respiratory drugs

RESPIRATORY DRUGS-DR.AKIF A.B

STEP TO PG-MD/MS-DR.AKIF A.B

BRONCHIAL ASTHMABeta 2 agonists Salbutamol, Salmeterol,terbutaline,

formoterol

Anticholinergics Ipratropium, Tiotropium

Methylxanthines Theophylline (Deriphylline)

Corticosteroids

Leukotriene pathway inhibitors Monteleukast, Zafirleukast

Mast cell stabilisers Cromolyn sodium, nedocromil sodium, Ketotifen

Anti Ig E monoclonal antibody Omalizumab


BRONCHIAL ASTHMA

Histamine

Activates T helper-2 cells to release IL-4

IL-4 induces IgE production by plasma cells

IgE binds to Mast cells

Mast cell degranulation releases

Inflammatory mediators

Arachidonic acid

Allergen

LT-C4/D4/E4

Bronchoconstriction

LOXChronic

InflammationSTEP TO PG-MD/MS-DR.AKIF A.B

RESPIRATORY DRUGS1) Long acting β2 adrenoreceptor agonist: (AIIMS Nov. 2009)

A Salmeterol

B Orciprenaline

C Penoterol

D Pexbaterol


Ans. A Salmeterol

Salmeterol: It is the long acting selective β2 agonist with a slow onset of action;

used by inhalation on a twice-daily schedule for maintenance therapy and for nocturnal asthma, but not for acute symptoms.


BRONCHODILATORSBeta 2 Agonists + Beta 2 receptor M3 receptor

Anticholinergics(-)

Increase C-AMP

Decrease Ca++

Increase Ca++

Bronchoconstriction

Bronchodilation

PDE5’AMP

Methylxanthines(-)


BETA 2 AGONISTSShort acting Beta Agonists(SABA)

Features Long acting Beta Agonists(LABA)

Salbutamol Given by inhalational route

Salmeterol

Terbutaline Given by subcutaneous route

Formoterol

Levalbuterol Most potent SABA


BETA 2 AGONISTSSIDE EFFECTS

1) Tremors : MC Side effect

2) Hypokalemia

3) Hyperglycemia

4) QT Prolongation


ANTI CHOLINERGICS1)Ipratropium= Short acting

2) Tiotropium = Longest acting

-Acts by inhibiting M3 receptors

-Bronchodilator of choice in COPD

-Side effects : Dry mouth(MC), Urinary retention


METHYLXANTHINES-Theophylline

-Inhibits Phophodiesterase 3 and 4 and thus prevents conversion of cAMP to 5’AMP and thus leads to Increase cAMP

-Dose : 8mg/kg for oral route

6mg/kg for I.V route

-Low therapeutic index

-Normal therepautic range : 5-15mg/L


Thereupatic Drug Monitoring is done

for-Low =Lithium

-Thereupatic =Theophylline

-Index = Immunosuppressants (Cyclosporine and tacrolimus)

-Thereupatic = TCAs

-Drug = Digitalis

-Administration = Aminoglycosides/AntiepilepticsSTEP TO PG-MD/MS-DR.AKIF A.B

METHYLXANTHINES S/E1)Cardiac Arrhythmias (MC)

2)Seizures

3)Hypokalemia

4)Hyperglycemia


RECENT ADVANCES1) Magnesium is used as bronchodilator since it causes inhibition of calcium transport into smooth muscle cell.

2) Cromakalin is a potassium channel opener under trial for asthma.

3) Aprepitant : It is an NK1 antagonist under trial for treatment for cough associated with Bronchial cancer

4) Baclofen : GABA-B agonist is also known to have Antitussive effect


2. Which of the following acts as a leukotriene receptor antoagonist? (AIIMS May 2011)

A Zafirlukast

B Zileuton

C Cromolyn sodium

D Deriphylline


Ans. A Zafirlukast

a. Used for mild to moderate asthma

f. Short duration of action and hepatotoxic potential limit it's use.


LEUKOTRIENE RECEPTORANTAGONISTS

-Monteleukast

-Zafirlukast

-5-LOX (5 Lipo-oxygenase) inhibitor: Zileuton

-S/E :Churg Strauss Sx


Zileuton:Lipooxygenase Inhibitor

Leukotriene receptor antagonists


3. Which one of the following is a side effect of beta2 agonist? (AIIMS May 2010)

A Hypoglycemia

B Hypomagnesemia

C Hypophosphatemia

D Hypokalemia


Ans. D Hypokalemia Beta2 agonists like salbutamol and terbutaline can cause several adverse effects like :

a. Tachycardia due to stimulation of chronotropic Βeta2 receptors and at high dose due to stimulation of Βeta1 receptors also.

b. Tremors may result due to stimulation of muscle spindles.

c. Tolerance may develop due to densensitization of receptors.

d. Transient hyperkalemia followed by prolonged hypokalemia is seen on continued use.

e. Hyperglycemia may develop due to release of glucagon and stimulation of glycogenolysis and gluconeogenesis.


BETA 2 AGONISTSSIDE EFFECTS

1) Tremors : MC Side effect

2) Hypokalemia

3) Hyperglycemia

4) QT Prolongation


4. A predictably dangerous side effect of nadolol that constitutes a contraindication to its clinical use in susceptible patients is the induction of

A Hypertension

B Cardiac arrhythmia

C Asthmatic attacks

D Respiratory depression


Ans. C Asthmatic attacks

The chief danger of therapy with beta -adrenergic blocking agents, such as nadolol and propranolol, is associated with the blockade itself.

Beta adrenergic blockade results in an increase in airway resistance that can be fatal in asthmatic patients.

Hypersensitivity reactions such as rash, fever, and purpura are rare and necessitate discontinuation of therapy


SABA (DOC)

Acute attack Persistent Prophylaxis

Asthma

ICS (DOC) LABA (DOC)

Systemic corticosteroids

Oranticholinergics

I.V Aminophylline

Add LABA Cromolyn

NR

NR

NR NR

NR –No ResponseSTEP TO PG-MD/MS-DR.AKIF A.B

CORTICOSTEROIDS-Decreases chronic inflammation by their anti inflammatory effect

-DOC in :1) persistent bronchial asthma

2) Prophylaxis of Exercise Induced Asthma

INHALATIONAL CORTICOSTEROIDS

1) Beclomethasone

2) Ciclesonide

3) Triamcinolone

4) Fluticasone


CORTICOSTEROIDS-All inhalational corticosteroids except Beclomethasone and Triamcinolone undergoes extensive first pass metabolism and hence produces less systemic toxicity.

-Most potent Inhalational Cortiocosteroid : Fluticasone

-MC S/E of ICS : Hoarseness of voice > Oropharyngeal candidiuasis

Soft Steroids-Prodrugs which are activated by acetylation in Lungs

-E.g: Beclomethasone

- Ciclesonide


DRUGS FOR PULMONARY HYPERTENSION

Calcium channel blockers

Endothelin antagonists

PGI2 Analogs Phosphodiesterase-5 Inhibitors

Bosentan

Ambrisentan

Epoprostenol

Ileoprost

Teprostinil

Sildenafil

Tadafil

Best antihypertensive for treatment of PAH.

DOC for class II & III PAH (Low Risk)

Best drug for treatment of PAH

-DOC for class IV PAH (High risk)

Sildenafil is the DOC for Erectile Dysfunction


ANTITUSSIVESCentrally acting drugs

Features Peripherally acting drugs

Features

OpioidsCodeinePholcodeineMorphine methadone

-acts by inhibiting mu receptors

Local anaesthetics

Lidocaine andBupivacaine is used topically

-Mexilitene by oral route

Dextromethorphan

-NMDA receptor Inhibitor- S/E: Hallucination & Addiction

Cromolyn Effective in ACEIs associated cough

Diphenylhydramine

S/E: SedationAnticholinergic effect

Moguistine

Caramiphen

OPIOIDS-Antitussive of choice = Codeine

-Mild to moderate cough = codeine and pholcodeine

-Severe persistent cough of bronchial cancer = Morphine and methadone

-MC S/E : Constipation


MUCOLYTICS-These liquifies mucus in respiratory tract and facilitates removal.

-Acetylcysteine

-Bromhexine

-Ambroxol

-These 2 drugs acts by breaking the Disulfide bond


EXPECTORANTS-These are drugs that increase removal of secretion from respiratory tract by due to reflex stimulation caused by Gastric irritation.

- Guaifenesin


CONDITION DOCAllergic bronchopulmonary aspergillosis

Prednisolone

Cryptogenic organising Pneumonia Prednisolone

Sarcoidosis Prednisolone

Acute attack of asthma SalbutamolProphylaxis of asthma LABAExercise induced asthma Inhalational corticosteroids

Persistent asthma Inhalational corticosteroids

Brittle asthma Epinephrine

DRUG OF CHOICESTEP TO PG-MD/MS-DR.AKIF A.B

CONDITION DOCChylothorax Octreotide via chest tubeCOPD Anticholinergics(Tiotropium)

Non specific Cough CodeineBronchial cancer induced cough Morphine

Pleurodesis DoxycyclinePericardiodesis Doxycycline

Pulmonary edema (Diuretic of choice) Loop diuretics

Class II & III PAH BosentanClass IV PAH Epoprostenol

DRUG OF CHOICESTEP TO PG-MD/MS-DR.AKIF A.B

NEW DRUGSNEW DRUG

Pirfenedone Idiopathic pulmonary fibrosis

Nintedanib Idiopathic pulmonary fibrosis

Umeclidinium COPD

Oladetrol COPD

Ivacaflor Cystic fibrosis

Rufilomilast COPD


INHALATIONAL DEVICES-Size of Drug particle appropriate for inhalational route is 2-5microns

1) Metered dose inhaler

2) Dry powder inhalers

3) Nebulisers


METERED DOSE INHALER


DRY POWDER INHALERS


NEBULISERS


NASAL CANNULA


SIMPLE OXYGEN MASK


VENTURI MASK


NON BREATHING MASK


FACE TENT


respiratory drugs

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