1. Is a genetic metabolic disease that decreases DNase 1 leading to decreased secretions in various organs. Dornase alpha is a rhDNase inhaler  that hydrolyses the proteins in the bronchial mucosa making the more fluid.

2. Surface active agents( surfactant, which covers airways and is essential for gaseous exchange) is only formed shortly after birth. Corticosteroids (betamethasone) can be given as it starts surfactant production. O2 may be used to ensure oxygenation.

3. O2 is to ensure oxygenation but an increase for a long term periods leads to retinal damage and blindness.

4. It is a respiratory centre in brain not yet fully developed to stimulate continuous breathing seen in new borns and premature babies. Methylxanthines stimulate CNS. Examples include caffeine / theophylline IV for a few weeks

1. Cold, allergies, physical damage, drug or chemical damage.

2. Alpha- antagonist- phenylephrine, corticosteroids- betamethasone, antihistamines- Loratadine, antibiotics- mupirocin, mucolytics- mensa, mast cell stabilizers- ketoifen.

3.  Decongestants cause vasoconstricion of mucosal blood vessels that reduces oedema of nasal mucosa. Local Decongestants have fewer SE eg oxymetazoline (drops). Short acting drugs have a duration of 4 to 6 hours, intermediate acting drugs have a 8 to 10 hour duration and long acting drugs have a 12 hour duration.

4. Rhinitis medicamentosa is the permanent vasoconstriction that has a poor local blood supply leading to the damage of mucosa membranes in the nose and gives permanent swelling and inflammation. Xylomethazoline may only be used for a few days cause rhinitis medicamentosa may develop.

5. 1st gen, used for rhinorrhea, 2nd gen used for allergic rhinitis. 2nd gen doesn't block muscarinic receptors and doesn't cause sedation like the first gen.

6. Corticosteroids- used for allergic rhinitis, administration is topical, anti-allergic drugs- prophylactic treatment of allergic rhinitis given as a nasal spray. Mensa- makes mucus a liquid given as a nasal spray. Normal salt solution- nasal lavage.

1.  COPD has a different degree of combinations such as bronchial asthma, chronic bronchitis and emphysema. This limits the limit air flow as well as gaseous exchange.

2. Chronic bronchitis is a non-specific COPD that is characterised by increased mucus secretion, decreased mucociliary clearance, regular bacterial respiratory infections, structural changes in bronchial walls and a chronic cough due to thick mucus.

Emphysema is often developed from smoking and irritants. Irreversible widening of respiratory bronchioles and alveoli. Air is trapped in lungs which equals difficult expiration. A decreased capillary blood vessels. Impededs gaseous exchange.

3. Treatment includes stop smoking. You may develop bacterial infection such as influenza immunization and broad spectrum antibiotics which can be treated with tetracycline, amoxicillin, ampicillin erythromycin. In the airflow obstruction give bronchodialtors. In mucus secretion dilate mucus with rehydration and steam. In hypoxia give oxygen inhalation. In poor lung capacity light moderate exercise will help.

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

6.  The combination of beta-sympathomimetic, ipratropium and Theophylline may help bring relief however corticosteroids may be given if the above medications don't work. Corticosteroids are mostly ineffective so if needed oxygen therapy should be given.

Fluvoxamine has an anti-inflammatory effect which binds to sigma-1 receptors, reducing the building of inflammatory cytokines, this therefore can help patients that have covid. 

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

Since covid can lead to serious illnesses, Fluvoxamine can prevent deterioration of the immune cells seen due to fluvoxamine regulating cytokine production.

1. It increases the intracellular Ca levels causing the synthesis of NO going to smooth muscle and causing vasorelaxation.

2.Constitutive-enzymes being synthesized at the constant rate, in constant amounts being regulated by Ca. Inducible- enzymes present in minute concentrations, which when a substrate is added it incraeses the enzyme. However this enzyme is not regulated by Ca causing and accumulation of iNOS producing an increase in NO.

3. Endotoxin components produce TNF which iduces iNOS synthesis in T cells, smooth muscles and macrophages. This inturn can cause shock and hypotension.

4. NO gas

5.NO reacts with heme which converts NO to nitrate, NO reacts with hemoglobin which can transport NO all round the vasculature.

6. NO acts as a pro-inflammatory due to it being an immune regulator. Disadvantage include extended production leading to worsened tissue injury. 

7. Stroke and parkinsons disease

 

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

This disease is Hypertension ,an increase in the angiotensinogen through renin causes it to convert to angiotensin II. This causes vasoconstriction and increases the secretion of aldosterone.

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

Drugs which block ACE will also reduce the amount of bradykinin 2.However, drugs which act on angiotensin receptors may not inhibit the breakdown of bradykinin.

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

ACE inhibitors block the conversion of angiotensin 1 to angiotension 2. This prevents the breakdown of natriuretic peptides which decreases angiotension 2 synthesis leading to vasodilation, decreasing blood pressure. Aldosterone secretion is also decreased which would normally reabsorb NaCl if the BP is low in order to increase it . Since aldosterone is decreased the blood pressure will be decreased leading to the treatment of hypertension.

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?

Angiotensin 2 type 1 receptors which have no effect on type 2 receptors.

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 causing dilation of arteries and veins, and many autacoids play a role such as Natriuretic peptides, vasoactive peptides, substance P, neurokinin A and B and CGRP.

Which receptor is probably the most involved in the important clinical effects of kinins? Bradykinin 2 receptors.

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

Natriuretic peptides cause vasodilation which can cause a decrease in blood pressure, effective in the treatment of hyperstion. It increases GF and Na secretion, decrease renin and aldosterone secretion, which relieves fluid build up helping with congestive heart failure.

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.

Neprylisin metabolises natriuretic peptides ANP and BNP. In a reduction of ANP and BNP their effect on CHF patients will be reduced, leading to vasoconstriction with an increase in GF and Na excretion as well as renin secretion being increased causing an increase in blood pressure. Sacubitril which is a Neprilysin inhibitor.

Give examples of endothelium-derived vasodilators and vasoconstrictors.

Endothelium-derived vasodilators: NO and PGI2,  Endothelium-derived vasoconstrictors: ET1,2,3 and ETA,B

Migraine Pathology:

The trigeminal nerve is a vascular nerve that supplies neurotansmitters, such as CGRP, to the intracranial and extracranial arteries.

This neurotransmitter causes the blood plasma and plasma proteins to enter the perivascular space, which then activates the mechanical stretching of the dura.

These neurotransmitters can produce vasodilation, which can cause perivascular oedema. It can also cause mechanical stretching and activation of pain nerve endings.

Treatment for migraine: 5-HT 1D/B receptor agonists such as sumatriptan. 

Ergot alkaloids that are vasoselective such as ergotamine which causes marked smooth muscle contraction.

Furthermore Beta blockers can also be used for the treatment of migraine as well as NSAIDS.