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

Cystic  fibrosis is a chronic metabolic  disease characterised by the decrease  in secretions in various organs, of which the lungs are the most affected. The body cant eliminate the thick and sticky mucus produced and creates the perfect environment for recurrent infections  to occur. Dornase alfa inhalations hydrolyze  the muco-polysaccarides in the mucus increasing its liquidity and improving the body's ability to rid of this mucus. 

• 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 occurs when the surfactant which cover the airways and is essential for gas exchange, has not developed before birth  and can lead  to atelectasis. Treatment includes oxygen therapy/ventilation, exogenous surfactants (beractant or poractant) administration or prophylactically administering two doses of a corticosteroid (betamethasone) to the mother, before labour, to induce the formation of the baby's surfactants.

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

The role of this therapy is to improve the gas exchange of the baby even though the surfactants aren't completely developed yet. This allows for normal oxygen levels. Dangers of this therapy if oxygen levels remain high over a  period of time includes retinal damage and ultimately blindness.

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

Neonatal apnoea occurs when the respiratory centrum in the brain has not yet fully developed in a baby and thus there is not continuous stimulation for breathing. Resulting in periods of  oxygen shortage due to the lack of breathing by the baby. Methylxanthines stimulate the CNS and makes you more aware and awake thus improving respiration stimulation in this  condition. Theophylline  or caffeine can be used.

What are the general causes of rhinitis and rhinorrhoea?

There are various causes of these conditions, including:

1. Allergens (allergic rhinitis)
2. The environment (non-allergic rhinitis in reaction to cold air)
3. Chemicals
4. Physical damage

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

1. Alpha1-agonists eg: oxymethazoline
2. Antihistamines eg: rupatadine
3. Corticosteroids eg: betamethasone
4. Mast cell stabilisers eg: ketotifen
5. Mucolytics eg: mesna
6. Antibiotics eg: neomycin
7. Diverse drugs eg: normal saline solutions

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

Decongestants can be administered vie IV, orally or topically. The various administration forms  have different duration of actions. Their mechanism of actions also differ for example topical administrations have less side effects than those administered systemically. this is also the reason decongestants are applied topically in rhinitis  and rhinnorrheoa. 

• What is rhinitis medicamentosa?  How is it treated?

This is the severe drying of the nasal mucosa and is often caused by the prolonged us (more than 7days) of a topical decongestant. it is treated by cessation of the decongestant and rehydrating the patient.

• 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?

They 1st generation causes severe sedation as  well as antimuscarinic effects, which isn't seen nearly as prominantly in the 2nd generation antihistamines. the second generation antihistamines are used more often in allergic rhinitis for these drugs has the ability to prevent the release of histamine from mast cells, something that 1st generation drugs can not do.

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

corticosteroids are used prophylactically and chronically (topically).

Anti-allergic drugs are used in allergic rhinitis where they prevent the release of inflammation mediators (topically)

Mesna is a mucolytic used when thick and tough mucus needs to be eliminated from the nasal cavity.

Normal saline solutions are ideal for they have no adverse effects. It should be used  to rinse the nasal cavity (topically.) it is ideal in children and geriatric patients seeing that they are more susceptible  to systemic decongestant's side effects. 

• COPD definition

It is a chronic inflammatory lung disease, which causes obstruction of airflow to and from the lungs, causing oxygen and gas exchange shortages.

• Aetiology & pathophysiology

AETIOLOGY: COPD is mainly caused by damage to the lung walls. This then leads to a persistent bronchodilation. Triggers include regular smoking or oxidative stress within the lungs. 

PATHOPHYSIOLOGY: This is know for thee chronic inflammation seen in and affecting the airways and pulmonary vasculature. Repeated injury and repair leads to structural and physiological changes.

• Therapy types for COPD

anticholinergic drugs, B2-sympathomimmetics, Corticosteroids, oxygen therapy

• Ipratropium superiority in COPD treatment

Ipratropium has a superior effect in COPD rather than Asthmatic cases for this drug is a n anti-cholinergic drug, which supresses the  Vasoconstricting actions of the parasympathetic nervous system. The PNS has a larger  role in COPD than in asthma which react better to direct stimulation of the B2 receptors than by indirect blockade of the muscarinic receptors via Ipratropium.

• Theophylline effects in COPD treatment

Theophylline's skeletal muscle effects prove beneficial as it improves the efficacy of the diaphragm, meaning that better inspiration and exhalation can occur and an  improved gas exchange will be seen.

• Oxygen therapy role

Due to the persistent bronchodilation seen in COPD a shortage of gas exchange occurs. Thus an increase in oxygen levels provided to the patient will increase the amount of O2 inhaled even with the bronchodilation seen. Improving the oxygen intake of the patient and improving quality oflife and  the symptoms.

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

Elevated levels of Angiotensinogen is associated with the following diseases:

- High Blood pressure, Ischemic heart disease, Ischemic cerebrovascular disease.

The implications of these diseased conditions include the occurrence of cardiac as well as vascular hypertrophy. This will ultimately lead to decreased cardiac output, vasoconstriction, increased blood volume due to increased renal Na+ and H2O retention.It can develop into a stroke and cell death.

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

ACE inhibitor administration leads to an increase in Bradykinin activity for it decreases the extent of Bradykinin's metabolism. Bradykinin then interacts  with a number of systems due tot non-specificity and leads to the  serious cough which is unwanted. It also has a serious vasodilating effect. The inhibitors of  the angiotensinogen system only works in on this system by decreasing the renin produced, renin enzymatic actions, the conversion of ANG1 to ANG2, and extreme selective blockage of the AT1 receptors (which cause vasoconstriction).

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

The ACE inhibitors:

Prevents the metabolism of Bradykinin allowing this molecule to exert its vasodilating effects on the vasculature, this leads to a decrease in vascular resistance and so a decrease in hypertension.

They also decrease the peripheral vascular resistance, hence vasodilation occurs and a decrease in blood pressure is seen.

• 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?

Losartan is an Angiotensin 2 receptor antagonist.

These drugs block (direct effect) the AT1 receptor, which is under normal conditions responsible for vasoconstriction. Thus these drugs will lead to an indirect effect which includes the subsequent domination of the AT receptor's biological effect (Vasodilation). 

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

Kinins are vasodilator peptides. Thus the diameter of the lumen of the veins and especially arteries will increase. Other autacoids such as histamine, serotonin also play a role in this action for NO & PGI is released after the activation of the kinin (ex, bradykinin).

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

Bradykinin 2 receptor (B2)

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

Natriuretic peptides lead to  the following physiological occurrences:

- Increased renin production, increased ANG2, vasodilation and natriuresis.

Thus these effects will cause a decrease in the peripheral vascular resistance, counteracting the high vascular resistance required to establish hypertension. It is also used in congestive heart failure seeing that the cardiac load is decreased by the use of this drug due to vasodilation, volume decrease and so an overall decrease in the cardiac output. Making it better and safer for the failing heart.

• 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 the catalytic enzyme that break down the Natriuretic peptides to their metabolites and so inactivate them. The rationale of inhibiting this (ANRi usage) is to ensure an increase in the systemic concentration of the Natriuretic peptides and so ensure that their physiological effects (as mentioned above) will predominate the cardiovascular system. Ultimately decrease cardiac work.

ANRi drug name: Sacubitril & Entresto.

• Give examples of endothelium-derived vasodilators and vasoconstrictors

Vasodilators: Bosentan, NO, PGI2, vasoactive intestinal  peptide, Substance P, Neurokinin A/B.

Vasoconstrictors: ET1,2,3 & ETA receptor stimulants, Neuropeptide Y