Question 1: Briefly explain what cystic fibrosis is and how dornase alpha acts to solve the problem

It is a genetic defect that can cause a decrease in secretions in many organs. The most problematic symptom is in the airways. The airway has a very thick sticky mucus secretion which allow a good environment for bacterial infections. The continuous infections that are present cause continuous chemotaxis of neutrophils which later cause deposits of DNA, as a result the mucus becomes even more sticky. it is very difficult to clear the mucus therefore more infections occur. 

Dornase alfa hydrolyses extracellular DNA from neutrophils in the bronchial mucus, this causes an increase in the liquidity. 

Question 2: Briefly explain what neonatal respiratory distress syndrome is, what the general treatment strategies involve and hw cortisone and exogenous surfactants solve the problem

The surface active material that covers the respiratory tract of the airway is only formed during the final weeks of pregnancy. When premature babies are born the surface active material is not formed, this causes gas exchange to be disrupted and the lungs might collapse. Treatment needs to be followed quickly in order to save the babys life. 

The general treatment options would be: oxygen as this ensure oxygenation, ventilation for positive pressure and medications (exogenous surfactants like poractant alfa and beractant )

Cortisone increases surfactant production and can be administered prophylactically 

Exogenous surfactants increase the lungs surfactant 

Question 3: What is the role of oxygen therapy in neonatal respiratory distress syndrome? what do the dangers of oxygen toxicity involve?

Oxygen is given in order to guarantee oxygenation. A continuous oxygen pressure from the ventilator helps increase respiration and allows the alveoli to stay open and not collapse. The arterial partial oxygen however needs to be continuously monitored.  In order for respiration to take place there needs to be enough oxygen present. It is therefore administered to prevent hypoxia. However, when oxygen is inhaled in large quantities or over a long time it has toxic effects. It can cause inter alia, reduced gaseous exchange, hypoxia and in very severe cases even death. In neonates it can also cause retinal damage which leads to blindness

Question 4: Briefly explain what neonatal apnea is and how the methylxanthines solve the problem. which methylxanthine is used ?

It occurs when your respiratory center in the medulla of a premature baby has not been able to develop enough to stimulate continuous breathing. Therefore, making the breathing center very sensitive to stimulation and effect of CO2. Apneas typical duration is not longer than 15seconds and comes together with bradycardia. The continuous episodes of apnea can lead to neural damage. 

Methyxanthines like caffeine and theophylline stimulate the CNS. IV administrations tend to aid the problem. Therapy will be stopped usually after a few weeks in the ICU. The neonate will thereafter receive oxygen therapy. It is important to always monitor the oxygen levels in the blood.

 

Question 1: What are the general causes of rhinitis and rhinorrhea?

Rhinitis is linked to cold and flu.

Mucosal rhinitis which is linked to sinusitis.

Allergic rhinitis is linked to allergen exposure and IgE mediated inflammation.

Non-allergic rhinitis is he physiological reaction because of stimuli like the cold or smoke.

Question 2: Which drugs can be used for the treatment of rhinorrhea? name examples of each group

• Alpha1-agonist (naphazoline)
• Corticosteroids ( Budesonide)
• Mast cell stabilizer (ketotifien)
• Antihistamines (loratidine)
• Mucolytics (Mesna)
• Diverse drugs (normal saline)
• Antibiotics (neomycin)

Question 3: How do decongestants differ with respect to the moa and duration of action? how are they administered typically?

MOA: decongestants present are alpha adrenoceptor sympathomimetics, They therefore cause vasoconstriction, as a result reducing nasal airway resistance and allows breathing through the nose.

Duration of action: they provide quick relief that can last up to 12 hours however, they can only be used for 5-7 days.

Decongestants are administered topically by metered-dose sprays, which is the safest.

Question 4: What is rhinitis medicamentosa ? How is it treated?

Rhinitis medicamentosa is a condition that develops if the topical decongestants are repeatedly used for more than 7 days. this happens when an overstimulation of the alpha receptor (in the nasal mucosa) occurs. Therefore leading to the drying of the mucosal tissue. As a result you are left with a blocked nose that can be treated with cortisone nasal sprays.

Question 5: How does the first and second gen of antihistamines differ with respect to the mechanisms according to which rhinitis and rhinorrhea are delivered? What are the advantages of the second gen of antihistamines? why should they not be used to relieve cold rhinitis?

1st gen antihistamines are used for non allergic rhinorrhea since they reduce inflammation in the nose. They also treat the symptoms.

2nd gen antihistamines are used to treat allergic rhinitis since they inhibit the release of histamine from  mast cells as well as other inflammation mediators. The advantages would be that they have almost no CNS distribution and have a low incidence to patients who have sedation and anticholinergic side effects.

However, antihistamines should never be used to alleviate cold rhinitis since symptoms which are caused by the bodys response are not related to histamine production. Antihistamines will have no effect. Therefore, we can say that histamine is not the major cause of a runny nose.

Question 6: When are corticosteroids, anti-allergic drugs, mesna and normal salt solution valid and how are they administered?

• Corticosteroids: they are acceptable for the use of allergic rhinitis and is administered topically via nasal spray.
• Anti-allergic drugs: they are acceptable for prophylactic treatment of allergic rhinitis, administered topically via nasal spray.
• Mesna: this is acceptable for sticky nasal secretion, since it aids the mucus to become more of a liquid, administered topically via nasal spray.
• Normal salt solution: acceptable for humidifying dry and swollen mucus membranes of your nose during dry, cold weather, allergy like hay fever, nose bleed and other irritants, it is administered topically via nasal drops.

Question 1: Giver your own definition of COPD

It is a combination of lung diseases that prevent airflow resulting in difficulty in breathing. Some of the most common conditions that make up COPD are: Emphysema (condition where the walls of the air sacs of the lungs are damaged), bronchial asthma (condition where a persons airway become swollen and produces extra mucus which makes breathing difficult) and chronic bronchitis (inflammation of lining of bronchial tubules). Damage to the lungs from COPD can not be reversed.

Question 2: Briefly describe the proposed aetiology and pathophysiology of chronic bronchitis and emphysema

• Emphysema:                                                                                                                                                   

The cause of emphysema is generally continuous exposure to irritants that  damage your lungs and their airways.  The damage done to the alveoli eventually leads to reduced elasticity and over-inflation. This therefore causes swelling of the bullae where the CO2 becomes trapped. Due to this reason the lungs are being deprived of continuous flow of oxygen therefore causing deeper breathing. Emphysema is therefore known as a lung condition that causes shortness of breath.

 

• Chronic bronchitis:

It is a non-specific obstructive airway disease which is characterized by: reduced mucus secretion and mucosal clearance, recurring bacterial respiratory infections, changes in bronchial walls and chronic cough due to sticky mucus. The bronchial lining becomes inflamed and continuous exposure to smoke, excessive dust or chemicals will eventually cause damage to the bronchioles. Chronic bronchitis is due to hypersecretion of mucus by the goblet cells. The epithelial cells lining the airway responds to infectious stimuli by freeing inflammatory mediators.

 

Question 3: Which types of therapy are included in the treatment of a COPD patient?

• stop smoking.
• Airway obstruction: Bronchodilators.
• Hypoxia: Oxygen inhalation.
• Poor lung capacity: Regular exercise.
• Bacterial infection: antibiotics against influenza.
• surgery: lung transplant.

 

Question 4: Why is ipratropium more effective in the treatment of chronic bronchitis than in the treatment of bronchial asthma?

Ipratropium is a muscarinic Ach receptor antagonist which prevents the function of parasympathetic nervous system. The function includes: the production of bronchial secretions as well as constriction. If this is prevented it will result in bronchodilation and less secretions. Ipratropium is therefore more effective in the treatment of chronic bronchitis since it is characterized by increased mucus secretion. With bronchial asthma, the increased mucus secretion does not have the same effect.

 

Question 5: In which way do the skeletal muscle effects of theophylline have advantages in the treatment of COPD 

Theophylline improves ventilation response, decreases hypoxia and dyspnea in COPD patients. It causes the smooth muscle relaxation which further causes bronchodilation. This allows for easier flow of air to the bronchial air passage therefore, significantly improves breathing.

 

Question 6: What is the role of oxygen therapy in COPD?

Increases the amount of oxygen that flows into your lungs and bloodstream and as a result this improves breathing.

 

Question 1: Give a short critical explanation of the rationale of using fluvoxamine (a selective serotonin reuptake inhibitor (SSRI)) in the treatment of Covid19 patients.

Fluvoxamine is an SSRI which has been FDA approved in the treatment of depression, OCD etc, but has not been approved for the treatment of infections (NIH, 2021). 

Fluvoxamine has a great affinity for S1R. This receptor controls the endonuclease activity of the ER stress sensor, IRE1 as well as controlling expressions of cytokines. This therefore means that Fluvoxamine hinders the inflammatory signaling pathways but hinders inflammatory cytokines synthesis. Upon further research, cytokine expression causes inflammation in Covid19. 

As a result Fluvoxamine still needs further research to determine its success in the treating Covid19 patients. 

 

References: 

NIH (National institute of health). 2021. https://www.covid19treatmentguidlines.nih.gov/therapies/immunomodulators/fluvoxamine/ Date of access: 19 Oct. 2021

NIH (National institute of health). 2021. https://pubmed.ncbi.nlm.nih.gov/33403480/ Date of access: 19 Oct. 2021

 

 

Question 1: What do you understand by the term "endothelium-dependent" vasodilation? Explain

Endothelium-dependent vasodilators like bradykinin increase the intracellular calcium levels in the endothelium. This therefore leads to the synthesis of NO (an EDRF) in the endothelium. NO them makes its way to the vascular smooth muscle to cause a vaso-relaxing effect.

Question 2: When we talk about NOs enzyme, what is meant by "constitutive" and "inducible" enzymes and what are the pathological and physiological implications thereof?

They are enzymes that are repeatedly being synthesized irrespective of physiological need. They have a greater physiological and pathological importance because they are always present in one are. 

On the other hand, Induced enzymes are enzymes which emerge after a particular substance has been added. This implies that the enzyme is in fact present before a substance, therefore the body has to excrete a substance before the enzyme "works". The effects are small.

Question 3: Explain how NO contributes to fatal pathology of septic shock

It is a systemic inflammatory response which is caused by an infection. Some components which are present in bacteria (endotoxins, cytokines and tumor necrosis) cause the formation of iNOS in macrophages, smooth muscle cells etc. formation of NO in a large area therefore leads to severe hypertension, shock and may also lead to death. 

Question 4: Which autacoids mechanism of action depends on effects on the guanylyl cyclase-cGMP system

Nitric oxide (NO)

Question 5: NO may be toxic to the cell. Which mechanisms are available to the body to counter this detrimental effect of NO?

our bodies release NOS enzyme inhibitors that competitively bind to the binding site of arginine  in NOS. Thus, arginine is not converted to nitric oxide. 

Question 6: Name a way in which NO can act pro-inflammatory. Give examples of where it will have advantages or disadvantages. 

When you body reacts to infection or even injury it leads to the activation of leukocytes and release of inflammatory mediators. This causes an increase in iNOS levels in leukocytes. The NO produced is an important microbial agent. the function of TH1 which synthesizes NO. This is a good protective response. The vasodilator effects of NO and effects of COX2 carry a huge role in inflammation, it causes red skin, it increases vascular permeability and increases edema in acute conditions. The disadvantage of NO however would be, in both acute and chronic inflammation the excess NO production may cause tissue damage, psoriasis lesions, airway epithelium in asthma patients and inflammatory bowel lesions.

Question 7: In which possible neurological and psychiatric disease is NO involved?

Parkinson's disease, stroke and amyotrophic lateral sclerosis, which result because of over stimulation of NMDA receptors and therefore causing an increase in the synthesis of NO which inevitably causes excitotoxic neuronal death. 

Question 1: In which diseases are angiotensinogen levels increased? What are the implications of this?

They are increased by estrogens, corticosteroids, thyroid hormones and ANG II. However, these levels are increased when women take estrogen from oral contraceptives and during pregnancy. Therefore explaining the raised angiotensinogen concentration which may result in hypertension. 

Question 2: Why do drugs which inhibit the angiotensin system by acting on angiotensin receptors have fewer side effects than those that inhibit ACE?

Since there is an increase in the levels of bradykinin, ACE inhibitors can lead to angioedema and a dry cough.

Question 3: In which way does ACE inhibitors have a two-folded mechanism of action in the treatment of hypertension?

ACE inhibitors block the conversion of ANG I to ANG II. They also prevent the breakdown of substances namely, enkephalins, bradykinin and substance P. The Action of ACE inhibitors which hinders substances like bradykinin and contributes to lowering blood pressure. 

Question 4: At which type of angiotensin receptor does Losartan and similar drugs act? Do they have any effect, direct or indirect, at other angiotensin II receptors?

Drugs act on  AT1 receptors and when ANG II is increased they act on AT2 receptors. 

Question 5: What are the physiological effects of kinins on arteries and veins? Do other autacoids play a role? Explain

They cause vasodilation in the arteries, this is because of the direct inhibitory effect of kinins on the arteriolar smooth muscle. It can also be explained by the release of vasodilator prostaglandins (PGE2 and PGI2) or NO. Kinins cause the vein to contract because of the release of vasoconstriction prostaglandins (PGF2 alpha) or the direct stimulation of the venous smooth muscle. Autacoids like bradykinin is a potent vasodilator. 

Question 6: Which receptor is probably  the most involved in the important clinical effects of kinins?

B2 receptor.

Question 7: In which way are natriuretic peptides possibly effective in the treatment of hypertension, as well as congestive heart failure?

Natriuretic peptides (namely, ularitide, carperitide, nesiritide and urodilatin) causes natriuresis and vasodilation in the treatment of congestive heart failure. 

Question 8: what is neprylisin and what is the rationale for inhibiting its action in the treatment of heart failure? can you name the drug being used for such? 

It is a key enzyme in the breakdown of natriuretic peptides. The initial motive of neprylisin in cardiovascular disease was to increase endogenous natriuretic peptide levels, therefore achieving vasodilation and natriuresis.

Question 9: Give examples of endothelium-derived vasodilators and vasoconstrictors.

• Vasodilator: PGI2 and Nitric oxide.
• Vasoconstrictors: ET1 and the receptor subtypes ETA and ETB.

Migraine Pathology:

Migraines that are involved in the release of peptide neurotransmitters, a peptide that is associated with CGRP (from the nerve through the cerebral arteries). Therefore, this neurotransmitter induces vasodilation and extravasation of blood plasma and plasma protein into the perivascular oedema, as a result causing mechanical stretching in the dura and the pain nerve endings are activated. 

Migraine treatment:

• Anticonvulsants have prophylactic efficacy for migraines since they suppress excessive activation of the trigeminal nerve endings.
• Anti-inflammatory pain relievers have high efficacy as well.  
• Calcium blockers  and beta blockers are also effective for treating migraine prophylaxis in many patients. 
• Triptans are considered therapy for migraine and the partial agonists of serotonin 1B/1D receptors. It increases intercranial vasoconstriction which prevents vasodilation, which causes pain by stretching the sensory nerve endings. These agents also play a role in decreasing  the release from CGRP and as a result will reduce perivascular oedema in the intercranial circulation. 
• Lastly, ergot alkaloids have a mixed partial agonist effect on alpha-adrenoceptors and serotonin-2-receptors. They therefore block the alpha-agonist vasoconstriction and cause a noticeable contraction of smooth muscle (thus preventing vasodilation which leads to the pain)