Prescribing for respiratory patients Flashcards
Describe the mechanism of action of selective beta 2 agonists
Stimulate B2 adrenoreceptors in the smooth muscle of the airway
Simulate adenylyl cyclase - enzyme catalyses adenosine triphosphate (ATP) - cAMP
Increased cAMP activates protein kinase
Inhibition of enzyme myosin light chain kinase, inhibiting smooth muscle contraction
Results in bronchial smooth muscle relaxtion and bronchodilation
Name 2 short acting beta 2 agonists
Salbutamol
Terbutaline
How long is the onset of short acting beta 2 agonists
5min
How long is the duration of action for short acting beta 2 agonists
4-6 hrs
What do beta 2 agonists improve?
Symptoms
FEV1
What are the side effects of beta 2 agonists
Tremor
Resting sinus tachycardia
Hypokalemia
How does nebulised or inhaled beta 2 agonists cause fewer side effects
Less systemic absorption
Name two long acting beta 2 agonists
Formeterol
Salmeterol
What is the onset of action for long acting beta 2 agonists
15-45 mins formoterol has faster onset of action
Describe the mechanism of action of antimuscarinincs
Muscarinic antagonists - bind to muscarinic receptors in bronchial smooth muscle. Inhibits Ach release from parasympathetic nerve endings
What muscarinic receptor subtypes are there?
M1-M5
Name some antimuscarinics
Ipratropium
Tiotropium
LAMA
SAMA
What does M3 receptor do?
Bronchoconstriction
What does M2 receptor do?
Limits Ach release
Describe the selectivity of ipratropium
No selectivity - blocks M2 and M3
Which muscarinic receptor do we want to block?
M3 (not the M2 and M2 limits Ach release by negative feedback)
Describe the selectivity of tiotropium
Same affinity for all receptors but selective to M3 due to very slow dissociation from M3 in comparison to M2
Which two antimuscarinics should not be prescribed together?
Nebulised LAMA and SAMA
What are the side effects of antimuscarinics?
Headache
Dry mouth
GI motility disturbances
What is the onset of tiotropium?
2 hours
What is the duration of action of tiotropium?
24 hrs
What are the combined bronchodilators used in COPD?
LAMA/LABA
Describe the mechanism of action of corticosteroids in asthma
Decreased formation of cytokines which activate eosinophils and are responsible for IgE production and expression of IgE receptors
Inhibit induction of COX2 by cytokines - anti inflammatory effect
Inhibit production of leukotrienes - leukotrienes trigger contraction in the smooth muscle and overproduction results in inflammation
Name some inhaled steroids used in asthma as preventer therapy
Beclomethasone
Budesonide
Fluticasone
Mometasone
What are the differences between different inhaled steroids?
Different potencies
What are the side effects of inhaled steroids
Oral candidiasis
Hoarse voice
Systemic symptoms if long term and high dose therapy
What drug can be given to reduce oral candidas?
Nystatin - antifungal
Who are triple combination inhalers given to?
LAMA/LABA/ICS to people with COPD with asthmatic features
How do you choice which treatment to give a patient
How much they improve symptoms
Persons preference and ability to use inhaler
The drugs potential to reduce exacerbations
Side effects
Cost
Reduce the number of inhalers
When are oral corticoisteroids used in patients with COPD and asthma
In severe cases
Which oral corticosteroid is most often used in severe asthma or COPD
Prednisolone
What monitoring must be done for someone on high dose steroids
Glucose
What adjuvant therapy must be given to a patient who is steroid dependant
PPI
Bone protection
Who should you wean from oral corticosteroids?
> 40mg prednisolone daily for more than a week
Repeat doses in evening
Received > 3 weeks of treatment
Recently received repeated courses
Taken a short course within 1 week of stopping long term therapy
Adrenal suppression
Describe the mechanism of action of methylxanthines
Unclear
Relaxant effect on smooth muscle
Increases cAMP - inhibition of phosphodiesterase
Bronchodilator action
What are the indications for methylxanthine use?
Asthma
COPD
Name an IV methylxanthine
Aminophylline
What is aminophylline used for?
Acute exacerbations of asthma
Name some oral methylxanthines
Theophylline and aminophylline
Describe the metabolism and clearance of theophylline
Cytochrome P450
Clearance declines with age and comorbidity
Describe the therapeutic index of methylxanthines
Narrow
What is the level of methylxanthines
10-20mg/L
When do you measure methylxanthine levels
IV- 6 hrs after infusion starts and daily if continues for >24 hrs
Oral - 4-6hrs post dose and at least 5 days after starting treatment
Which rugs increase the levels of methylxanthine
Ciprofloxacin
Erythromycin
Smoking - reduction in dose required by 33%
Which drugs decrease the levels of methylxanthine
Rifampicin
Ritonavir
What are the side effects of methylxanthine
Headache
Nausea
Insomnia
Describe signs of toxicity of methylxanthine
Vomiting Headache Tachycardia Ventricular arrhythmia Convulsions
How do you convert IV aminophylline to oral theophylline?
Calculate the total amount administered in 24 hours by multiplying the hourly infusion rate by 24. This calculation assumes infusion concentration prepared is 1mg/ml.
Multiply the total aminophylline dose administered in 24 hours by 0.8, which is the salt correction factor.
Divide the total amount administered in 24 hours by the dosing interval for oral administration, e.g. divide by 2 for twice daily dosing.
How do you convert IV aminophylline to oral aminophylline?
Calculate the total amount administered in 24 hours by multiplying the hourly infusion rate by 24. This calculation assumes infusion concentration prepared is 1mg/ml.
Divide the total amount administered in 24 hours by the dosing interval for oral administration, e.g. divide by 2 for twice daily dosing. It is assumed that oral aminophylline has 100% bioavailability.
Name some mucolytics
Acetylcysteine
Carbocysteine
Describe the mechanism of action of mucolytics
Reduces goblet cell hyperplasia
Reduces mucus glycoprotein production
Helpful in chronic productive cough
Describe the mechanism of action of leukotriene receptor antagonists
Leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released from mast cells and eosinophils with bronchoconstrictor and pro-inflammatory actions
LTRA bind to cysteinyl leukotriene (CysLT) receptors in airway smooth muscle cells and airway macrophages, and on other pro-inflammatory cells (including eosinophils)
Blocking bronchoconstriction and mucous secretion
What are the side effects of LTRA
Headache
Psychiatric
GI
Describe how LTRAs are prescribed
Asthma step 3+ (NICE) Review response to treatment in 4 to 8 weeks Additive effect only Useful in exercise induced asthma Best taken at night
Name some LTRAs
Montelukast
Zafirlukast
Describe the treatment of an acute COPD exacerbation
Antibiotics - only if infective. Amox/doxy for 5 days
Bronchodilators - nebulised salbutamol/ipratropium or salbutamol via aerochamber
Corticosteroids - prednisolone 30mg for 5 days
