PHARMACOLOGY OF RESPIRATION
Learning Objectives
1. Evaluate interventions based on the etiologies, status, and control of asthma.
2. Develop and justify optimal therapeutic regimens based on the underlying pathophysiology of
asthma and current evidence.
3. Devise an asthma education care plan for a patient or family member(s).
4. Demonstrate an understanding of pharmacogenomic testing and how results influence treatment
decisions in patients with asthma
5. Demonstrate an understanding of emerging therapies in the treatment of asthma and judge when
they would be applicable in patient care
6. Display insight into technological advances in asthma care and recommend them to patients
when appropriate.
BRONCHIAL ATHMA
Bronchial Asthma means:
paroxysmal attack of expiratory dyspnea with wheezing, tight in chest and tenacious, scanty
sputum.
Pathology:
The cause of an asthma attack is usually completely reversible. Three factors are operating
as pathology:
1) Broncospasm
2) Oedema of the bronchi , congestion , inflammation.
3) Retention of tenacious scanty, secretions.
Etiology: unknown
Predisposing factors: common in children , women, low socioeconomic
1- Hypersensitivity this due to occupation, smoking, pollen, dust, septic foci.
Extrinsic ( atopic ) mainly in children.
Intrinsic mainly in adult.
2- Emotion.
3- Sever exercise in children.
4- Cold.
5- Infection.
6-genetic(Arg16), obesity,
7- Iatrogenic (drug induced asthma)
. NSAI (allow paracetamol only)
. Histamin releaser (morphine , curare , trimetaphan )
. Cholinomimetic as methacholine
. Sympatholytic (non selectiveBB )
. PGF2
. Penicillin.
. Food preservation , dye.
Contraindicated drugs:
1) Barbiturate
- inhibits respiratory center decreases sensitivity to co2.
- induces respiratory failure.
2) Morphine
- induces bronchospasm.
- Histamine releaser.
- inhibit respiratory center by decrease sensitivity to co2 lead to inhibition
of cough center.
3) Atropine induces tenacious secretion.
Prognosis:
The prognosis for asthma is good especially children with mild disease 54% of cases will no
longer carry the diagnosis after a decade. Early treatment with glucocorticoid prevents or ameliorate
decline in lung function.
Mortality rate from asthma is low, better control of the condition may help prevent of deaths.
Measures for Identifying High-Risk
patient is considered at high risk if any of the following criteria were met in the past year:
 ≤ 1 emergency department visit for asthma



≤ 1 hospitalization for asthma
Use of ≥4 asthma medication prescriptions
≤ 4 ambulatory visits for asthma with ≥2 asthma drug prescriptions
Risk Factors for Persistent Asthma Children younger than 3 years who, in the past year,
have experienced 4or more episodes of wheezing that lasted more than 1 day and affected sleep
are more likely to have persistent asthma after the age of 5 years if they also have:
One of the following:
Parental history of asthma
Diagnosed atopic dermatitis
Evidence of sensitization to aeroallergens
Or two of the following:
Evidence of sensitization to foods
≥4% peripheral blood eosinophilia
Wheezing apart from colds
Physiology:
- Sympathetics stimulate bronchial dilatation and cause vasoconstriction decreases bronchial
secretion.
- Parasympathetics induce bronchoconstriction and vasodilatation increases secretion.
-Non cholinergic non catecholamine.
* Neuropeptid ( adenosine ) act on P1 A1 receptor.
* PGE1,2 , F2.
* Platelet activity factor (PAF).
* Prostanoids (thromboxane)
* Histamine.
* K C O.
* Leuckotrein D, B.
Mangement of asthma:
- Acute attack.
- Status athmaticus.
- In between attack.
A) Avoid predisposing factors:Desensitization , avoid antigen , if possible , change occupation , stop smoking.
. avoid sever exercise , avoid exposure to air draft.
. avoid infection , rapid treatment.Obesity
. avoid iatrogenic drugs , stable emotion , if possible.
Bronchial athma divided into:
Mild
Shortness of breath or wheezing > 2 days/week ,
Nighttime awakenings absent
No limitation in normal activity
Use of quick-acting agent> 2 days/week
FEV1 or peak flow < 80%
Moderete
Shortness of breath or wheezing > 2 days/week
Nighttime awakenings > 1 day/week
Some limitation in normal activity
Use of quick-acting agent > 2 days/week
FEV1 or peak flow 60% to 80% predicted or personal best
Sever
Continuous symptoms frequent exacerbations
Nocturnal symptoms.
Limited activity
Lung function is less than 60%
Tests of bronchial athma
*
*
Spirometer
Impulse Oscillometry diagnostic purposes when spirometry is not an option, such
as in the frail elderly and in young children The impulse oscillometry evaluates both
respiratory resistance (i.e., the energy required to propagate the pressure wave through
the airways) and reactance (i.e., the amount of recoil generated against the pressure wave
at different oscillatory frequencies
*NO(nitric oxide) may be an indicator of eosinophilic inflammation in the airway.
B) Treatment:1-Bronchodilators:
a) Sympathomimetics.
b) Direct smooth muscle relaxants as Methyl xanthines.
c) Anticholinergic drugs Ipratropium bromide.
2-Non specific reduction of allergic reaction
a) Mast cell stabilizes.
b) Cortizone.
c) Leukotriene inhibitors.
d) Immune modulators.
3-Symptomatic:
a) Expectorant , mucolytics.
b) Oxygen therapy.
c) Sedative , tranqulizer.
d) Chemotherapy.
Sympathomimetics:- consider 1st line of ttt
Mechanism of action:Direct bronchodilator, acts as β2 agonist
They act by increasing the level of cAMP found in smooth muscle through activation
of adenyl cyclase ,increase synthesis of cAMP , decrease free ca ++
ATP----------adenyl cyclase by increase synthesis-↑---------↑CAMP----- Free Ca by
increasing ca binding lead to:
a) Bronchodilatation.
b) Decrease bronchial secretion.
c) Vasoconstriction.
d) Decrease edema.
e) Increase activation of bronchial cilia (muco-ciliary clearance activity).
f) Mast cell stabilizers.
Preparations:
B adrenergic Agonist: inhalation of selective B2 adrenergic agonist is the preferred
form bronchodilator therapy. Metered-dose aerosol formulations offer the greatest
convenience. Nabulizer solutions may be more useful for more intensive therapy in the
home or hospital
Short acting B2 adrenoceptor agonist: such as salbutamol ( albuterol) , terbutaline ,
levalbuterol.
Mode of administration of salbutamol: oral, tablet 2-4mg initial dose3to4times daily;a total
daily dose of 32mg should not exceeded.syrup2mg 5ml . *Not use in acute, *more side
effects,*
inhalation Metered dose aerosol * Each inhalation delivers approximately90ug of the drug
* No more than 2 inhalation every 4-6hours is recommended.
*Onset 5 min used in short term acute athma, then 2days /week
Major side effects:
-Tremors (via B2 receptor in skeletal muscle)
- CVS in high doses
HR
B.P lead to hypertension (due to its action on B1).
- Patient must be cautioned against using these medication too frequent because their
efficacy may decline. Producing desensitization resulting in exacerbation of
symptoms which lead to refractory asthma( bronchial hyper-response) and death.
So,patient should be encouraged to seek medical attention as soon as possible after they detected a
marked decline in the efficacy of usual therapeutic regimen.
- Older less selective adrenergic agonists such as inhaled epinephrine and ephedrine
tablet cause cardiac and CNS side effect due to non selectivity limited their use
epinephrine may be used as inhaled or S.C. in emergencies with exclude of
cardiovascular disease .
Long acting B2 agonists: A typical inhaler:include salmeterol,formoterol
,bambuterol and sustained release oral albuterol
Salmeterol 21gm/puff, 2 puff/12hr.has relatively slow onset action and a prolonged
effect. Twice daily inhalation of salmetrol has been effective for maintenance
treatment
It is not recommended for treatment of acute bronchospasm.
[formoterol can be an effective reliever agent (Barnes 2007) because of its rapid onset of
effect (within 1 minute to 3 minutes) and its long duration of action (12 hours or more)
(McCormack 2007)]. it demonstrated that the budesonide/formoterol combination for both mainte
nance and quick relief significantly reduced total severe exacerbations,{ avoided exposure to oral
corticosteroids,} reduced reliever-drug use, and relieved nighttime symptoms, including
awakenings, and mild exacerbation days when compared with budesonide/formoterol or high-dose
budesonide for maintenance (both with SABA for quick-relief use) (O’Byrne 2005)investigators
also found SMART resulted in both lower overall ICS dose (a reduction by approximately 300
mcg/day of budesonide equivalents) and significantly lower drug costs (by 25%)
Side effect :
*CVS tachycardia, palpitation.
* Ttremor.
* paradoxical bronchospasm can occur.
* and high doses can cause hypokalemia.
To ensure safe use, clinicians should recognize that LABAs are contraindicated without
a controller drug such as an ICS and should be used chronically and long term only if
the patient’s asthma is not otherwise controlled. In addition, LABAs should be used for
the shortest duration possible, and their use in pediatric and adolescent patients
is restricted to the form of a combination product. Long-term use of LABAs
is appropriate only for patients whose asthma cannot be managed without them (e.g.,
patients unable to remain controlled on ICS monotherapy. Also, a recent
meta-analysis showed that in trials in which LABA therapy was discontinued in patients
controlled on LABA plus ICS, the LABA step-off approach resulted in increased
asthma impairment, worsening of asthma quality of life questionnaire scores, and fewer
symptom-free days (Brozek 2012).
=======================
Methyl xanthines: Aminophylline:
Aminophyllin is most common thiophylline preparation which is one of
methylxanthines.
Aminophylline is potent direct bronchodilator. It has positive inotropic and
chronotropic action .It increases cardiac output, reduces venous pressure and has
diuretics action.
Mechanisms of action:
1. It competes with adenosine at P1 (A1) purinoceptors.
2. It inhibits phosphodiesterase enzyme, thus increase cAMP. This may explain the
cardiac stimulation and bronchodilation.AMP-----phosphodiestrase---↑CAMP by
decrease destruction
3. It also stimulates the release of catecholamines from the adrenal medulla and inhibits
COMT (enzyme metabolism of catecholamines).
4. Mast cell stabilizer.
Adminesteration:
* Oral : Tablets
Slow release tablet
Syrup
* I.V or I.V.I
* Suppository
Oral dose : start by loading dose 6mg/kg then 3mg/kg/8h
I.V , I.V.I. with cation slow over 20-40 min to avoide sever toxic symptoms
I.V 250-500 mg slowly, I.V.I initial loading dose 6mg/kg slowly maintenance dose 0.7
mg/kg/h with plasma level determination.
Rectal suppository is irritant and fluctuating.
Preparations:
* Aminophylline dehydrate, enprophylline ( less toxic, more potent )
* Choline theophylline ( less irritant )
* Sustain release tablets and syrup are as slophylline (6-12h) or somophylline (12h) and
lasma (12-24h) especially in nocturnal asthma.
Toxicity: NOT PREFERE why?
* Aminophylline has narrow safety margin means therapeutic plasma level
from 10-20Ug/ ml, more than20Ug/ml is toxic level so, must titrate the dose, periodic
determination of drug in plasma .Also,
due to irrigular absorption.
* If toxicity occurs or suspected diazepam administrated.
* Most toxicity is the result of repeated administration of theophylline by either oral
tablets sustained released or parental routes . Result from rapid I.V administration may
be sudden death, toxic encephalopathy, convulsion (focal or general seizures), may
hypotension, cardiac arrhythmias.
* Manifestation of toxicity:
CNS : alertness, dizzness, restlessness, insomnia, agitation, convulsion, brain damage.
CVS : tachycardia, cardiac arrhythmias, palpitation, hypotension, precardial pain.
GIT : nausea, vomiting, peptic ulcer.
Kidney : duiresis.
Muscle : become tense and tremulous.
Indication:
* Inhaled B agonist, inhaled corticosteroid is most better than oral theophylline.
* Oral is effective in prophylactically
# in nocturnal symptom and
# as protection in exercise
# allergen induced asthma.
* Supplement with corticosteroid gives good result and decrease the dose of steroid.
* Supplementation with B agonist decrease hyper-responsivness of bronchi and decrease
the need for repeated B agonist administration.
* In status athmaticus I.V infusion.
=================
The use of anticholinergic drugs in asthma is fitting. Acetylcholine, a parasympathetic
neurotransmitter, stimulates muscarinic receptors; this results in smooth muscle contraction, release
of mucus from submucosal glands, airway inflammation, and airway remodeling (Gosens 2006).
Cholinergic tone can also become exaggerated when stimulated by inflammatory mediators such as
histamine, prostaglandins, and bradykinin. Other mechanisms that may increase cholinergic tone in
airways include increased release of acetylcholine from cholinergic nerve terminals, abnormal
muscarinic receptor expression (increase in M3, decrease in M2), and a decrease in
neuromodulators such as nitric oxide and intestinal peptide (Kanazawa 2008).
Ipratropium: it is a quaternary ammonium compound which prevent absorption after
inhalation and thus minimizes side effects outside airways and no cardiac effect. So can
use in patient with heart disease or thyrotoxicosis.
Mechanism of action block muscrinic receptor of Ach, it renders the bronchial secretion
less dry and not sticky. Also, used as maintenance therapy or older patient with chronic
obstructive pulmonary disease. Ipratropium does not inhibit mucociliary clearance
Administrated as metered dose inhaler 20Ug/puff dose 2 puff/6hrs. It is slow onset after 1 hour and
prolonged action 4-6 hr. combination of B2 adrenoceptor agonists and Ipratropium give good
result bronchodilator with sustain action e.g (Duovent combination of ipratropium + fenoterol) this
combination can use in acute sustain asthma.
Uses in sever exacerbation, prophylactic. acute sustain asthma.
Improve lung function ---decrease hospitalization
Role of Tiotropium for Asthma
Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or
anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors,
when topically applied it acts mainly on M3 muscarinic receptors[7] located on smooth muscle cells
and submucosal glands. This leads to a reduction in smooth muscle contraction and mucus secretion
and thus produces a bronchodilatory effect. There is strong evidence supporting improvement in
spirometry and asthma exacerbations with tiotropium in patients with moderate and severe asthma;
therefore, tiotropium may be an effective intervention in patients with asthma.
The use of anticholinergic drugs in patients with asthma has been relegated primarily to the acute
setting. The use of ipratropium results in fewer hospitalizations if given in combination with a
SABA to patients experiencing exacerbations in the emergency department (EPR-3 2007).
Tiotropium added sustained bronchodilation over24 hours and reduced severe exacerbations in
patients with asthma who had been symptomatic with persistent airflow limitation despite the use of
high-dose ICS plus LABA (Kerstjens, 2012).If a patient’s asthma does not respond as assessed by
symptom scores, quality-of-life measures, or pulmonary function after an 8- to 12-week trial,
tiotropium should be discontinued. hrs TIOTROPIUM: Onset 30 min Duration24h.
===================
Corticosteroids: can suppress inflammation, decrease bronchial hyper responsiveness and
decrease symptoms in mild, moderate persistent asthma as well as with severe disease.
Mechanisms of action:
[1]Anti-inflammatory:
* Inhibits AB formation. *Decreasing inflammatory cells
* Inhibits AB/Ag reaction. * Inhibits congestion, edema, mucus.
[2] Inhibits inflammatory mediators: Increase synthesis of lipocortine that inhibit the activity
of phospholipase A2 (cell wall)
* Which lead to decrease arachidonic acid which affect on (PG 2 LTS, PAF)
*Increase stability of cell membrane of endothelial cells, smooth muscle and mast cells
[3] Stabilization of mast cell wall: through increases synthesis of cAMP by stimulation of
adenyl cyclase.
[4] Direct bronchodilator: through increases synthesis of cAMP by stimulation of adenyl
cyclase.ddddxddqq
[5] Potentiate endogenous catecholamine ,β agonist.
[6] Improve lung function & decrease relapse rate
Indication:
*After fail of other therapies.
*In acute sever athma exacerbation.
Adminstration: Onset 4-12 hrs so, start early
* Corticosteroids are given orally, injection or by inhalation according each case.
* Course of adminstration 3-10d or 2weeks for complete ttt.Not need tapering dose.
* Inhalated corticosteroids are usually free of toxicity.
*Intravenous & intravenous infusion are used in sever or persistant case.
*Oral corticosteroids are usually considered preventive medication or supplement treatment
*Douple dose ---no benefit.
*More effective than LTA,cromoglycate, theophyllin.
Preparations: Hydrocortisone and their preparation:
* oral 10-20 mg.
* I.V. , I.V.I. or I.M. vial 100 mg/2ml.
Prednisolone:
* oral 5 mg. e.g(hostacortico , deltcortril)
* I.V , I.M methylprednisolone 500 mg/8ml.
Dexamethazone:
* oral Decadrone 0.5 mg.
* inhalation Dexamethazone sodium phosphate 100 Ug/dose.
* I.V.,I.M. Dexamethazone acetate 8mg/ml.
Beclomethazone:
* inhalation 40Ug/dose.
Betamethazone:
* oral 0.5 mg
* I.V. ,I.V.I. 4-6 mg /ml
Side effects:
* Inhaled corticosteroids usually lesser toxicity due to decrease systemic effects. Dysphonia
cough hoarsness of voice and oral candidas can occur. The use of spacer device and rinsing
the mouth after inhalation decrease the incidence of candidas.
* delayed growth may occur within 6-12 weeks of systemic cortisone therapy in some
children.
* osteoporosis, cataracts, glaucoma, glucose intolerance, weight gain, hypertension,
depression, peptic ulcer, cl , k
Others alternate-day use of corticosteroid can decrease the incidence of adverse effect.
* Steroid dosage must be tapered after long course therapy. Short course therapy does not
have
to be tapered.
Children therapy is continued for 5days and maximum dose 60 mg/dose .children more than 3-4
years
when pediatric patients remain symptomatic on low-dose ICS. During each 16-week
period, subjects received either 250 mcg fluticasone twice daily, or 100 mcg fluticasone
plus 50 mcg salmeterol twice daily, Those authors found that the addition of salmeterol
to medium-dose fluticasone was not inferior to doubling the dose of ICS with regard to
symptoms during 6 months of treatment. There have been concerns that the use of
LABAs in children may lead to increased risk of exacerbations. However,
a Cochrane analysis concluded that adding LABAs did not increase exacerbations
requiring oral steroids or hospitalizations when compared with ICS alone.
===========================
Mast cell stabilizer
Disodium cromoglycate (DSCG) (Intal)( cromolyin sodium),Nidocromil and Ketotifen
Indication:
* It is used in treatment of asthma that is not adequately controlled by B agonist inhalation (In
persistence athma).
* But it is used in prophylactic, chronic, taken 15 min before exercise induced asthma and allergens
exposure,
* decrease bronchial hyper-responsiveness
* and decrease of frequency of administration of drug after several months.
Mechanisms of action:It inhibits antigen induced bronchospasm and released of histamine and
other mediators from sensitized mast cells in respiratory tract through increasing of cAMP
which prevent Ca permeability of mast cell membranes through inhibition of
phosphodiesterase witch lead to
* stabilization of mast cells. Prevent early & late allergic phase response in R Tract
*It may act as axon mediate the release of adenosine.
* It may inhibit platelet aggregation factor(PAF) & esinophils.
N.B: (DSCG)*Not bronchodilator
* Not inhibit Ag/AB
reaction
Administration: by inhalation in prophylactic before exercise or potential exposure to antigen.
DSCG is available as capsule inhaled by special inhaler contain 20 mg of finely powder or as
Solution 10 mg by neubulizer /4times/d, complete effect 4-6 weeks .
Effectveness as low dose of CS or β agonist.
Side effects:
mainly suffocation due to bronchospasm through irritation of fine particle of drug to bronchial
mucosa .This is avoided by inhalation of B2 agonist prior to inhalation of DSCG.
*Kitotifen (Zaditen):It is mast cell stabilize,H1&5HT blockers.It can be given orally
(tablet 1mg& syrp1mg/5ml) . Used in prophylactic .Side effect: sedation ,dry mouth, dizziness at
the beginning of treatment.
============================
Leukotriene Inhibitors:
They are medications that block the formation or activity of leuktrienes (small mediators
produced by cells in body).
Preparations:
1-Zafirlukast(Accolate)
2-Montelukast(Singulair)
3-Zileuton (Zyflo)
* zafirlukast (accolade)
* montelukast (singulair)
Mechanism: Leukotriene receptor antagonists, compete with LT receptor and prevent their role on
bronchial athma . Attenuates bronchoconstriction and inflammation due to
* zileuton (zyflo)
Mechanism: Leukotriene synthesis inhibitor, inhibits 5- lipooxygenase enz.,synthesis inhibitor
Indication:
1-Adjunctive in asthma : Moderate Persistent Asthma , Sever Persistent Asthma,
2-Aspirin-Induced Asthma
3-Exercise-Induced Bronchospasm
4-Moderate Chronic Obstructive Pulmonary Disease.
5-Allergic Rhinitis better than antihistaminic, both drugs better than each drug alone.
6-In contraindication, or due to side effect of corticosteroids, or to decrease the dose.
Adverse Effects
1-Not recommended in pregnancy or lactation,,liver dse., old age and children in young age.
2-drug interaction
3-Neuropsychiatric events (behavior or mode changes).
4-Hepatotoxicity with Zileuton, zafirlukast less in Montelukast Hepatotoxicity in 5%(every month
for 3 months;4 times next year; increase enzyme may detected within 2 months of starting
treatment)
5-Some association with Churg-Strauss Syndrome & lupus; Vasculitic Rash;Pulmonary and cardiac
condition.
6-Most expensive agent.
Zafirlukast (Accolate)
1-leukotriene Receptor antagonist
2-Avoid at meal time *Take 1 hour before or2 hours after meals
*Dose: Child 7-11 years old:10mg PO bid
Age>11years old:20mg PObid
3-Avoid in patient aged55 years old due to increase risk of respiratory infection.
4- Drug interactions: Zafirlukast with aspirin, B.P. medication, some seizure medication
Montelukast ( singulair)
1-leukotriene Receptor antagonist
2-Dose *Adults :10mg PO once daily at evening
*Child age 6-14 years: 5mg once daily at evening
*Child age2-5 years : 4mg once daily at evening
3-Drug interactions: montelukast with NSAIDS, phenobarbiton, rifampin.
Zileuton(Zyflo)
1-Leukotriene Synthesis inhibitor (5 lipooxygease pathway inhibitor)
2-Indicated in age only 12 and over
3-Dose:600mg orally four times daily
4-Drug interactions: Warfarin ,theophylline, propranolol, β agonist
Efficacy
1-less effective than low dose of corticoid
2-LTRA+ ICS less than βA+ ICS
3- LTRA+ βA used to avoid corticoid, and decrease the dose of β A
=====================================================================
Immune modulators:
Recombinant humanized monoclonal Anti IgE Antibody Omalizumab, a 95% humanized
monoclonal antibody that binds to circulating IgE, is currently approved for moderate to severe
persistent allergic asthma and for those patients not well controlled on combination medium
dosages of ICS and LABA.
Indication: *moderate & sever athma esp. fall or high dose of CS+LA β A
Advantages * Decrease Number and length of exacerbation.
* Improve quality of life
Disadvantages: *Act after 2-3h or after 3doses
*Cost
* Anaphylaxis has been added, and patients should be observed in the clinician’s
office for 2 hours after each of the first three injections and for 30 minutes after each subsequent
dose, because 75% of reported anaphylaxis cases occurred within those periods (Cox 2009). a
patient medication guide is still required. Patients should have access to self-injectable
epinephrine and be educated on the signs and symptoms of anaphylaxis and on the
administration of self-injectable epinephrine.
* affect the skin at the site of injection.
*The dose depend on weight of pt., initial total serum level of IgE, +ve skin test
* Age of pt. at12y.
*arterial thrombotic events risk of myocardial infarction or stroke.
Oligonucleotides, Anticytokine Therapy, Anti-IL-5(Mepolizumab), TNF-α inhibitor,
================================================================
.
Treatment of acute attack
- start with short acting B adrenergic bronchodilators (inhalers)
- inhaled corticosteroid if no contraindication or I.V.
Long term control medications are used on a regular basis to prevent attacks
such as
- inhaled corticosteroid.
- long acting B adrenergic agonist.
- Ipratropium.
- Na cromoglycate ( intal ).
- leukotriene inhibitor.
- aminoplyllin or theophylline ( not used as frequent as in past )
- some times a single medication that combines steroid and long acting B bronchodilator are used
symbicort ( budesonide + formoterol ) duovent combination of( ipratropium + fenoterol).
In status asthmaticus:1. Hospitalization.
2. Humidified oxygen O2 + Helium to alleviate hypoxia.
3. I.V. infusion to correct fluid imbalance.
4. Slow I.V. corticosteroid.
5. Short & long B2 adrenergic agonist or non specific.
6. Slow I.V. aminophylline.
7. Inhaled anaesthesia that have a bronchodilator or as halothane.
8. Intubation and mechanical ventilation.
9.Antibiotic
=======================================================================
Cough therapy
Types of cough:
Productive cough when it effectively expels secretions,exudate or foreign body from respiratory
tract. This is helped by expectorants and mucolytics .
Non productive dry cough This type should be stopped by antitussives
Antitussive Drugs:They suppress the dry cough which may arise from airway irritation
Peripheral Antitussives suppress the irritated sensory stretch receptor
1-Demulcents:Pastilles,lozenges e.g.Liquoric.It form a protective coat over irritated pharyngeal
mucosa e.g.sore throat.
2-Steam inhalation :One teaspoonful tincture benzoin Co or manthol+ boiling water stimulate
bronchial gland to secret smooth,thin protective mucus
3-Benzonatate chemically related to local anesthesia,it has peripheral effect on receptor and centeral
effect on cough center.
Centeral Antitussives suppress the cough center in the medulla.
1-Codeine has antitussive effect equal to morphine with less ( addictive ,constipating, analgesic and
respiratory center inhibition).Dose:tablet 15mg before sleeping.
2-Pholcodeineis less addictive than codeine .Dose 10mg orally.
3-Narcotine,Dextro-methorphan and Levo-propoxyphene are antitussive with No narcotic or
analgesic or addiction
Productive Cough
Expectorants : They facilitate the removal of bronchial secretion through liquification and
increasing the amount of secretions thus increasing the efficacy of coughing.
1-Sodium or potassium citrate, bicarbonate, benzoate .They are transformed into bicarbonate
increase the alkali reserve which excreted by bronchial glands lead to increase broncial secretion
and disolve thick sputm.
2-Tincture Ipecacuana and Ammonium choloride :They irritate gastric mucosa with reflex increase
bronchial mucus
.
3-Sodium and potassium iodide: it secretes in all exocrine gland .It increases nasal, salivary ,
conjuctival and bronchial secretion and liquefy the tenacious sputum.Uses :In chronic bronchitis
and hyperthyroidism. Side effects:*Skin rash *Iodism:headach ,conjunctivitis , rhinitis , gastritis
and parotid swelling. Contraindication: **Iodide allergy **Acute bronchitis,bronchial athma (It is
sever irritant to mucosa **pulmonary T.B **Thyrotoxic patient under control of K perchlorate.
Mucolytic Agents:They liquify the viscid bronchial secretion by fragmentation or split of mucus.
They increase volume and decrease viscosity.
1-Bromohexine(Bisolvon):fragmentation of mucopolysaccharides of mucus.
2-Acetylcysteine, methylcysteine (Mucolase): split the disulphide bonds in mucus.
Uses:by inhalation and oral.
.===============================================================
Therapeutic Gases
1-Oxygen
2-carbon dioxide
3-Helium
Oxygen
Normobaric oxygen: Humidified ,40-60% oxygen under positive pressure.
Indication of normobaric oxygen:
1-All types of hypoxia EXCEPT cyanide poisoning
2-To dilute general anesthesia e.g.Halothane
3- Abdominal distention as in paralytic illus.
Indication of Hyperbaric oxygen: 100%oxygen under more than atmospheric pressure(2-3times)
in special champers
1-Carbon monoxide poisoning
2-Anaerobic infection
3-Surgical cardiac operation
4-Organ transplantation
5-Pulmonary Oedema
6-Circulatory cause as shock, coronary thrombosis
7- Radiotherapy.
Side effects:
1-Fire or explosions so,must care no flam or electric switch
2-Rapid withdrowal of oxygen lead to sever hypoxia.
3-Retrolental fibrosis in premature
4-Oxygen apnea
5-Pulmonary atelectasis
6-Oxygen toxicity due to use pure oxygen 80%for long period and under pressure which are:
Respiratory irritation,sore throat, cough ,nasal snuff.
CNS: vertigo, mood changes, convulsion and loss of consciousness, muscle twitches.
Helium
*Used with oxygen(80%Helium+20%oxygen) this combination easy breath than oxygen due to low
denisty
*Non inflammable so used with explosive anesthesia as cyclopropane because it is inert gas.
*Low solubility reduces decompression time after diving.
*In laser airway surgery because it reduces the spread of tissue damage due to high thermal
conductivity.
Carbon dioxide
Action:
1- Respiration.
Carbon dioxide is a potent respiratory stimulant, acting both directly or reflex via
chemoreceptors. Both rate and depth of respiration are increased, with maximum increase at 10%
CO2 concentration.
2- Cardiovascular system:
Carbon dioxide has two opposing actions on heart and blood vessels.
A direct action, causing depression of the heart and vasodilatation.
Autonomic action through sympathetic increase catecholamine and stimulate the heart and
vasoconstriction. The net result balance between both actions.
* Increased cardiac out put and heart rate.
* Elevation of systolic and diastolic pressures
* Dilation of cerebral and coronary vessels.
3- Central nervous system:
* Low concentration of CO2 up to 10%------depresses the excitatory cerebral cortex.
* High concentration (10-30%) produces unconsciousness and convulsion.
Therapeutic use:
1- not use as respiratory stimulant because it cause respiratory acidosis.
Uses :
1- In carbon monoxide poisoning.
2- Hypoxia.
3- With anaesthesia accelerates induction and recovery with ether.
4- Carminative as carbonated water.
5- Local as CO2 snow.( CO2 solidifying at -78 C'' ) used in wart.
.‫ المواقد التي تعمل بالغاز‬- :‫ من أيا من المصادر التالية‬،‫ما هي مصادر غاز أول أكسيد الكربون؟ من الممكن أن يتسرب هذا الغاز‬
.‫الشوايات التي تعمل بالغاز أو بالفحم‬. - ‫ األفران الخشبية‬- .‫ سخانات المياه التي تعمل بالغاز‬- .‫ مجففات المالبس التي تعمل بالغاز‬‫)أجهزة المسطحات‬. - ‫ الدراجات البخارية (الموتوسيكالت‬- .‫ القوارب التي تعمل بمحرك‬- .‫ المولدات التي تعمل بالغاز أو بالديزل‬‫ بعض أنواع السجائر‬- .‫ المدفأة التي تعمل بالغاز أو الزيت‬- .‫الخضراء التي تعمل بالغاز‬
Choose the ONE best answer.
.1 A 12-year-old girl with a childhood history of asthma
complained of cough, dyspnea, and wheezing after
visiting a riding stable. Her symptoms became so
severe that her parents brought her to the emergency
room. Physical examination revealed diaphoresis,
dyspnea, tachycardia, and tachypnea. Her respiratory
rate was 42 breaths per minute, pulse rate 110
beats per minute, and blood pressure 132/65 mm
Hg. Which of the following is the most appropriate
drug to rapidly reverse her bronchoconstriction?
A. Inhaled fluticasone.
B. Inhaled beclomethasone.
C. Inhaled albuterol.
D. Intravenous propranolol.
E. Oral theophylline.
.2 A 9-year-old girl has severe asthma, which required
three hospitalizations in the last year. She is now
receiving therapy that has greatly reduced the frequency
of these severe attacks. Which of the following
therapies is most likely responsible for this
benefit?
A. Albuterol by aerosol.
B. Ipratropium by inhaler.
C. Fluticasone by aerosol.
D. Theophylline orally.
E. Zafirlukast orally.
.3 A 68-year-old male retired police officer who has
smoked half of a pack of cigarettes a day for the past
40 years is diagnosed with chronic obstructive pulmonary
disease. He has difficulty in expiration during
breathing, but the symptoms are mild and intermittent.
Which one of the following agents would be
most appropriate as initial therapy?
A. Systemic corticosteroids.
B. Albuterol.
C. Salmeterol.
D. Tiotropium plus salmeterol.
E. Theophylline.
Correct answer = B. All symptomatic patients with
chronic obstructive pulmonary disease (COPD)
should be prescribed a short-acting bronchodilator
to be used on an as-needed basis. A regularly
scheduled long-acting bronchodilator, such as
salmeterol, could be added if symptoms are inadequately
controlled with short-acting bronchodilator
therapy. Systemic corticosteroids are used to treat
exacerbations in patients with COPD. Tiotropium
plus salmeterol is indicated in moderate to severe
disease. Theophylline is an oral bronchodilator that
is beneficial to some patients with stable COPD.
Because of its toxic potential, it would not be considered
for initial therapy
Correct answer = C. Inhalation of a rapid-acting β2
agonist, such as albuterol, usually provides immediate
bronchodilation. An acute asthmatic crisis often
requires intravenous corticosteroids, such as methylprednisolone.
Inhaled beclomethasone and fluticasone
will not deliver enough steroid to fully combat
airway inflammation. Propranolol is a β-blocker and
would aggravate the patient’s bronchoconstriction.
Theophylline has been largely replaced with β2
agonists and is no longer recommended for acute
bronchospasm.
Correct answer = C. Administration of a corticosteroid
directly to the lung significantly reduces the frequency
of severe asthma attacks. This benefit is accomplished
with minimal risk of the severe systemic
adverse effects of corticosteroid therapy. Albuterol
is only used to treat acute asthmatic episodes. The
other agents may reduce the severity of attacks but
not to the same degree or consistency as fluticasone
(or other corticosteroids).
Correct answer = B. All symptomatic patients with
chronic obstructive pulmonary disease (COPD)
should be prescribed a short-acting bronchodilator
to be used on an as-needed basis. A regularly
scheduled long-acting bronchodilator, such as
salmeterol, could be added if symptoms are inadequately
controlled with short-acting bronchodilator
therapy. Systemic corticosteroids are used to treat
exacerbations in patients with COPD. Tiotropium
plus salmeterol is indicated in moderate to severe
disease. Theophylline is an oral bronchodilator that
is beneficial to some patients with stable COPD.
Because of its toxic potential, it would not be considered
for initial therapy
exercise and no symptoms and normal or nearly normal lung
function between episodes. f32-Agonists should be used as
required, preferably by inhalation in doses ofone to two puffs
from a metered-dose inhaler (MDI) or the equivalent dose
from a powder inhaler, every three to four hours as needed,
for the relief of acute symptoms of asthma and for the prevention
of symptoms caused by exercise or exposure to allergens
or other stimuli. Alternatively, cromolyn sodium, one to two
puffs from an MDI, may be used for prophylaxis before
exposure to provocative stimuli. For patients with mild
asthma, this may be the only treatment required. For more
symptomatic, newly detected mild asthma, an inhaled corticosteroid
administered twice a day was recently found to be
an effective first-line treatment and superior to regular dosing
with an inhaled ,82-agonist.
Moderate is defined as symptoms occurring more
than once or twice a week. Exacerbations can affect sleep
and activity level and may last several days. There is an
occasional need for emergency care. Lung function is 60% to
80% ofexpected and varies greater than 30% during the worst
exacerbations. In patients with chronic persistent asthma of
more than mild severity, regularly scheduled maintenance
therapy is required to achieve satisfactory control-defined
as minimal symptoms, normal activity tolerance, and optimum
lung function. Asthma severity and the need for therapy
are thought to be linked to the degree of airway inflammation.
Therefore, the primary emphasis for maintenance treatment
is now placed on anti-inflammatory therapy, especially
the use of inhaled corticosteroids, supplemented, if necessary,
by short courses of oral corticosteroids. In patients with
moderate to severe asthma, the currently recommended practice
is to prescribe inhaled corticosteroids (three to four puffs
Severe asthma is defined as continuous symptoms, limited
activity tolerance, frequent exacerbations, and nocturnal
symptoms. Occasional hospital admissions and emergency
treatment may be required. Lung function is less than 60% of
predicted, and there is more than 50% variation during the
worst exacerbations. Inhaled corticosteroids are prescribed
in larger doses-four to six puffs two to four times a daytogether
with inhaled $2-agonists, one to two puffs by MDI as
needed and two to four puffs, or nebulized treatment, for the
worst exacerbations. An oral sustained-release theophylline,
oral ,32-agonist, or inhaled anticholinergic (such as ipratropium
bromide) may also be added. In addition, oral corticosteroids
are usually required in relatively short "bursts" for
active symptoms (such as prednisone, 40 mg once a day or in
divided doses for a week, then 10 mg once a day for a week).
Some patients with severe asthma may require daily or
alternate-day corticosteroids (single morning dose) for the
adequate control of symptoms.
Mild is defined as intermittent, brief symptoms
two times per week or less. It includes brief symptoms with
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