• Briefly explain what cystic fibrosis is and how dornase alfa acts to solve the problem.

Cystic fibrosis is a genetic defect that can lead to a decrease in secretions in various organs. The most prominent manifestation and problematic symptom is in the airways. The airway has exceptionally thick and sticky mucus secretions which provides an excellent environment for bacterial infections. The repeated infections cause continuous chemotaxis of neutrophils which then leads to deposits of DNA (this occurs during disintegration),which makes the mucus even stickier. The mucus then becomes virtually impossible to clear and a vicious circle of sticky mucus and further infections results.

Dornase alfa (rhDNase I) hydrolyses extra-cellular DNA from the neutrophils in the bronchial mucus, which increase it`s liquidity drastically. It is related to the natural enzyme doexyribonuclease I (DNase I) which is normally produced by the pancreas and salivary glands.

 

• Briefly explain what neonatal respiratory distress syndrome is, what the general treatment strategies involve and how cortisone and exogenous surfactants solve the problem.

Neonatal respiratory distress syndrome is also known as hyaline membrane disease.  The surface-active material which covers the respiratory unit of the airways is formed only in the last weeks of pregnancy.  When babies are born prematurely, this surface-active material has not yet formed, resulting in disrupted gas exchange and also the possibility that the lungs may collapse.  Treatment must follow rapidly in order to save the life of the premature baby.

General treatment strategies include oxygen to ensure oxygenation, ventilation used for positive pressure and drugs: exogenous sufactants (beractant and poractant alfa).

Cortisone: Boosts endogenous surfactant production and can be administered prophylactically.

Exogenous surfactants: Increases the lung surfactant.

 

• What is the role of oxygen therapy in neonatal respiratory distress syndrome?  What do the dangers of oxygen toxicity involve?

Oxygen (mixed with air at room temperature) is administered in order to ensure oxygenation.

A continuous positive pressure (as obtained with a ventilator) improves respiration and keeps the alveoli open to prevent collapse.  It is critically important that the arterial partial oxygen pressure is continuously monitored.

Sufficient oxygen is a basic requirement for normal respiration.  Therapeutically it is administered generally to prevent or reverse hypoxia (of various causes).  When oxygen is inhaled in excessive quantities and/or over too long a period of time, it has toxic effects.  Paradoxically, oxygen toxicity causes, inter alia, reduced gas exchange, hypoxia and, in extreme cases, death.  In neonates, it can cause retinal damage and blindness.

 

• Briefly explain what neonatal apnoea is and how the methylxanthines solve the problem.  Which methylxanthine is used?

Neonatal apnoea occurs when the respiratory centre in the medulla of the premature baby has not yet developed sufficiently to stimulate continuous breathing.  The breathing centre is, therefore, still insensitive to the stimulating effect of carbon dioxide.  Apnoea has a duration, typically, of longer than 15 seconds and is accompanied by bradycardia. Repeated episodes of apnoea with hypoxia can eventually lead to neural damage.

Methylxanthines, especially caffeine and theophylline, stimulate the central nervous system and intravenous administrations of these drugs usually help to solve the problem.  Therapy is however, usually discontinued as soon as possible – usually after a few weeks in intensive care.  The neonate then also receives oxygen therapy and the oxygen levels in the blood are continuously monitored.

• What are the general causes of rhinitis and rhinorrhoea?

1.  Rhinitis associasted with colds and flue
2. Mucosal Rhinitis (associated with sinusitis)
3. Allergic rhinitis (allergen exposure, IgE mediated inflammation)
4. Non-allergic rhinitis (physiological response due to stimuli such as cold, heat or smoke)

 

• Which drug groups can be used for the treatment of rhinorrhoea? Name examples from each group.

1. Alpha1-agonists eg: naphazoline
2. Antihistamines eg: loratadine
3. Corticosteroids eg: budesonide
4. Mast cell stabilisers eg: ketotifen
5. Mucolytics eg: mesna
6. Antibiotics eg: neomycin
7. Diverse drugs eg: normal saline

 

• How do the decongestants differ with respect to the mechanism of action and duration of action?  How are they administered typically?

MOA: The decongestants are alpha-adrenoreceptor sympathomimmetics, which causes vasoconstriction, which opposes vasodilation; this will reduce the nasal airway resistance and thus facilitate nose breathing.

Duration of action: Decongestants provide rapid relief that my last up to 12 hours, but may only be used 5-7 days.

Decongestants are usually administered topically via metered-dose sprays (which is the safest).

 

• What is rhinitis medicamentosa?  How is it treated?

Rhinitis medicamentosa is a condition which develops if topical decongestants are used for a period longer than 7 days. This conditions happens when there is an overstimulation of the alpha receptors in the nasal mucosa, which leads to the drying out of the mucosal  tissue. This leads to a blocked nose which is difficult to treat with medication. It can however be treated by cortisone nasal sprays.

 

• How does the first and second generations of antihistamines differ with respect to the mechanisms according to which rhinitis and rhinorrhoea are relieved?  What are the advantages of the second generation of antihistamines?  Why should they not be used to relieve cold rhinitis?

First generation antihistamines can be used for non-allergic rhinorrhoea, because it reduces the inflammation in the nose and in effect treats the symptom.

Second generation antihistamines can be used to treat allergic rhinitis. This medicine acts by inhibiting mast cell release of histamine and some other mediators of inflammation.

The advantages of the second generation of antihistamines are that they have little to no CNS distribution and in effect have a low incidence of patients who experience sedation and anticholinergic side effects.  

Antihistamines should not be used to relieve cold rhinitis, because some symptoms caused by body`s responses are not related to histamine production, in effect antihistamines will have no effect. In other words histamine is not the major cause of a runny nose. (Bradykinin plays a role.)

 

• When are corticosteroids, anti-allergic drugs, mesna and normal salt solution valid and how are they administered? 

*Corticosteroids: These drugs are valid for the use of allergic rhinitis and is administered topically in the form of a nasal spray.

*Anti-allergic drugs: These drugs are valid for the prophylactic treatment of allergic rhinitis and is administered topically in the form of a nasal spray.

*Mesna: This drug is valid when the nasal secretion is sticky as it helps to make the mucus more liquid. It is administered topically in the form of a nasal spray.

*Normal salt solution: This drug is valid for the use of humidifying the dry  and inflamed mucous membranes of the nose during colds, dry weather, allergy (hay fever), nose bleeding, overuse of decongestants and other irritations. This drug is administered topically in the form of nasal drops.

Pathology of Migraines

Migraines usually occur at the reduction of blood flow and occurs during cerebral hyperperfusion in the headache phase. Migraine is viewed as a disorder that influences cerebral hemodynamics. It can be said that blood flow changes do not always correlate with the symptoms seen in a migraine attack. Multiple factors influences a migraine: chemical, metabolic, neurogenic and myogenic. https://scite.ai/reports/10.1097/00002508-199009000-00011

Vascular pathology is often associated with migraines, because endothelial dysfunction may be an early marker for migraines.

Larrosa-Campo D, Ramón-Carbajo C, Álvarez-Escudero R, et al. [Arterial pathology in migraine: endothelial dysfunction and structural changes in the brain and systemic vasculature]. Revista de Neurologia. 2015 Oct;61(7):313-322. PMID: 26411276.

 

Current treatment and mechanism of action

• Ergot alkaloids: If it is an acute migraine= ergotamide, if migraine prophylaxis=methysergideInduces vasoconstriction which is long-lasting.
• Autocoids:migraine prophylaxis=flunarizine.