Pharmacology - Respiratory Pharmacology Flashcards
Asthma
- Reversible bronchonconstriction and inflammation
- Decrease in FEV1 <70% –> Increase in airway resistance
COPD
- not fully reversible
- chronic bronchitis and emphysema
- loss of lung function
- mostly caused by smoking
- typically late onset
- high energy demand and difficulty eating –> use inhalers before meal
COPD Severity
Mild: 80% - little to no breathlessness
Moderate: 50-79% - breathless on moderate exertion
Severe: 30-49% - Breathless at rest/mild exertion, usually with wheeze and cough
Very severe: <30%
Asthma Phases
Early/Immediate Phase:
Allergen interacts with mast cell –> degranulation of mast cell –> histamine, PGD2, LT C4, LTD4
Late Phase:
Chemokines, cytokines –> WBC (leukocytes ex: T cells, neutrophils, basophils)
Asthma Therapy
Bronchodilators: relief of symptoms by blocking early phase of asthma attack caused by bronchoconstriction
Anti-Inflammatory Agents: prevention of attack by preventing late phase caused by release of cytokines
Bronchodilators
- reverse bronchospasm
- rapid relief
Brochodilator types
β2-adrenoceptor agonists:
- act on β-adrenoceptors (on mast cells)
- increase cAMP –> prevent release of histamine
- affect mucous secretion
- increase FEV1
- given by inhalation
- long acting agents for long term prevention
Phosphodiesterase Inhibitors
- Roflumilast (PDE4) inhibitor
- COPD
- inhibit phosphodiesterase (PDE) –> inhibit ATP into cAMP
- Potential to enhance β-AR effects
- Reduce inflammation
Muscarinic M-receptor anatagonists:
- block bronchoconstriction by PNS
- inhibit mucous secretion
- inhalation
- atropine: naturally occurring
- ipratropium: non-selective
- tiotrpium: slow dissocioation from receptor –> long-acting
- aclidinium –> newer, long-acting
ex: viagra –> PDE5 inhibitor
Desinsitisation
Long term use of β-adrenoceptors –> internalisation of receptors –> tolerance/desensitisation
Prevented by steroids
LABA
- long action –> long fatty chain, absorb into lipid bilayer, keep re-attaching to receptors
salmeterol, formoterol (2x daily)
indacaterol (4x daily)
SABA (salbutamol) (4x daily)
β2 Adrenoceptor agonists adverse effects
High doses: Tremor, palpitations, hypokalaemia
MR Antagonists Side Effects
Dry mouth Nausea/headache Constipation Urinary retention Atrial Fibrilation, tachycardia and palpitation Blurred vision
Xanthines uses and method of action
theophylline - in tea (COPD)
aminophylline (theophylline & ethylenediamine 2:1 to imporve solubility) in emergency (Asthma, COPD)
measure plasma theophylline (toxic) 4-6 hours after start of iv infusion
PED inhibitors at a far greater dose than clinically given (probs not method of action here)
Adenosine receptor antagonist?
Anti-inflammatory effects
Xanthines side effects
Tremor, palpitations, nausea CNS stimulation (sleep disturbance, overactivity)
Xanthines drug interactions
inhibition of metabolism increase risk of toxicity
ex: cimetidine
Induction of metabolism reduce plasma levels
ex: smoking (careful of smoking cessation)
Anti-Inflammatory agents
Preventative, does not reverse asthma attack
corticosteroids/steroids:
- lipophilic
- cross lipid membrane
- act at intracellular glucocorticoid receptors
- dimer moves across nuclear membrane
- affect gene transcription
- increased/decreased gene expression
Steroid examples and delivery
Inhaled:
- beclametasone
- budenoside
- fluticasone
Oral:
-prednisolone (acute asthma attack)
IV & cream:
Hydrocortisone (life-threatening acute asthma
steroids activate what genes
Annexin A1
β2-adreoceptors
IkB (inhibitor of NF-kB)
anti-inflammatory cytokines
steroids repress what genes
Inflammatory cytokines
chemokines
inflmmatory enzymes and peptides
Annexin 1
- lipocortin
- act through formyl peptide receptors
- inhibit release of histamine from mast cells
- inhibit cPLA2 leading to less leukotrienes and PGs
Corticosteroids side effects
- throat infections/oral candidiasis with ICS (wash mouth after)
- long term –> osteoporosis (Ca+ supplements)
-Adrenal suppression in children (lowest effective dose, monitor height)
growth rate slowed not reduced
- indigestion (oral)
- chickenpox more severe, immune response
- withdrawal effect (reduce oral dose gradually if >3 weeks)
Steroid resistance
asthma, COPD patients have poor response to steroids
reasons:
- genetic resistance
- GR receptor modification
- dec nuclear translocation of GR
- inc efflux of steroids
Leukotrienes
- stimulate mucus secretions
- bronchoconstriction
- hypersensitivity to allergens
- linked with exercise-induced asthma
- role in airwayb remodelling
CystenylLeukotriene receptor antagonists
- act at CysLT1 receptor
- oral
Leukotriene synthesis inhibitors
block synthesis of LTs and LTB4
ex: zileuton
LT antagonists side effects
- headache/rash
- nausea, jaundice, other signs of liver toxicity (monitor levels)
- mood disorders/suicidal thoughts with montelukast
Omalizumab
- monoclonal antibody against free IgE and prevent it from binding to immune cells and causing allergen-indu ced mediator release
- sever allergic asthma, cannot be controlled by steroids
- injection every 2-4 hours
Bronchoconstriction as adverse drug reactions
NSAIDs
β-adrenoceptor antagnosits
Drug allergies (penicillins, excipients wtc.)
NSAID adverse drug reaction
-inhibit cox, more AA, more LT, increased inflammation
Cromones
- sodium cromoglicate
- preventative
- inhalation.eye drops
- may benefit exercise asthma
Mucolytics
antioxidants
break up thick mucus
used in COPD
ex: carbocysteine
erdosteine
Cough
-protective mechanism
Anti-tussive agents
Codeine (opioid)
- not particularly effective
- avoid in under 18 yo
Dextromethorpan (non-opioid)
- not particularly effective
- 6 yo and above
Levodropropizine
-may inhibit realease of sensory neuropeptides
