Microsoft word - respiratory vivas.docx


2011-1, 2009-2
What are the effects of corticosteroids on airways in asthma treatment?
-­‐ Increase in airway calibre by inhibition of airway inflammation, decrease in bronchial
reactivity and local immune suppression

Describe the cellular mechanisms by which corticosteroids are believed to exert their effects
-­‐ Decrease the synthesis of AA by PLA2 and inhibitthe expression of COX-2 (inducible)
-­‐ Bind to glucocorticoid response elements (GRE) in the nucleus resulting in the synthesis of
substances that prevent the full expression of inflammation and allergy 1. Decreased cytokine production and action, especially leukotrienes 2. Decreased activation of lymphoid cells/eosinophils 3. Decreased production of IgE and IgG 4. Decreased histamine release 5. Decreased production vasodilator prostaglandins
Outline the groups of drugs that might be used in asthma and give an example of each?
-­‐ Sympathomimetics: β2 agonist e.g. salbutamol (Ventolin, short acting) or salmeterol (Serevent,
-­‐ Corticosteroids: hydrocortisone, prednisone, fluticasone propionate (Flixotide, inhaled)
-­‐ Muscarinic antagonists: Ipatropium (Atrovent)
-­‐ Other bronchodilators: magnesium
-­‐ Leukotriene inhibitors (antagonists): montelukast, zafirlukast,zileuton -­‐ Heliox: changing airflow dynamics -­‐ Other smooth muscle dilators: ketamine, calcium channel blockers -­‐ Experimental: IgE monocloncal antibodies - omalizumab 2008-2
Describe the pharmacokinetics of salbutamol?
1. Absorption
-­‐ Complete all routes w/ less systemic toxicity with respiratory delivery
-­‐ Gut fast, resp tract slower - depends on mechanism delivery (gut 80% with Neb)
2. Metab/elimination
-­‐ 50% 1st pass (less if IV)
-­‐ Sulphated => inactive in liver -­‐ Rest renal/unchanged
-­‐ No resp metabolism
-­‐ t1/2 3-6hr prolonged if resp
What are the pros and cons of the different routes of delivery (Prompt: MDI vs nebuliser)
1. Inhaled MDI +/- spacer
-­‐ Targeted/ low dose w/minimal systemic and local effects
-­‐ Requires co-ordination and education 2. Nebuliser -­‐ Less co-ordination required -­‐ Greater dose and systemic effects -­‐ No benefit in co-ordinated patients 3. Oral -­‐ Easier in very young/disabled -­‐ Possible increased deaths 4. IV/IM/SC -­‐ Useful in asthma extremis or other indications -­‐ IV: pain/cost/staff use/high SE profile + high risk pts
What are the actions of beta 2 agonists in the treatment of asthma?
-­‐ β2 agonists => Gs protein/adenylyl cyclase ↑cAMP in bronchial SMC => bronchodilatation
-­‐ Inhibit mast cell release
-­‐ Increase mucociliary activity act via Gs protein, adenylyl cyclase and cAMP -­‐ Not entirely β2 selective so some systemic β1 side-effects
Compare salmeterol and salbutamol
Salbutamol (Ventolin)
-­‐ IV, oral, or inhaled
-­‐ Acute treatment, not prophylaxis Salmeterol (Serevent) -­‐ Long acting (12 hours) -­‐ High lipid solubility - dissolves in SMC membrane (partial agonist) -­‐ Not useful for acute, only prophylaxis (BD regular dosing)
What are the side effects of beta 2 agonists?
Skeletal muscle tremor, (lactic acidosis), tachycardia, arrhytmias (esp w/ concurrent disease),
tachyphylaxis, hypokalaemia, transient hypoxaemia
What are the organ system effects of theophylline? (Prompt: both therapeutic and toxic)
Methylxanthine (naturally found in tea)
1. Respiratory
-­‐ Bronchodilation (PDE inhibition leading to increased cAMP levels)
-­‐ Inhibits antigen-induced release of histamine from lung tissue 2. CVS -­‐ Positive chronotropic and inotropic effects by inhibiting presynaptic adenosine receptors in sympathetic nerves and increasing catecholamine release at nerve endings -­‐ Produces tachycardia, increased cardiac output and BP -­‐ May cause arrhythmias, b-blockers used in OD 3. CNS -­‐ Mild cortical arousal with increased alertness and deferral of fatigue -­‐ Overdose causes medullary stimulation, seizures and death 4. GIT -­‐ Stimulates gastric acid and digestive enzymes secretion -­‐ Nausea and vomiting
5. Kidney
-­‐ Weak diuretic from increased glomerular filtration and reduced tubular sodium reabsorption
How do these effects of theophylline correlate to its serum concentrations?
Theophylline has a narrow therapeutic window, and its therapeutic and toxic effects are related to its
blood level
-­‐ 5–20 mg/L: Improvement in pulmonary function, anorexia, nausea
-­‐ 15-20 mg/L: Vomiting, abdominal discomfort, headache, and anxiety occur at concentrations of in -­‐ >40 mg/L: Cause seizures or arrhythmias
Outline the types of drugs used as preventers in the management of asthma?
-­‐ Corticosteroids (e.g. fluticasone propionate)
Long acting β2 blocker (salmeterol)
-­‐ Cromolyn and nedocromil (poor oral availability, poorly understood – reduced mediators)
-­‐ Leukotriene antagonsists (receptor blockers: zafirlukast, montelukast or lipoxygenase inhibitor: -­‐ Long acting anti-cholinergic (tiotropium) -­‐ Anti IgE antibodies (parenteral only, omalizumab)
What are the potential adverse clinical effects of inhaled steroid therapy
-­‐ Small degree of adrenal suppression (rarely significant)
-­‐ Oral candiasis
-­‐ Mild growth retardation in children, but eventually reach normal predicted stature -­‐ Hoarseness, Osteoporosis, Cataracts Describe the mechanism of action of cromoglycate?
-­‐ Poorly understood, but decreases release of mediators
-­‐ Inhibiting IgE mediated mast cell degranulation -­‐ Changed function of delayed Cl channels => inhibits cellular activation, airway neurones (cough),
What are the clinical uses of cromoglycate?
Antigen induced, exercise induced, occupational, young with extrinsic asthma



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