Week 4: Respiratory - Asthma, COPD, Nicotine Cessation Flashcards
What is the pathophysiology of asthma?
Asthma causes the stimulation of IgE antibodies which causes mast cell activation or degranulation - leads to inflammation and mucus production causing the flare of asthma
Acute inflammation - symptoms (bronchoconstriction)
Chronic inflammation - exacerbations nonspecific hyperreactivity
Airway remodeling - persistent airflow obstruction
Symptoms of Asthma
Symptoms include
- Increase mucus production
- Thickened bronchial walls
- Wheeze
- Shortness of breath
- Chest tightness
- Cough
- Expiratory airflow limitation
Pathophysiological effects of asthma attack
- Altered immunological response -> chemical mediators released (histamine, protaglandins, bradykinins etc.
- Increased airway resistance -> mucus secretion, inflammation, bronchospasm
- Increased lung compliance -> lungs become hyper-inflated
- Impaired mucocillary function -> increased mucus production (can cause cough)
- Altered O2-CO2 exhcange -> increased airway resistance
Asthma effect on airways
Asthmatic airway during attack
- Tightned smooth muscles, wall inflamed and thickened, enlarged alveolar as air is trapped
How to control asthma?
- Good control
- Partial control
- Poor control
Good control (all of following)
- Daytime symptoms <2 days per week
- Need for reliever <2 days per week
- No limitation of activities
- No symptoms during night or on waking
Partial control (one or two of following)
- Daytime symptoms >2 days per week
- Need for reliever >2 days per week
- Any limitation of activities
- Any symptoms during night or on waking
Poor control (three or more of following)
- Daytime symptoms >2 days per week
- Need for reliever >2 days per week
- Any limitation of activity
- Any symptoms during night or on waking
Lifestyle management of ashma
- Smoking cessation (including second degree)
- Identify and avoid triggers
- Manage comorbidities
- Healthy eating and body weight
- Regular physical activity
- Regular immunisations
Pharmaceutical management options for asthma
Short acting beta agonist (SABA)
Long acting beta agonist (LABA)
Inhaled corticosteroids (ICS)
SABA
- MOA
- Clinical use
- Drug options
MOA
- Agonist of beta-2-adrenergic receptors in lungs
- Cause bronchodilation by relaxing bronchial smooth muscle and allowing airway to open
Clinical use
- Relievers
- Used as needed to relieve symptoms
- May be used before exercise
- Rapid onset 3-4 min
- Duration of 3-4 hrs
Drug options
- Salbutamol (Ventolin, Asmol)
- Terbutaline (Bricanyl)
Contraindications/Cautions of SABA
Pregnancy/Breastfeeding/Heptic impairment/Renal impairment
- Safe
Elderly:
- Start with low dose and slowly titrate
Children:
- Safe for children aged 2+ (need specialist if younger)
Cautions in:
- CVD
- Hyperthyroidism
- Diabetes
- History of PACG
- Other sympathomimetics
- Corticosteroids
- Theophyline
- Diuretics
LABA
- MOA
- Clinical use
- Drug options
MOA
- Agonist of beta 3 adrenergic receptors
- Activate receptors in bronchial smooth muscles to allow relaxation and bronchodilation
Clinical use
- Preventor
Drug options
- Salmeterol (Serevent, Seretide)
- Eformoterol (Oxis, Symbicort)
- Indacaterol (Onbrez)
Contraindications/cautions of LABA
Hepatic and renal impairment
- No precautions
Elderly:
- Start low dose and slowly titrate
Pregnancy:
- Limited data
Breastfeeding:
- Salmeterol is safe
Children:
- Safe for children 2+ (specialist if younger)
Cautions in:
- CVD
- Hyperthyroidism
- Diabetes
- History of PACG
- Other sympathomimetics
- Corticosteroids
- Theophyline
- Diuretics
ICS
- MOA
- Clinical use
- Drug options
MOA
- Immunosuppressant
- Reduce airway inflammation and bronchial hyper-reactivity
Clinical use
- Maintenance therapy
- Can be combined with LABA or given on its own
- Useful for prevention even if only occasional flare up
Drug options
- Beclomethasone (QVAR)
- Budesonide (Pulmicort)
- Fluticasone (Flixotide, Breo)
Contraindications/cautions for ICS
Pregnancy/breastfeeding/hepatic impairment/renal impairment:
- Safe and no precautions
Elderly:
- More susceptible to skin thinning and bruising
- Use lower dose
Children:
- Avoid high dose without specialist involvement
Cautions in:
- COPD (pneumonia risk)
Inhaled Anticholinergics
- MOA
- Clinical use
- Drug options
MOA
- Antagonist of cholinergic receptors in bronchial tissue
- Relax smooth muscle to allow bronchodilation
- Specifically antagonise the muscarinic effects of cholingeric receptors (also referred to as SAMA or LAMA)
Clinical use:
- Short acting (SAMA) -> relief of asthma symptoms
- Long acting (LAMA) -> maintenance/prevention of asthma symptoms in combination with LABA or ICS
Drug options
- Short acting -> Ipratropium
- Long acting -> Tiotripium
Contraindications/Cautions of inhaled anticholingeric
Pregnancy/Breastfeeding/Hepatic impairment/Renal impairment:
- Safe and no cautions
Elderly:
- Likely to be susceptible to urinary retension
Children:
- SAMA can be used
- LAMA’s cannot
Caution in:
- Bladder obstruction/urinary retension or PACG
Device techniques for asthma
MDI - metered dose inhaler (under pressure)
DPI - dry powder inhaler (uses inspiration of patients)
Nebules - liquids that are suspended and inhaled via nebuliser
Oral capsule
Spacers - greatly increase amount of dose MDIs reachs lungs
Asthma Management plan
Do they have one?
Are there copies?
Do they know what to do in an attack?
What is COPD?
Chronic obstructive pulmonary disease
- Umbrella term describing progressive lung diseases including emphysema, chronic bronchitis, refractory asthma and bronchiectasis
All of which are characterised by increasing breathlessness
COPD Pathophysiology
Chronic inflammation causing damage to lung elasticity therefore over-expanded lungs make it difficult to breath out fully
Chronic over-expansion leads to more air trapped causing hyperinflation and muscles have to work harder thus require more oxygen
Chronic inflammation also causes narrowing of airways and excess sputum which further restricts airflow
The cycle of inactivity
- Shortness of breath and difficulty with day-day activities
- Poor confidence and less physical activity
- Muscles loose strength and heart function decreases
- Fitness declined and social isolation
- Worse shortness of breath as well as anxiety or depression
- Loss of independence and symptoms worsen
Complications of COPD
- Increased susceptibility to chest infection
- Pneumothorax
- CVD
- Anxiety/depression
- Oedema
- Hypoxaemia
- Obesity
- Osteoporosis
- Death
Lifestyle modifications for COPD
- Smoking cessation
- Maintain healthy weight
- Regular, appropriate exercise to improve CV fitness
- Breathing techniques
> Pulmonary rehabilitation (Relaxed breathing, prolonged expiration breathing, recovery position) - Manage anxiety
- Manage comorbidities (infection, regular vaccines, BP)
1st line drug therapy for COPD
For exacerbations of breathlessness, patients are almost always started on either
- SABA (short acting beta2 agonist - salbutamol, terbutaline)
SAMA (short acting muscarinic antagonist - ipratropium)
2nd line drug therapy for COPD
Used if SABA or SAMA are not enough to control exacerbation
- LABA (Long acting beta2 agonist - salmeterol or eformoterol)
- Ultra LABA (ultra long acting - indacaterol
- LAMA (long acting muscarinic antagonist - tiotropium)
3rd line drug therapy for COPD
Combination of 1st and 2nd line drugs
- LAMA + LABA
- ICS + LABA
- ICS + LAMA (no single inhaler device available = less compliance)
- ICS are not indicated for single use in COPD
Drug therapy as COPD progresses
Oxygen therapy
- For patients with significant hypoxaemia or presenting 18hrs/day
Theophylline
- Lots of contraindications and requires lots of monitoring
Mucolytics
Long term low dose antibiotics (infections that cause exacerbation in late stage)
Nicotine Pharmacology
- Half life
- Metabolism
- Distribution/Duration
Nicotine is colorless and odorless
Half life <40 min
Nicotine receptors (nACh) in liver are quickly unregulated therefore a higher dose is needed to achieve the same effect Metabolism changes between individuals - CYP4502A6 enzyme
Inhalation results in very rapid (within 10 sec) distribution within CNS however, it also rapidly declines inducing withdrawal (use regularly to keep dopamine levels up and minimize withdrawal)
Definition of addiction
- Nicotine
Addiction is chronic, relapsing brain disease that is characterized by compulsive drug seeking and use despite harmful consequences
Nicotine is a highly addictive substance
- Poisonous plant alkaloid found in tobacco
- Ingestion/inhalation results in activation of the reward pathway (dopamine in mesolimbic pathway)
The ‘good’ effects of nicotine
Activates many different neurotransmitters
- Dopamine -> pleasure, appetite suppression
- NA -> arousal, appetite suppression
- Ach -> arousal, cognitive enhancement
- Vasopressin -> memory improvement
- 5HT -> mood enhancement, appetite suppression
- Beta-endorphines -> reduction in tension and anxiety
Why is it so difficult to quit smoking?
Withdrawal symptoms - Physiological addiction - Emotional addiction Fear of failure Social pressure Unwanted side effects of quitting - Weight gain - Stress - Increased addiction to alcohol, food Lack of compliance with medications/quitting aids/CBT
Nicotine withdrawal symptoms
- Craving
- Irritability/restlessness
- Sleep disturbances
- Headache
- Depression
- Anxiety
- Difficulty concentrating
- Increased appetite
- Constipation
Smoking health outcomes - increased risk of other health conditions
- Mortality (premature death with 10 cigarettes per day doubling the risk)
- CVD
- Asthma/COPD/Emphysema/Pneumonia
- Premature aging
- Staining of skin and teeth
- Peridontal disease (gum disease)
- Cancer
- Diabetes
- Ostoporosis/RA
- Sexual dysfunction/infertility/still birth/premature birth
- Blindness/Cataracts
Physiological changes timeline as someone quits
- 20 min (return normal BP, HR, temp)
- 8 hrs (O2 level normal)
- 24 hrs (decreased chance of heart attack)
- 48 hrs (taste and smell begin to improve)
- 1 month (immune system begins to recover)
- 1-3 months (circulation to extremities return)
- 3 months (lung function begins to normalize)
- 1 yr (50% reduction in risk of heart attack)
- 5 yrs (risk of stroke returns to non smoker level)
- 10 yrs (risk of lung cancer reduced by 30-50%)
- 15 yrs (CVD risk almost back to non smoker level)
Nicotine replacement therapy (NRT)
- Inhalation
- Oral/Buccal
- Transdermal
Aim to decreased withdrawal/cravings and increase success rate
Inhalations - e-cigarettes, inhalers - Fast delivery Oral/Buccal - Moderate fast - Strip, mist, lozenges, gum Transdermal - Slowest - Patches
NRT approaches
- First line
First line
- Combination of NRT products
Pre quit patches
- Helps reduce anxiety around quitting
- Reduce no. cigarettes smoked therefore reduced toxins
Reduced no. to quit in combination with NRT
Pharmacotherapy for smoking cessation: Varenicline (Champix) - MOA - ADR - Practice points
MOA
- Partial agonist at nACh receptor
- Blocks nicotine from binding - stops pleasurable effects of smoking
- Partial agonist - reduced sx of withdrawal
ADR
- Commonly causes sleep disturbances (vivid dreams, nightmares and nausea)
- May cause depression, agitation, behavior changes, suicidal idealization (rare)
Practice point
- Needs to be started at least 7 days before trying to quit
Pharmacotherapy for smoking cessation:
Varenicline (Champix)
- Contraindications and cautions
Hepatic impairment
- Can raise liver enzymes
Pregnancy
- No data - avoid
Breastfeeding
- No data
Renal impairment
- Reduce dose
Caution in history of seizures
Pharmacotherapy for smoking cessation:
Bupoprion (Zyban)
- MOA
- Practice point
MOA
- Unknown for smoking cessation
- It inhibits re uptake of dopamine and noradrenaline
Practice point
- Needs to be started at least 7 days before trying to quit
Pharmacotherapy for smoking cessation:
Bupoprion (Zyban)
- Contraindications and cautions
Elderly
- Reduce dose
Hepatic impairment
- Reduce dose
- Contraindicated in severe impairment
Pregnancy
- Avoid
Breastfeeding
- Appears safe
Renal impairment
- Reduce dose
Contraindicated in bipolar or tx with MAOI within 14 days, seizures, CNS tumor, bulimia, anorexia
