Transcript antitussives 4 stude..

Dr. Yieldez Bassiouni
How pain is transmitted?
 The injury will cause release of various pain chemical
mediators like prostaglandin, histamine, serotonin,
bradykinin and substance P.
 These mediators will stimulate the pain receptors in
the skin.
Analgesia means no pain
Analgesics are agents which relieve the
pain without disturbing consciousness
Analgesics are divided in to two main
classes:
1) Opioid analgesics
2) Non-opioid analgesics
(analgesics-antipyretics)
Opioid
analgesics
Non-Opioid
(analgesics-antipyretics)
 Are the most powerful
 Are mild analgesics that
 Act mainly at the level
 Act at the level of the
 Can produce addiction
 No addiction
 Example: Morphine and
 Example: NSAIDs e.g.
analgesics that can
relieve any type of pain
of the cortex.
codeine
treat mild types of pain as
headache…..
thalamus & hypothalamus
salicylates, and
paracetamol
Opioid Analgesics
Opioids are drugs acting at opioid
receptors, morphine is the prototype
of opioid agonists.
Opioid analgesics are potent drugs
which selectively depress the CNS and
relieve pain.
 They are mainly obtained from unripe
capsules of Opium poppy plant.
The important alkaloid isolated from
opium is morphine.
 Other alkaloids isolated from opium
are codeine and papaverine.
Examples of Opioid Drugs
Natural
morphine
codeine
semisynthetic
heroin
synthetic



Pethidine or meperidine
methadone
fentanyl
Opioids exert their
major effect by
interacting with opioids
receptors in the CNS
and ANS, such as GIT
and urinary bladder.
Mechanism
of action
Morphine inhibits
release of many
excitatory transmitters
from nerve terminal
carrying painful stimuli.
Opioid Receptors
• Several types of opioid receptors
have been identified at various sites
in the nervous system and other
tissues.
• These are Mu (μ), Kappa (κ) , sigma
and Delta (∂) receptors .
Analgesia
Action
• Raising the pain threshold at the spinal cord level
• Altering the brain’s perception of pain. Patients are aware of the presence
of pain, but the sensation is not unpleasant.
Euphoria
• Morphine produces a powerful sense of contentment and well being.
Respiration
• Morphine depresses respiration by reducing of the sensitivity of
respiratory centre to carbon dioxide . (most common cause of death in
opioid overdose)
Gastrointestinal tract
• decreases the motility and increasing the tone of intestinal smooth muscle.
• Morphine also increases the tone of GIT sphincters
• Overall, morphine produces constipation, with little tolerance
Therapeutic uses
Analgesia
• Morphine is strong analgesic
• Opioids induce sleep
Relief of cough
• Morphine suppress the cough reflex
Treatment of
diarrhoea
Morphine decreases the motility and
increase the tone of intestinal circular
smooth muscle.
Adverse effects
Sedation
Constipation
N&V
Urinary
retention
Potential for
addiction
Respiratory
depression
Why do we
?
It is a defensive mechanism to
removes excessive secretions
 Removes potentially harmful
foreign substances (beneficial)

In some situations, coughing can be
harmful, such as after hernia repair surgery
Cough receptors
 bronchi, diaphragm, external auditory canal, larynx,
nose, paranasal sinuses , pericardium, pharynx,
pleura, stomach, trachea and tympanic membrane.
Two Basic Types of Cough
Productive
cough
• cough that
brings up
sputum or
mucus during
expulsion
Dry cough
• cough that
does not bring
up any
sputum
during
expulsion
Cough interferes with sleep and work
Antitussives = cough suppressant
Drugs used to stop or reduce coughing
 Opioid and non-opioid
 Used only for nonproductive cough
MoA of Antitussives
Depression of medullary center
2) Increases threshold of the cough center
3) Interruption of impulses peripherally in the
respiratory tract
4) Inhibition of conduction along the motor
pathways
1)
1- Centrally acting Antitussives
Narcotic antitussives
Codeine
Pholcodine
Hydrocodone
Non narcotic antitussives
Dextromethorphan
Noscapine
2- Peripheral Antitussives
Inhibition of the cough receptors of Pharynx:
Larynx
1 Demulcents
Linctus
Lozenges
Liquorice
2 Inhalation
Benzoin
Menthol
3 Local anaesthetics on pulmonary stretch
receptors of alveoli:
Benzonatate
Lignocaine (only in special circumstances)
Narcotic Antitussives
Codeine
An opium alkaloid similar to morphine
 less potent than morphine as analgesic and
respiratory depressant.
 60% effective orally.
 A standard antitussive
 A small fraction of administered codeine is
metabolized to morphine which is responsible for
analgesic effects of codeine.
MOA of Codeine:
 Directly suppresses cough centre in Medulla.
 Suppresses cough for about 6 hrs.
Adverse effects of Codeine:
 In therapeutic doses minimum side effects
 Sedations, nausea, constipation
 At higher doses respiratory depression and
drowsiness can occur.
 Contraindicated in asthmatic patients.
Pholcodeine
 Pholcodeine has similar efficacy as codeine with
longer duration of action of 12hrs
 It has no analgesic or addiction property
Non Narcotic Antitussives
Dextromethorphan Hydrobromide
A synthetic compound.
Strong and partial µ agonist.
As effective antitussive as codeine.
MOA:
1. Controls cough spasm by depressing cough center in
medulla
2. Increase the threshold for coughing
Advantages of Dextromethorphan




No effect on ciliary activity
No CNS depression
No addiction potential
No constipation
 Contraindicated in children below 6 yrs of age and also in
patients taking Monoamine oxidase inhibitors.
Noscapine
 An opium alkaloid
 No narcotic, analgesic or dependance inducing
properties.
 Equally effective antitussive as codeine
 Useful for spasmodic cough.
 Headache and nausea are usual side effects
 Contraindicated in asthamatic patients.
 Peripherally acting antitussive agent are acting
through inhibition of cough receptor or pulmonary
stretch receptor as
 Inhibition of cough receptor of
 Pharynx: demulcent and soothing pastilles, and gargles
 Larynx: emollient and soothing spray of menthol and
eucalyptus
 Tracheobronchial airway: inhalation of hot steam
medicated with tr. Benzoin co.
Inhibition of pulmonary stretch receptor of
alveoli: benzonanatete “tesselone”
Chemically related to tetracaine.
MOA :Reduces the cough reflex by anesthetizing the
stretch receptors in the respiratory passages, Lungs
and Pleura.
It has some central effects also.
 Benzonatate begins to work within 15 to 20 minutes,
and its effects last for approximately 3 hours.
Adverse effects:
Headache, Dizziness
Nasal Congestion, burning of eyes & tightness in chest.