VIVA: Pharmacology - Respiratory Flashcards
Outline the groups of drugs that might be used in asthma and give an example of each
Sympathomimetics* (e.g. salbutamol)
Corticosteroids* (e.g. dexamethasone)
Muscarinic antagonists* (e.g. ipatropium)
Other bronchodilators (e.g. magnesium)
Antihistamines (for allergic asthma)
Methylxanthines (e.g. aminophylline)
Cromolyns (mast cell stabilisers; e.g. sodium cromoglycate)
Leukotriene inhibitors (e.g. montelukast)
Heliox (changes airflow dynamics)
Other smooth muscle dilators (e.g. ketamine, calcium channel blockers)
IgE monoclonal antibodies (e.g. omalizumab)
*needed to pass + one other with one correct drug example per group
Outline the mechanism of action of corticosteroids in asthma
Increase in airway calibre by:
- Reduce bronchial reactivity*
- Inhibit lymphocytic and eosinophilic airway mucosal inflammation*
- Local immune suppression
*needed to pass
Outline the types of drugs used as preventers in the management of asthma
Corticosteroids* (e.g. budesonide, fluticasone)
Cromolyn* / nedocromil
(+/- long-acting cromolyn - tilade)
Leukotriene pathway inhibitors (e.g. montelukast)
Long-acting anticholinergic
Long-acting B2 agonist
Anti-IgE monoclonal Ab (omalizumab)
Calcium channel blockers
NO donors
*needed to pass
What are the potential adverse clinical effects of inhaled corticosteroid therapy?
Oropharyngeal candidiasis*
Hoarseness
Osteoporosis
Cataracts
Slows rate of growth in children
*needed to pass + one other
Describe the mechanism of action of sodium cromoglycate?
Mast stell stabilisation*
Inhibits cellular activation of airway neurones (responsible for cough), mast cells, and eosinophils
Changed function of delayed Cl channels
*needed to pass
What are the clinical uses of cromoglycate?
- Asthma:
- Antigen-induced
- Exercise-induced
- Occupational
- In young children with extrinsic asthma - Systemic mastocytosis
- Allergic rhinoconjunctivitis
What B receptor types are there?
B1 *, B2 *, B3
*needed to pass
What cellular processes do B-agonist - B-receptor coupling initiate?
Activation of all three receptor types results in stimulation of adenylyl cyclase*, and increased conversion of ATP to cAMP
Mediated by stimulatory coupling protein (Gs) via GDP and GTP
*needed to pass
What are the clinical uses of B2 selective agonists?
Respiratory*, uterine (tocolytic) and vascular smooth muscle relaxation
Skeletal muscles K+ uptake
*needed to pass + one other
What are the actions of B2 agonists in the treatment of asthma?
Smooth muscle relaxation/bronchodilation*
Inhibits mast cell release
Increases mucociliary activity
Acts via Gs protein, adenylyl cyclase and cAMP
*needed to pass
Compare salmeterol and salbutamol
Salbutamol:
- IV, oral or inhaled
- Short-acting (4hrs)
- Partial agonist
Salmeterol:
- Inhaled
- Long-acting (12hrs) due to high lipid solubility (dissolves in smooth muscle membrane)
- Partial agonist
- Not useful for acute asthma
What are the side effects of B2 agonists?
Need any two to pass:
- Skeletal muscle tremor
- Lactic acidosis
- Tachycardia
- Tachyphylaxis
- Hypokalaemia
- Transient hypoxaemia
Describe the cellular mechanisms by which corticosteroids are believed to exert their effects in asthma acutely
2/5 needed to pass:
- Decreased activation of lymphoid cells/eosinophils
- Decreased cytokine production and action
- Decreased production of vasodilator prostaglandins
- Decreased histamine release
- Decreased production of IgE and IgG
What class of drug is salbutamol?
Selective B2 agonist* used as a bronchodilator
*needed to pass
What are the different routes of administration of salbutamol?
Inhaled: nebulised, puffer +/- spacer*
Oral, IV*, IM, subcut
*needed to pass
What are the advantages of the different methods of administration of inhaled salbutamol?
Nebulised:
- Rapidly absorbed
- No coordination required
- Not much education required
- No first pass metabolism
Puffer +/- spacer:
- As effective as nebulised* when used properly
- Targeted
- Lower dose
- Less side effects*
*needed to pass
Describe the pharmacokinetics of salbutamol
Absorption:
- Fast and complete (all routes including inhaled)*
- Rapidly absorbed in GIT, respiratory tract slower
- For inhaled: rapid onset with bronchodilation maximal within 15-30mins* and persists for 3-4hrs
Metabolism:
- 50% first pass metabolism: sulphated in the liver with metabolites excreted in kidneys
- Rest excreted unchanged in kidneys
- No metabolism in lungs
- Half-life 3-6hrs*
*needed to pass
Describe the pros and cons of the different routes of delivery of salbutamol?
Spacer/inhaler*:
- Pros: targeted, low dose, minimise systemic side effects, as effective as nebulised, no first pass metabolism
- Cons: coordination and education required
Nebulised*:
- Pros: less coordination required and minimal education
- Cons: larger particles and hence dose required, noisy (children may get frightened), higher incidence of systemic side effects
Oral:
- Pros: easier in very young/disabled, longer half-life
- Cons: big doses, high side effect profile (tachycardia, tremor, nervousness, weakness), minimal advantage to inhaled, 50% first pass metabolism
IV/IM/subcut (useful in severe asthma):
- Pros: no first pass metabolism
- Cons: needle, painful, higher cost and side effect profile
*need to describe pros and cons of inhaled + one other route
What are the organ system effects of theophylline?
CNS:
- Mild cortical arousal with increased alertness and deferral of fatigue
- Nervousness, tremor
- Overdose causes medullary stimulation, convulsions and death
CVS*:
- Positive chronotropic and inotropic effects by inhibiting presynaptic adenosine receptors in sympathetic nerves and increasing catecholamine release at nerve endings
- Increased HR, BP and CO
- May cause arrhythmias
GIT:
- Stimulates gastric acid and digestive enzymes secretion
Kidney:
- Weak diuretic from increased glomerular filtration and reduced tubular sodium reabsorption
Lung*:
- Bronchodilation by relaxing airway smooth muscle
- Inhibits antigen-induced release of histamine from lung tissue
*needed to pass
How do the organ 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:
- 5-20mg/L: improvement in pulmonary function *, anorexia, nausea
- 15-20mg/L: vomiting, abdominal discomfort, headache, anxiety
- >40mg/L: seizures, arrhythmias *
*needed to pass
What are the advantages and disadvantages of IV salbutamol in asthma?
2/4 needed to pass
Advantages:
- No first pass metabolism
- May be useful in severe/life-threatening asthma
Disadvantages:
- Requires IV access (disadvantage particularly in children)
- More systemic side effects
