What are the common causes of rhinitis and rhinorrhea?
These conditions are usually the result of allergies, colds, chemical or drug damage, cold air or physical damage

 What drug groups can be used in the treatment of rhinorrhea? Give examples to each group.
Anti-infective: Mupirosin, Neomasin
α1 agonists (decongestants): phenylephrine, ephedrine, oxymetazoline
Antihistamines: Diphenhydramines, Promethazine, Loratadiene
Corticosteroids: Betamethasone, Prednisone, Budesonide
Antiallergic drugs: Sodium chromoglycate, Nedochromyl sodium
Mucolytics: Mesna, acetylcysteine

Miscellaneous: Steam, saline, essential oils, menthol

 How do the decongestants differ from each other in terms of mechanism of action and duration of action? 
How are they typically administered?

MVW: decongestants are α1 agonists and therefore cause vasoconstriction of mucosal blood vessels and 
decreased edema of nasal mucosa
Operating time: it takes about 4hrs. however, it should not be used for more than 3 days in a row and
 should not be drunk after 16:00.

 What isrhinitis medicamentosa? How is it treated?
It is very severe nasal congestion caused by overuse of decongestant nasal sprays or drops.
It is treated with corticosteroid nasal sprays

 How do the first and second generation antihistamines differ in the mechanisms of action by 
which rhinitis and rhinorrhea are relieved? What are the benefits of second generation antihistamines? 
Why should they not be used to relieve cold sores?

Antihistamines are rarely used due to mucus thickening.

1st generation:
It is effective but causes sedation and decreased concentration
2nd generation:
Effective in allergic rhinitis.
Advantages: can be used in the long run.
It should not be used in cold rhinitis as 2nd generation antihistamines are effective in allergic rhinitis
 and colds are therefore not an allergic reaction.

When are corticosteroids, anti-allergic drugs, mesna and normal saline useful 
and how are they administered?
 Corticosteroids:
is used in reversal of rhinitis medicamentosa
Administered by nasal spray

Antiallergic drugs:
is used for allergic rhinitis
is applied by means of a nasal spray

Mesna:
Used in the treatment of sticky nasal mucus

Normal saline solution:
To dilute mucus in sinusitis.
Rinse with salt dissolved in water 2-4 times a day

Give your own definition of COPD.
COPD is chronic obstructive airways disease.

It consists of different degrees and combinations of bronchial asthma, chronic bronchitis and emphysema. There are several characteristics associated with COPD and include:
Limited airflow
Poor gas exchange
Shortened quality of life
Increased anxiety
Hypoxia
COPD can even lead to death.

 Briefly describe the proposed etiology and pathophysiology of chronic bronchitis and emphysema.
Chronic bronchitis:

It is a non-specific obstructive airway disease characterized by:

Increased mucus secretions
Decreased mucosal clearance
Frequent bacterial respiratory infections
Structural changes in bronchial walls
Chronic cough due to sticky mucus
Airway narrows when filled with mucus - the changes restrict the flow of oxygen into and out of the lungs

Emphysema:

Develops mostly due to smoking and irritating
It is irreversible dilation of respiratory bronchioles and alveoli
The widening is due to structural damage
Air is trapped in the lungs and makes breathing difficult
It causes a decrease in capillary blood vessels which makes gas exchange difficult
It is characterized by damaged alveoli that cause old air to get trapped in it and that new air cannot penetrate it.
 


What types of therapy are included to treat a COPD patient?
Quitting smoking

If there is a bacterial infection:
Immunization against influenza
Broad spectrum antibiotics with infection, eg tetracyclines, amoxicillin, ampicillin, erythromycin, co-trimoxazole
If there is an airflow obstruction:
Bronchodilators
Secret:
Dilute mucus (rehydration and steam)
Hypoxia:
Oxygen inhalation
Weak lung capacity:
Regular light to moderate exercise
 
Why is ipratropium more effective in treating chronic bronchitis than in treating bronchial asthma?
Ipratropium is an anticholinergic drug.

In the treatment of chronic bronchitis:
Ipratropium mimics the actions of atropine by inhibiting salivary and mucosal secretions and dilating bronchial smooth muscle.

In the treatment of bronchial asthma:
It blocks cholinergic receptors and lowers cGMP production
The decrease in lung airway causes a decrease in the contraction of smooth muscle.
 
In what ways do the skeletal muscle effects of theophylline have benefits in the treatment of COPD?
Theophylline improves contraction function of the diaphragm and thus improves ventilatory capacity

 What is the role of oxygen therapy in COPD?
Oxygen treatment increases the amount of oxygen that flows into your lungs and bloodstream. In severe cases of COPD, the patient's oxygen count is very low and so getting more oxygen can help the patient breathe better.

Give a short and critical explanation of the rationale of using fluvoxamine (a selective serotonin reuptake inhibitor (SSRI) in the treatment of Covid patients

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is approved by the Food and Drug Administration (FDA) for the treatment of obsessive-compulsive disorder and is used for other conditions, including depression. Fluvoxamine is not FDA-approved for the treatment of any infection.

In a murine sepsis model, fluvoxamine was found to bind to the sigma-1 receptor in immune cells, resulting in reduced production of inflammatory cytokines. In an in vitro study of human endothelial cells and macrophages, fluvoxamine reduced the expression of inflammatory genes.² Further studies are needed to establish whether the anti-inflammatory effects of fluvoxamine observed in nonclinical studies also occur in humans beings and are clinically relevant in the setting of COVID-19.

References

Anderson, G.M., 2021. Fluvoxamine, melatonin and COVID-19. Psychopharmacology, 238(2), pp.611-611.

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

The concept that the endothelium controls vascular tone in a paracrine fashion (i.e. by secreting diffusible soluble mediators able to act on physically contiguous cells, in this case smooth muscle) was extremely innovative and relevant to vascular physiology

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?

iNOS are expressed through transcriptional induction (inducible) when exposed to inflammatory mediators and this expression, and thus NO synthesis, is not regulated by calcium. eNOS and nNOS are expressed constituvely (=continuously produced regardless of cells' needs) and NO synthesis is dependent on calcium regulation. Cytosolic calcium forms complexes with calmodulin which then binds and activates eNOS and nNOS.

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. 

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

Nitric oxide (NO)

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

the body makes sure that there is not an excess of NO present, for example through homeostasis.

6.Name a way in which NO can act pro-inflammatory. Give examples where it will have advantages or disadvantages.
NO is pro-inflammatory because it induces inflammation when there is an overproduction in abnormal conditions.
Benefits- Accelerates the healing of injured tissue, as the inflammation increases blood flow to the affected area.
Adverse- in a swollen joint, where it can cause pain when the joint is used.

7. In what possible neurological and mental illnesses is NO involved?
Parkinsonism, Alzheimer's, Huntington's disease, stroke

1.In what disease states were angiotensinogen levels increased? What are the implications of this?
Hypertension and heart failure, because there is an over activity of renin-angiotensin-aldosterone system (RAAS). This leads to more angiotensin II in the body and thus it will increase the production of angiotensinogen. The implication of this is more angiotensinogen is present for the formation of angiotensin II which worsens the disease state because it causes vasoconstriction effects for example.

2.What is the reason why drugs that inhibit the angiotensin system by acting on angiotensin receptors have fewer side effects than those that inhibit AOE?
The angiotensin antagonists act directly on the receptors and will immediately elicit the therapeutic effect without exerting an effect on another system and thus there are fewer side effects present, where with the ACE inhibitors it will have an effect on the bradikini system. AOE converts bradykinin to its inactive peptide, when the enzyme is inhibited it means there will be increased levels of bradikinin. These high levels give rise to side effects, namely a dry cough and bronchoconstriction, which can have a bad effect on asthma leaders, for example.

3.In what way do ACE inhibitors have a dual mechanism of action in the treatment of hypertension?
AOE acts on two systems namely where angiotensin II is formed and bradykinin is converted to inactive form.
 When AOE is inhibited it gives rise to the inhibition of angiotensin II formation because it means angiotensin II is not present to elicit vasoconstrictive and increase in blood volume effects so blood pressure will decrease.
Bradykinin has hypotensive activity because it is a vasodilator and if the AOE is not present to convert bradikinin to inactive peptide, it means that there is an increased concentration of bradikinin present and therefore a greater effect on the decrease in blood pressure.

4.What type of angiotensin receptors does losartan and similar drugs work on? Do they have any effects, directly or indirectly, on other angiotensin II receptors?
Lorsartan is a competing antagonist and acts on the AT1 receptors. They have an indirect effect on AT2 receptors. This is because the long use of these antagonists can lead to an increase in renin release and therefore there is an increase in angiotensin II that can bind to these AT2 receptors and elicit a vasodilatory effect that can be beneficial for treatment.

5.What are the physiological effects of quinines on arteries and veins? Do other autacoids play a role in this action? Explain.
The physiological effect is arterial dilatation and venous contraction, other autacoids namely prostaglandins also play a role in the blood vessels because they are released in response to quinines.

6.Which receptor is probably most involved in the clinically important effects of quinines?
Bradycin receptors. (B1 & B2)

7.In what ways are natriuretic peptides potentially effective in treating hypertension as well as congestive heart failure?
Atrial natriuretic peptide (ANP) and Brain natriuretic peptide (BNP) are both effective in both conditions because they are vasodilatory and decrease blood volume by inducing natriuresis and diuresis. This can lead to a decrease in blood pressure as well as preload and afterload on the heart.

8.What is neprylisine and what is the rationale for inhibiting its activity in the treatment of heart failure. Can you name the remedy that is used as such. Also refer to study unit 1 where you also dealt with the specific remedy.
Niprylisine is the enzyme that breaks down ANP and BNP. A niprylisine inhibitor such as Sucubitril is effective in treating heart failure because it prevents the breakdown of ANP and BNP which means they increase their concentration. This therefore leads to a better effect of natriuresis and diuresis which decreases the blood volume and it relieves tension on the heart. This drug can be combined with valsartan, valsartan is an angiotensin II antagonist and will therefore counteract the effects of RAAS. The name of the combined remedy is Entresto.

9.Give examples of endothelial-derived vasodilators and vasoconstrictors.
Vasodilators: Bosentan. (endothelial antagonist)
Vasoconstrictors: Endothelin 1, 2 and 3.

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.

Treatments:

1. Triptans - It is a first line drug therapy for migraines. It is selective agonists for 5-HT 1D and - 1B receptors. These drugs activate the 5-HT 1D and - 1B receptors on the presynaptic trigeminal nerve endings preventing the release of the peptide neurotransmitters. E.g. Sumatriptan.

2. Ergot alkaloids - They have mixed partial agonistic effects on the 5-HT2 receptors and the alpha adrenergic receptors. They cause contraction of the smooth muscle but also blacks alpha agonist vasoconstriction which helps to reduce the vasodilation which causes migraines. E.g. Ergonovine.

3. Anti-inflammatory analgesics - These drugs are used to control the pain caused by migraines. E.g. Aspirin.

4. Anticonvulsants - it suppress excessive activation of the nerve ends and it is used as a prophylactic treatment. E.g. Valproic.

5. Beta- and calcium channel blockers - are also used in the prophylactic treatment of migraines. E.g. Propranolol and Flunarizine.