Pharmacology Flashcards
the ___1___ division drives asthma symptoms and the ___2____ division is a good target for alleviating acute asthma symptoms. There is however a branch of the parasympathetic division that can be used to mediate smooth muscle relaxation using ________ fibres.
1- Parasympathetic
2- Sympathetic
3- noncholinergic e.g. NO and VIP
Explain muscle contraction and relaxation in relation to phosphorylation of myosin light chain
- Contraction results from phosphorylation of the regulatory myosin light chain (MLC) in the presence of elevated intracellular Ca2+ (and ATP)
- Relaxation results from dephosphorylation of MLC by myosin phosphatase which has constitutive activity
What is asthma?
A recurrent and reversible (in the short term) obstruction to the airways in response to substances (or stimuli) that are not necessarily noxious/harmful and normally do not affect non-asthmatic subjects.
List four potential causes of asthma attacks
- Allergens (in atopic individuals)
- Exercise (cold, dry air)
- Respiratory infections (e.g. viral)
- Smoke, dust, environmental pollutants etc
What does asthma cause?
Intermittent attacks of bronchoconstriction resulting in tight chest, wheezing, difficulty breathing and coughing.
What are the pathological changes to the bronchioles in people with chronic asthma?
1) Increased mass of smooth muscle (hyperplasia and hypertrophy). Thickness of smooth muscle increases as it is constantly contracting and relaxing in response to allergens.
2) Accumulation of interstitial fluid (oedema)
3) Increased secretion of mucus
4) Epithelial damage (exposing sensory nerve endings)
5) Sub-epithelial fibrosis
Explain hypersensitivity and hyperreactivity
- Hypersensitivity refers to the increase in sensitivity to the bronchoconstrictors or more generally hypersensitivity is any heightened immune response.
- Hyperreactivity is increased responsiveness usually due to hypersensitivity
Explain the two categories of asthma treatment
Relievers- these act as bronchodilators Controllers/preventors- Act as anti-inflammatory agents that reduce airway inflammation
Examples of Bronchodilators?
Beta-2-adrenoreceptor agonists
CysLT1 receptor antagonists
Explains the three categories of beta-2-adrenoreceptor agonists.
SABAs- these are short acting e.g. salbutamol and are relievers that are taken when needed. They are usually administered by inhalation.
LABAs- these are long acting e.g. salmeterol. They are not recommended for acute relief of bronchospasm but are useful for nocturnal asthma as they act for approximately 8 hours. Not used as mono therapy.
Ultra-LABAs- last for much longer time.
How do CysLT1 antagonists work?
Cysteinyl leukotriene (CysLT1) receptor antagonists act competitively at the CysLT1 receptor. CysLTs are derived from mast cells and the infiltrating inflammatory cells cause smooth muscle contraction, mucus secretion and oedema. Antagonists will stop this.
Example includes oral montelukast
What are xanthines used for in asthma?
• They combine bronchodilator (at high doses) and anti-inflammatory action and inhibit mediator release from mast cells and cause increase mucus clearance
• They are second line drugs used in combination with beta-2-adrenoceptor agonists and glucocorticoids
An example of a methylxanthine is oral theophylline
What is an anti-inflammatory drug that can trigger bronchospasm in sensitive individuals?
Ibuprofen
What is omalizumab?
Monoclonal antibody against IgE that could be used in treatment of asthma by preventing allergic response
What are the main drugs used in the prophylaxis of asthma
Glucocorticoids (steroids)
Name three glucocorticoids
beclometasone, budesonide, fluticasone
Glucocorticoids have no _______ effect but do have an _______ effect
No bronchodilator
Do have anti inflammatory effect
Glucocorticoids signal via….
nuclear receptors (specifically GRalpha)
Four effects of glucocorticoids relevant to asthma?
1) Decrease formation of TH2 cytokines and causes apoptosis of T cells.
2) Prevent production of IgE antibodies
3) Prevent allergen induced influx of eosinophils into lungs and causes apoptosis of these cells
4) Reduce number of mast cells and decrease IgE receptors
What are the most common adverse effects of glucocorticoids due to deposition of steroids in the oropharynx?
Dysphonia (hoarse and weak voice) and oropharyngeal candidiasis (thrush
What are the cromones used as in treatment of asthma?
Second line drugs now infrequently used prophylactically in the treatment of allergic asthma
Explain the role of M1,2 and 3 receptors in the airway
- M1 – ganglia – facilitate fast neurotransmission mediated by ACh acting on nicotinic receptors
- M2 – postganglionic neurone terminals – act as inhibitory autoreceptors reducing release of ACh
- M3 – ASM –mediate contraction to ACh (also present on mucus-secreting cells evoking increased secretion)
Blocking of what muscarinic receptors is desirable in treatment of COPD?
Block of M3 and M1 is desirable but not M2 as this will increase the rate of release of acetyl choline.
Muscarinic receptor antagonists end in ___1____
and ____2_____ is the only SAMA the rest are LAMAs. They have a ____3____ effect
1 - ium
2- Ipratropium
3- Bronchodilator effect
Oral ___1_____ is used for COPD and relieves ____2_____
Carbocysteine relieves viscosity of sputum
What drug is a phosphodiesterase-4-inhibitor, given orally for severe COPD?
Rofumilast
Sodium cromoglicate….
is a cromone that acts as a mast cell stabiliser and is used in asthma and allergic rhinitis
Prednisolone is an…
oral steroid used in allergic rhinitis, acute asthma or an exacerbation of COPD
Describe anti-histamines in treatment of allergic rhinitis
- Mechanism – competitive antagonists that reduce effects of mast cell derived histamine including:
- Vasodilatation and increased capillary permeability
- Activation of sensory nerves
- Mucus secretion from submucosal glands
• Examples include (second generation only):
o Loratadine
o Fexofenadine
o Cetirizine (also has mild anti-inflammatory action)
Describe anti-cholinergic drugs in treatment of rhinnorhoea
- Mechanism – ACh released from post-ganglionic parasympathetic fibres activates muscarinic receptors on nasal glands causing a watery secretion that contributes to rhinorrhoea – blocked by muscarinic antagonists. Important treatment for constant runny nose.
- Ipratropium is the sole agent used in this class
Describe sodium cromoglicate in treatment of allergic rhinitis
- Mechanism – purportedly mast cell stabilization, but this is uncertain
- Used for maintenance treatment of allergic rhinitis with an onset of action of 4 to 7 days, but weeks may be required for full effect
- Nasal administration - less effective than nasal corticosteroids
Describe cysteine leukotriene receptor antagonists and when they are used
- Mechanism – CysLT1 receptor antagonists reduce the effects of CysLTs upon the nasal mucosa
- Should be considered in patients with allergic rhinitis and asthma (if allergic rhinitis driving asthma symptoms)
- Montelukast is the sole agent used in this class
Describe vasoconstrictors in treatment of rhinitis and rhinnorhoea
- Mechanism – act as directly, or indirectly, to mimic the effect of noradrenaline. Produce vasoconstriction via activation of 1-adrenoceptors to decrease swelling in vascular mucosa
- Oxymetazoline, a selective 1-adrenoceptor agonist (given intranasally), is effective, short term, in reducing congestion in allergic rhinitis
- Administration not recommended for more than a few days
