COPD • Adverse effects: -Airway irritation -Anticholinergic effects -GI upset, urinary retention • Tiotropium – longer acting, -OD dose 18 mcg (24 hours) -LAMA : Long Acting Muscarinic Antagonists
What are the other drugs that treat asthma?
- Anti IgE monoclonal antibodies
- Ketotifen
- Magnesium
- Ketamine
What does then anti IgE monoclonal antibody do?
• Omalizumab • Inhibits binding of IgE to mast cells • Repeated administration -Lessens asthma severity -Reduces magnitude of response -Reduced requirement of steroids
What does ketotifen do?
- Histamine receptor antagonist (H1)
- Some anti-asthma effect
- Side effects: drowsiness etc
- No proven benefit
What does magnesium and ketamine do?
• Magnesium
-Patients who fail to respond to inhaled bronchodilators
-By intravenous infusion
• Ketamine / Volatile anaesthetic agents
-Anaesthetic agents
-Bronchodilator properties
-No role in routine management
-Used in life-threatening or near fatal asthma
How do you treat COPD?
- Antimuscarinics > effective than β2 agonist sin COPD
- Smoking cessation: Major role in COPD
