DRUG THERAPY OF COUGH Dr. Shujauddin - PowerPoint Presentation

Slide1

DRUG THERAPY OF COUGH

Dr. Shujauddin

Department of

Pharmacology

JNMC, AMU

Slide2

INTRODUCTION

D

efensive reflex

that

enhances

clearance

of secretions and

particulates from airways

Provides protection

from aspiration

of foreign materials

particulate matter

Pathogens

accumulated secretions

postnasal drip

inflammation

mediators associated

with inflammation

Slide3

Cough reflex arc

Slide4

Neuro-pathophysiology of

the cough reflex arc

Each cough occurs

by stimulation

of a

complex reflex arc initiated

by

irritation

of cough

receptors

Laryngeal and

tracheobronchial receptors respond to both

mechanical

and

chemical

stimuli

Receptors

in external auditory canals, tympanic membrane,

paranasal

sinuses, pharynx, diaphragm, pleura, pericardium, and stomach are mechanical receptors

only

Stimulated

by triggers such as touch or

displacement

Chemical receptors sensitive to acid, heat, and capsaicin-like compounds trigger

cough

reflex via activation of

type

1

vanilloid

(capsaicin)

receptors

Slide5

Slide6

Afferent pathway

V

agal

afferents

found in abundance

in

tracheobronchial tree and lung parenchyma

Classified broadly into

1. Rapidly Adapting Receptors (RAR)

2. Slowly Adapting Stretch Receptors (SARs)

3.

C-Fibers

Slide7

Slide8

Slide9

Rapidly Adapting Receptors (RARs)

Terminate within

or beneath

epithelium

of both

intrapulmonary & extra-pulmonary airway

Differentiated

from other

airway afferents

by

rapid

adaptation (in 1 - 2

seconds) to

sustained lung

inflations

Sustained

activation

produced

by

dynamic lung

inflation, bronchospasm, or lung

collapse

H

istamine

, capsaicin,

substance

P, and

bradykinin

activate RARs

Act synergistically

with C

-fibers

to

induce cough

Slide10

Slowly Adapting Stretch R

eceptors

(SARs)

Highly

sensitive to

mechanical

forces

on

the lung during

breathing

Activity increases

during inspiration and peaks just prior to

initiation

of

expiration

Involved

in

Hering

-Breuer reflex

terminates inspiration and initiates expiration when lungs adequately inflated

A

central cough

network in

which SARs facilitate cough via activation

of brainstem

second-order neurons (termed

pump cells

) of the SAR reflex pathway has been

proposed

Slide11

C-fibers (Unmyelinated)

Majority

of afferent nerves innervating

airways and lungs

Distinguished from

RARs and SARs by

its relative insensitivity

to mechanical stimulation and lung

inflation

Generally

quiescent throughout the

respiratory cycle

but

activated

by chemical

stimuli

capsaicin

,

bradykinin

, citric acid, hypertonic saline

solution and

sulfur dioxide (

SO

2

)

Slide12

C-fibers

Reflex responses

evoked include

Increased

airway

parasympathetic activity, and

Chemoreflex

characterized by

apnea (followed by rapid shallow breathing

), bradycardia

, and

hypotension

Slide13

Central Pathway (cough center):

Central coordinating

region

located

in

medulla

Modulation from cerebral cortex

Cortical potentiation or suppression of cough

Slide14

Efferent pathway

Impulses

from cough center travel

via

vagus

,

phrenic

, and

spinal

motor

nerves

to diaphragm, abdominal wall and muscles.

Nucleus

retroambiguus

, by phrenic and

other

spinal motor nerves, sends impulses to

inspiratory

and expiratory

muscles

Nucleus

ambiguus

, by the laryngeal branches of the

vagus

to

larynx

Slide15

The mechanical events of a cough

Inspiratory

phase

:

generates the volume

necessary for

effective cough

2

.

Compression phase

: Closure of the larynx

combined with

contraction of muscles of chest

wall, diaphragm

, and abdominal wall result in

rapid rise in

intrathoracic

pressure

3

.

Expiratory phase

:

Glottis opens

R

esulting

in

high expiratory

airflow and

coughing sound

Large airway

compression

occurs

High

flows

dislodge mucus

from

airways

and allow removal from

tracheobronchial

tree

Slide16

Categories of Cough

•

Acute Cough = < 3 Weeks Duration

• Sub-acute Cough = 3 – 8 Weeks Duration

• Chronic Cough = > 8 Weeks

Duration

Slide17

Differential Diagnosis of Acute Cough

•

Upper Respiratory Tract infections:

-Viral syndromes, sinusitis viral / bacterial

• Allergies

• Exacerbation of Chronic Obstructive Pulmonary

Disease (COPD)

• Left Ventricular Heart Failure

• Pneumonia

• Foreign Body Aspiration

Slide18

Chronic Cough

•

Post Nasal Drip (Nose and Sinus Conditions)

•

Gastro-

esophogeal

Reflux Disease

• Chronic

Bronchitis

• Chronic Obstructive Pulmonary Disease

• Left Ventricular Heart Failure

• Lung Cancer

• Tuberculosis

• Asthma

Slide19

Types of cough (sputum production)

DRY COUGH

Post nasal

drip

G

astro-esophageal reflux

A

sthma

P

ost-viral cough

ACE

inhibitors

PRODUCTIVE COUGH

Brochiectasis

A

sthma

A

llergy

B

ronchitis

T

uberculosis

Slide20

Treatment

Whenever possible, treat the underlying cause, not the cough

Slide21

Symptoms

associated with cough: Aid to diagnosis

A runny nose or nasal congestion, headache, or postnasal drip from chronic sinusitis, cold, or flu

Wheezing from asthma

Heartburn from GERD

Fever, chills, night sweats from bronchitis, pneumonia, tuberculosis, or other lung infection

Chest pain, shortness of breath, or swelling of legs from fluid retention due to CHF

Coughing of blood (hemoptysis) may be from TB, lung cancer

Slide22

ETIOLOGY OF

COUGH

TREATMENT

APPROACH

Upper/lower respiratory tract infection

Appropriate antibiotics

Smoking/ chronic bronchitis

Cessation of smoking/avoidance of pollutants

Pulmonary tuberculosis

Antitubercular

drugs

Asthmatic cough

Inhaled

ᵦ

2

agonist/corticosteroids

Post

nasal drip due to sinusitis

Antibiotic, nasal decongestant,

H

1

-antihistaminic

Post nasal drip due to allergic rhinitis

Avoidance of allergen,

corticosteroid nasal spray, H

1

-antihistaminic

Gastroesophageal

reflux

Head end elevation of bed, light dinner, H

2

blocker, PPI

ACE inhibitor associated cough

Substitute ACE inhibitor by losartan, calcium channel blocker

SPECIFIC TREATMENT APPROACH TO COUGH

Slide23

Dry cough

PHARYNGEAL DEMULCENTS

-

Glycerine

,

Liquorice

ANTITUSSIVE

-

Opioids

– Codeine,

Phalcodeine

Non-opioids

– Dextromethorphan,

Noscapine

Local

anaesthetics

-

Benzonatate

Neuromodulators-

Gabapentin

and

pregabalin

Novel Antitussives-

Transient receptor potential antagonists

,

ATP

Receptor Antagonist

Slide24

Pharyngeal Demulcents

Glycerine

,

Liquorice

, honey, wild cherry syrup

Sooth

the throat

Reduce afferent impulses from

inflamed/irritated

pharyngeal mucosa

Provide symptomatic relief in dry

cough

Dosage forms-Lozenges or syrups

Slide25

Antitussives

Raise threshold of

cough (CNS)

or

Reduce

tussal

impulses (periphery)

Slide26

CODEINE

Semisynthetic

opiod

MOA: Suppress cough by depression of the cough center in the medulla

through mu opioid receptors or

the cough receptors in the trachea or

lungs

Dose- 10mg

BD or TDS

Uses: Dry cough that interferes with

sleep

ADR –

constipation, respiratory

depression &

drowsiness

Slide27

Dextromethorphan 

Dextrorotatory

 enantiomer of the methyl 

ester

 of 

levorphanol

, a

opioid analgesic

M

echanism

of

action-

 NMDA receptor antagonist

,

it may

also antagonize opioid

receptors

Dose – 10mg TDS

ADR

– Hallucinations at higher doses

Advantages:

least addiction potential, no analgesia,

no

constipation, minimal drowsiness

Slide28

Local Anesthetics

BENZONATATE

MOA-By

dampening the activity of

pulmonary stretch receptors, reduce cough reflex

DOSE- 100 mg TDS, and up to 600 mg/d, if needed

ADR - Dizziness

and

dysphagia

Severe

allergic reactions

have been

reported in patients allergic to

para-amino benzoic

acid

, a

metabolite of

benzonatate

.

Slide29

Neuromodulators

Gabapentin

and

pregabalin

are GABA analogues that inhibit

neurotransmission and used

in neuropathic pain

syndromes

Benefit in

chronic idiopathic cough, which also

involves neural hypersensitivity

Side

effects

of somnolence

and dizziness are common at higher

doses

Slide30

PRODUCTIVE COUGH

Expectorants

MUCOKINETICS

Guaiphenesin

MUCOLYTICS

A

cetyl-cysteine

Bromhexine

,

Ambroxol

Dornase-alfa

Slide31

Guaifenesin

Obtained from creosote wood

Increase bronchial secretion &

mucociliary

action

After absorption from the gut, they are secreted by

tracheo

-bronchial glands

Dose – 100-200 mg BD or TDS

ADR – gastric upset & rash

Slide32

Mucolytic

Drugs

ACETYLCYSTEINE

MOA: Decreases viscosity of mucous by breaking specific disulfide bonds in

mucoproteins

Uses

:

Relief of abnormal viscous

mucus

that decrease airflow and gas

exchange in Cystic Fibrosis & Chronic Bronchitis

D

ose – 3-5 ml of 20% solution by nebulization

Mechanical suction of liquefied secretions is

necessary

ADR –

N/V, stomatitis

, bronchospasm

Slide33

BROMHEXINE

Alkaloid from

vasaka

plant

Depolymerises MPS of mucus directly and also by increasing

lysosomal

activity

So network of

fibres

in tenacious sputum is broken

Dose -8-16 mg TDS

ADR – lacrimation,

rhinorrhoea

Ambroxol is a

metabolite

Slide34

DORNASE – ALFA

Purified solution of rec.

DNase

.

Purulent pulmonary

secretions in cystic fibrosis

contain very high amounts of EC DNA which is released by degeneration of

neutrophils

Dornase

–

alfa

hydrolyses this accumulated DNA

Suction

necessary

Dose – 2.5 mg OD through inhalation

Slide35

Thank you…………….