Flashcards in pharmacology Deck (71)
what happens when postganglionic cholinergic fibres are stimulated in the parasympathetic?
- bronchial smooth muscle contraction mediated by M3 muscarinic ACh receptors on ASM cells
- increased mucus secretion mediated by M3 muscarininc ACh receptors on gland cells
what happens when postganglionic non-cholinergenic fibres are stimulated in the parasympathetic?
- bronchial smooth muscle relaxation medicated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)
what does stimulation of sympathetic cause?
- bronchial smooth muscle relaxation via B2-adrenoceptors on ASM cells activated by adrenaline released from the adrenal gland
- decreased mucus secretion mediated by B2-adrenoceptors on gland/goblet cells
- increased mucociliary clearance mediated by B2-adrenoceptors on epithelial cells
- vascular smooth muscle contraction, mediated by a1-adrenoceptors on vascular smooth muscle cells
steps of inhibition of contraction of Ca 2+ in smooth muscle
1. Ca2+ converts calmodulin to Ca2+- calmodulin
2. Ca2+-calmodulin activates MLCK
3. active MLCK dephosphorylates ATP and uses Pi to phospharlate and activated the myosin cross bridge
4. this permits binding with actin
how do smooth muscles contract and relax?
- contraction = phosphorylation of MLC by MLCK in the presence of elevated intracellular Ca2+ and ATP
- relaxation = dephosphorylation of MLC by myosin phosphatase
- in the presence of elevated intracellular CA2, the rate of phosphorylation exceeds the rate of dephosphorylation
- relaxation thus requires return of intracellular Ca2+ concentration to basal level - achieved by primary and secondary active transport
definition of asthma
recurrent and reversible (short term) obstruction to the airways in response to substances that are
- not noxious
- do not affect non-asthmatic subjects
what are asthma attacks?
intermittent attacks of bronchoconstriction causing tight chest, wheezing, difficulty in breathing, cough
what is the pathology changes for poorly controlled chronic asthma?
- pathological changes to the bronchioles result from long standing inflammation
1. increased mass of smooth muscle (hyperplasia and hypertrophy)
2. accumulation of interstitial fluid (oedema)
3. increased secretion of mucus
4. epithelial damage (exposing sensory nerve endings)
5. sub-epithelial fibrosis
- airway narrowing by inflammation and bronchoconstriction increase airway resistance decreasing FEV1 and PEFR
what causes bronchial hyper-responsiveness in asthma?
- epithelial damage, exposing sensory nerve endings, contributes to increase sensitivity of the airways to bronchoconstrictor influences (and may cause neurogenic inflammation by the release of various peptides)
- the two components are hypersensitivity and hyper-reactivity
what happens when IgE receptors are activated on mast cells?
1. stimulates calcium entry
2. releases leukotrienes that cause airway smooth muscle contraction
what is a normal persons response to an allergen?
1. phagocytosis by antigen presenting (dendritic) cell
2. low-level Th1 response, cell-mediated immune response involving IgG and macrophages
what is an atopic individuals response to an allergen?
1. allergen through airway epithelium
2. CD4+ express to THO cells that mature to TH2 cells
3. these activate B cells that mature to IgE secreting P cells
what are the key events in immediate phase of asthma?
- eliciting agent: allergen or non-specific stimulus plus mast cells, mononuclear cells
1. spasmogens, CysLTs, Histamine = bronchospasm, early inflammation
2. chemotaxins chemokines = late phase
what are the key events in late phase of asthma?
- infiltration of cytokine releasing Th2 cells and monocytes, activation of inflammatory cells, particularly eosinophils
1. mediatorys, CysLTs and others
2. eosinophil major basic and catonic proteins = epithelial damage = airway hyper-responsiveness / airway inflammation = bronchospasm, wheezing, mucous oversecretion, cough
what drugs are used as relievers?
- CysLT1 receptor antagonists
what drugs are used as controllers / preventers?
- humanised monoclonal IgE antibodies
pharmacokinetics of aerosol and oral
aerosol = Slow absorption from lung surface and rapid systemic clearance
oral = Good oral absorption (with exceptions) and slow systemic clearance
dose of aerosol and oral
aerosol = Low dose delivered rapidly to target
oral = High systemic dose necessary to achieve an appropriate concentration in the lung
systematic concentration of drug of aerosol and oral
aerosol = low
oral = high
distribution of drugs of aerosol and oral
aerosol = reduced in severe airway disease
oral = unaffected by airway disease
incidence of adverse effects of aerosol and oral
aerosol = low
oral = high
compliance of aerosol and oral
aerosol = Good with bronchodilators, less so with anti-inflammatory drugs
oral = good
ease of administration of aerosol and oral
aerosol = difficult for small children and infirm people
oral = good
effectiveness of aerosol and oral
aerosol = good to mild in moderate disease
oral = good even in severe disease
what drugs are used in treatment of asthma bronchodilators?
- b2-adrenoceptor agonists - act as a physical antagonist of all spasmogens
b2-adrenoceptor agonists classification
- short-acting (SABA)
- long-acting (LABA)
- ultra long-lasting (ultra-LABA)
what are SABAs? (short acting B2-adenoreceptors)
eg = salbutamol, albuterol, terbutaline
- rapid - 5 minutes
- fine tremor
- first line treatment
LABA (long acting B2-adenoreceptors)
eg = salmeterol, foroterol
- nocturnal use - 8 hours
- must be co-administered with a glucocorticoid
CysLT receptor agonists
- blocks CysLT1 receptor for LTs from mast cells