Asthma Flashcards
State the sympathetic and parasympathetic innervation of the resp system and effects thereof
B2 adrenoceptors (cause relaxation of bronchial smooth muscle, leading to dilation)
M3 receptors: cause bronchial muscle contraction»_space; bronchoconstriction
Common symptoms of pulmonary disease
Wheezing
SOB
Cough (wet or dry), or hemoptysis
chest pain
What causes respiratiory conditions? (2)
Infection
Malignancy
What is asthma? Explain. (2)
Inflammatory condition with
recurrent reversible airway
obstruction in response to
irritant stimuli.
* Intermittent attacks
Common sysmptoms of asthma(4)
Symptoms include wheezing,
shortness of breath, difficulty
breathing out, sometimes cough
(worse at night)
Who mostly become affected by asthma?
Common in children with atopy
(allergic rhinitis and atopic
dermatitis) = allergic asthma
Asthma is characterised by: (3)
Inflammation of the
airways
* Bronchial
hyperreactivity
* Reversible airway
obstruction
What happens in the immediate phase of asthma?
Inciting agent: alletgen or non-specific stimulant» activation of mast cells and mononuclear cells»_space; release of H, cystLTs, and PGD2, AND release of chemokines and chemotaxins»_space; Bronchospasm
What is the treatment of immediate phase asthma?
M3 antagonists
B2 adrenoceptor agonists
cysLT antagonists
Theophylline
Explain the late phase of asthma
The chmokines released during the immediated phase will lead to the production of chemokine releasing Th2 cells, mononuclear cells and inflammatory cells esp eosinophils»_space; release of cysLT, NO, adenosine, neuropeptides, AND Eosinophil Major Basic Protein (EMBP) and Eosinophil Cationic Protein (ECP).
EMBP and ECP cause epithelial cell damage, which causes airway hyperactivity. Together with other secretions, also causes Airway inflammation.
All this ultimately leads to bronchospasm, wheezing, and coughing
Treatment of the late phase
Glucocorticoids
What does PEFR do? Why is it important?
Volume of air forcefully
expelled from the lungs in
one quick exhalation
* Reliable indicator of
ventilation adequacy as
well as airflow obstruction.
List 3 factors leading to differences in PEFR
Age, Height, Sex
How does one calculate predicted peak flow rate? (4)
CALCULATING % PREDICTED PEAK
FLOW RATE
* Take the best of 3 of the patient’s observed peak flow rate
* Find the patient’s sex, age and height predicted value from nomogram or table:
* Divide patient’s observed peak flow rate over their predicted peak flow.
rate
* Multiply by 100
List 5 drug classes used in the treatment of asthma
B2 agonists
M3 antagonists
Glucocorticoids
Xanthines
Leukotrine receptor antagonist
Examples of B2 adrenoceptor agonists. Classify into short acting and long acting
Salbutamol and fenoterol, terbutaline - SABA,
Salmeterol and Formoterol - LABA
Examples of M3 antagonists and ROA
iptratropium bromide, tiotropium (Inhaled)
Examples of Glucocorticoids and ROA
Beclomethasome, budesonide, fluticasone (INHALED)
Examples of Xanthines and ROA
Aminophylline, theophylline (IV, Oral)
Examples of Leukotriene receptor antagonists and ROA
Montelukast, ORAL
What is the MOA of B2 agonists?
β₂ activation causes relaxation of the bronchial smooth muscle
* May increase mucous clearance by an action on cilia
SABA clinical use/indication, ROA,
Onset of action (time),
Max effect (time),
overall duration of action (time)
Clinical use/indication: acute bronchospasm
* Inhaled (Onset of Action: 5-15 min)
* Max effect within 30 min
* Duration of Action: 4-6 hrs
Salbutamol dosage
1 or 2 puffs, prn as required
________________ can develop to bronchodilator effects
with continuous/inappropriate use.
Tolerance
Indication of LABA
COPD, Uncontrolled persistent asthma
LABA must always be used with ________________ in asthma
steroid
Give the following info for LABA
ROA
Duration of action
Administer how many times?
Inhaled (onset of action – longer than for SABAs)
* Duration of action: 8-12 hours
* Administer twice daily consistently
You cannot use salmeterol in which circumstance?
– do not use
salmeterol in an acute attack
Give Adverse effects of B2 agonists (9)
Skeletal muscle tremor, headache dizziness, tachycardia, palpitations – dose-related
* Nervousness (β₂ stimulation increase the release of catecholamine’s
at nerve terminals)
* Dry mouth, taste alteration and discolouration of teeth
T/F: B2 Agonists adverse effects are less pronounced with oral administration
F
B2 agonist cautions
Cardiac arrhythmias, IHD, CHF,
uncontrolled HT,
hyperthyroidism
Pregnancy
Why is B2 agonist cautioned in pregnancy?
may delay labour,
asthma need to be well
controlled, inhaled preparations
preferred
Which drug class may cause interactions if/when used with B2 agonists?
(non-selective) B-Blockers
Importance of glucocorticoids:
Anti-inflammatory – mainstay in preventing acute attacks.
* NOT bronchodilators
* Prevent progression of chronic asthma
MOA of glucocorticoids in asthma
Restrain clonal proliferation of Th cells by reducing the transcription of the gene for IL-2 and decrease formation of cytokines, in particular the Th2 cytokines that recruit and activate eosinophils and are responsible for promoting the production of IgE and the expression of IgE receptors.
MOA of glucocorticoids in asthma cont… (5)
Inhibit the allergen-induced influx of eosinophils into the lung.
*Up-regulate β 2 adrenoceptors,
*Decrease microvascular permeability
*Indirectly reduce mediator release from eosinophils by inhibiting the
production of cytokines (e.g. IL-5 and granulocyte–macrophage
colony-stimulating factor) that activate eosinophils.
*Reduce synthesis of IL-3 (the cytokine that regulates mast cell
production) i.e. may explain why long-term steroid treatment
eventually reduces the number of mast cells in the respiratory
mucosa, and hence suppresses the early-phase response to allergens
and exercise
which glucocorticoids are inhaled and what is their effect?
Inhaled corticosteroids (ICS) (beclomethasone, budesonide,
fluticasone): chronic treatment of persistent asthma
which glucocorticoids are taken oral and what is their effect?
Oral treatment (prednisone): for exacerbation (attack) or when
asthma is uncontrolled.
which glucocorticoids are taken IV and what is their effect?
IV treatment (hydrocortisone): severe bronchospasm, not able to
take oral.
Frequency of dose for glucocorticoids
2x a day
How much of glucocorticoid is distributed to the lung?
10-15%
After how long can u see improvement from glucocorticoid use?
1-4 WEEKS
adherence is
important for optimal effectiveness (educate on prophylactic use,
continue treatment even when symptom free)
What education can u give a pt regarding glucocorticoid use?
continue Tx even when symptom free (prophylaxis)
Rinse mouth after use to prevent oral candida
adverse effects of inhaled glucocorticoids (3)
Oral candida, hoarseness, sore throat
MOA of M3 antagonist
block contraction of airway smooth muscle
mediated via M₃-receptors and inhibit augmentation of mucous
secretion that occurs in response to vagal stimulation. Increase
mucociliary clearance of bronchial secretions.
Response vary among individuals: only inhibit portion of bronchoconstrictive response mediated via parasympathetic pathways, more effective in COPD and the elderly
Onset of action and duration of action of Ipratropium
Onset of action: 30 minutes
* Duration of action: 4 hours
Cautions and adverse effects of ipratropium
- Cautions: prostatic hypertrophy & narrow angle glaucoma
- Adverse effects: dry mouth, bitter taste
MOA of Xanthines
unclear. Relax smooth muscle via inhibition of
phosphodiesterase isoenzymes. Antagonise adenosine receptors
General CNS and resp stimulation
Pharmacokinetics of Xanthines: Therapeutic index and absorption
Pharmacokinetics: narrow therapeutic index
* Oral absorption good (sustained release preferred, do not change
formulation is patient has been stabilised on it)
Pharmacokinetics of Xanthines: Half life and metabolism
Half-life variable
* prolonged in infants and older patients, heart failure, hepatic disease,
concurrent infections,
* shortened by smoking and drug-interactions
* Metabolised in the liver
* Only use when other bronchodilators have failed
Common side effects of theophylline: GI effects
GI effects and CNS stimulation.
* GI irritation may be minimised by taking with food to prevent N/V, epigastric
pain and intestinal bleeding.
Common Adverse effects of theophylline: CNS effects (6)
- CNS effects: headache, irritability, nervousness, tremor, insomnia,
convulsions
UNCOMMON ADVERSE EFFECTS OF Theophylline
Uncommon: tachycardia, palpitations, hypotension, arrhythmias,
hyperglycaemia, depression
Cautions of theophylline (8)
IHD, Hypertension, hyperthyroidism, epilepsy, hx of PUD, liver disease, CCF,
older patients
Theophylline drug interactions
Hepatic enzyme inhibitors: cimetidine, erythromycin, ciprofloxacin,
ritonavir, etc.
* Hepatic enzyme inducers: smoking, alcohol, barbiturates rifampicin,
phenytoin, carbamazepine
* Sympathomimetic agents: potentiate cardiac effects
Montelukast indication
prophylaxis and chronic treatment of atopic asthma (also
treat allergic rhinitis), inhibit exercise-induced asthma
MOA of montelukast
exhibit bronchodilator and anti-inflammatory activity by
blocking effects of cysteinyl leukotrienes in the airways
ROA of montelukast
Administered orally
* Not indicated for acute attack (controller, take regularly)
Adverse effects of Montelukast
Uncommon in general
* Hypersensitivity
* Eosinophilia (rarely)
* Neuropsychiatric events: agitation, aggression, anxiousness, hallucinations,
depression, insomnia, irritability, suicidal thinking and behaviour – Warn
patient
How to treat mild and moderate acute asthma attack
Salbutamol, inhalation using a metered-dose inhaler (MDI), 4–8 puffs, using a spacer.
* Inhale one puff at a time. Allow for 4 breaths through the spacer between puffs.
* If no relief, repeat every 20–30 minutes in the first hour.
* Thereafter, repeat every 2–4 hours if needed.
* Note: Administering salbutamol via a spacer is as effective as, and cheaper than, using a nebuliser.
* OR
* Salbutamol 0.5%, solution, nebulised, with oxygen.
* 1 mL (5 mg) salbutamol 0.5% solution, in 4 mL of sodium chloride 0.9%.
* If no relief, repeat every 20–30 minutes in the first hour.
* Thereafter, repeat every 2–4 hours if needed.
* AND
* Corticosteroids (intermediate-acting) e.g.: Prednisone, oral, 40 mg immediately
* Follow with prednisone, oral, 40 mg daily for 7 days.
Tx of severe acute asthma
Give oxygen with care (preferably by 24% or 28% facemask, if available). Observe patients
closely, as a small number of patients’ condition may deteriorate.
* AND
* Salbutamol 0.5%, solution, nebulised, with oxygen.
* 1 mL (5 mg) salbutamol 0.5% solution, in 4 mL of sodium chloride 0.9%.
* If no relief, repeat every 20–30 minutes until PEF > 60% of predicted.
* Once PEF > 60% of predicted, repeat every 2–4 hours if needed.
Corticosteroids (intermediate-acting) e.g.: Prednisone, oral, 40 mg immediately.
* Follow with prednisone, oral, 40 mg daily for 7 days.
ADD (If poor response after first salbutamol nebulisation/inhalation):
* Ipratropium bromide solution, nebulised,
2 mL (0.5 mg) added to salbutamol solution every 20–30 minutes for 3 doses depending on clinical response.
OR using MDI, 80–160 mcg (2–4 puffs), using a spacer every 20–30 minutes as needed for up to 3 hours.
Management of chronic persistent asthma (patient eductaion)
Non-pharmacological advice and patient education:
* No smoking by an asthmatic or in the living area of an asthmatic.
* Avoid contact with household pets.
* Avoid exposure to known allergens and stimulants or irritants.
* Education on early recognition and management of acute attacks.
* Patient and caregiver education:
* emphasise the diagnosis and explain the nature and natural course of the condition;
* teach and monitor inhaler technique; and
* reassure parents and patients of the safety and efficacy of continuous regular
controller therapy
Medical management of severe persistent asthma
Medicine treatment is based on the severity of the asthma and
consists of therapy to:
(1) prevent the inflammation leading to bronchospasm (controller)
ICS: beclomethasone – use twice daily
(2) relieve bronchospasm (reliever)
SABA: salbutamol – use as needed
Mx of exercise induced asthma
Administer: SABA: salbutamol 30 minutes before exercise
