1)ANTI-HISTAMINES
2)ANTI-TUSSIVE
MODIFIED BY
Israa
Classification of antihistamines
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They are classified into H1-blockers & H2-blockers.
No currently available antagonist for H3 or H4 Receptors
H1-blockers:
They block the histamine action on H1 receptors
Best work if given before histamine release
(prophylactically ) because they only bind to the free
receptors
• Can be divided in to
1. First Generation: Sedating
2. Second Generation: Non-sedating
First Generation Agents
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Ethanol-amines: DIPHEN-HYDRAMINE
Ethylene-di-amine: TRI-PELENNAMINE
Alkyl-amine: CHLORPHENIRAMINE
Phenothiazine: PROMETHAZINE (Phenergan)
Piperazines: HYDROXYZINE
First Generation Agents uses
• In anaphylaxis (serious allergic reaction that is rapid in
onset and may cause death.) and other cases where
histamine release can occur (epinephrine must also be
used)
• Anti-allergy (allergic rhinitis, allergic dermatoses, contact
dermatitis)
• Sedative/sleep aid
• To prevent motion sickness
• Antiemetic: prophylactic for motion sickness
• Antivertigo
• Local anesthetic
• Antitussive
Pharmacokinetics for the first
generation
• Are absorbed from the GIT.
• Can also be given parenterally & topically.
• Most of them are widely distributed
throughout the body, but some do not
penetrate the BBB,
• Are most effective when used prophylactically.
• Most of the them are metabolized extensively
in the liver.
additional effects of the first
generation
• Block H1 receptors in CNS→ sedation,
dizziness & fatigue.
• Anticholinergic effect → dry mouth, urinary
retention, tachycardia
• α- blocking effect →postural hypotension,
reflex tachycardia.
• Antiserotonin effect → ↑appetite
Adverse Effects of the first generation
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Sedation (Paradoxical Excitation in children)
Dizziness
Fatigue
Tachydysrhythmias in overdose - rare
Peripheral antimuscarinic effects
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dry Mouth
blurred Vision
constipation
urinary Retention
Adverse effects observed with first generation antihistamines
The use of first generation
H1 antihistamines is
contraindicated in
treatment of individuals
working in jobs where
wakefulness is critical
Second generation H1-blockers
• Examples for this group: loratadine
,fexofinadine, cetirizine, astemazole
• Are specific for H1 receptors.
• Do not penetrate the BBB so they show less
CNS toxicity.
Pharmacokinetics for the second
generation
• Cetirizine (C), loratadine (L), fexofenadine (F)
are well absorbed and excreted mainly in
unmetabolized form.
• C and L are primarily excreted in the urine
• F is primarily excreted in the feces
• They induce Cyt P450 liver enzymes
Adverse Effects of the second
generation
• in general, these agents have a much lower
incidence of adverse effects than the first
generation agents.
• terfenadine and astemizole were removed from
the market due to effects on cardiac K+ channels prolong QT interval (potentially fatal arrhythmia
“torsades de pointes”)> is an uncommon variant
of ventricular tachycardia that can be the result
of lengthening the QT interval.)
Treatment of cough
Modified By :ISRAA
Treatment of Cough
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Antitussives (cough center suppressants)
Expectorants
Mucolytics
Antihistamines
Pharyngeal Demulcents (>is an agent that
forms a soothing film over a mucous
membrane, relieving minor pain and
inflammation of the membrane.)
1) Antitussive
• Antitussive drugs act by ill defined effect in the
brain stem , depressing an even more poorly
defined “cough center”.
• All opioid narcotic analgesic have antitussive
properties in doses lower than those required for
pain relief
• They have minimum analgesic and addictive
properties
• Newer agent that only act peripherally on
sensory nerves in bronchi are being assessed
i) CODIENE
• It is the gold standard treatment for cough suppression
• It decreases the sensitivity of cough center in the CNS
to peripheral stimuli, decrease the mucosal secretion
which thicken the sputum, and inhibit ciliary activity
• These therapeutic effect occur at doses lower than
those required for analgesia but still observed some
common side effect like constipation, dysphoria(An
emotional state characterized by anxiety, depression,
or unease.), and fatigue, in addition to addiction
potential
ii) DEXTROMETHORPHAN
• Is a synthetic derivative of morphine that
suppresses the response of the central cough
center
• It has no analgesic effect, has low addictive
profile, but may cause dysphoria at higher
doses(An emotional state characterized by
anxiety, depression, or unease.)
• Has significantly better side effect profile than
codeine and has been demonstrated to be
equally effective for cough suppression
2) Expectorants (Mucokinetics)
• Act peripherally
• Increase bronchial secretion
OR
• Decrease its viscosity and facilitates its
removal by coughing
• Loose cough ►less tiring &more productive
Classification of Expectorants
Classified into
a) Directly acting
E.g., Guaifenesin (glyceryl guaiacolate), Na+ &
K+ citrate or acetate,
b) Reflexly acting
E.g., Ammonium salt
Directly acting expectorants
i) Sodium & potassium citrate or Acetate
• They increase bronchial secretion by salt action
ii) Guaifenesin
• Expectorant drug usually taken by mouth
• Available as single & also in combination
• MOA=Increase the volume & reduce the viscosity of
secretion in trachea & bronchi
• Reflexly acting expectorants:
• Ammonium salts:Its expectorant action is caused by
irritative action on the bronchial mucosa.It is also a
Gastric irritants causing reflex increase in bronchial
secretions + sweating
3) Mucolytics
• Help in expectoration by liquefying the viscous
tracheobronchial secretions
• E.g., Bromhexine, Acetyl cysteine,
i) Bromhexine
• Synthetic derivative of vasicine(*Alkaloid & like
Theophylline)
MOA of Bromhexine
• a) Thinning & fragmentation of mucopolysaccaride
fibers
• b) ↑ volume & ↓ viscosity of sputum
3) Mucolytics
ii) Acetylcysteine
• Given directly into respiratory tract
• MOA of acetylcysteine: Opens disulfide bond in
mucoproteins of sputum =↓ viscosity
• Uses:
• Cystic fibrosis, Onset of action is quick---used 2-8
hourly
• Adverse effects:
• Nausea, vomiting, bronchospasm in bronchial
asthma
4) Antihistamines
• Added to antitussives/expectorant formulation
• Due to sedative anticholinergic actions produce
relief from cough but lack selectivity for cough
center
• No expectorant action =▼secretions
(anticholinergic effect)
• Suitable for allergic cough
• E.g., Chlorpheniramine and diphenhydramine
5) Pharyngeal demulcents(>is an agent that
forms a soothing film over a mucous membrane,
relieving minor pain and inflammation of the
membrane.)
• Soothe the throat (directly & also by promoting
salivation
• Reduces afferent impulses from inflamed/irritated
pharyngeal mucosa
• Provide symptomatic relief in dry cough arising
from throat
• E.g. lozenges, cough drops, glycerine,
liquorice(*Sweet tea), honey
Good luck