Blog #3.5

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

• It is a genetic metabolic disease that leads to decreased DNase 1 enzymes (responsible mor metabolism of mucus) that results in reduced secretions in various organs. It mainly attacks the alveoli in the lungs that leads to a sticky mucus build up as the body loses the ability to clear mucus. This affects gaseous exchange within the lungs. Dornase alfa hydrolyses proteins in the bronchial mucus to make them more fluid like to make it easier to cough out.

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

• It is a condition that is seen in premature babies, as they are born before the surfactants that cover their airways to allow gaseous exchange are not formed yet. This can lead to their lungs falling flat – leading to death. Giving oxygen is an important strategy to help, as well as mechanic ventilation as positive pressure. Cortisone and endogenous surfactants given prophylactically to mothers can solve this problem by stimulating premature maturation of the babies’ lungs such as surfactant formulation.

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

• Oxygen therapy is just to increase the blood oxygen levels of the baby to prevent hypoxia. Too much oxygen can damage the retina of the baby and can even lead to blindness.

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

• This occurs in new-borns and in premature babies. It is caused by incomplete development of the respiratory centre within the brain, leading to incomplete continuous stimulation of breathing. Thus, the baby repeatedly stops breathing and has a slowing of heartbeat for 15 seconds or longer.
• This can lead to hypoxia or neuronal (brain damage)
• Theophylline as a methylxanthine is used
• It works by stimulating the CNS to increase stimulation within the respiratory system, leading to less attacks.

Blog #3.4

What are the general causes of rhinitis and rhinorrhoea?

• General causes of these two conditions are usually allergies, colds, Drug damage, Chemical damage, cold air and Physical damage

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

• Alfa 1 agonists such as phenylephrine, ephedrine  and naphazoline, etc
• Antihistamines such as the 1^st generation diphenhydramine, promethazine, chlorpheniramine, etc
• Corticosteroids such as Betamethazone, prednisone, budesonide, etc
• Mast cell stabilizers such as sodium chromoglycate and ketotifen
• Mucolytics such as acetylcysteine
• Antibiotics such as mupirocin, neomycin, etc
• Diverse drugs such as steaming with essential oils (menthol/eucalyptus oil)

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

Decongestants can work in 2 ways – they can be systemic decongestants, or they can be topical decongestants. They are probably mediated by alfa 1 receptors – thus leading to vasoconstriction of mucosal blood vessels and decreased oedema of nasal mucosa. Duration of action for systemic decongestants is longer than for those administered topically – but longer duration of action increases risk of CNS toxicity. Systemic decongestants are designed to be administered orally, whilst topical decongestants are prepared as nasal sprays and gels/drops.

What is rhinitis medicamentosa?  How is it treated?

Rhinitis medicamentosa is a condition that develops as a side effect of overuse of topical nasal decongestants – It is the Drying of nasal tissue that develops after 5 – 7 days of topical use (more than 3 days ) – leading to a blocked nose.

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?

1st generation antihistamines have a lot of side effects due to their high lipophilicity – leading to their ability to easily cross the BBB and cause CNS side effects, such as sedation – It thus must be used in a decreased concentration – whereas 2^nd generation antihistamines are less lipophilic and doesn’t cross the BBB easily – thus not having those side effects. It is thus a good medication to use long term in allergic rhinitis where stimulus can continue for long periods of time (months). They work by blocking the histamine 1 receptors that would have been stimulated by different allergens. Cold rhinitis (caused by colds and flu) is not caused by stimulants such as pollen, they also cause mucus thickening which is undesirable in cold rhinitis.

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

• Corticosteroids are used in cortisone nasal sprays for prophylactic use. They are used chronically in allergic rhinitis, nasal polyps, inflammatory rhinitis and reversal of rhinitis medicamentosa
• Antihistamines are rarely indicated, but is used for prophylaxis of allergic rhinitis as a nasal spray

Mesna and normal salt solution are both used to loosen touch nasal mucus by diluting it. It is administered via nasal lavage. Can also be administered via steaming

Give your own definition of COPD.

• Chronic Obstructive pulmonary disease is an inflammatory airway disease characterized by the presence of Bronchial asthma, chronic bronchitis and emphysema and their characteristics in varying degrees. It cannot be cured but the symptoms can be lessened as response to treatment is generally poor. It is also characterized by progressive loss of lung function that leads to difficulty breathing

Briefly describe the proposed aetiology and pathophysiology of chronic bronchitis and emphysema.

• The proposed cause of Chronic Bronchitis and emphysema is believed to be an abnormal inflammatory response due to noxious particles/gases such as cigarette smoke (directly linked – but other irritants can have this effect as well). The prolongation of the presence of the irritant leads to a higher incidence even if the irritant is then removed at a later stage.
• Chronic bronchitis is characterized by increased mucus secretion, decreased mucosal clearance, frequent bacterial respiratory infections, structural changes in the bronchial walls (which negatively affects gaseous exchange) and sticky mucus due to decreased clearance.
• Emphysema is characterized by the irreversible dilation of respiratory bronchioles and alveoli due to structural damage. This effectively “traps” air within the lungs as the bronchioles lose their elasticity due to damage – making them ineffective during respiration. Exhalation is thus difficult and decreased capillary blood vessels (due to damage to infrastructure) impede gas exchange.

Which types of therapy are included in the treatment of a COPD patient?

• Treatment mainly is for symptoms/secondary diseases
  • You need to stop smoking
  • You need to get immunized against influenza ( as chronic bronchitis causes frequent bacterial infections) and you need to use broad spectrum antibiotics when you get infections.
  • Bronchodilators are used to treat airway obstructions
  • Increased mucus secretions and sticky mucus is treated by diluting the mucus with rehydration and steam. (using nebulizer)
  • Hypoxia is treated with oxygen inhalation
  • Poor lung capacity is increased with light to moderate exercise (this could also lead to decreased incidence of hypoxia
  • Surgery - Lung transplantation
  • Corticosteroids can also help (don’t work often but helps sometimes)

Why is ipratropium more effective in the treatment of chronic bronchitis than in the treatment of bronchial asthma?

• chronic bronchitis is characterized by increased mucus secretion, whereas in bronchial asthma, even though there is a formation of mucus plugs, the main causative of asthma is reduced airflow due to broncho constriction.
• Ipratropium is a competitive inhibitor of muscarinic receptors (M3 – type) on bronchial smooth muscle – it thus works by antagonising Ach action – preventing an increase in intracellular calcium concentrations – leading to bronchodilation and decrease in nasal and bronchial gland secretions. It unfortunately also decreases mucociliary clearance – which would have helped with mucus plugs.
• It thus is more effective in chronic bronchitis because of the effect it has on the mucus secretions – as it is equally effective in both diseases regarding its broncho-dilatory effects.

In which way do the skeletal muscle effects of theophylline have advantages in the treatment of COPD?

• Theophylline strengthens the contraction of the skeletal smooth muscle – diaphragm – thus increasing the ventilatory capacity.

What is the role of oxygen therapy in COPD?

Oxygen therapy is simply there to decrease signs of hypoxia, as gaseous exchange is impeded within the lungs – thus increasing the amount of oxygen taken into the lungs will directly impact the amount of oxygen exchange within the lungs – decreasing the signs of hypoxia by increasing the oxygen within the body. It does not have any structural function or interact with any drugs whatsoever. It simply increases your oxygen intake and uptake

There is a connection between vasodilators/vasoconstrictors and migraine, however it seems that migraines are more complicated than simple changes in vascular functions. As said in the Blog Summary - drugs that cause vasodilation aren’t necessarily the culprits which precipitate migraines, especially if we take into consideration that anti-inflammatory drugs which have no direct vasoactive action, are also effective. Thus, put more simply – migraines aren’t simply caused by vasodilation within the brain as other drugs that do not have any direct vasoconstricting effects are still able to help with migraines.

The pathophysiology of migraines are still poorly understood. The main culprits that have been identified to cause migraines involve trigeminal nerve distribution to intracranial arteries. It is argued that extracranial arteries my also play a role in migraines. The nerves release CGRP that are extremely powerful vasodilators. This most likely increases the intracranial pressure to such an extent that the “swelling” in the brain leads to pain, nausea, vomiting, visual scotomas, etc. Substance P and Neurokinin A may also be involved.

Medications that may help with migraine are in a large variety. Triptans, ergot alkaloids, NSAID’s, Beta blockers, Calcium channel blockers, tricyclic antidepressants, SSRI’s and several antiseizure agents all have a diminishing effect on migraines.

Some of these drugs can only be used to prevent a migraine attack, or as a prophylactic, whilst others can be used during an attack.

There are only 2 MAIN hypotheses so far as to how these medications lessen the effects of migraines.

The first one argues that medications that fall under the classification as ergot alkaloids, triptans and antidepressants might activate the very specific serotonin receptor (5-HT_1D/1B). This receptor can be found on the presynaptic trigeminal nerve ending. By agonizing the receptor – you inhibit the release of vasodilating peptides that would’ve led to increased intracranial pressure. Antiseizure agents may suppress the excessive firing of these nerves

The second hypothesis argue that the direct vasoconstrictive effects of direct serotonin (5-HT) receptors may prevent vasodilation and stretching of pain endings. – some drugs work by both hypotheses.

The second hypothesis has more to do with directly antagonizing the vasodilatory effects

So far sumatriptan is the first-line medication for migraines – It’s a serotonin 1 agonist – but is contra indicated in coronary artery diseases. The mechanism of action is mainly debated as vasoconstrictor effects

Anti-inflammatory analgesics such as aspirin could also help – they however have no effect on vasculature and is only helpful in controlling pain…

Beta blockers and some calcium channel blockers are good prophylactic medications to use for migraines by preventing vasodilation. Some anticonvulsants help as well. Verapamil also has modest efficacy as a prophylactic agent.