Pharmacology: asthma Flashcards
What are the 3 key characteristics of asthma?
Airway obstruction
Airway inflammation
Airway hyperreactivity
Is airway obstruction in asthma reversible?
Airway hyperactivity involves:
Does asthma involve an immediate stage and a late stag?
Yes
hyperreactivity - irritants have stronger effects on asthmatic airways than healthy airways
Yes
What are 4 potential triggers for asthma?
Viral infections
Physical activity (inhalation of cold air)
Pollutants
Allergens
List the steps for the immediate phase of asthma
What is the link between the immediate and late phase of asthma?
Chemotaxins and chemokines - attract leukocytes
List the steps of the late stage of asthma
How does allergic asthma fit into this pathway?
Allergen engulfed by APC and presented to helper T cells. Which differentiate into B cells which secrete IgE (the allergy antibody).
IgE receptors are expressed on eosinophils and mast cells.
Describe bronchiole inflammation resulting from asthma
What are 2 non pharmacological asthma management strategies?
- Allergen avoidance
- Monitoring severity
Asthma drugs work on which 2 processes?
The two main categories of asthma medications are:
Inhibiting bronchoconstriction or inflammation
Preventers and relievers
What are the 7 classes of asthma drugs?
SABA, LABA
SAMA, LAMA
ICS
Leukotriene receptor antagonists
mAb’s
Beta 2 adrenoceptor agonists:
- Mechanism of action?
- Side effects?
- Does it impact inflammation?
Activate B2 receptors - bronchodilation
Increased HR rate, skeletal muscle tremor
Not very much
SABAs: short acting beta adrenoceptor agonists
- Indications for use?
- When asthma is mild, can SABAs sometimes be used alone?
- Onset and duration?
- 2 examples?
Use when required for mild/intermittent asthma
Yes
Onset: 5-15 minutes; duration: 3-6 hours
Salbutamol (ventolin), terbutaline
LABAs: long acting beta adrenoceptor agonists
- What must they be used in combination with, and why?
- Duration?
- 2 examples?
ICS - when used alone, can lead to tachyphylaxis (tolerance to LABAs –> doesn’t work during attack)
12 hours
Salmeterol, eformoterol
Muscarinic receptor antagonists
- What receptor does it primarily act on? And its usual function?
- What is its mechanism of action?
M3 receptors; bronchoconstriction
Blocks these receptors –> bronchodilation
SAMAs - short acting muscarinic receptor antognists
- Example?
- Which muscarinic receptor subtypes do they act on? Implications?
- What is it helpful in doing?
- Is it effective in allergic asthma?
- Describe the absorption and consequent effect on ADRs
Ipratropium
M2/M3
- Less M3 –> smaller role in bronchodilation
- M2 autoregulates to release ACh –> counteracting drug effects
Reducing mucus secretion, improving mucus clearance
No
Polar, so is not well absorbed systemically - minimal ADRs apart from dry mouth
LAMAs - long acting muscarinic receptor antagonists
- 2 examples?
- Describe M receptor selectivity
- Compared to SAMAs, does it take shorter or longer to dissociate from it’s receptor? Implications on duration of drug?
- Indications for drugs?
Tiotropium, glycopyrrolate
More selective for M2
Longer - longer action
More used in COPD; and glycopyrrolate in palliative care
INHALED CORTICOSTEROIDS
Mechanism of action:
- Which process does it reduce?
- What are the non cellular and cellular mechanisms through which it does this?
- What effects does this have on the bronchi?
Inflammation
Non cellular: less cytokines, prostaglandins, leukotrienes, IgG
Cellular: less mast cells (hence histamine), less eosinophils
Reduced swelling, secretions, bronchial hyperreactivity
INHALED CORTICOSTEROIDS
- 2 examples?
- Is it a preventer or reliever?
- Can it be used alone and with B2 agonists? Do they have an additive effect?
- How long does it take for them to work?
- What 3 adverse effects are common, and do these arise from improper technique?
- Generally, when used with proper technique, does it have minimal systemic effects?
- Can oral corticosteroids also be used?
Fluticasone, budesonide
Preventer
Yes - penetration of ICS’s is increased by B2 agonists
Around 6 months
Angular chelitis, oral thrush, exacerbation of diabetes symptoms; yes
Yes
Yes - but short term
LEUKOTRIENE RECEPTOR ANTAGONISTS
What is the nromal role of leukotrienes?
Inflammatory cell migration
Mucus secretion
Bronchoconstriction
Bronchial hyperactivity
LEUKOTRIENE RECEPTOR ANTAGONISTS
Montelukast
- What specific receptor does it antagonist?
- What are it’s two indications?
CysLT1
Allergic asthma (especially in children)
Reducing exercise induced asthma
LEUKOTRIENE RECEPTOR ANTAGONISTS
Montelukast
- Can it be used alone or in combination?
- Does it work less well than salbutamol, but additive in combination?
- Describe formulation
Yes - with ICS, or ICS+LABA
Yes
Tablet with chewable option
LEUKOTRIENE RECEPTOR ANTAGONISTS
Montelukast
- Common ADRs?
- Rare ADRs?
Headache, abdominal pain, diarrhoea
Meuropsychiatric events (nightmares, hallucinations, aggression, suicidal thoughts and behaviours)
mAb’s
Which one targets IgE?
Which one targets IL-5?
Omaluzumab
Mepoluzumab
Omaluzumab:
- Mechanism of action
- Additional indication?
Binds to IgE, preventing it from attaching to mast cells –> prevents allergic asthma
Urticaria unresponsive to antihistamines
Mepoluzumab:
- Mechanism of action
- Indication?
Ordinarily, IL-5 regulates eosinophil production. So Mepoluzumab blocks eosinophil production via IL-5
Severe, refractory eosinophilic asthma
What are the 2 main types of inhalers?
Metered dose inhaler: quick delivery in an inert propellant gas
Dry powder inhalers: drug is delivered in powder form
What are the 2 inhaler accessories
Spacers (used with MDI)
Nebulisers: creates larger droplets which deposit deeper into the airways
Inhalers:
- Are spacers + inhalers together than inhaler alone at getting the drug into lungs?
- If there is static electricity in the spacer, can the drug stick there andnot get to the lungs?
Yes
Yes
The 7 types of inhalers? (Probably don’t need to know!)
