STUDY UNIT 3.5

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

Cystic Fibrosis is a genetic metabolic disease that decreases DNase1 which results in reduced secretions in various organs. Dornase alpha inhalations hydrolyses proteins in bronchial mucus which in turn allows it to be more fluid.

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

AKA as hyalin membrane disease and only occurs in premature babies. It is when surfactants which cover the airways and essential for gas exchange are only formed after birth. Corticosteroids are giving to the mother before labour which will initiate the baby’s surfactant production.

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

Oxygen will assist in oxygenation.

Increased oxygen over a long term will lead to retinal damage and blindness

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

This is when the respiratory in the brain has not fully developed to stimulate continuous breathing, occurs in new-born and premature babies. Methylxanthine help to stimulate the CNS and examples include caffeine and theophylline IV for a few weeks.

STUDY UNIT 3.4

1. What are the general causes of rhinitis and rhinorrhoea?

• Allergies
• Cold
• Chemical or drug damage
• Cold air
• Physical damage

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

• α1- agonists: Phenylephrine

• Antihistamines: Promethazine
• Corticosteroids: Betamethasone
• Mast cell stabilizers: Sodium chromoglycate
• Mucolytics: Acetylcysteine
• Antibiotics: Mupirocin
• Diverse drugs: Normal saline

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

MOA: They present α -adrenoceptor sympathomimetics and therefore cause vasoconstriction this will reduce nasal airway resistance and allow breathing through the nose.

Duration of action:

• Short-acting drugs (4 to 6 hours), e.g. ephedrine, phenylephrine, propylhexedrine, naphazoline and tetrahydrozoline;

• Intermediary acting drugs (8 to 10 hours), e.g. xylometazoline;

• Long-acting drugs (12 hours), e.g. oxymetazoline.

Should however only be used for 5-7 days

They administered topically as it is the safest

4. What is rhinitis medicamentosa?  How is it treated?

It is the drying out of the nasal mucosal tissue which will lead to a blocked nose. It is treated with a topical cortisone in the form of a nasal spray e.g., beclomethasone

5. 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?

1^st generation antihistamines are multipotent competing antagonists which block muscarinic receptors. These muscarinic antagonists reduce the secretions of the upper and lower airways. They will therefore be used in the preparations for colds which will clear up rhinorrhoea.

2^nd generation antihistamines do not block muscarinic receptors and are used in both long- and short-term treatment for allergic rhinitis.

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

• Corticosteroids: Allergic rhinitis, administration is topical,
• Anti-allergic drugs: Prophylactic treatment of allergic rhinitis; nasal spray
• Mensa: Makes mucus a liquid; nasal spray.
• Normal salt solution: Nasal lavage.

STUDY UNIT 3.4

1. What are the general causes of rhinitis and rhinorrhoea?

• Allergies
• Cold
• Chemical or drug damage
• Cold air
• Physical damage

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

• α1- agonists: Phenylephrine

• Antihistamines: Promethazine
• Corticosteroids: Betamethasone
• Mast cell stabilizers: Sodium chromoglycate
• Mucolytics: Acetylcysteine
• Antibiotics: Mupirocin
• Diverse drugs: Normal saline

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

MOA: They present α -adrenoceptor sympathomimetics and therefore cause vasoconstriction this will reduce nasal airway resistance and allow breathing through the nose.

Duration of action:

• Short-acting drugs (4 to 6 hours), e.g. ephedrine, phenylephrine, propylhexedrine, naphazoline and tetrahydrozoline;

• Intermediary acting drugs (8 to 10 hours), e.g. xylometazoline;

• Long-acting drugs (12 hours), e.g. oxymetazoline.

Should however only be used for 5-7 days

They administered topically as it is the safest

4. What is rhinitis medicamentosa?  How is it treated?

It is the drying out of the nasal mucosal tissue which will lead to a blocked nose. It is treated with a topical cortisone in the form of a nasal spray e.g., beclomethasone

5. 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?

1^st generation antihistamines are multipotent competing antagonists which block muscarinic receptors. These muscarinic antagonists reduce the secretions of the upper and lower airways. They will therefore be used in the preparations for colds which will clear up rhinorrhoea.

2^nd generation antihistamines do not block muscarinic receptors and are used in both long- and short-term treatment for allergic rhinitis.

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

• Corticosteroids: Allergic rhinitis, administration is topical,
• Anti-allergic drugs: Prophylactic treatment of allergic rhinitis; nasal spray
• Mensa: Makes mucus a liquid; nasal spray.
• Normal salt solution: Nasal lavage.

 

STUDY UNIT 3.2

1. Give your own definition of COPD.

COPD is comprised of different degrees and combinations of bronchial asthma, chronic bronchitis and emphysema which in turn limits air flow and has poor gaseous exchange.

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

Chronic bronchitis is a non-specific airway disease which is characterised by, an increase in mucus secretion and a decrease of mucus clearance. It is alos characterised by frequent bacterial respiratory infections and a chronic cough due sticky mucus.

Emphysema is developed by smoking and irritants. It is an irreversible dilatation of respiratory bronchioles and alveoli due to structural damage. We find that air is trapped in the lings which makes it difficult exhalation.

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

Treatment of COPD incused to stop smoking. In the event of a bacterial infection developing, immunization against influenza and broad-spectrum antibiotics is recommended. Bronchodilators are used in the event of airway obstruction. In mucus secretion dilate mucus with rehydration and steam and in hypoxia oxygen inhalation is key. Light to moderate exercise will help in poor lung capacity.

4. Why is Ipratropium more effective in the treatment of chronic bronchitis than in the treatment of bronchial asthma?

Beta-sympathomimetics can improve mucociliary clearance. Ipratropium inhalation is currently the first line of drug treatment for COPD, the bronchodiatory effect is better achieved with beta-sympathomimetics.

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

Theophylline improves the contraction function of the diaphragm, improves cardiac contractions and increases ventilatory capacity.

6. What is the role of oxygen therapy in COPD?

The combination of beta-sympathomimetic, ipratropium and Theophylline may help bring relief to the patient but if the above medications do not work, corticosteroids. Most of the time however, corticosteroids are ineffective and this is where oxygen therapy maybe put into play to assist the patient. Oxygen therapy is also used used in the treatment of Hypoxia.

Fluvoxamine is a SSRI; it is FDA approved for the treatment of obsessive-compulsive disorder however it has recently been used for the treatment of COVID and for the prevention of patients being hospitalized. The mechanism of action of fluvoxamine in the treatment of COVID is that fluvoxamine binds to sigma-1 receptors found on immune cells. This then inhibits the production of the cytokines responsible for the inflammatory process, as seen in viral and other infections.

https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/#:~:text=Anti%2DInflammatory%20Effect%20of%20Fluvoxamine,reduced%20production%20of%20inflammatory%20cytokines. 

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

Endothelium is responsible for vasodilation.

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

2. 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 are ever present, they are produced at constant rates no matter the demand and are also constantly synthesized regardless of physiological or pathological implications.

Inducible enzymes are only produced when there is a need for them and that is in the presence of other enzymes Pathological or physiological implications can affect the synthesis of these enzymes.

iNOS is not regulated by , but after synthesis it is constitutively active.

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

Systemic shock is a systemic inflammatory response that is caused by infection. Endotoxins from the bacterial cell wall, TNf-α as well as other cytokines, induce the formation of iNOS to NO. Excessive increase in NO may lead to hypotension, shock or in some cases even death.

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

Nitric Oxide

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

The body releases NOS enzyme inhibitors and it will compete with NOS for the binding site of arginine thus preventing arginine from being converted NO.

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

NO plays a role in the body via immune cell function. When foreign antigens enter the body Th1 cells synthesizes NO and NO stimulates the inflammatory prostaglandins by activating COX 2. The inflammatory response of releasing NO can lead to erythema, vascular permeability and subsequent edema along with acute inflammation. Prolonged or excessive NO production can aggregate tissue injury. This can lead to psoriasis lesions, airway epithelium in asthma and inflammatory bowel lesions iNOS induction may also lead to disease pathogen

7. In which possible neurological and psychiatric diseases is NO involved?

• Parkinson's disease
• Amyotrophic lateral sclerosis
• Stroke

1.  In which diseases are angiotensinogen levels increased?  What are the
implications of this?
Hypertension
Corticosteroids, estrogens, thyroid hormones, and ANG II all increase the production of angiotensinogen.

2. Why do drugs which inhibit the angiotensinogen system by acting on angiotensin
receptors have fewer side effects than those that inhibit ACE?
ACE inhibitors block the bradykinin metabolism and bradykinin levels are increased which leads to a common side effect of ACE inhibitors which is a dry cough. 
Angiotensin receptor blockers however, do not influence bradykinin metabolism and therefore no
dry cough is experienced.

3. In which way do ACE inhibitors have a two-fold mechanism of action in the
treatment of hypertension?
ACE inhibitors block the conversion ANG I and ANG II as well as the metabolism of
bradykinin to an inactive metabolite. ANG II leads to an increase in Blood pressure
thus, blocking the conversion of ANG I to ANG II , ACE inhibitors will decrease blood
pressure

4. 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 and other similar drugs are specific competitive antagonists at angiotensin
AT1 receptors
When ANG II is increased AT2 receptors are receptors.

5. What are the physiological effects of kinins on arteries and veins?  Do other
autacoids play a role in this action?  Explain.
Kinins are potent vasodilators and increase the blood flow in the body.                                       Histamine and Serotonin also play a role in this action.
Histamine - H1 and H2 receptors dilatate blood vessels and capillaries
Serotonin- 5-HT2 receptors for vasoconstricting activity and 5-HT1 for vasodilating activity

6. Which receptor is probably the most involved in the important clinical effects of
kinins?
ß2 Receptors 

7. In which way are natriuretic peptides possibly effective in the treatment of
hypertension, as well as congestive heart failure?
Natriuretic peptides increase sodium and water excretion hence causing vasodilation.
The excretion of sodium and water will decreases the volume of fluid leading to blood pressure decreasing while the vasodilation causes better blood flow and therefore 
reducing blood pressure.

8. What is neprilysin 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 neutral endopeptidase and is responsible for degradation of natriuretic
peptides in liver, lungs and kidneys. Neprilysin inhibitors prevent degradation
of natriuretic peptides, increases ANP and BNP and also cause natriuresis and
diuresis.   
A drug used as such is Sacubitril.

Give examples of endothelium-derived vasodilators and vasoconstrictors.
Vasodilators: Nitric oxide and PGI2
Vasoconstrictors: ET1

The Pathology of Migraines:

Migraines involves the distribution of the trigeminal nerve to intra-cranial arteries. The trigeminal nerves release peptide neurotransmitters especially CGRP, a strong vasodilator. Extravasation of plasma proteins and plasma into the perivascular space causes mechanical stretching and in turn activities the pain nerves in the dura.

Treatment:

Triptans eg Rizatriptan– Selective agonists for 5-HT1D and 5-HT1B. Causes
vasoconstriction and prevents the vasodilatory effects and pain associated with migraines.

Ergot alkaloids eg Ergotamine – Partial agonist at 5-HT and at alpha adrenoreceptors especially in
vessels. Prevents vasodilation associated with migraines

Anti-inflammatory analgesics eg Aspirin- Controls migraine pains.

Calcium channel blockers eg Verapamil- Used in the prophylaxis of migraine

Beta blockers eg Timolol–Used in the prophylaxis of migraine.