pharmacology Flashcards
one major cause of asthma
due to an immune imbalance between TH1 and TH2 lymphocyte mediated responses
asthma definition
is a recurrent and reversible obstruction to the airways in response to substances that are not necessarily noxious, normally do not affect non-asthmatic subjects
causes of asthma attack
allergens - atopic individuals
exercise - cold, dry air
respiratory infections - viral
smoke, dust, environmental pollutants
pathological changes in chronic asthma
increased mass of smooth muscle - hyperplasia and hypertrophy
accumulation of interstitial fluid - oedema
increased secretion of mucus
epithelial damage - exposing sensory nerve endings
sub-epithelial fibrosis
bronchial hyper responsiveness
epithelial damage exposing sensory nerve endings, contributes to increased sensitivity of the airways to bronchoconstrictor influences and may cause neurogenic inflammation by the release of various peptides
TH2 lymphocyte activation
involve IgE
activated by TH0, that produce a cytokine environment
TH2 cells activate B cells by binding to them and by IL-4 production
role of mast cells
cross links IgE receptors
stimulates calcium entry into mast cells release of Ca from intracellular stores evoking
release of secretory granules containing preformed histamine and the production and release of other agents that cause airway smooth muscle contraction
release of substances that attract cels casuing inflammation into the area
immediate phase of asthma attack
bronchospasm
type 1 hypersensitivity reaction
allergen or non-specific stimulus
mast cells, mononuclear cells
delayed phase of an asthma attack
inflammatory reaction
type 4 hypersensitivity reaction
infiltration of cytokine releasing TH2 cells and monocytes activation of inflammatory cells - eosinophils
stimulation of postganglionic cholinergic fibres causes
parasympathethic
bronchial smooth muscle contraction mediated by M3 muscarinic ACh receptors on ASM cells
increased mucus secretion mediated by M3 muscarinic ACh receptors on gland goblet cells
stimulation of postganglionic noncholinergic fibres causes
parasympathetic
bronchial smooth muscle relaxation mediated by NO and vasoactive intestinal peptide VIP
stimulation of sympathetic causes
bronchial smooth muscle relaxation via beta ADR on ASM cells activated by adrenaline released from the adrenal gland
decreased mucus secretion mediated by beta ADR on epithelial cells
vascular smooth muscle contraction mediated by alpha 1 ADR on vascular smooth muscle
intracellular calcium
elevated Ca rate of phosphorylation exceeds the rate of depolarisation
relaxation requires the return of Ca to basal level achieved by primary and secondary active transport
pharmacological management of asthma
beta 2 adrenoceptor agonists - bronchodilators
airway smooth muscle relaxation - reduction in intracellular Ca conc and activation of large conductance K channels
SABA
reliever
salbutamol
first line treatment for mild, intermittent asthma
inhalation, taken as needed, act rapidly
increase mucus clearance and decrease mediator release from mast cells and monocytes
few adverse effects
LABA
reliever salmeterol slow to act useful for noctural asthma not used as monotherapy coadministered with glucocorticoid
cysteinyl leukotriene receptor antagonists
reliever montelukast act competitively derived from mast cells and infiltrating inflammatory cells cause smooth muscle contraction, mucus secretion and oedema add on therapy effective against antigen-induced and exercise induced bronchospasm oral route headache and GI upset side effects
methylxanthines
theophylline
combine bronchodilator and anti-inflammatory actions, inhibit mediator release from mast cells, increase mucus clearance
second line combination with LABA and glucocorticoids
narrow therapeutic values
numerous drug interactions
glucocorticoids
controllers/preventors beclometasone, fluticasone, prednisolone anti-inflammatory agent main hormone is cortisol regulates numerous essential processes inhaled to reduce systemic effects
cromoglicate
controllers/preventors
humanised monoclonal IgE antibodies
controllers/preventors
binds IgE via Fc to prevent attachment to Fcz receptors - suppresses mast cell response to allergens
IV
monoclonal antibodies directed against IL-5 - mepolizumab
mineralcocorticoids
mainly aldosterone
regulate the retention of salt by the kidney
not wanted in inflammatory conditions
cromones
second line drugs now infrequently used
mast cell stabilizers
no direct effect upon bronchial smooth muscle
weak anti-inflammatory effect
chronic bronchitis
inflammation of bronchi and bronchioles cough clear mucoid sputum infections with purulent sputum increasing breathlessness
emphysema
distension and damage to alveoli
destruction of acinial pouching in alveolar sacs
loss of elastic recoil
COPD pathogenesis
smoking/air pollution
stimulation of resident alveolar macrophages
cytokine production
activation of neutrohils CD8 T cells increased macrophage numbers
release of matrix metalloproteinases, free radicals
muscarinic acetylcholine receptors in the airways
reducing parasympathetic neuroeffector transmission with muscarinic receptor antagonists is an important treatment of COPD
muscarinic receptor antagonists
pharmacological antagonists of bronchoconstriction caused by smooth muscle M3 receptor activation in response to ACh released from postganglionic parasympathetic fibres
M1
ganglia
facilitate fast neurotransmission mediated by ACh acting on nicotinic receptors
M2
postganglionic neurone terminals - act as inhibitory autoreceptors reducing release of ACh - blockage increases release of ACh`
M3
ASM
mediate contraction to ACh, evoke increased mucus secretion
SAMA
ipratropium
non-selective blocker of M1 M2 and M3 receptors preferred agents with some selectivity for M3 are available
LAMA
tiotropium glycopyrronium aclidinium umeclidinium have few adverse effects mainly palliative decrease mucus secretion reduce bronchospasm caused by irritant stimuli and also block ACh mediated basal tone
PDE4 inhibitor
rofumilast
suppresses inflammation and emphysema
PDE4
is the prominent PDE expressed in neutrophils, T cells and macrophages
rhinitis
acute or chronic inflammation of the nasal mucosa
rhinorrohea, sneezing, itching, nasal congestion and obstruction
allergic, non-allergic or mixed
allergic rhinitis
seasonal, perennial, episodic
similarities to allergic asthma and are strongly linked
non allergic rhinitis
any rhinitis that does not involve IgE dependent events
causes - infection, hormonal inbalance, vasomotor disturbances, nonallergic rhinitis with eosinophilia syndrome NARES, medications
occupational rhinitis
may involve both allergic and non-allergic components
rhinitis and rhinorrhoea
involve increased mucosal blood flow increased, blood vessel permeability, increases the volume of nasal mucosa and cause difficulty breathing
targets and treatment of rhinitis
anti-inlammatory - glucocorticoids
mediator receptor blockade - H1 receptor antagonists, CysLT1 receptor antagonists
nasal blood flow - vasoconstrictors
anti-allergic - sodium cromoglicate
anti-histamine
H1 receptor antagonists
competitive ntagonists that reduce effects of mast cell derived histamine - vasodilation and increased capillary permeability, activation of sensory nerves, mucus secretion fro submucosal glands orally, intranasal spray azelastine effective as a monotherapy ioradidine fexofenadine cetrizine
alpha adrenoceptor agonist
decrease swelling in vascular mucosa
vasoconstrictors
oxymetazoline
effective, short-term, in reducing congestion in allergic rhinitis
