Cystic fibrosis is an inherited life-threatening disorder that damages the lungs and digestive system. It is associated with thickened and stickey mucus, which eventually blocks the airways. With regards to treatment, it is treated using dornase alfa as it breaks down the thick secretions in the airways, allowing air to flow better and preventing bacteria from building up.

Neonatal respiratory distress syndrome (NRDS) is a breathing disorder in new-borns caused by immature lungs.

Treatment for NRDS:

1. Oxygen. Provide oxygen to improve oxygenation.
2. Ventilator. Used to provide positive pressure.
3. Exogenous surfactant. It eventually promotes gaseous exchange. It is regarded as a therapeutic option for new-borns, children, and adults to improve surfactant.
4. Corticosteroids. It initiates baby’s surfactant production. It is administered to child/new-born and to the mother before birth.

The purpose of oxygen therapy is to increase oxygen levels in blood.

The dangers of oxygen toxicity involve retinal damage and blindness.

Neonatal apnoea is a pause in breathing that lasts approximately 20 seconds or longer for full-term infants. It is treated using a central nervous system (CNS) stimulant, methylxanthines.

Methylxanthines relaxes smooth muscles, including those of the bronchi, oesophagus, and gastroesophageal sphincter. They can reduce fatigue and improve concentration.

Rhinitis and rhinorrhoea are usually a result of allergy, cold, chemical, drug, or physical damage.  

Rhinorrhoea treatment:

• Anti-infective drugs (Mupirocin, Neomycin, Chlorhexidine)
• Decongestants (Phenylephrine, Ephedrine, Oxymetazoline, Pseudoephedrine)

Oral decongestants

Decongestants cause blood vessels in the nasal passages to contract (vasoconstrict). Vasoconstriction reduces nasal congestion by preventing fluid from draining from blood vessels into the tissues lining the nasal passages. This happens through activation of the alpha₁ – receptors.

Topical decongestants

Topical decongestants are vasoconstrictors, and work by constricting the blood vessels within the nasal cavity.

Rhinitis medicamentosa (RM) is a condition resulting from overuse of nasal decongestants.

A sudden stop in use of nasal spray, may lead to greater swelling and congestion. Thus, a gradual decrease in the use of the medication may be recommended; then once congestion is mild, Beclomethasone may be administered.

Antihistamines prevent the release of histamine. They should not be used in cold rhinitis as they thicken mucus due to muscarinic effect.

1^st generation antihistamines

• First-generation antihistamines block both histamine and muscarinic receptors as well as passing the blood-brain barrier.
• Has sedative properties

2^nd generation antihistamines

• Second-generation antihistamines mainly block histamine receptors and do not pass the blood-brain barrier.
• Has no sedative effects.

Therefore, the advantage of 2^nd generation antihistamine over 1^st generation antihistamine is that they have no sedative effects.

Corticosteroid nasal sprays use with caution in infection-induced conditions, this is due to increased systemic uptake. It is administered via the nasal route.

Anti-allergic drugs are used in treatment of allergen-induced rhinitis or/and rhinorrhoea. It is administered via the oral or parenteral route.

Normal salt solutions are used to dilute mucus and are administered nasally.

Mesna is regarded as a chemoprotective and anti-neoplastic drug. It reduces toxicity in urinary passages. It is adverse reactions includes respiratory disorders such as nasal congestion, cough, dry mouth, bronchoconstriction, etc. It is administered parenterally (intravenous injection).

COPD (Chronic obstructive pulmonary disease) is a group of diseases pertaining to the lungs that lead to obstruction of airways, eventually causing difficulty in breathing.

It is a combination of:

• Bronchial asthma. A condition in which a person’s airways become inflamed, narrow, swollen and produce extra mucus, which makes it difficult to breathe.
•  Chronic bronchitis. Inflammation of the lining of bronchial tubes, which carry air to and from the lungs.
• Emphysema. A condition that involves damage to the walls of the air sacs of the lungs.

Treatment of COPD:

• Patient is advised to avoid irritants such as smoke, therefore patient is advised to stop smoking.
• Board spectrum antibiotics or influenza immunisation used in the presence of bacterial infection.
• Bronchodilators used in combatting of obstruction of airflow.
• Rehydration and steaming helps dilute mucus. This reduces mucus secretion.
• Oxygen inhalation used especially in treatment of hypoxia.
• Light-moderate exercise to improve lung capacity.
• Surgery, lung transplant.

Ipratropium acts as an antagonist of the muscarinic acetylcholine receptor. This effect produces the inhibition of the parasympathetic nervous system in the airways and hence, inhibit their function. The function of the parasympathetic system in the airway is to produce bronchial secretions and constriction and thus, inhibition of this action can lead to bronchodilation and fewer secretions.

Ipratropium is more effective in treatment of chronic bronchitis than in the treatment of bronchial asthma, for chronic bronchitis is characterised by inter alia, increased mucus secretion. Whereas in bronchial asthma, increased mucus secretion does not have the as effect as in chronic bronchitis.

Theophylline is a xanthine used to manage the symptoms of asthma, COPD, and other lung conditions caused by reversible airflow obstruction. It causes smooth muscle relaxation, thus inducing bronchodilation.

Bronchodilation allows for easier airflow due to expansion of the bronchial air passages. This improves breathing.

Oxygen therapy in COPD increases the amount of oxygen that flows into the lungs and bloodstream, this improves breathing.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is approved for the treatment of obsessive-compulsive disorder (OCD), including depression.

Studies show that fluvoxamine binds to the sigma-1 receptor in immune cells, resulting in reduced production of inflammatory cytokines and inflammatory genes (NIH,2021). According to The Medical letter published on the 3^rd of May 2021, sigma-1 agonism inhibits SARS-CoV-2 replication and modulates the inflammatory response. It assumes that fluvoxamine theoretically prevents the development of life-threatening cytokine storm and acute respiratory distress syndrome in coronavirus COVID-19.

Fluvoxamine has shown to prevent clinical deterioration (such as shortness of breath and hypoxemia) in patients who tested positive for COVID-19 (The medical letter, 2021).

“Endothelium-dependent” vasodilation explains that the endothelium controls vasodilation. Endothelium-dependent vasodilation is stimulated by increased blood flow, this is done by increasing shear stress on the endothelium.

Septic shock occurs when infectious microorganisms in the bloodstream induce a profound inflammatory response causing hemodynamic decompensation.

Endotoxin components from the bacterial wall along with endogenously generated tumour necrosis factor (TNF)-α and other cytokines induce synthesis of iNOS in macrophages, neutrophils, and T cells, as well as hepatocytes, smooth muscle cells, endothelial cells, and fibroblasts. This widespread generation

of NO results in exaggerated hypotension, shock, and, in some cases, death.

Nitric oxide. Nitric oxide activated the conversion of guanylyl cyclase to activated guanylyl cyclase, this will eventually lead to the conversion of GTP to cGMP. The elevation of cGMP will lead to vasodilation and relaxation of smooth muscle.  

If inhaled, NO leads to increased blood flow to parts of the lung exposed to NO and decreased pulmonary vascular resistance.

Arginase is an enzyme in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. It suppresses nitric oxide production through numerous mechanisms.

NO plays an essential role in protecting the body via immune cell function. When there is an invasion of foreign antigens. During an inflammatory response, Th1 cells respond by synthesizing NO, which has effects on activity of Th1 cells.

NO stimulates the synthesis of inflammatory prostaglandins by activating cyclooxygenase isoenzyme 2 (COX-2). Through its effects on COX-2, its direct vasodilatory effects, and other mechanisms, NO generated during inflammation contributes to the erythema, vascular permeability, and subsequent oedema associated with acute inflammation.

NO is involved in physiological functions such as noradrenaline and dopamine releases, memory and learning and certain pathologies such as schizophrenia, bipolar disorder, and major depression.

Increased levels of angiotensinogen are associated with essential hypertension. Essential hypertension is primary hypertension.

The synthesis of angiotensin is stimulated by glucocorticoids, thyroid hormone, estrogens, and angiotensin II. Therefore, abnormally high levels of the glucocorticoids, thyroid hormone, estrogens, and angiotensin II.

A decreased blood pressure leads to more conversion of angiotensinogen to angiotensin II mediated by renin enzyme. This will thus increase the synthesis of angiotensinogen. 

Angiotensin-converting enzyme (ACE) inhibitors are medications that help relax the veins and arteries to lower blood pressure. ACE inhibitors inhibit the production of angiotensin II, a substance that narrows blood vessels. These inhibitors also prevent the conversion of bradykinin to an inactive metabolite (thus enhancing vasodilation, as bradykinin is a vasodilator).

Side effects of ACE inhibitors may include:

• Dry cough
• Increased potassium levels in the blood (hyperkalaemia)
• Fatigue
• Dizziness from blood pressure going too low
• Headaches
• Loss of taste

Angiotensin II receptor blockers help causes vasodilation lower blood pressure and making it easier for heart to pump blood. Angiotensin is a chemical in the body that narrows blood vessels. This narrowing can increase blood pressure and increase workload on the heart. This narrowing is due to release of aldosterone (A steroid hormone that regulates salt and water in the body, thus influencing blood pressure) which is stimulated by angiotensin II. Aldosterone increases blood pressure by causing retention of water and salt, eventually increasing fluid volume.

Inhibition of the angiotensinogen system by angiotensin receptors is associated with fewer effects as the receptors only influence aldosterone release activity, whereas ACE inhibits affect the activity of angiotensin I (thus, alter the activity of angiotensin II and aldosterone) and bradykinin.   

ACE inhibitors are considered to have a two-fold mechanism of action in treatment of hypertension, as these inhibitors prevent the conversion of:

• Angiotensin I to angiotensin II, thus inhibiting the release of aldosterone. Aldosterone-release inhibition promotes water and salt excretion, decreasing fluid volume and eventually blood pressure.
• Bradykinin to an active metabolite. Bradykinin is a vasodilator which widens the blood vessels allowing easier flow of blood, eventually decreasing blood pressure. 

Losartan is an angiotensin II receptor blocker (ARB) used to treat hypertension. Losartan reversibly and competitively prevents angiotensin II binding to the AT₁ receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and its active metabolite bind the AT₁ receptor with more affinity than they bind to the AT₂ receptor, thus having a direct effect on the angiotensin II receptors.

Kinins are proteins in the blood that cause inflammation and affect blood pressure (especially low blood pressure). They increase blood flow throughout the body by causing vasodilation, which is widening of the blood vessels. Make it easier for fluids to pass through small blood vessels.

Autacoids are biological factors (molecules) which act like local hormones, have a brief duration, and act near their site of synthesis. Histamine and serotonin (5-hydroxytryptamine) are two important amine autacoids.

Histamine is associated with the relief of joint pain or muscle aches and pains. Histamine acts directly on the blood vessels to dilate arteries and capillaries; this action is mediated by both H 1- and H 2-receptors.

Serotonin is the key hormone that stabilizes our mood, feelings of well-being, and happiness. It enables brain cells and other nervous system cells to communicate with each other. Serotonin also helps with sleeping, eating, and digestion.

Serotonin possesses both vasoconstrictor and vasodilator properties. The constrictor action of the monoamine can be due to:

1. Direct activation of vascular smooth muscle; in most blood vessels, this is mediated by S2-serotonergic receptors.
2. Enhancement of action of other endogenous vasoconstrictors such as catecholamines, angiotensin II and the prostanoids (a family of lipid mediators generated by the action of cyclooxygenase).
3. Release of norepinephrine from adrenergic nerves.

The dilator action of serotonin can be due to:

1. 1. Activation of endothelial cells which release endothelium-derived relaxing factor(s); this response appears to be mediated by S1-serotonergic receptors.
   2. Direct inhibition of vascular smooth muscle.
   3. Inhibition of adrenergic neurotransmission by an action on S1-serotonergic receptors.
   4. Release of other endogenous mediators.

Therefore, the effects are similar.

Kinin B2 receptors

Natriuretic peptides may be regarded as treatment for hypertension as it increases sodium and water excretion and causes vasodilation.

The excretion of sodium(salt) and water decreases fluid volume, in turn decreasing blood pressure, will vasodilation allow for widening of blood vessels which facilities easier flow of blood, eventually reducing blood pressure.

Neprilysin inhibitors are used to treat high blood pressure and heart failure. They work by blocking the action of neprilysin thus preventing the breakdown of natriuretic peptides.

Omapatrilat (including entresto and sacubitril/valsartan) is a neprilysin inhibitor, it decreases metabolism of natriuretic peptides and formation of angiotensin II, thus causing vasodilation and increased sodium and water excretion.

The three most important endothelial-derived substances are: nitric oxide (NO), endothelin (ET-1), and prostacyclin (PGI2). NO and PGI2 act as vasodilators, whereas ET-1 serves as a vasoconstrictor

Drugs which act as endothelium-derived vasodilators.

•  Bosentan, macitentan. Nonselective antagonists of endothelin ETA and ETB receptors.
• Sitaxsentan, ambrisentan.  Selective antagonists for ETA receptors.
• Daglutril. Block formation of endothelins and breakdown of natriuretic peptides.

Endothelium-derived vasoconstrictors (factors that stimulate the release of ET-1).

• Low shear stress
• Adrenalin        
• Thrombine      
• Angiotensin II            
• Vasopressinc
• Endotoxin (LPS)        
• Insuline
• Calcium ions