Respiratory- MEDIUM Flashcards
What is asthma?
A chronic inflammatory disorder of the airways
An exaggerated bronchoconstrictor response to a wide variety of exogenous and endogenous stimuli
Recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning
What are the treatment options for asthma?
- Beta 2 agonists
- Antimuscarinics
- Theophylline
- Corticosteroids
- Cromoglicate
- Leukotriene antagonists
- Omalizumab
When is oral route for asthma considered for use?
Why is inhaled preferred?
When inhalation is not possible
Preferred because:
* Drug delivered directly to lungs (avoids first pass metabolism)
* Smaller dose required than with oral admin.
* Fewer S/E than with oral admin.
What is the treatment pathway for asthma?
What is COPD?
Chronic Obstructive Pulmonary Disorder (COPD)
- Airflow limitation, not fully reversible
- Usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases
Who should be considered for COPD spirometry testing?
People over 35, current or ex-smokers, and have a chronic cough
How is COPD diagnosed?
- The Medical Research Council dyspnoea scale graded breathlessness
- Post-bronchodilator spirometry to confirm diagnosis
- Chest radiograph to exclude other pathologies
- FBC to identify anaemia or polycythaemia
- BMI calculated
What are the main points of COPD treatment?
- Smoking cessation!!
- Vaccinate against infection- can complicate COPD
- Pulmonary rehabilitation, if indicated
What is the treatment pathway for COPD?
When should LAMA+LABA or LABA+ICS be offered to patients?
- Have spirometry confirmed COPD
AND - Do not have asthmatic features
AND - Remain breathless or have exacerbations despite treatment for tobacco dependence, relevant vaccinations and use of a short acting bronchodilator
When should LAMA+LABA+ICS be considered for patients already taking LABA+ICS?
- Those who’s symptoms continue to adversely impact their quality of life or have a severe exacerbation (requiring hospitalisation)
OR - Have 2 moderate exacerbations within a year
When should LAMA+LABA+ICS be considered for patients already taking LABA+LAMA?
*Those having a severe exacerbation (requiring hospitalisation)
OR
*They have 2 moderate exacerbations within a year
What is the advice surrounding oral corticosteroid use in COPD?
*Long-term use is not normally recommended
* Those with advanced COPD may need long-term oral corticosteroids, but the dose should be kept as low as possible
What is a spirometry test?
Tests how an individual inhales or exhales volumes of air as a function of time
The primary signal measured in spirometry may be volume or flow
Define Forced Vital Capacity (FVC)
Forced Vital Capacity (FVC)- the maximal volume of air exhaled with maximally forced effort from a maximal inspiration
Define FEV1
Forced Expired Volume in one second (FEV1)- volume expired in the first second of maximal expiration after a maximal inspiration
What is FEV1/FVC
FEV1 expressed as a percentage of the FVC, gives a clinically useful index of airflow limitation
What is a clinically healthy FEV1/FVC?
And that of airflow limitation?
Healthy = 70-80%
Limited airflow = < 70%
What are the benefits of spacers for inhalers?
- Suitable for children and elderly who find pMDIs difficult
- Reduces aerosol velocity, gives more time for evaporation of propellant therefore, larger proportion of particles reach target
- Useful for high dose ICS and patients prone to candidiasis (thrush)
Points to consider for spacers?
- Size of spacer is very important, as well as size of face mask (if using)
- Replace spacer every 6-12 months
- Clean once monthly with mild detergent, air dry
- Inhale from spacer asap after activation as aerosol is short-lived
What is the mode of action of sympathomimetics?
- Relax airway smooth muscle
- Inhibit mediator release
- Increase ciliary activity
Examples:
* Epinephrine (adrenaline)
* Isoprenaline (isoproterenol)
* β2 selective agents
What is formoterol (Oxis, flutiformm symbicort)
typically indicated for?
- Chronic asthma
- Exercise-induced bronchospasm
What is indacterol (Onbrez) indicated for?
COPD
- Improves the ability of patients with COPD to exercise
- Ultra-long acting and fast onset of action
- As effective as tiotropium bromide
What is salbutamol (Salamol, Ventolin) indicated for?
Asthma and other conditions associated with reversible airways obstruction
Rapid onset of action; drug of choice as relief for symptoms of bronchospasm
What is salmeterol (Severent) indicated for?
- Prophylaxis of bronchospasm
- NOT for acute attacks, has long onset of action
What is terbutaline (Bricanyl) indicated for?
- Treatment of asthma and other conditions associated with reversible airways obstruction
What is the mode of action of beta-2 agonists?
Act directly on Beta-2 receptors, causing smooth muscle relaxation and dilation of the airways
What are the common S/E for Beta-2 agonists?
- Palpitations (less common with non-selective; vasodilation and reflex tachycardia; direct stimulation of β-2 in the heart)
- Hypokalaemia (K+ in skeletal muscle and in serum; tolerance)
- Fine tremor of skeletal muscle (hands)
- Nervousness, sleep disturbances
Where do Beta-2 agonists need to be used in caution?
- Hyperthyroidism
*CVD (HTN, arrhythmias, susceptibility to QT prolongation)
Diabetes (risk of ketoacidosis- glycogenesis in liver)
What is the mode of action of adrenaline (epinepherine)?
- Effective and rapidly acting bronchodilator (inh/SC)
- Simulates Beta-1+2 receptors (non-selective)
Common S/E of adrenaline?
- Tachycardia
- Arrhythmia
- Dry mouth
- Insomnia
- Restlessness
What are adrenaline’s uses in emergencies?
- Acute allergic reactions (anaphylaxis)
- Angioedema
- Management of severe croup (RTS- seal coughing in children)
- Cardiopulmonary resuscitation
What is the mode of action of antimuscarinic bronchodilators?
- Reduce vagal cholinergic tone, the main reversible component of COPD
- Inhibit the effect of acetylcholine at muscarinic receptors
- Block contraction of airway smooth muscle
- Block the secretion of mucus
Give an example of a naturally occurring antimuscarinic
Atropine
Give examples of synthetic antimuscarinics
- Ipratropium bromide
- Oxitropium bromide
- Tiotropium bromide
When should antimuscarinic therapy be used in caution?
- Glaucoma
- Prostatic hyperplasia
- Bladder outflow obstruction
What is ipratropium indicated for?
- Short term relief in chronic asthma (SABA preferred)
Can be added if asthma fails to improve with standard therapy - Short-term relief in COPD (if not on LAMA)
Onset is 15-30 mins
Maximum effect is 60-90 mins after admin. (COPD)
What is aclidinium (Eklira) indicated for?
Maintenance for COPD (not suitable for acute bronchospasm)
What is glycopyronium bromide (Seebri) indicated for?
Maintenance therapy for COPD and hyperhidrosis (excessive sweating)
What is tiotropium (Spiriva) indicated for?
Dosing regimen?
- COPD maintenance- 18mcg OD
- Once daily dosing
- Maximum effect 90-120 mins after inhalation
Spiriva RESPIMAT restricted for use in COPD for patients with poor manual dexterity
What are the common S/E for tiotropium?
- Dry mouth
- GI motility (diarrhoea, constipation)
- Cough
- Nausea
- Angle closure glaucoma
Under what class does Theophylline fall under?
What do these class of med do?
Any downsides?
Xanthines
- Have bronchodilator and anti-inflammatory effects
- β2 agonists are more effective as bronchodilators and corticosteroids have greater anti-inflammatory effect
Points to consider for theophylline therapy?
- Despite extensive use in respiratory disease, molecular action not fully understood
- Metabolised by CYP450
- Has a very narrow therapeutic window (requires close monitoring)
What is the effective therapeutic window for theophylline?
Plasma conc. : 10-20 mg/L
Doses must be adjusted in individual patients according to their their plasma concentration
What are the monitoring requirements for theophylline?
Plasma concentration
What can cause increases plasma concentrations of theophylline?
- Heart failure
- Hepatic impairment
- Viral infection
- Elderly
What can cause a decrease in plasma concentrations of theophylline?
- Smokers
- Alcohol consumption
Does prescribing need to be by brand on theophylline?
What is the most common brand?
Yes- the rate of release from MR preps varies
If no brand mentioned on Rx- contact prescriber
Most common- Uniphyllin Continus
What is the MAX dosing for theophylline?
400mg 12-hourly
What are the S/E associated with theophylline?
- CNS: increased alertness, insomnia, tremor, headache
- CVD: inotropic and chronotropic positive effects tachycardia
- GI: stimulates gastric acid secretion, anorexia, nausea, vomiting, gastro-oesophageal reflux
- Kidney: diuretic
- Smooth muscle: Bronchodilation
What decreases the metabolism of theophylline?
and therefore increases serum concentration
- Old age
- Arterial hypoxemia (low oxygen sat.)
- Respiratory acidosis
- Congestive cardiac failure
- Liver cirrhosis
- Erythromycin
- Quinolone antibiotics
- Cimetidine (NOT ranitidine)
- Viral infections
- Herbal remedies (St. John’s Wort)
What increases the metabolism of theophylline?
and therefore decreases serum concentration
- Tobacco smoking
- Alcohol
- Anticonvulsant drugs
- Rifampicin
What is aminophylline?
Differences to theophylline?
Theophylline + ethylenediamine
- Given by very slow IV infusion
- Too irritant for IM use, 20x more soluble than theophylline
Does branded prescribing need to take place?
Yes- MR preps vary in rate of release
When should phylloctonin continus forte tablets (aminophylline) be used?
In patients where theophylline has a shorter half life
What is the most common compound bronchodilator preparation?
What is it indicated for?
Combivent: 500mcg
* Ipratropium + 2.5mg salbutamol
Indicated for bronchospasm in COPD
When and why is use of compound bronchodilator therapy used?
When patients are stable on both constituent drugs
Used because it is best to treat with single drug- can adjust dose more easily
What is the benefit of nebulisers?
Delivers a greater proportion of the drug to the lungs compared with standard inhalers
When should nebulisers be used with caution?
- Acute angle-closure glaucoma associated with nebulised drugs i.e. ipratropium
- NB: eye care during nebulisation
What are nebulisers indicated for?
- Beta-2 agonist or ipratropium in acute exacerbation asthma
- Beta-2 agonist, corticosteroids ipratropium in severe asthma
- Antibiotic or mucolytic in cystic fibrosis
- Budesonide or adrenaline to child with severe croup
- Pentamidine for treatment/prophylaxis of pneumocystis pneumonia
What is the mode of action of corticosteroids?
More specifically in respiratory care?
- Once in the cell they bind to specific receptors in the cytoplasm- ‘activated glucocorticoid-receptor complex’ translocates to the nucleus to interact with the DNA
- This induces transcription of particular genes and synthesis of some proteins and vice versa
In respiratory care:
* Transcription of various pro-inflammatory gene products are modified
* This reduces airway inflammation and hyper responsiveness
How are inhaled corticosteroids (ICS) used in asthma?
Effects of regular ICS use?
- They reduce airway inflammation, oedema and secretion of mucus
- ICS used prophylactically if Beta-2 agonist required > 2 weeks, or if sleep disturbances or exacerbations in last 2 years requiring systemic CS
- Regular use reduces risk of exacerbation
- Smoking reduces effectiveness of CS
How are ICS used in COPD?
CS reduce exacerbations when combined with LABA
What can high doses of ICS lead to?
- Adrenal suppression
- Associated with pneumonia in elderly with COPD
What can long-term treatment with ICS leads to?
Reduced bone mineral density, predisposes to osteoporosis
Height of children on prolonged treatment should be monitored
What are the common S/E of ICS?
- Hoarseness, dysphagia, throat irritation, oropharyngeal candidiasis
- Hyperglycaemia with high doses
- Anxiety, depression, sleep disturbances
How can patients manage oral candidiasis?
- Reduce risk by using spacer and rinsing mouth/ brushing teeth after use
- Antifungal oral gel can be used to treat OTC without stopping treatment
Give 5 examples of ICSs
- Beclomethasone (Becotide)
- Budesonide (Pulmicort)
- Fluticasone (Flixotide)
- Mometasone (Asmanex)
- triamcinolone (Nasacort)
What are the systemic S/E associated with long-term, high dose treatment with ICS?
- Skin thinning, easy bruising
- Glaucoma, cataracts
- Adrenal suppression
- Slow growth rate in children
- Low bone mineral density –> osteoporosis
How does poorly controlled asthma affect a foetus during pregnancy?
- Low birth weight
- Increased perinatal mortality
- Prematurity
- Risk of foetal hypoxia
How are acute exacerbations controlled in asthmatic pregnant patients?
- SABA- nebulised
- Oxygen
- Systemic glucocorticoid therapy, when necessary
What is the mode of action of leukotriene receptor antagonists?
- Block effect of cysteinel leukotrienes on airway
- Improve lung function and reduce asthma exacerbations
What are the effects of leukotrienes?
- Increase in microvascular permeability (oedema)
- Increased mucus secretion
- involved in smooth muscle proliferation and remodelling
- Increased infiltration of eosinophils into airways
What are the side effects associated with leukotriene receptor antagonists?
- Churg Strauss Syndrome
- GI upset
- Headache
Give an example of a leukotriene receptor antagonists and its dosing regimen
Montelukast- 10mg at night
5mg at night for child < 15 y/o
What is Churg Strauss Syndrome?
How can it be spotted?
An autoimmune disorder marked by blood vessel inflammation (vasculitis)
Monitor for signs of eosinophilia, vascularitic rash, peripheral neuropathy and cardiac complications
What is the mode of action of phosphodiesterase type-4 inhibitors?
- Prevent activation of the intracellular cyclic adenosine monophosphate (cAMP)/ cyclic guanosine phosphodiesterase (cGMP)
- May improve lung function, decreasing inflammation around the small airways
What is roflumilast indicated for?
Adjunctive therapy to bronchodilators (severe COPD)
Has anti-inflammatory activity
S/E associated with roflumilast?
- Increased risk of psychiatric disorders: insomnia, anxiety, nervousness and depression
- Diarrhoea, nausea, abdominal pain
- Headache
When is roflumilast contra-indicated?
- Moderate/severe hepatic impairment
- Immunological diseases
Not recommended if psychiatric symptoms
When are antihistamines used in caution?
Epilepsy- can increase seizure susceptibility
Where must antihistamines be avoided?
Patients with severe liver disease- increased risk of coma
What is the mode of action of H1 receptor antagonists?
They bind competitively bind to H1 receptors present on nerve endings, smooth muscle and glandular cells
What are H1 receptor antagonists indicated for? (5)
- Allergic rhinitis/ allergic conjunctivitis
- Urticaria (hives)
- Drug hypersensitivity
- Anti-emetic
- Sedation
S/E associated with H1 receptor antagonists? (4)
- Sedation
- Tinnitus
- Dizziness
- Antimuscarinic S/E e.g. dry mouth, constipation etc
Counselling points for antihistamines?
Do not drive/ operate heavy machinery
Adverse effects associated with antihistamines?
Children and elderly more prone to S/E
- Drowsiness
- Paradoxical stimulation (opposite effect of drug)
- Headache
- Psychomotor impairment
- Antimuscarinic S/E (dry mouth, urinary retention, blurred vision, GI upset)
Examples of non-sedating vs sedating antihistamines
What is the principle behind allergen immunotherapy?
Vaccines containing allergens i.e. house dust, cat dander, can reduce asthma symptoms
Vaccines with wasp, bee venom reduce anaphylaxis
What is Omalizumab and its mode of action?
a monoclonal antibody that binds to immunoglobulin E, mitigating its allergic reaction effects on the body
What is Omalizumab indicated for?
Severe, persistent asthma uncontrolled with ICS
S/E associated with Omalizumab?
Associated with Churg Strauss Syndrome
- Injection side reactions
- Rash, diarrhoea, nausea, vomiting, menorrhagia, epistaxis (nose bleed)
How is anaphylaxis characterised, and how is it treated?
- A severe, life-threatening, systematic hypersensitivity reaction
- Rapid cardiopulmonary symptoms
Adrenaline licenced for emergency treatment of acute anaphylaxis (angioedema, cardiopulmonary resuscitation)
How should patient-carried adrenaline pens be administered?
What are next steps should anaphylaxis not resolve?
- Lie patient flat
- Raise legs (put in recovery position if nauseous)
- Administer adrenaline into thigh
- Should reverse immediate symptoms associated with hypersensitivity
- Second dose should be 5-15 mins after, if first is unsuccessful
- Continuous respiratory deterioration requires treatment with bronchodilators i.e. inhaled, IV salbutamol, ipratropium, IV aminophylline
What are the potential risks causing anaphylaxis reactions?
- Insect stings
- Medication (e.g. NSAIDs, vaccines, neuromuscular blockers, latex)
- Milk, eggs, fish, shellfish, soya
- Arachis oil, other excipients
3 examples of adrenaline pens
- Epipen
- Anapen
- Jext
What are respiratory stimulants?
Stimulate respiratory and non-respiratory muscles (can be harmful). Only effective given IV, and have a short duration of action. Expert supervision required
What is Doxapram HCl indicated for?
- Post operative respiratory depression
- Acute respiratory failure
What is Caffeine citrate indicated for?
Neonatal apnoea (specialist supervision in hospital)
What is the mode of action of pulmonary surfactants?
They reduce the surface tension at the air/water interface in the alveoli, thereby preventing collapse of these structures at end-expiration. Also enables the lung to inflate more easily, reducing workload
What are pulmonary surfactants indicated for?
Give 2 examples of these
Respiratory Distress Syndrome in neonates
Examples:
* Baractant
* Poractant alfa
How is oxygen generally indicated?
What is its mode of action?
For hypoxemic patients, prescribed to achieve near-normal oxygen saturation (Aim: 94-98%)
- Increases alveolar oxygen tension
- Reduces workload of breathing
In which medical conditions is high conc. oxygen suitable?
- Pneumonia
- Sepsis
Points to consider for oxygen therapy
- Consider smoking cessation before starting oxygen
- Discuss with airlines before travelling abroad
- Concentration used depends on condition being treated
What is the mode of action of mucolytic drugs?
Where do they need to be used in caution?
What else could be used to the same effect?
Facilitate expectoration of mucus by reducing sputum viscosity
They disrupt the mucosal barrier, use in caution in peptic ulcer/ history of ulcer
Steam inhalation could also be effective
S/E associated with carbocisteine?
At what age is it licenced for?
GI side effects
Used from 2 years old on
What is erdostine indicated for?
S/E?
Treat acute exacerbations of chronic bronchitis
GI S/Es
What is Dornase Alfa?
It’s function and indication?
Genetically engineered enzyme- glycosylated recombinant human rhDNAse
Cleaves extracellular DNA
Increase lung function, used in cystic fibrosis
How is Dornase Alfa administered, and how often?
- Admin. with jet nebuliser
- Up to BD
What is Ivakaftor (Kalydeco) indicated for?
How is this identified?
Cystic fibrosis in patients with G551D mutation in CFTR gene
Genotyping method should be performed to confirm G551D mutation in at least one allele
What are the monitoring requirements for ivakaftor?
LFTs prior to treatment, also be checked every 3 months during first year of treatment, then annually thereafter
S/E associated with ivakaftor?
- Abdominal pain
- Nausea
Dosing schedule with ivakaftor?
BD dosing- reduce dose if taking with “-zoles” or “-mycins”
What is mannitol indicated for and its administration method?
Cystic fibrosis- non-responsive to Dornase Alfa
Administered by inhalation
What is the mechanism of action of mannitol?
Not fully understood but improves mucus clearance
What are the potential causes of a cough?
- GORD
- Chronic bronchitis
- Rhinitis, rhinosinusitis, post natal drip syndrome
- a S/E of ACEi!!
- Associated with smoking, environmental causes e.g. pollution
What are the respective lengths of acute and chronic coughs
- Chronic cough- > 8 weeks
- Acute cough- < 3 weeks
Recommendations for acute cough management
- Acute viral cough often self-limiting and doesn’t require treatment
- Simplest and cheapest option may be ‘home remedy’ like honey and lemon
- Opiate antitussives have significant adverse effect profiles so aren’t recommended
Examples of expectorant cough medicines
Guaifenisin, ipecacuana
Examples of suppressant cough medicines
Dextromethorphan, pholcodeine, codeine
Examples of decongestant cough medicines
Phenylephrine, pseudoephedrine, oxymetazoline, xylometazoine
Examples of antihistamine cough medicines
Chlorphenamine, diphenhydramine, doxylamine, promethazine, tripolidine
At what age should people not be offered liquid codeine as antitussive?
< 18 years old
At what age should people not be offered couh and cold remedies?
< 6 years old
Give an example of a systemic nasal decongestant
Pseudoephedrine (Sudafed)
Advantages and disadvantages of systemic nasal decongestants
Advantage- not associated with rebound congestion
Disadvantage- not as effective as local decongestant
When does pseudoephedrine need to be used in caution?
- Diabetes
- Hypertension
- Hyperthyroidism
- Ischaemic heart disease
S/E associated with pseudoephedrine
- Nausea
- Vomiting
- Tachycardia
Typical dosing schedule for pseudoephedrine
60mg TDS-QDS
Which high risk drugs can be used in cough suppression in palliative care?
Methadone
* Licenced for cough in terminal illness
* Long duration of action, accumulates
Morphine
* Shorter acting
