15. Pulmonary Pharmacology Flashcards
What are the inflammatory mediators involved in the initial phase of asthma?
Mast cell IgE
Histamine
Prostaglandins
What effect do the mediators in the initial phase of asthma have?
Bronchoconstriction
What are the inflammatory mediators involved in the intermediate phase of asthma?
IL-4,5,13
What effect do the mediators in the intermediate phase of asthma have?
Leukocyte release
What is the pathophysiology of the late phase of asthma?
Influx of Th2 cells> activate neutrophils and eosinophils> release proteins that damage the lung epithelium
Name a protein that damaged the lung epithelium in asthma
Eosinophil cationic protein
What is the parasympathic control of asthma?
M3 receptors and ACh cause bronchoconstriction
What is the sympathetic control of asthma?
B2 adrenoceptors and adrenaline inhibit bronchoconstriction
Name 3 types of bronchoconstrictors
B2 adrenoceptor agonists
Muscarinic antagonists
Xanthines
What is the MOA of B2 adrenoceptor agonists?
Increase cAMP by GPCR-linked activation of adenylate cyclase, causing relaxation of bronchial smooth muscle
Inhibit mediator release from mast cells
Increase mucociliary clearance
Name a short acting and long acting B2 adrenoceptor agonist
Short: salbutamol and terbutaline
Long: Salmeterol
What are the side effects of B2 agonists?
Tremor
Arrhythmias
Hypokalaemia
Muscle cramps
Name 2 muscarinic antagonists
Ipatropium
Titropium
What is the MOA of ipatropium?
Inhibits action of ACh and M1,2,3
Causes bronchodilation and decreased mucous production
Which acts quicker: B2 agonists or muscarinic antagonists?
B2 agonists
What is the MOA of titropium?
Selective inhibition of M1 and M3
What are the side effects of muscarinic antagonists?
Very well tolerated: dry mouth and urinary retention
What is the MOA of xanthines?
Inhibit phosphodiesterase> increases cAMP and cGMP, causing bronchodilation
Also anti-inflammatory so inhibits the late phase
Give 2 examples of xanthines
Theophylline (PO)
Aminophylline (IV)
What are the side effects of xanthines?
Have a narrow therapeutic range so side effects common
Nausea, anorexia
Arrhythmias, nervousness, tremors, seizures
What isoenzyme of CYP450 breaks down theophylline?
CYP1A2
What substances can affect the break down of theophylline?
Rifampicin increases CYP450 so increases clearance
Macrolides inhibit clearance, so increase toxicity
Smoking and caffeine can alter blood levels of theophylline
Name 3 classes of anti-inflammatories that are used in asthma
Glucocorticoids
Cromones
Leukotriene synthesis inhibitors and receptor antagonists
What is the MOA of corticosteroids?
Bind to intracellular glucocorticoid receptor
Transactivate responsive genes via glucocorticoid response elements
Transrepress pro-inflammatory TFs
Name a glucocorticoid response element
Lipocortin 1: activation results in decreased prostaglandins
Name 2 pro-inflammatory transcription factors
AP-1
NFkappaB
Name 3 inhaled corticosteroids
Beclomethasone
Budesonide
Fluticasone
Name a PO corticosteroid
Prednisolone
Name an IV corticosteroid
Hydrocortisone
Name 2 cromones
Sodium cromoglycate
Nedocromil
What route are cromones given?
Inhaled
What is the MOA of cromones?
Mast cell stabilisation (decrease degranulation and mediator release)
Inhibit sensory neurons
Inhibit eosinophil accumulation in lungs
What are the side effects associated with cromones?
Cough and wheeze transiently after administrating
Which are more effective: steroids or cromones?
Steroids
What side effects are associated with PO steroids?
Adrenal suppression Infection Effects of mineralocorticoids Structural effects Glucose intolerance
What structural effects can steroids have?
Osteoporosis
Myopathy
Growth retardation
Obesity
What are the side effects associated with inhaled corticosteroids?
Oral candidiasis
Dysphonia (myopathy of laryngeal muscles)
What enzyme converts arachiodonic acid to leucotrienes?
LOX
What drug inhibits LOX?
Zileuton
What drugs inhibit the leucotriene receptor?
Zafirlukast
Montelukast
What are the effects of leucotriene receptor antagonists?
Reduce mucosal inflammation, oedema, mucous and bronchoconstriction
How are leucotriene receptor antagonists administered?
PO
When are leucotriene receptor antagonists useful?
Exercise, cold, aspirin and NSAID induced asthma
Not in acute attacks
What are the side effects of leucotriene receptor antagonists?
Headaches
GI upset
EGPA rarely
Where is the mutation for A1ATD found?
SERPINA-1 gene, chromosome 14
What other diseases does A1ATD increase the risk for?
Liver disorders
Vasculitis
Skin disease
What is the treatment for A1ATD?
Augmentation therapy: infused pooled A1AT
What is type 1 respiratory failure?
PO2 is low but PCO2 normal
Due to a V/Q mismatch
What conditions can cause type 1 respiratory failure?
PE
High altitude
What is type 2 respiratory failure?
Low PO2 and high PCO2
Hypoventilation throughout lung
What conditions can cause type 2 respiratory failure?
COPD
Asthma
Sedation overdose
What is the treatment for type 2 respiratory failure?
Low dose O2 (24%) while monitoring ABG
Through a NIPPV (pressurised face mask)
Mechanical ventilation only for acute cases
Explain class 1-5 CF mutations
- no functional CFTR
- misfolded CFTR that doesn’t reach surface
- non-functional CFTR
- Faulty opening of CFTR
- Not enough
Name a class 2 mutation
delta F508
Name a class 3 mutation
G551D
Name a class 4 mutation
R117H
Name a CF potentiator
Ivacaftor
What is the function of potentiators?
Help the CFTR transport Cl- across the cell surface
Used in G551D
What is the function of correctors?
Bind to CFTR and help it fold into the right shape so more gets to membrane
Name a CF corrector
Lumacaftor
What name is given to the triple combo CF treatment?
TRIKAFTA
