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

It is a genetic defect which leads to reduced secretions in various organs. Dornase alpha hydrolyses extra-cellular DNA from the neutrophils in bronchial mucus and increases its liquidity drastically.

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 and occurs in premature babies. It is basically when the surface-active material that covers the respiratory unit of the airways is not form, when babies are born prematurely.

Intensive monitoring of respiratory and circulatory status is essential . Exogenous surfactants are administered exogenously at room temperature( by means of  a catheter into the lungs

A short course of corticosteroids is effective to boost endogenous surfactant production and is a cheaper alternative.

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

Oxygen therapy is administered with air at room temperature to ensure oxygenation. a continuous positive pressure improves ventilation and keeps the alveoli open in order to prevent collapse. It is administered in order to prevent collapse.

Dangers. oxygen toxicity causes reduced drug exchange, hypoxia and death in extreme cases. It can also 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 has not yet fully developed in premature babies to stimulate continuous breathing.

Methylxanthines, caffeine and theophylline stimulate the CNS and IV administration of these drugs help solve the problem.

• What are the general causes of rhinitis and rhinorrhoea?

 Rhinitis and rhinorrhoea are caused by cold and flu, sinitus, allergen exposure (IgE mediated inflammation and physiological response due to stimuli (heat, smoke and cold weather).

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

Antihistamine e.g. diphenhydramine

corticosteroids e.g. mometasone

mucolytics e.g. mesna

alpha-1 agonists e.g. phenylephrine 

Anti-allergy drugs (sodium cromoglycate)

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

Decongestants MOA ( causes vasoconstriction of the mucosal blood vessels and decreases oedema of nasal mucosa)

short-acting drugs (4-6 hours) ephedrine, phenylephrine

intermediate acting drugs (8-10 hours), xylometazoline

long acting drugs (12 hours) oxymetazoline

They are administered  in the topical dosage form (nasal spray, drops and jellies) and inhalation of volatile compounds.

• What is rhinitis medicamentosa?  How is it treated?

Also known as rebound congestion or Privinism results from an overdose of local preparations. basically presents after chronic treatment with decongestants, where the permanent vasoconstriction with poor local blood supply leads to damage of the mucous membranes of the nose with inflammation and swelling.

Treatments: stop using the decongestants. gradually decrease your use of the medicine and for mild congestion use a saline nasal spray.

 

• 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 are multipotent competing antagonist and blocks muscarinic receptors. Antimuscarinic drugs will reduce the secretions of both the upper and lower airways and are included in preparations for colds and clear up rhinnorhoea. 1st generation anti-histamines can cause sedation.

2nd generation anti-histamine do not block muscarinic receptors and are used in the long term or short term treatment of allergic rhinitis. these drugs do not help with the clear up of cold rhinitis, because histamine plays no part in cold rhinitis ( only bradykinin)

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

 corticosterioids- administered for allergic rhinitis, nasal sprays administered through nasal cavity.

anti-allergy drugs- allergic rhinitis and administered as a nasal spray

mesna- when nasal spray secretions is sticky and administered as a nasal spray.

normal salt solution- allergic rhinitis, mild congestion (nose drops)

 

• Give your own definition of COPD. 

Chronic obstructive pulmonary disease is basically a group of diseases (emphysema, Bronchial asthma, and chronic bronchitis) which causes blockage of airflow and breathing problems.

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

Chronic bronchitis- aetiology- long term exposure to irritants, smoking.

  -pathophysiology- obstructive airway disease due to an increase secretion of mucus, decrease in mucus clearance and frequent bacterial respiratory infections.

Emphysema- aetiology- smoking and irritant

-pathophysiology- air sacks (alveoli) is damaged and the inner walls of the alveoli weakens and rupture creating larger than normal air spaces and this reduces the surface area of the lungs and amount of oxygen reaching the lungs.

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

Treatment includes anticholinergics, B2-agonists and slow-release theophylline, corticosteroids and oxygen therapy.

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

It is first line bronchodilator in the treatment of chronic bronchitis and it is used in treating the symptoms of chronic bronchitis and not in the treatment of bronchial asthma

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

It improves the contraction function of the diaphragm and thus increases ventilatory capacity.

• What is the role of oxygen therapy in COPD?

If a patient presents with low oxygen levels in their blood oxygen therapy can be used to restore the oxygen levels in the blood and prevention of hypoxia.

• Give a short and critical explanation of the rationale of using fluvoxamine (a selective serotonin reuptake inhibitor (SSRI) in the treatment of Covid patients. Your answer must be properly and appropriately referenced (in-text references as well).

According to Hashimoto (2021) Sars Cov-2 binds itself to the ACE2 receptor on the cells and this ultimately results in the activation of the acid sphingomyelinase which is responsible for the conversion of  sphingomyelin to ceramide. ASM/Ceramide system can facilitate viral entry. Fluvoxamine, which is an antidepressant inhibits ASM and formation of ceramide-enriched membrane domains and this results in decreased viral entry. The sigma-1-receptor agonist fluvoxamine may alternate ER stress due to SARS-COV-2 replication in cells, thus resulting in blockade against inflammatory events. thus early administration of fluvoxamine may block/delay clinical deterioration in individuals with SARS-COV-2 infections.

Resource

Hashimoto, Y., Suzuki, T., Hashimoto, K. 2021. Old drug Fluvoxamine, new hope for covid-19. Eur Arch Psychiatry an Neurosci (2021). https://doi.org/10.1007/500406-021-01326-z

 

 

• What do you understand by the term “endothelium-dependent” vasodilation?  Explain.

An increase in blood flow stimulates endothelium-dependent vasodilation by increasing shear stress on the endothelium, both in conduit and resistance vessels.

• When we talk about the NOS enzyme, what is meant by “constitutive” and “inducible” enzymes and what are the pathological and physiological implications thereof?

Constitutive enzymes: they are always produced whether or not a suitable substrate is present and this affects the process by which the synthesis occur and it is always present in the organism in constant amounts .

inducible enzymes: only expressed under conditions in which it is clearly of adaptive value ( used for breaking down of things in the cell).

• Explain how NO contributes to the fatal pathology of septic shock.

The physiological production of NO is important for blood pressure regulation and blood flow distribution. A hyperproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardio depression and vascular hyporeactivity in septic shock. 

• Which autacoids’ mechanism of action depends on effects on the guanylyl cyclase-cGMP system?

Nitric oxide.

• NO may be toxic to the cell.  Which mechanisms are available to the body to counter this detrimental effect of NO?

Nitric oxide is a potent and rapid inducer of methemoglobinemia. Exposure to Nitric Oxide may result in changes of the pulmonary system.

• Name a way in which NO can act pro-inflammatory.  Give examples of where it will have advantages or disadvantages.

NO is considered as a pro-inflammatory mediator. It induces inflammation due to over production in abnormal circumstances. Advantages: NO inhibitors represents an important therapeutic advance in the management of inflammatory diseases. They are proved to be used for the treatment of of NO-induced inflammation. Disadvantages: due to impaired production of vasoconstriction, inflammation and tissue damage.

• In which possible neurological and psychiatric diseases is NO involved?

Autism spectrum disorder, schizoprenia, (may play a role in the development of it). Bipolar disease, migraine, epilepsy, addiction.

• In which diseases are angiotensinogen levels increased?  What are the implications of this?   

  Decrease in blood pressure (hypotension). It increases blood pressure by constricting the blood vessels, it triggers thirst and the desire for salt. Increased levels of angiotensin can result in excess fluid being retained by the body.

• Why do drugs which inhibit the angiotensinogen system by acting on angiotensin receptors have fewer side effects than those that inhibit ACE?

The ACE inhibitors lowers blood pressure by preventing the production of Angiotensin II, while Angiotensin receptor blockers reduce the action of angiotensin II  to prevent blood vessel constriction.

• In which way do ACE inhibitors have a two-fold mechanism of action in the treatment of hypertension?

It helps to relax the veins and arteries to lower blood pressure and it prevents an enzyme in the body from producing angiotensin II which is a substance that narrows blood vessels.

• At which type of angiotensin receptor do losartan and similar drugs act?  Do they have any effect, direct or indirect, at other angiotensin II receptors?

They bind the AT1 receptor found in vascular smooth muscle and adrenal gland.

• What are the physiological effects of kinins on arteries and veins?  Do other autacoids play a role in this action?  Explain.

Kinins induce vasodilation, Increasing blood flow  throughout the body and a brief fall in blood pressure. 

• Which receptor is probably the most involved in the important clinical effects of kinins?

Bradykinin displays the highest affinity for B2 ( bradykinin 2 Receptors)

• In which way are natriuretic peptides possibly effective in the treatment of hypertension, as well as congestive heart failure?

Natriuretic Peptides may be administered as recombinant ANP, recombinant BNP or ularitide. They produce vasodilation and natriuresis and have been investigated for the treatment of congestive heart failure. Natriuretic Peptides causes vasodilation and this helps to dilate the arteries (increase in blood flow) and this leads to a fall in blood pressure and this is effective in the treatment of hypertension. 

• What is neprylisine and what is the rationale for inhibiting its action in the treatment of heart failure? Can you name the drug being used as such? Refer to Study unit 1 where you have also come across this drug.

Neprilysin is a zinc-dependent metalloprotease and it blocks Ang II receptors. It is used to treat high blood pressure and heart failure. By blocking its action it prevents the breakdown of natriuretic peptides. Drugs are omapatrilat, sampatrilat and fasidotrilat. 

• Give examples of endothelium-derived vasodilators and vasoconstrictors.

endothelium-derived vasodilator/ endothelium-derived relaxing factor- Nitric oxide: plays a role in endothelial functions.

endothelium-derived vasoconstrictors/ endothelium-derived contracting factors- Endothelin-1 and Cox-derived thromboxane.