Drug control in Asthma Flashcards
Asthma definition
recurrent reversible obstruction of airflow in airwaves in response to non-noxious stimuli
- genetic susceptibility
- Allergic in >30%
Extrinsic
-atopic, allergic
Intrinsic
non-atopic, non-allergic
Antigen induces antibody synthesis:
-mast cells - IgE
Cells release chemical mediators (cytokines):
- interleukins
- prostaglandins (PG)
- leukotrienes (LT)
- thromboxanes (Tx)
- histamine
- platelet activating factor (PAF)
Effects of cytokine mediators:
- vasodilation
- pain/itch
- oedema
- smooth muscle contraction
Immediate phase of Asthma:
bronchoconstriction +- vasodilation (anaphylaxis –> death)
Late phase of Asthma:
- oedema –> congestion
- hypersecretion –> mucus
- inflammatory cells
- bronchoconstriction + hyperreactivity
Innervation:
- parasympathetic
- sympathetic
- non-adrenergic non-cholinergic (NANC)
- sensory - irritation –> reflex constriction via parasympathetic
affect on Upper airways:
-constricted by ACh via M3 receptors (parasympathetic nerves)
affect on Lower airways:
-constricted by excitatory NANC transmitters; relaxed by inhibitory NANC transmitters (eg NO) and circulating adrenaline (beta2)
Blood vessel smooth muscle:
-constricted by NA from sympathetic nerves (alpha1); relaxed by circulating adrenaline (beta2)
Glands:
- mucus secretion decreased by sympathetic system and increased by parasympathetic system
- inflammatory mediators and chemical/physical stimuli
Drug therapy:
Immediate phase
-smooth muscle relaxants (to treat bronchoplasm)
Drug therapy:
Late phase
-steroids (treat inflammation)
DRUGs USED:
- Beta-adrenoceptor agonists
- Muscarinic antagonists
- Theophylline
- Antihistamines
- LT antagonists
- Glucocorticoids
- B-adrenoceptor agonists:
adrenaline:
alpha + beta agonist
beta1 - heart
beta2- bronchi
Beta-adrenoceptor agonists:
Salbutamol:
- beta2 only
- inhaled aerosol or powder
-Relaxed bronchioles: decreased secretion and increased FEV1 -Mechanism: - increased adenylate cyclase - increased cAMP -decreased Ca2+ entry
- Muscarinic antagonists:
Ipratropium: N+ (poor absorption)
- blocks bronchoconstriction due to parasympathetic reflex
- more useful in bronchitis
Tiotropium:
- prolonged (24hr) M3 selective muscarinic antagonist
- better than the older ipratropium
- Theophylline:
- bronchodilator; relaxes smooth muscle by inhibition of phosphodiesterase
- also increased release of NA and Adr (?)
- Antihistamines
-little benefit in asthma
- Antagonists of Leukotrienes (LTs)
-drugs to block either the LT receptor or the synthesis of LTs
(eg MONTELUKAST)
- Glucocorticoids (anti-inflammatory steroids)
Beclomethasone - very important as prophylactic -suppress immune system by: decreased: -lymphocyte &mast cell no. -mediator synthesis & release
Mechanism of Glucocorticoid:
- cytoplasmic receptor; nuclear binding; RNA for lipocortin (Annexin-1), block PLA2
- Block COX-2
Advantages of inhalation
- rapid response
- targetted at bronchi
- need less drug
- less side effects
- avoid liver metabolism
