Dental student

1. DRUGS FOR DISORDERS OF
RESPIRATORY SYSTEM
( L E C . 1 2 )
B Y
D R . H A L A A Q E E L

2. Antihistamines
ü Histamine ( HT) is a chemical messenger mostly generated and stored in the mast
cells.
ü HT, via multiple receptor systems, mediates a wide range of cellular responses,
including allergic and inflammatory reactions, gastric acid secretion, and
neurotransmission in parts of the brain.
ü It has no clinical applications, but agents that inhibit the action of HT have important
therapeutic applications.
ü The stimuli for release of HT include: 1-destruction of cells as a result of cold
2-toxins from organisms, venoms from insects and spiders
3- Allergies and anaphylaxis 4-trauma

4. ROLE IN ALLERGY AND ANAPHYLAXIS
1- Contraction of airway smooth muscle.(bronchoconstriction)
2- Stimulation of secretions.
3- Dilation and increased permeability of the capillaries.
4- Stimulation of sensory nerve endings.
Ø If the release of HT is slow enough to permit its inactivation before it enters
the bloodstream, a local allergic reaction result. However, if HT release is
too fast for efficient inactivation, a systemic anaphylactic reaction occurs.

5. H1-ANTIHISTAMINE
ü The Hl-receptor blockers can be divided into 1st - and 2nd -generation drugs
ü The older 1st -generation drugs (FGDs) are still widely used because they
are effective and inexpensive, most of these drugs penetrate the CNS and
cause sedation.
• The 2nd-generation agents (SGAs) are specific for peripheral Hl receptors
and do not penetrate the CNS causing less CNS depression than the FGDs.
• Among the SGAs, loratadine, desloratadine and fexofenadine, show the
least sedation, except cetirizine and levocetirizine are partially sedating

6. Actions
1. Block Hl-receptor of a target tissue. They are much more effective
in preventing symptoms than reversing them once they have
occurred.
2. Hl-receptor antagonists can bind to cholinergic, adrenergic, or
serotonin receptors as well.
3. Antihistamines such as azelastine and ketotifen also have mast
cell-stabilizing effects in addition to their HT receptor-blocking
effects.

7. Therapeutic uses
1. Allergic and inflammatory conditions
• H1-receptor blockers are useful in treating and preventing allergic reactions caused
by antigens acting on immunoglobulin E (IgE) antibody for example:
a- Oral antihistamines are the drugs of choice in controlling the symptoms of allergic
rhinitis and urticaria
b- Ophthalmic antihistamines, such as azelastine and ketotifen are useful for
the treatment of allergic conjunctivitis.
Ø Note: Epinephrine has antihistamine actions on smooth muscle. Therefore,
epinephrine is the drug of choice in treating systemic anaphylaxis and other
conditions that involve massive release of histamine.

8. 2. Motion sickness and nausea:
• Diphenhydramine and promethazine are H1-receptor blockers, effective agents
in prevention of the symptoms of motion sickness. They are usually not effective
if symptoms are already present and, thus, should be taken prior to expected
travel. antiemetic action due to blockade of central H1 and M1 muscarinic
receptors.
3- Somnifacients(Sedative ): many FGDs such as diphenhydramine and
doxylamine, have strong sedative properties and are used in the treatment of
insomnia. The use of FGDs H1 antihistamines is contraindicated in the treatment
of individuals working in jobs in which wakefulness is critical. The SGAs of
antihistamines have no value as somnifacients.

9. Adverse effects
1. Sedation: FGDs such as chlorpheniramine and diphenhydramine
2. Paradoxical hyperactivity in young children: diphenhydramine
3. Fatigue, dizziness, lack of coordination, and tremors
4. Anticholinergic effects: dryness in the oral and nasal passage, blurred vision and
retention of urine all associated with use of FGDs,
Overdoses: especially in young children. The most common and dangerous effects of
acute poisoning are those on the CNS, including hallucinations, excitement and
convulsions. If untreated, the patient may experience coma and collapse of the
cardiorespiratory system.

10. HISTAMINE H2-RECEPTOR BLOCKERS
ü Histamine H2-receptor blockers such as (cimetidine and ranitidine) have
little, affinity for H1 receptors.
ü their main clinical use is as inhibitors of gastric acid secretion in the
treatment of ulcers and heartburn.

11. ASTHMA
ü Asthma is a chronic inflammatory disease of the airways characterized by
episodes of acute airflow obstruction, due to bronchoconstriction that results
from 1)contraction of bronchial smooth muscle 2) inflammation of the
bronchial wall 3) increased secretion of mucus.
ü The underlying inflammation of the airways contributes to airway
hyperresponsiveness, airflow limitation
ü Asthma attacks may be triggered by exposure to allergens, exercise, stress,
and respiratory infections leading to shortness of breath, cough, chest
tightness, wheezing, and rapid respiration.

12. Preferred drugs used to treat asthma
1- 𝜷2-Adrenergic agonists
Inhaled ß2-adrenergic agonists directly relax airway smooth muscle. They are
used for the quick relief of asthma symptoms, as well as adjunctive therapy
for long-term control of the disease.
Quick relief drugs
• Short-acting 𝜷2 agonists (SABAs)( albuterol and levalbuterol) have a rapid
onset of action (5 to 30 minutes) and provide relief for 4 to 6 hours. They are
used for symptomatic treatment of bronchospasm, providing quick relief of acute
bronchoconstriction. So, all patients with asthma should be prescribed a SABA
inhaler

13. • 𝛽2 agonists have no anti-inflammatory effects, and they should never be
used as the sole therapeutic agents for patients with persistent asthma.
However, monotherapy with SABAs may be appropriate for patients with
intermittent asthma or exercise-induced bronchospasm.
• Direct acting 𝛽2-selective agonists can provide significant bronchodilation
with little of the undesired effect of a or 𝛽1 stimulation.
• Adverse effects, such as tachycardia, hyperglycemia, hypokalemia, and
hypomagnesemia, skeletal muscle tremors.

14. Long-term control drugs:
• Salmeterol and formoterol are long-acting 𝛽2 agonists (LABAs).
They have a long duration of action, providing bronchodilation for
at least 12 hours. Neither salmeterol nor formoterol should be used
for quick relief of an acute asthma attack.
• Inhaled corticosteroids (ICS) remain the long-term controllers
of choice in asthma, and LABAs are considered to be useful
adjunctive therapy for attaining asthma control.

15. 2- Corticosteroids (CS)
ü Inhaled corticosteroid (ICS) are the drugs of choice for long-term control
in patients with any degree of persistent asthma.
ü CS has anti-inflammatory effect by inhibiting the release of arachidonic
acid, in the airways.
ü To be effective in controlling inflammation, glucocorticoids must be used
regularly.
ü Severe persistent asthma may require the addition of a short course of oral
glucocorticoid treatment.

16. Actions on lung:
1. Reduces inflammation
2. Reduces bronchial hyperesponsseveness
3. Reduces mucosal inflammation
4. Potentiate effects of B2 agonist
5. Reduces Asthma exacerbation
ü To reduce systemic side effects CS is given by inhalation

17. ü S.E of inhaled corticosteroid:
1. Oropharyngeal candidiasis
2. Hoarseness of the voice
3. Increase risk of cataract and osteoporosis
ü Patients should be instructed to rinse the mouth in a "swish-and-
spit" method with water following use of the inhaler to decrease
the chance of these adverse events.

18. Routes of administration
1) Inhalation: Metered-dose inhalers and dry powder inhalers
• MDIs have propellants that eject the active medication from the canister.
Patients should be instructed to inhale slowly and deeply_just before and throughout
actuation of the inhaler to avoid impaction of the medication onto the laryngeal
mucosa, rather than the bronchial smooth muscle.
• A large fraction (typically 80% to 90%) of inhaled glucocorticoids is either
deposited in the mouth and pharynx or swallowed while the remaining (10% to 20%
of the dose) is deposited in the airway.
2) Oral/systemic: Patients with a severe exacerbation of asthma (status asthmaticus)
may require intravenous methylprednisolone or oral prednisone to reduce airway
inflammation.

19. Prevention of asthmatic attacks
A. Leukotriene inhibitors
Leukotrienes (LT), are important materials in the inflammatory cascade as a potent
chemoattractant for neutrophils and eosinophils, and constrict bronchiolar smooth muscle,
increase endothelial permeability, and promote mucus secretion.
1- Zileuton inhibitor of 5-lipoxygenase,thus preventing the formation of leukotrienes.
2- Zafirlukast and Montelukast are leukotriene receptor blocker,
ü Prevent bronchoconsitriction
ü Prevent mucosal oedema
ü Prevent neutrophils and eosinophils chemoattractant
ü All three drugs are orally active and highly protein bound.

20. B- Cromolyn
ü prophylactic anti-inflammatory agent that inhibits mast cell release of HT.
ü It is an alternative therapy for mild persistent asthma.
ü not useful in managing an acute asthma attack, because it is not a bronchodilator.
ü It is available as a nebulized solution for use in asthma and as drops for
allergic conjuctivites
ü Due to its short duration of action, this agent requires dosing three or four times
daily, which affects adherence and limits its use.
ü S.E: cough, irritation, and unpleasant taste.

21. C. Cholinergic antagonists (Ipratropium, Tiotropium, atropin)
ü Block M3 receptors
ü Block acetylcholine effect on bronchial smooth muscles
ü Less potent than B2 agonist
ü Onset is much slower than inhaled SABAs. However, it may be
useful in patients who are unable to tolerate a SABA or patients
with concomitant COPD.
ü Adverse effects such as xerostomia and bitter taste

22. D. Theophylline
• Bronchodilator effective in chronic asthma
• It may also possess anti-inflammatory activity
• Previously, the mainstay of asthma therapy, theophylline has been
largely replaced with B2 agonists and corticosteroids due to its narrow
therapeutic window, adverse effect profile, and potential for drug interactions.
• Overdose may cause seizures or potentially fatal arrhythmias.

23. Drugs treat allergic rhinitis
1. H1-receptor blocker: diphenhydramine
2. A-agonist: locally like oxymetazoline, not used for long time due to rebound
congestion
3. Corticosteroid
4. Cromolyn: intranasaly
Drugs treat cough
1) Dry cough treated by drugs that inhibit cough center, like: Codien, hydrocodon,
hydromorphone
2) Productive cough treated by:
• Expectorant: guaicialate that increase sputum fluidity and ease the expectoration
• Mucolytic: Bromohexin(bronchium) that breake silfid bond of mucoid make it
smaller