Clinical and pharmacological approaches for treatment of bronchial asthma: Flashcards
define bronchial asthma
chronic, inflammatory disease of the respiratory tract, which is characterized by bronchial hyperreactivity and respiratory obstruction.
what causes intermittent airway narrowing in asthma
⦁ bronchoconstriction,
⦁ congestion or edema of bronchial mucosa,
⦁ mucus,
⦁ or a combination of these
classification of asthma
extrinsic- atopic
intrinsic-non atopic
specific - occupatio/ aspirin
symptomatic classification
intermittent
mild persistant
moderate persistant
severe persistent
intermittent asthma
one day attack a week
one night attack per month
mild persistent
more than one day attack a week but less than one attack per day
night attacks 2x / month
moderate persistent
everyday attacks
night attack 1x a week
severe persistent
everyday frequent excacerbations
frequent night attacks
limited physical activity
what is GINA
GLOBAL INITIATIVE for ASTHMA maNAGEment
stepwise approach to the management of bronchial asthma
goals in rx of asthma
⦁ Avoid troublesome symptoms during day and night;
⦁ Need little or no reliever medication;
⦁ Have productive, physically active lives;
⦁ Have normal or near normal lung function;
⦁ Avoid serious asthma flare-ups (exacerbations, or attacks);
drug classificatino for asthma
Relievers – used for the treatment of the asthmatic attack:
Controllers – used to control the symptoms:
list the relievers
⦁ Short-acting β2 agonists (SABA).
⦁ Short-acting antimuscarinics.
⦁ Short-acting phosphodiesterase inhibitors.
⦁ Systemic corticosteroids
Controllers
⦁ Long-acting β2 agonists (LABA) ⦁ Inhaled corticosteroids ⦁ L-acting antimuscarinics ⦁ L-acting phosphodiesterase inhibitors ⦁ Leucotrien modifiers and mast cell stabilizers
devices used in asthma
Metered Dose Inhaler (MDI) : Spacers can help patients who have difficulty with inhaler use and can reduce potential for adverse effects from medication.
Nebulizer : Machine produces a mist of the medication/ Used for small children or for severe asthma episodes
Dry powder inhalers (DPI) : Single dose/ Multiple doses
Inhaled
step waise approach to bronchial asthma guidline
step 1: intermittent
step2: mild persistent
step3: moderate persistent
step 4: severe persistent
step 1
daily therapy : none
supplementary therapy: none
step 2
daily therapy; Low dose ICS
supplementary therapy:
leukotriene antagonise/ slow release theophyline
step 3;
daily therapy;
MOD ICS + LABA
supplementary therapy:
mod ICS + slow release thophyline
step 4
daily therapy;
high dose ICS + LABA
supplementary therapy: more than one slow release theophyline leukkotriene antagonist ige antibodies
effects of CS on asthma
⦁ Suppress inflammatory response to Ag-Ab reaction
Reduced bronchial hyperreactivity
effects of ICS on bronchi
Do Not have direct bronchodilating effect but potentiates the effects of β2-adrenergic agonists.
effects of CS on PT
⦁ Ιncrease lung function;/
reduce symptoms;/ improve quality of life;/ reduce the risk of exacerbations;/
reduce asthma-related hospitalizations and death.
how often must CS be taken
every day to controll inflammation even if symptoms are absent
list the inhaled corticosteroids
⦁ Beclomethasone (Becotide) – spray 50 µg
⦁ Fluticasone (Flixotide) -spray 25 µg
⦁ Budesonide (Pulmicort) - inhalation powder - 100 µg
ICS ADR’S
rare
⦁ Oropharyngeal candidiasis
⦁ Dysphonia.
indication of short term systemic corticosteroids rx
early in the treatment of severe acute exacerbation for 5-7 days
systemic CS ADRS
⦁ Adrenal supression – should be stopped gradually
⦁ Retention of sodium and water, peripheral edema./ Hypertension.
⦁ Thinning of the skin, striae.
⦁ Increased risk of infections.
⦁ Impaired wound healing.
⦁ Mood changes e.g. depression/ Increased intraocular pressure - risk of glaucoma./ Cataract/ Gastric ulcer/ Hyperglycemia/ Osteoporosis
list Short acting β2 agonists:
⦁ Salbutamol (Ventolin) – spray 0,02 % 10 ml,
⦁ Fenoterole(Berotec)
⦁ Terbutaline – inhalation powder 250 and 500 µg
List Long acting β2 agonists:
⦁ Salmeterole (Serevent) – discus 50 µg pro doses
⦁ Formoterole – caps
effects of b2 agonists in astma
⦁ Directly relax airway smooth muscles (β2 effect)
effects of SABA
relievers”
⦁ Onset of action within 1 to 5 minutes.
⦁ Bronchodilatation lasts for 2 to 6 hours.
⦁ used only as-needed at the lowest dose and frequency required.
LABA
⦁safe for asthma when used in combination with ICS.
without ICS in asthma is associated with increased risk of ADRs.
which can be used as both controller and reliever
⦁ Formoterol – rapid onset and long duration of action – 12 h
b2 agonist adr
⦁ Tachycardia – with high doses selectivity is lost.
⦁ Hyperglycemia, hypokaliemia.
⦁ Headache, agitation.
⦁ Finger tremor.
⦁ Tolerance!!! Development of tolerance to long-term used LABA decreases the efficacy of SABA in the treatment of acute asthmatic attack.
which drug interactions increase ADR of b2 agonists
TCA
MAOI
thyroid hormones
drug interxn reducing effect of b2 agonist
beta blockers
drug interxn potentiating effect of b2 agonist
⦁ Inhaled corticosteroids and antimuscarinic drugs
Methylxanthines (Phosphodiesterase inhibitors) effect
inhibit phosphodiesterase
this increases CAMP
effects of increased cAMP
⦁ bronchodilation;
⦁ inhibition of the release of histamin from mast cells;
⦁ improve mucociliary clearance in respiratory tract.
⦁ Short acting methylxanthine
Aminophylline (Novphyllin) – tab. 100 mg
⦁ Long acting methylxanthine
Theophylline (Theotard) – tab. 300 mg
what are methylxanthines used for
⦁ Prophylaxis of night–time attacks.
absoprtion of methyl xanthines
circadian rhythms in the absorbtion.
High oral bioavailability absorbtion is faster in the morning and slower in the evening
what causes increased clearance of methylxanthines
smoking
ez inducers e.g.
-rifampicin
-phenytoin/phenobarbital
causes of decreased methylxanthine clearance
pt’s over 50
ez inhibitors
- cimetidine
- macrolides
- ciprpofloxacin
methyl xanthine adr
cns: restless, insomnia, convulsion
cvs: tachy K, palpitation, arrythmia-death
antimuscarinics drug effects
bronchodilation (slower than b2 agonists
reduce mucosal secretion
- more effective in COPD
-elderly w/ less b2 receptors
additive effect when combo w/ b2 agonists
short acting antimuscarinic for asthma
Ipratropium bromide (Atrovent) – spray 15 ml
⦁ Long acting antimuscarinic for asthma
Thiotropium (Spiriva) – caps. pro inh. 18 µg
why is ipratropium less effect at relieving than SABA’s
slower onset of action
less bronchodilating effect.
ipratropium indication
⦁ Short-term use in acute asthma added to SABA reduces risk of hospitalisation.
indication for thiptropium
add-on option at step 4 or 5 for adults whose asthma is uncontrolled by ICS±LABA.
antimuscarinic adrs
⦁ Dry mouth.
⦁ Increased intraocular pressure, mydriasis.
⦁ Tachycardia.
⦁ Obstipation.
⦁ Retention of urine.
⦁ Caution in patients with benign prostate gland hypertrophy, arrhythmias and glaucoma
leukotriene modifiers
mech
Target leucotriene inflammatory pathway of asthma
⦁suppress bronchial inflammation on long term, decrease bronchial hyper-reactivity.
⦁ Used as controller therapy.
⦁ Preferred in children.
⦁ Less effective than low dose ICS.
⦁ Added to ICS – less effective than combination ICS/LABA.
classification of leukotriene modifiera
Leucotriene receptor antagonists (lukasts)
suppress asthmatic response to allergens
⦁ Montelukasr (Singulair) – tab. 10 mg
Lipoxygenase inhibitors:
block leukotriene synthesis
⦁ Zileuton (Zyflo) – tab. 600 mg
⦁ Zafirlukast (Accolate) – tab. 20 mg
adr’s of leukotriene modifiers
zileuton and zafirlukast increase liver function tests
Mast cell stabilizers
used for phyophylaxis
by preventing release of allergic mediators from mast cells
⦁ Sodium chromoglucate – caps. pro inh. 20 mg
⦁ Nedocromil sodium
which drugs are used for prophylaxis in BA
methylxanthines
mast cell stabilizers
mast cell stabiliser drugs
⦁ Sodium chromoglucate – caps. pro inh. 20 mg
⦁ Nedocromil sodium
ketotifen tab 1mg
which mast cell stabilser has antihistaminic effect
KETOTIFEN
mast cell stabiler ADR
cough when inhaled
which drug is used for severe persistent asthma
Anti-IgE (Omalizumab):
when ICS and LABA fail to controll symptoms
how is omalizumab admin
subcutaneously
how to manage an acute asthm attack
⦁ Inhaled SABA – repeat every 20 minutes for 1 hour.
⦁ Sort-acting antimuscarinic drug – Ipratropium (Atrovent).
⦁ Oral corticosteroids 1 mg/kg bw – no more than 50 mg for adults.
⦁ Oxygen.
CI antiasthmatic drugs and pregnancy
ICS in first trimester
cause low baby weight and malformation
recc drugs in pregnancy
beta aganosis
theophylline
ICS after first trimester
