Verduidelik kortliks wat sistiese fibrose is en hoe dornase-alfa werk om die probleem op te los?

• Sistiesefibrose is genetiese metaboliese siekte(verlaag DNase 1) wat lei tot verlaagde sekresies in verskeie organe. Die manifestasie in die lugweë is die mees prominente en problematiese simptoom, die mucus sekresies in die lugwe is besonder dik en taai wat die ideale omgewing vir bakteriële infeksies skep.
• Dornase-alfa (rhDNase) inhalasies help om die probleem op te los deur proteïene (ekstrasellulêre DNS vanaf die neutrofiele) in die brongiale mucus te hidroliseer om vloeibaarheid te verbeter.

 

Verduidelik kortliks wat neonatale respiratoriese noodsindroom is, wat die algemene behandelingstrategieë behels en hoe kortisoon en eksogene surfaktante werk om die probleem op te los?

• Dit is bekend as hialienmembraansiekte wat by premature babas voorkom waar die oppervlak-aktiewe stof wat die lugweë bedek en noodsaaklik is vir gaswisseling ,eers kort voor geboorte gevorm word en dit kan veroorsaak dat die longe dus kan platval.
• Behandeling strategieë sluit in:

• Suurstofom oksigineringteverseker
• Ventilator gebruikvirpositiewedruk
• Verhoogdesuurstofoorlang termynlei tot retinaleskadeenblindheid
• Gm: eksogene surfaktant: beraktant, poraktant alfa. Word aan die neonaat toegedien om longsurfaktant aan te vul.
• Kortikosteroïede soos betametasoon–word profilakties aan moeder voor kraam toegedien om baba se surfactant produksie te inisieer.

 

Wat is die rol van suurstofterapie by neonatale respiratoriese noodsindroom?  Wat behels die gevare van suurstoftoksisiteit?

• Suurstof terapie word toegedien om oksigenering te verseker.
• Langtermyn se verhoogde suurstof kan lei tot retinale skade asook blindheid, verminderde gaswisseling, hipoksie en in uiterste gevalle, die dood

 

Verduidelik kortliks wat neonatale apnee is en hoe die metielxantiene werk om die probleem op te los.  Watter metielxantiene word gebruik?

• Asemhalingsentrum in brein nog nie volledig ontwikkel om voordurende asemhaling te stimuleer nie. Dit kom by pasgebore en premature babas voor. Die asemhalingsentrum is dus nog onsensitief vir die stimulerende effek van koolsuurgas.
• Metielxantiene help om die probleem op te los deurdat dit die SSS stimuleer. Soms word daar suurstof terapie aangedui en voortdurende monitoring van die suurstofvlakke in die bloed.
• Metielxantiene is bv. Kaffeïen, teofillien IV vir paar weke

Wat is die algemene oorsake van rinitis en rinoree?

• Algemene oorsake is allergie, verkoue, chemieseof gm skade, kouelug of fisiese skade.

 

Watter geneesmiddelgroepe kan by die behandeling van rinoree gebruik word?  Noem voorbeelde by elke groep.

• Alfa 1 agoniste (dekongestante) - Efedrien, fenielefrien
• Antihistamiene – Difenhidramien, prometasien
• Kortikosteroïde – Betametasoon, prednisoon
• Mastselstabiliseerders – Natriumchromoglikaat, nedochromielnatrium
• Mukolitika – Mesna, asetielsistein
• Antibiotika - Mupirosien, neomisien, topikaalbinneneusholte
• Diverse – Stoom, soutoplossing, mentol

 

Hoe verskil die dekongestante onderling ten opsigte van werkingsmeganisme en werkingsduur?  Hoe word hulle tipies toegedien?

• MVW: Simpatomimetiese agente is, alfa 1 agoniste wat vasokonstriksie van die mukosale bloedvate veroorsaak, verlaag dus edeem van die nasale mukosa.

Die a-agoniste gee kan ook verdeel word in:

• kortwerkende middels (4 tot 6 ure), bv. efedrien, fenielefrien, propielheksidrien, nafasolien en tetrahidrosolien
• intermediêrwerkende middels (8 tot 10 ure), bv. silometasolien
• langwerkende middels (12 ure), bv. Oksimetasolien.
• Hulle word dus topikaal of oral toegedien – soos ʼn sproei

 

Wat is rhinitis medicamentosa?  Hoe word dit behandel?

• Rhinitis medicamentosa (privinisme) en terugslagrinitis kan met oordosering van dekongestante ontstaan.  Privinisme is ’n toestand wat ontstaan na chroniese behandeling met dekongestante. Daar is gedurig vasokonstriksie met swak lokale bloedvoorsiening wat kan aanleiding gee tot skade van die neusslymvliese met permanente inflammasie en swelling. Persone met privinisme behoort behandeling te staak en tydelik lokale kortikoïedterapie te ontvang.

 

Hoe verskil die eerste en tweede generasie antihistamiene ten opsigte van die werkings­meganismes waarvolgens rinitis en rinoree verlig word?  Wat is die voordele van die tweede generasie antihistamiene?  Waarom behoort hulle nie gebruik te word om verkouerinitis te verlig nie?

• Die eerste generasie antihistaminika MVW: Multipotente kompeterende antagoniste en blokkeer ook muskariniese reseptore.  Antimuskariniese middels verminder die sekresies van die hoër en die laer lugweë, en kan dus by verkouepreparate ingesluit word om rinoree op te klaar.
• Die tweede generasie antihistamiene MVW: Blokkeer nie muskariniese reseptore nie. Voordele is dat dit bruikbaar is by lang- of korttermynbehandeling van allergiese rinitis.  Aangesien histamien geen rol by verkouerinitisnie speel nie, maar wel bradikinien, help hierdie middels nie om verkouerinitis op te klaar nie.

 

Wanneer is kortikosteroïede, anti-allergiese middels, mesna en normale soutoplossing bruikbaar en hoe word dit toegedien?

• Die gebruik van Anti-allergiese middels is baie effektief by die profilaktiese behandeling van allergiese rhinitis en word toegedien in ‘n neussproei vorm.
• Kortikosteroïde word gebruik teen allergiese rinitis en is in die vorm van ‘n neussproei.
• Mesna word gebruik wanneer die nasale sekrete taai is by rinoree en rhinitis en is in die vorm van ʼn topikale mesna (neursproei).
• Normale soutoplossing is die eerste keuse vir mucus verdunning, stoom inhalasies is effektief.

Give your own definition of COPD.

• Chronic obstructive pulmonary disease is an inclusive term for chronic bronchitis, bronchial asthma and emphysema with the progressive limitation of airflow. This involves constriction of the airways and result in discomfort and makes it difficult to breathe.

 

Beskryf kortliks die voorgestelde etiologie en patofisiologie van chroniese brongitis en emfiseem.

• Chronic bronchitis: Non-specific obstructive airway disease with increased mucus productions and decreased mucosal clearance. Also the appearance of structural changes in the bronchial wall, frequent bacterial airway infections and chronic cough due to sticky mucus.
• Emphysema: This develops usually due to smoking and other irritants (air pollution, chemical fumes). Causes irreversible removal of respiratory bronchiole and alveoli due to structural damage which leads to decreased capillary blood vessel gas exchange.

 

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

• Stop smoking
• Bacterial infections – Immunization against influenza, wide spectrum antibiotics (tetracyclines, erythromycin)
• Airflow obstruction – Bronchodilators
• Mucus secretion – Dilute mucus (steam and rehydration)
• Hypoxia – Oxygen inhalations
• Poor lung capacity – Regular light to moderate exercise

 

Why is ipratropium more effective in the treatment of chronic bronchitis than in the treatment of bronchial asthma

• In asthma a person’s airways become inflamed and ipratropium does not have anti-inflammatory effects. Ipratropium is an anticholinergic agent which inhibits vagus-mediated bronchoconstriction which is more suitable for chronic bronchitis.

 

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

• Theophylline improves contractility of skeletal muscle and reverse fatigue of the diaphragm in patients with COPD. This effect improves the ventilatory response to hypoxia and to diminish dyspnea even in patients with irreversible airflow obstruction.

 

What is the role of oxygen therapy in COPD.

• This will increase oxygen levels in the lungs and blood circulation that will help improve the shortness of breath (dyspnea) and hypoxia.

Wat beteken die term “endotelium-afhanklike” vasodilatasie vir jou? Verduidelik.

The term refers to the action of the increase of intracellular calcium levels in endothelial cells, leading to NO synthesis and NO then diffuses to the vascular smooth muscle leading to the effect of vasodilatation/vasorelaxation.

 

As ons praat van die NOS-ensieme, wat beteken “konstitueel” en “geïnduseerde” ensieme, en wat is die patologiese en fisiologiese implikasies hiervan?

Constitutive enzymes are synthesized at a constant level and also constant amounts. These enzymes are always produced whether or not a suitable substrate is present or regardless of its metabolic state and these enzymes are regulated by calcium.

Inducible enzymes are not regulated by calcium, the presence of an inducer leads to an increase in gene expression. When substrates are added, it results in a major increase of this enzyme leading to iNOS accumulation and produces a great amount of NO.

 

Verduidelik hoe NO tot die noodlottige patologie van septiese skok bydra.

Endotoxin components from the bacterial wall along with endogenously generated tumor necrosis factor and other cytokines induce the synthesis of iNOS in macrophages, neutrophils, T cells as well as hepatocytes, smooth muscle cells, endothelial cells and fibroblasts. This widespread generation on NO results in exaggerated hypotension, shock and in some case death.

 

Watter outakoïede se meganisme van werking berus op effekte op die guanilielsiklase-cGMP-stelsel?

Nitric Oxide (NO)

 

NO kan vir die sel toksies wees.  Watter maniere het die liggaam om hierdie nadelige effek van NO teen te werk?

NO can react with hemoglobin which leads to S-nitrosylation of hemoglobin, resulting in the transport of nitric oxide throughout the vasculature.

NO can be inactivated by reacting with O2 to form nitrogen dioxide.

NO can also react with heme and hemoproteins so that NO can be oxidized to nitrate.

 

Noem ‘n manier hoe NO pro-inflammatories kan optree.  Gee voorbeelde waar dit voor- of nadele sal hê

NO is considered as a pro-inflammatory mediator that induces inflammation in response to abnormal situations meaning that NO helps to regulate the immune system.

Advantages: NO appears to play an important protective role in the body via immune cell function. When foreign antigens are present, TH1 cells respond by synthesizing NO and the importance of this action is demonstrated by the impaired protective response to injected parasites in animal models after inhibition of iNOS.

Disadvantages: Prolonged or excessive NO production can exacerbate tissue injury in both acute and chronic inflammatory conditions.

 

In watter moontlike neurologiese en psigiese siektes is NO betrokke?

Parkinson’s disease, stroke, amyotrophic lateral sclerosis.

In watter siektetoestande is angiotensinogeenvlakke verhoog?  Wat is die implikasies hiervan?

Increased levels of angiotensinogen are associated with Hypertension. High levels of angiotensinogen in the plasma can lead to elevated blood pressure and the body will retain too much fluid. This can also cause the heart to work harder and to grow, can result in heart failure. The synthesis of angiotensinogen is increased by estrogens, thyroid hormones, corticosteroids, ANG II and it is also elevated during pregnancy or when taking estrogen contraceptives.

 

Wat is die rede daarvoor dat middels wat die angiotensienstelsel deur werking op angiotensienreseptore rem, minder newe-effekte het as die wat AOE rem?

Angiotensin receptor blockers are similar to ACE inhibitors, but they have a lower incidence of cough. The blocking of the angiotensin I receptors, the metabolism of Bradykinin to inactive metabolites is not affected which result in the lower incident of dry cough.

 

Op watter wyse het AOE-remmers ‘n tweevoudige meganisme van werking by die behandeling van hipertensie?

ACE inhibitors inhibit the conversion of ANG I to ANG II which is useful in the treatment of hypertension and it also inhibits the degradation of other substances like bradykinin, substance P and enkephalins. This helps with vasodilatation and decreases peripheral resistance and therefore lowers the blood pressure.

 

Op watter tipe angiotensienreseptore werk losartan en soortgelyke middels?  Het hulle enige effekte, direk of indirek, op ander angiotensien II-reseptore?

Losartan and Valsartan are specific competitive antagonists at the AT1 receptors. These drugs are AT1 selective and prolonged treatment will result in the disinhibit of renin release which leads to an increase in the circulating ANG II levels. There might be an increased stimulation of the AT2 receptors which have a indirect effect on AT2 receptors.

 

Wat is die fisiologiese effekte van kiniene op arterieë en vene?  Speel ander outakoïede ‘n rol in hierdie werking?  Verduidelik.

Kinins are known as potent vasodilator peptides. The vasodilatation may be mediated by the release release of NO or vasodilator prostaglandins like PGE2 and PGI2. Other effects of bradykinin include increased release of cAMP, IP3, DAG and also increased capillary permeabilty. All of these contribute to the vasodilatory effects of kinins.

 

Watter reseptor is waarskynlik die mees betrokke in die klinies-belangrike effekte van kiniene?

Bradykinin 2 receptors (B2 receptor)

 

Op watter wyse is natriuretiese peptiede moontlik effektief in die behandeling van hipertensie, asook kongestiewe hartversaking?

The effects of ANP and BNP include vasodilatation, increased Na excretion and GFR, decreased renin secretion, aldosterone mechanism (less Na reabsorption) and inhibits angiotensin II. Because of the vasodilatation and natriuresis, these peptides have been investigated for the treatment of congestive heart failure.

 

Wat is neprilisien en wat is die rasionaal om sy aktiwiteit te inhibeer by die behandeling van hartversaking. Kan jy die middel noem wat sodanig gebruik word. Verwys ook na leereenheid 1 waar julle ook met die spesifieke middel te doen gekry het.

Neprilysin is a neutral endopeptidase (enzyme) that metabolizes ANP and BNP. When this enzyme is inhibited, it results in increased levels of circulating ANP and BNP which leads to increased natriuresis, diuresis and vasodilatation as well as a compensatory increase in renin secretion and plasma ANG II. Due to the increased levels of ANG II, these drugs are not effective as monotherapy in the treatment of heart failure, but in combination with ACE inhibitors. The drug that is used to inhibit neprilysin is Sacubitril.

 

Gee voorbeelde van endotelium-afgeleide vasodilatore en vasokonstriktore.

Vasodilators: CGRP, VIP, Substance P

Vasoconstrictors: NPY

 

 

Migraine involves the trigeminal sensory nerve distribution to intra-cranial arteries. These nerves stimulate the release of peptide neurotransmitters which leads to vasodilatation. The peptide neurotransmitters are calcitonin gene-related peptide (CGRP), which is a potent vasodilator, and also substance P and neurokinin A. This action of the neuropeptides may be the immediate cause of a pain response. Characteristics of migraine include aggravation by routine physical activity, moderate or severe intensity, association with nausea and usually it lasts about 4 to 72 hours.

Treatment of migraine

• Ergot Alkaloids - The action of Ergot derivatives specifically relates to the vasoconstriction effects. They have affinity for a wide range of receptors including dopaminergic, serotonergic and adrenergic receptors (alpha), with cause contraction of the smooth muscles. Drug examples are ergotamine, dihydroergotamine and methysergide.

 

• Triptans - These drugs are currently the first line therapy for acute migraine having a high affinity for 5-HT 1D and 5-HT 1B receptors. The mechanism of action for triptans is the constriction of dilated cranial blood vessels and to inhibit the release of the sensory neuropeptides ( which causes the dilation). Drug examples are sumatriptan, naratriptan and rizatriptan.

 

• Anti-inflammatory analgesics can be used to control the pain, such as aspirin and ibuprofen.

 

• Agents for prophylaxis of migraine include beta-blockers like propranolol, antidepressants such as amitriptyline, calcium channel blockers like flunarizine and also anticonvulsants like valproic acid.