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Drugs Affecting the RespiratoryDrugs Affecting the Respiratory

BronchodilatorsBronchodilators

Beta 2 agonists:Beta 2 agonists:ShortShort-- acting SABAacting SABALongLong--acting LABAacting LABA

Anticholinergics:Anticholinergics:ShortShort-- acting acting

LongLong--acting acting

Theophylline Theophylline

SteroidsSteroids

SystemicSystemicInhaledInhaled

Antileukotriene drugs Antileukotriene drugs

AntiAnti--IgE medicineIgE medicine

AntihistaminesAntihistamines

AntitussivesAntitussives

Expectorants Expectorants –– MucolyticsMucolytics

OxygenOxygen

BronchodilatorsBronchodilators

►► Bronchodilators are medications used to Bronchodilators are medications used to relieve breathing problems such as shortness of relieve breathing problems such as shortness of breath or wheezing, and the sensation of chest breath or wheezing, and the sensation of chest tightness. They are often prescribed for people tightness. They are often prescribed for people suffering from asthma, chronicsuffering from asthma, chronic obstructive obstructive pulmonary disease pulmonary disease (COPD), emphysema or other (COPD), emphysema or other lung conditions.lung conditions.

BronchodilatorsBronchodilators

Beta 2 agonistsBeta 2 agonists

shortshort-- acting SABAacting SABA

longlong--acting LABAacting LABA

Anticholinergics Anticholinergics

shortshort-- acting acting

longlong-- acting acting

Theophylline Theophylline

Beta 2 agonistsBeta 2 agonists

ShortShort-- acting SABAacting SABA

LongLong-- acting LABAacting LABA

Beta 1 receptors & Beta 2 receptorsBeta 1 receptors & Beta 2 receptors

1. Beta 1 receptors1. Beta 1 receptors

►► Increase cardiac output : Increase cardiac output : increase HR and increase increase HR and increase contraction ( increase contraction ( increase ejection fraction) ejection fraction)

►► Renin release from Renin release from juxtaglomerular cells juxtaglomerular cells

►► Lipolysis in adipose tissueLipolysis in adipose tissue

Beta 3 receptorsBeta 3 receptors

►► Induce lipolysisInduce lipolysis

3. Beta 2 receptors3. Beta 2 receptors

►► Smooth muscle relaxation Smooth muscle relaxation eg: bronchodilator eg: bronchodilator

►► Dilate arteries to skeletal Dilate arteries to skeletal muscle muscle

►► Glycogenolysis and Glycogenolysis and gluconeogenesis gluconeogenesis

►► Increase renin secretion Increase renin secretion from kidney from kidney

►► Inhibit histamine release Inhibit histamine release from mast cellsfrom mast cells

AgentsAgents

1. Epinephrine- given subcutaneously

2. Ephedrine

3. Isoproterenol

4. B2 SelectiveMetaproterenolMetaproterenol (Alupent)(Alupent)

TerbutalineTerbutaline (Bricanyl)(Bricanyl)FenoterolFenoterol (Berotec)(Berotec)

ProcasterolProcasterol (Meptin)(Meptin)BambuterolBambuterol (Bambec)(Bambec)

SalmeterolSalmeterol ((Serevent)Serevent)

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LABALABA

►►Long acting beta Long acting beta –– receptor agonist , are receptor agonist , are analogs of albuterol and are long analogs of albuterol and are long acting(12 hrs) , more affinity to the beta 2 acting(12 hrs) , more affinity to the beta 2 receptor , has slow onset of action .receptor , has slow onset of action .

►► SSalmeterolalmeterol

►► FFormeterol ormeterol

Adverse EffectsAdverse Effects

1. Cardiac effects – arrhythmias

1. CNS effect – stimulation

3. Skeletal muscle tremor

AnticholinergicsAnticholinergics

Ipratropium bromide (AtroventIpratropium bromide (Atrovent))

- Is a quarternary ammonium deriv of atropine that is

given by aerosol. It does not cross Bld-Brain barrier and

is poorly absorb from GIT , thus minimizing Anti-

cholinergic side effects.

- Useful in chronic bronchitis , emphysema and in pnts

who cannot tolerate Beta receptors agonist.

Combivent – combination of albuterol + ipratropium bromide

Berodual - combination of fenoterol + ipratropium bromide

Anticholinergics:Anticholinergics:

�� Mech. of ActionMech. of Action –– competitively inhibit the effects competitively inhibit the effects of acetylcholine at muscarinic receptorsof acetylcholine at muscarinic receptors-- block the block the contraction of airway sm. Musclecontraction of airway sm. Muscle

�� BBlock - in secretion of mucus in response to vagal lock - in secretion of mucus in response to vagal activityactivity

�� Very effective in achieving bronchodilation in Very effective in achieving bronchodilation in patients with hyperreactive airway disease due to patients with hyperreactive airway disease due to vagal stimulation.vagal stimulation.

••

TheThe most most commonlycommonly reportedreported

adverseadverse drugdrug reactionreaction withwith

anticholinergicanticholinergic waswas

�� drydry mouthmouth , , whichwhich was was usuallyusually mildmild and and oftenoftenresolvedresolved duringduring continuedcontinued treatmenttreatment

�� OtherOther reactionsreactions reportedreported inin individualindividual patientspatientsand and consistentconsistent withwith possiblepossible anticholinergicanticholinergiceffectseffects includedincluded: : constipationconstipation, , increasedincreased heartheartraterate, , blurredblurred visionvision, , glaucomaglaucoma, , urinaryurinarydifficultydifficulty and and urinaryurinary retentionretention ..

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MethylxanthinesMethylxanthines -- TheophyllineTheophylline

Pharmacologic Effects:Pharmacologic Effects:A. Respiratory system

1. Rapid relaxation of bronchial sm. Muscle –

bronchodilation

2.Decrease histamine release

3.Stimulate ciliary transport of mucus

4. Improve respiratory performances by

improving contractility of the diaphragm and

by stimulating the medullary respiratory

center.

Pharmacologic Effects:Pharmacologic Effects:B.Effects on other systems

Caffeine - (+)

1. Heart (+) chronotropic and inotropiceffect cardiac stimulation

Theobromine - (++)

Theophylline - (+++)

Enprofylline - (++++)

Pharmacologic Effects:Pharmacologic Effects:B.Effects on other systems

1. Pulmonary and peripheral vasodilatation (↓ B.P)

3.Stimulation of gastric acid and pepsinogenrelease.

2. ↑ ↑ ↑ ↑ alertness and cortical arousal medullarystimulation – can cause severe nervousness andseizures.

4. Diuresis

The frequency and severity of side effects is The frequency and severity of side effects is dependant on many factors including dose, dependant on many factors including dose, duration of therapy and individual response. duration of therapy and individual response.

Possible unwanted effects include:Possible unwanted effects include:

►► nausea nausea ►► vomiting vomiting

►► diarrhea diarrhea ►► nervousness nervousness

►► loss of appetite loss of appetite ►► headache headache

►► trouble in sleeping trouble in sleeping ►► irritability irritability

►► tremor tremor ►► abdominal discomfort abdominal discomfort

Pharmacokinetics : Prototype drug Pharmacokinetics : Prototype drug TheophyllineTheophylline

• rapidly and completely absorb from GIT

• metabolize in the liver by oxidation anddemethylation

• half life – children – 3.5 hrs ; Adult – 8-9 hrsBronchodilator effect is achieve at bld levels of 10-20 mg/ml

(above this is associated with greater toxicity)

* Aminophylline – is a theophylline – ethylene diamine complex

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Drug Interactions Drug Interactions A. Drugs that ↑ theophylline effects

1. Cimetidine2. Erythromycin , troleandomycin3. Oral contraceptives

B. Drugs that ↓ effectiveness of theophylline1. Lithium2. blockers

3. Barbiturates4. Beta 5. Phenytoin

HalothaneHalothane -- given with theophylline given with theophylline may result to cardiac dysrhythmiasmay result to cardiac dysrhythmias

Adverse EffectsAdverse Effects1. Vomiting and GI bleeding

2. Cardiac arrhythmais3. Nervousness , seizures , behavioral problems in children

Clinical Uses

1. COPD2.Apnea in pre-term infants

* Initial loading dose – 5mg/kg – by infusion drip over 30 min.* Maintenance- 0.6 to 0.7 mg/kg/h* Pnts with heart or liver disease – 0.3 mg/kg/h

Asthma - GINA1 2 3 4 5rapid –acting

ß2

A

G

O

N

I

S

t

select one select one Add one or more Add one or both

Low dose inhaled steroids

low dose inhaled steroids

plus

LA ß2-agonist

medium or high dose inhaled steroids

plus LA ß2-agonist

Systemic steroids

medium or high dose

inhaled steroids

anti-leukotriene Anti-IgE

low dose inhaled steroids

plus

anti-leukotriene

low dose theophylline

low dose inhaled steroids

plus

theophylline

rapid - acting ß2agonist

DEFINITIONAsthma is a chronic inflammatory disorder of

the airways in which many cells play a role in particular mast cells, eosinophils, and T lymphocytes.

In susceptible individuals this inflammation causes reccurent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning.

These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible either spontanously or with treatment.

The inflammation also causes an associated increase in airway hyperresponsiveness to a variety of stimuli.

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ASTHMA

Inflammation > Bronchoconstriction

NOTHNG

ß2ß2--agonistsagonistsAntiAnti--muscarinic muscarinic

agentsagentsTheophyllineTheophylline

AcuteInflammation

AirwayRemodelling

ChronicInflammation

Where are the therapeutic targets?

CorcosteroidCorcosteroid

TheophyllineTheophylline

Leukotriens modyfiersLeukotriens modyfiers

AntyAnty--IgEIgE

MEDICATIONS for asthma are divided to:

CONTROLLERS

Must be taken daily on a long-term therapy and keeping asthma under control

RELIEVERS

Bronchodilating medications that act quickly to relieve bronchoconstriction

Broncho-constriction

++

++++

++

+

++

–

++

Plasmaprotein

exudation

–

++

?

+/–

+

–

++++

Neuralstimulation

++

–

–

++

–

–

+

Glandularsecretion

–

?

–

++

+/–

++

+++

Cromones

ß2-agonists

Theophylline

H1-antihistamines

Cyst-LT1-receptorantagonists

Anti-muscarinic agents

Corcosteroid

Comparative effects of drugs acting on acute inflammation

P Howarth Berlin 1999

PERIPHERALCIRCULATION⇒ 28%

INACTIVATION DURING FIRST WAY

LIVER

ADVERSEEVENTS

28%

72% ⇒ 11%

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Side effects of steroid inhalers :

Side effects are uncommon, mild and temporary.

Possible side effects are:

hoarse voice ,throat irritation,

fungay infection.

You can avoid by rinsing your throat well after inhaling the medicine.

Side effects of steroid inhalers :

The dose of inhaled steroid per day is a lot smaller and the side effects are less frequent and less severe than steroid tablets.

For example, 2 puffs of Pulmicort inhaler (200 micrograms) a day delivers 400 micrograms of inhaled steroid. In acute asthma attack, six 5 milligrams of steroid tablets a day will be given-30,000 micrograms , 75 times more than inhaled steroid.

lobal Initiative forChronic

bstructive

ung

isease

GOLD

Definition of COPDChronic obstructive pulmonary disease(COPD) is a disease state characterized by airflow limitation that is not fullyreversible. The airflow limitation is usuallyboth progressive and associated with anabnormal inflammatory response of thelungs to noxious particles or gases.

Management of COPD: All stages

Avoidance of noxious agents

- smoking cessation

- reduction of indoor pollution- reduction of occupational exposure

Influenza vaccination

Management of COPD Stage 0: At Risk

Characteristics Recommended Treatment

• Chronic symptoms- cough- sputum

• No spirometric abnormalities

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Management of COPD Stage I: Mild COPD

Characteristics Recommended Treatment

• FEV1/FVC < 70 %• FEV1 > 80 % predicted• With or without symptoms

• Short-acting bronchodilator as needed

Management of COPD Stage IIA: Moderate COPD

Characteristics Recommended Treatment

•FEV1/FVC < 70%•50% < FEV1< 80% predicted•With or without symptoms

•Regular treatment with one or more bronchodilators

•Rehabilitation•Inhaled glucocortico-steroids if significant symptoms and lung function response

Management of COPD Stage IIB: Moderate COPD

Characteristics Recommended Treatment

•FEV1/FVC < 70%•30% < FEV1 < 50% predicted•With or without symptoms

•Regular treatment with one or more bronchodilators•Rehabilitation•Inhaled glucocortico-steroids if significant symptoms and lung function response or if repeated exacerbations

Management of COPD Stage III: Severe COPD

Characteristics Recommended Treatment•FEV1/FVC < 70%

•FEV1 < 30% predicted or presence of respiratory failure or right heart failure

•Regular treatment with one or more bronchodilators•Inhaled glucocorticosteroids if significant symptoms and lung function response or if repeated exacerbations•Treatment of complications•Rehabilitation•Long-term oxygen therapy if respiratory failure•Consider surgical options

Manage Exacerbations

Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD.

The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified .

Manage Exacerbations

Inhaled bronchodilators (Beta2-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocortico-steroids are effective for the treatment of COPD exacerbations

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Manage Exacerbations

Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased volume and change of color of sputum, and/or fever) may benefit from antibiotic treatment

Oxygen

Oxygen is a powerful symbol of medical care that is probably more important than its actual therapeutic value in the relief of breathlessness. It is widely available and commonly prescribed by medical and paramedical staff but is often given without careful evaluation of its potential benefits and side effects. Like any drug therapy there must be clear indications for treatment with oxygen, appropriate prescription, vigilant monitoring and appropriate methods of delivery.

Definitions - Hypoxaemia

The following laboratory values, obtained while breathing ambient air: Arterial partial pressure of oxygen (PaO2) £55 mm HgArterial oxygen saturation (SaO2) £88%In the presence of secondary polycythaemia and pulmonary hypertension:PaO2 between 55-60mm Hg

Long Term Oxygen Therapy (LTOT)

Provision of oxygen therapy for continuous use at home for patients with chronic hypoxaemia. The flow rate must be sufficient to raise the waking oxygen tension in adults to above 60mm Hg.

It is nighttime

In the literature Long Term Oxygen Therapy

Is often used as a synonymous of:

Continuous Oxygen Therapy (COT)

Home Oxygen Therapy (HOT)

Home oxygen therapy

Home oxygen therapy is an effective but potentially expensive and inconvenient intervention. It should be prescribed only for patients in whom there is evidence of benefit, such as those whose disability relates to a chronic reduced arterial oxygen concentration (chronic hypoxaemia).

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Indications for home oxygen therapy:

Chronic hypoxaemia in:Chronic obstructive pulmonary diseaseDiffuse interstitial lung diseaseCystic fibrosisBronchiectasisWidespread pulmonary neoplasmPediatric bronchopulmonary dysplasia (BPD)Pulmonary hypertensionRecurring congestive heart failure due to chronic cor pulmonale

Nocturnal hypoventilation (With continuous positive airway pressure, CPAP)ObesityNeuromuscular / spinal / chest wall diseaseObstructive sleep apnoea

Palliative usePulmonary malignancy

1.Oxygen concentrators2. Compressed gas cylinders3. Liquid oxygen

1. Oxygen concentrators

Electrically poweredUses molecular sieve beds to filter and concentrate oxygen molecules from ambient air, generating oxygen concentrations of 90% to 98%Maximum flow of 3-5 L/minBackup oxygen supply with a cylinder is necessary

2. Compressed gas cylinders

H-sizedLarge and heavy (about 150lbs)Provides oxygen for about 57 hours at flow of 2 L/min

3. Liquid oxygen reservoirs

Can be used to refill portable unitsLast 5-7 days at 2 L/minRelatively high cost / occasional “freezing” of the valve at flow of about 8 L/min / evaporation of the liquid oxygen when not in use.

The ANTIHISTAMINES

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The ANTIHISTAMINES

are used to block the release or action of histamine- a chemical madiator of inflammation that increases secretions and constricts the air passegeway

Also called H1 blockers or H1 antagonits, these are agents designed to relieve respiratory symptomps and to treat allergic conditions.

Anti-Histamine

The Mechanism of Action

-These agents SELECTIVELY block the effects of histamine at the HISTAMINE-1 receptor sites in the target tissue by competing with histamine for receptor, decreasing the cellular responses - They also have anticholinergic and antipruritic properties.

The ANTIHISTAMINES

The anti-histamines are group according to the „generation”.- The FIRST GENERATION agents have greater anticholinergic effects and can cause more sedation and drowsiness!These agents cause drowsiness.- The SECOND GENERATION agents have fewer anticholinergic effects that is why they cause less sedation.

The ANTIHISTAMINESThe FIRST GENERATION ANTIHISTAMINES

1. Azatadine

2. Azelastine

3. Brompheniramine

4. Buclizine

5. Chlorpheniramine

6. Clemastine

7. Cyclizme

8. Cyproheptadine

9. Dexchlorpheniramine

10. Dimenhydrinate

11. Diphenhydramine

12. Hydroxyzine

13. Meclizine

14. Methdilazine

15. Promethazine

16. Tripelenamine

17. Carbinoxamine

18. Trimeprazine

19. Triprolidine

The ANTIHISTAMINES

The SECOND GENERATION ANTIHISTAMINES

- Fexofenadine

- Loratidine- Azelastine

- Cetirizine

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Anti-Histamine

Clinical Indications for Use in respiratory system

2. Rhinitis

3. Allergic sinusitis4. Uncomplicated urticaria and angioedema.

Anti-Histamine - Contraindications and Precautions for the use of the antihistamines

- Pregnancy and lactation are contraindications, and they agents are used cautiously in patient with impaired liver and kidney functions.

- Fatal arrythmias have been reported if some of these agents are given to patients with a condition called prolonged QT intervals.

Anti-Histamine

Pharmacodynamics: Drug effects on the body

1. CNS- drowsiness and sedation, most pronouced if first generation agents are used

2. Fatigue, dizzines and disturbed coordination.

3. Anticholinergic effects= drying of the respiratory mucus membrane, Gl upset and nausea, arrhytmias, dysuria, urinary retention

4. Skin dryness

Anti-Histamine

Implementation- The drug should be administer on an EMPTY stomach, or 1 hour before or 2 hours after meals to increase the absorption.- Give with food if GI upset occurs- Offer sugarless lozenges or hard candy to counteract dryness of the mouth. Give frequent oral care- Provide safety measures if drowsiness may occur. Side rails up, assist in ambulation, and advise not to drive or operate dangerous machineries or delicate tasks.

New medicationFDA approves new drug application for XyzalMonday 25th February 2008 The US Food and

Drug Administration (FDA), has approved a New Drug Application (NDA) for Xyzal (levocetirizine dihydrochloride) 0.5 mg/mL oral solution, a prescription antihistamine indicated for the relief of symptoms associated with indoor and outdoor allergies, as well as the treatment of chronic idiopathic urticaria.

Xyxal tablets received FDA approval on May 25, 2007, and both formulations are now approved for use in adults and children six years and older

New medication

Telfast (Allegra)Active Ingredients :

Fexofenadine Hydrochloride

120mg and 180mg

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MEDICATIONS THAT INTERFERE WITH ALLERGY SKIN TESTING

These medications interfere with allergy skin tests and SHOULD BE DISCONTINUED PRIOR TO TESTING:

Antihistamines:3 days prior to testing stop most over the counter allergy, cold and sleep

medications (Benadryl, Clortrimeton, diphenhydramine, etc.), and many prescription antihistamines (Allegra, Allerx, Astelin and fexofenadine, etc.) .

5 days prior to skin testing stop Alavert, Claritin, Clarinex, loratadine, Xyzal, Zyrtec, Atarax (hydroxyzine) and doxepin.

Antidepressants:Older antidepressants like Elavil (amitryptyline) should be stopped 3 days prior to

testing. Newer antidepressants (Prozac, Zoloft, etc.) do not interfere with testing.

Beta blockersPatients on beta-blockers (Inderal, Lopressor, etc.) should not be skin tested.

PregnancyWomen should not be skin tested if they are or may be pregnant.

Most medications do not interfere with skin testing, and may be continued

DO NOT STOP:Cortisone nasal sprays (fluticasone, Nasonex, Nasacort

AQ, Rhinocort, Veramyst, etc.) Asthma medications (Albuterol, Flovent, Singulair, Advair,

etc.) AntibioticsEye drops for allergy (Patanol, Elestat, Zaditor, etc.) Decongestants (Sudafed, Sudafed PE, etc.) Oral steroids (Prednisone, Medrol, Prelone, etc.) Medicines for other conditions such as diabetes,

arthritis, reflux, high blood pressure, birth control pills, etc.