Pyn is ’n ongename sensoriese en emosionele ervaring geassosieer met werklike of potensiele weefsel skade. Die persepsie van pyn word beïnvloed deur die pasiënt se gemoedstoestand, moraal/moed en die betekenis wat die pyn vir die pasiënt het.

AKUUT:

Agv skade veroorsaak deur ʼn besering en duur gewoonlik ʼn kort tyd. Bv. ʼn operasie kan akute pyn veroorsaak. Die pyn hou op wanneer die wond genees. Intussentyd sal pynstillers gewoonlik die pyn onder beheer hou.

CHRONIES:

Pyn wat veroorsaak word deur veranderinge aan die senuwees en duur voort lank nadat die besering of behandeling verby is, kan wissel van matig tot erg. Chroniese pyn kan moeilik wees om te behandel, maar pynstillers asook ander pynbeheermetodes kan dit dikwels suksesvol beheer.

Senuweepyn word veroorsaak deur druk op senuwees of rugmurg, of deur senuweeskade. Dit word ook neuropatiese pyn genoem. Mense beskryf senuweepyn dikwels as brand, skiet, tintelend of as 'n gevoel van iets wat onder hul vel kruip. Dit kan ook voorkom na ander kankerbehandelings soos radioterapie of chemoterapie.

Beenpyn: Die kankerselle in die been beskadig die beenweefsel en veroorsaak pyn. Mense beskryf hierdie soort pyn dikwels as seer, dof of kloppend.

Sagte weefselpyn van 'n liggaamsorgaan of spier. U kan byvoorbeeld pyn in u rug hê as gevolg van weefselskade aan die nier. U kan nie altyd hierdie pyn bepaal nie, maar dit word gewoonlik beskryf as skerp, krampagtig, seer of kloppend.

Spookpyn in 'n deel van die liggaam wat verwyder is. Byvoorbeeld pyn in 'n arm of been wat verwyder is as gevolg van sarkoom of osteosarkoom. Of pyn in die borsarea na verwydering van die bors (mastektomie). Spookpyn is baie werklik en mense beskryf dit soms as ondraaglik.

Verwysde pyn van 'n orgaan in die liggaam kan in 'n ander deel van die liggaam gevoel word. Dit word verwysde pyn genoem. 'N Geswelde lewer kan byvoorbeeld pyn in die regterskouer veroorsaak, alhoewel die lewer onder die ribbes aan die regterkant van die liggaam is. Dit is omdat die lewer op senuwees wat in die skouer eindig, druk.

• Stel m.b.v. jou handboeke ‘n klassifikasie op van die middels wat as antidepressante gebruik word.

1. Trisikliese antidepressante.
2. Mono-amien oksidase inhibeerders
3. Selektiewe serotonien heropname remmers
4. Serotonien en noradrenalien heropname remmers
5. Selektiewe noradrenalien heropname remmers
6. Tetrasikliese en unisikliese middels
7. Sirkadiese ritme reguleerders
8. Serotonien R moduleerders

• Met betrekking tot die bestaande middels se werkingsmeganismes, wat het hulle almal in gemeen?

Al die middle verhoog die konsentrasie van NA en serotonien by sentrale sinapse deurdat dit heropname en afbraak rem asook blockade van presinaptiese alfa2 outoreseptor.

• Hoe lank neem dit vir hierdie middels se antidepressiewe effekte om te verskyn?  Wat is die rede hiervoor?

14-21 dae omdat dit ’n stadige aanvang van werking het.

• Hoe verskil die TAD’e en die selektiewe serotonienheropname remmers (SSRI’s) van mekaar t.o.v.:

• Hoe werk mirtasepien: Blokkeer inhibitoriese alfa 2 reseptore wat dan NA en serotonien vrystelling bevorder.

• Hoe werk venlafaksien: Dit blokkeer beide serotonien sowel as noradrenalien heropname maar meer potent vir serotonien as vir NA.

• Hoe werk agomelatine: Dit is ’n MT1 en MT2 agonis sowel as serotonien2c antagonis. 5-HT2c veroorsaak disinhibisie van DA en NA vrystelling in frontale korteks wat lei tot verhoging in DA en NA vrystelling.

• Bespreek die moontlike werkingsmeganismes van litium.

Beinvloed cAMP, IP3 en DAG 2de boodskappersisteme, Ig deur afname van verskeie ensieme wat belangrik is in omskakeling en hersirkulasie van die membraanfosfoinositiede.

• Wat is litium se terapeutiese indeks en wat is die kliniese belang daarvan?

0.5-1.5mM

Groter as 2Mm is toksies

• Wanneer word litium as enkelmiddel gebruik en in watter gevalle en met watter tipe middels word litium gekombineer?

Bipolere steurnis

• Noem 3 klinies betekenisvolle interaksies wat litium met ander middels kan hê.  Lig jou antwoord toe met gepaste geneesmiddelvoorbeelde.

fluoksetien verhoog litium vlakke en kan lei tot toksisiteit

bikarbonaat en teofillien verhoog litium uitskeiding wat dus effektiwiteit verlaag.

Karbamasepien en fenitoien in kombinasie met litium is neurotoksies

• Noem die belangrikste newe-effekte van litium.

Tremore, ataksie, sedasie

Nefrogene diabetes insipidus

Tiroiedvergroting

Edeem

Leukositose

Polidipsie, poliurie, nokturie

• Wat is die status van litiumgebruik tydens swangerskap en laktasie?

Litium word geassosieer met 'n verhoogde voorkoms van aangebore kardiovaskulêre afwykings. Litium word in hoë konsentrasies in die borsmelk uitgeskei en borsvoeding word dus nie aanbeveel nie.

• Noem 3 ander belangrike indikasies vir litium.

Bipolere steurnis in kinders

Gemoedstabiliseerder

Depressie

skisofrenie

Evalueer die volgende geval en motiveer jou aanbevelings volledig:

Me B. Polar (21 jaar, 60kg) is ‘n student en het die afgelope 2 maande die volgende medikasie gebruik:

Camcolit 600mg bd. Plasmavlakke wat na twee weke geneem is, was 0.8mmol/L.  Sy het ‘n spierbesering opgedoen en gebruik ook die afgelope 10 dae Indocid R® 75mg n.  By verdere navraag meld sy dat sy “vreeslik gewig opgetel” het en nou sommer van haar ma se “waterpille” drink in die hoop dat sy van die ekstra kilo’s ontslae kan raak.  Sy kla egter dat sy baie moeg is, sukkel om haar oë in die klas oop te hou, dors bly en voortdurend bewerig en naar voel

Die pasient se simptome van moegheid,droe mond en bewerigheid kan toegeskryf word aan die newe effekte van die diuretikums wat sy gebruik om gewig te verloor. Toename in gewig is as gevolg van die litium. Die diuretikum verhoog ook die plasma vlakke van litium wat kan lei tot toksisiteit dus moet dit gestop word.

• Noem ‘n voorbeeld van elk van die drie fenotiasien-subfamilies en sê hoe hulle van mekaar verskil in terme van potensie en newe effekte?

Alifatiese syketting: Chloorpromasien (lae potensie, erge sedasie en sterk anticholinergiese effekte=veroorsaak posturale hipotensie. Is ook kardiotoksies)

Piperidien syketting: Perisiasien (lae potensie, erge sedasie, en sterk anticholinergiese effekte=veroorsaak postural hipotensie. Dit is kardiotoksies)

Piperasien syketting: Flufenasien, Perfenasien, Prochloorperasien (hoe potensie, swakker anticholinergiese newe effekte, minder sedasie, minder kardiovaskulere effekte)

• Watter reseptore word veral deur die tipiese antipsigotiese middels blokkeer?

D2-haloperidole, sulpiried, amisulpiried

D3- amisulpiried

• Hoe verskil die werkingsmeganisme van die atipiese middels van die van die tipiese middels?

Tipiese middels blokkeer mesolimbiese D2 reseptore. Atipiese middels blokkeer 5-HT 2A meer as D2.

• Watter van die ouer middels het ‘n hoë insidensie van ekstrapiramidale effekte? 

Haloperidol, Flufenasien

• Watter twee hoofgroepe middels is belangrik by die behandeling van Parkinsonisme?

1. Middels wat dopamienergiese aktiwiteit verhoog
2. Middels wat cholinergiese aktiwiteit verlaag.

• Hoe werk amantadien as antiparkinsonistiese middel?

Amantadine verhoog die vrystelling van dopamien sowel as die sintese daarvan. Dit blokkeer ook die heropname van dopamien.

Amantadine is ’n NMDA antagonis , dit wil sê dit het antidiskinese effekte.

Dit is ook ’n adenosine A2 antagonis = adenosine A2 inhibeer dopamien en moet dus antagoneer word om dopamien aktiwiteit te verhoog.

Dit verbeter rigiditeit , tremore en bradikinese. 

• Watter van die dopamienagoniste is ergotderivate en watter nie?

Broomkriptien: ergotderivaat

Pramipexole: nie ergotderivaat

Ropinirole: nie ergotderivaat

• Maak ‘n lys van die spesifieke dopamienreseptore wat deur elke agonis gestimuleer word.

Brookriptien: D2 reseptore

Pramipexole: D3 reseptore

Ropinirole: D2 reseptore

• Watter van hierdie middels word as neuronbeskermende middels geklassifiseer?  Wat beteken dit?

Selegilien en Rasagilien : Dit verlaag die progressie van die siekte.

• Wat is die belang van Monoamienoksidase B (MAO-B) selektiewe middels by die behandeling van Parkinsonisme?

MAO-B voorkeur vir dopamien as substraat. Dit verhoog dus dopamien konsentrasie in die sentrale senuwee stelsel. Dit dien ook neurobeskermende middle wat die progressie van die siekte verlaag.

• Hoe werk die COMT-remmers in Parkinsonisme?

COMT metaboliseer l-dopa na 3OMD wat met l-dopa komperteer vir aktiewe transportprosesse. Dit verlaag dus die terapeutiese effek van l-dopa omdat die konsenstrasie te min is en moet dus gerem word. COMT-remmers verleng die werkingsduur van l-dopa. Dit verlaag perifere metabolisme en verbeter dus die biobeskikbaarheid van l-dopa.

• Hoe werk Istradefilien?

Dit is ’n adenosien A2a antagonis

• Bespreek die werkingsmeganisme van safinamide

Dit verlaag glutamaat vrystelling.

Dit verhoog dopamien aktiwiteit deur MAO-B te inhibeer sowel as die heropname van dopamien.

• How does the sensitivity for blockade by a LA compare regarding the following types of fibers:

1. myelinated fibers with unmyelinated fibers:

small and myelinated fibers are easily blocked than unmyelinated fibers.

2. pressure/touch nerves with the dorsal nerves that transmit pain impulses?

Activated pain fibers fire faster, pain sensation selectively blocked by LA.

• Make a list of the effects of LA on other tissues.

• Skeletal muscles: weak blocking action
• Heart: class 1 anti-arrhythmic drug

• What is the basis for the selection of a LA?

Is the LA for small surgical procedures, spinal anesthesia or post-operative analgesia

• Why are LA solutions sometimes saturated with CO₂?

To potentiate the effects of LA

• Which of the LA are typically used for surface anaesthesia?

              Cocaine, benzocaine, oxybuprocaine

Major acute toxic effects of the inhalation drugs

1. Nephrotoxicity: metabolism of enflurane and sevoflurane are able to generate compounds that may lead to nephrotoxicity after prolonged exposure.
2. Hepatotoxicity: after surgery and general anesthesia, hepatic dysfunction may be caused by hypovolemic shock, infection through blood transfer or surgical stress.
3. Hematotoxicity: prolonged exposure to nitrous oxide can decrease methionine synthase activity that can lead to megaloblastic anemia.
4. Malignant hyperthermia: volatile anesthetics can induce malignant hyperthermia when a patient who suffers from malignant hyperthermia undergoes general anesthesia.

Which of the anti-epileptic drugs affect the metabolism of the Pill (oral contraceptive) and what are the implications of this? Which drugs are safe to use in combination with the Pill?  

• Phenobarbital 

• Topiramate 

• Phenytoin 

• Carbamazepine 

• Oxcarbazepine  

These drugs reduce the effectivity of oral contraceptives 

Drugs that are safe to use in combination with the Pill is: 

• Valproate  

• Lamotrigine  

• Gabapentin  

• Levetiracetam  

• Vigabatrin 

Can oral contraceptives also affect the effectivity of the anti-epileptic drugs? 

Yes. Oral contraceptives reduce the plasma concentration of valproate and lamotrigine.  

How does age affect the kinetics of these drugs (from neonates to old age)? 

In neonates the metabolism of these drugs is slow 

In children, these drugs are metabolized faster than in adults 

Elder people should be given a lower dosage as their renal function is lower 

In which cases is plasma blood level monitoring indicated? 

• During pregnancy 

• When breakthrough seizures occur 

• To guide dose adjustment 

• When an interacting medication is added or removed from the patient's regime  

•  To assess adherence 

• To determine whether adverse effects are related to drug levels. 

In geriatric it's important to monitor blood levels as their renal function is low thus drug clearing will be slowed down, meaning high levels of the drug remains in the patient's blood stream.  

Patient with kidney and liver diseases should also be monitored. 

What are the possible mechanisms involved in the occurrence of tolerance to chronic alcohol intake?  

Alcohol causes sedation, anxiety relieve, ataxia, impaired judgement and disinhibited behavior. These CNS effects occur a few hours after consuming and for people who drinks chronically, higher concentration are needed as they are tolerant to the effects of alcohol.  Like other sedative-hypnotic drugs, alcohol is a CNS depressant and can lead to coma, respiratory depression and death when consumed in large concentrations. 

What are the toxic effects of chronic alcohol consumption on the liver and hepatic metabolism? 

Liver disease is the most common medical complication of alcohol abuse. Large consumption of alcohol can lead to severe liver disease. Alcohol fatty liver may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. Cirrhosis contributes to elevated portal blood pressure and esophageal and gastric venous varices which can rupture and lead to massive bleeding.  

What is Wernicke-Korsakoff-syndrome and how is it treated? 

This syndrome is characterized by paralysis of external eye muscles, ataxia and confusion that can progress to coma and even death. It is associated with thiamine deficiency but is common seen with the use of alcohol. Treatment includes thiamine therapy  

Fully explain the fetal alcohol syndrome. 

Fetal alcohol syndrome is caused by alcohol use during pregnancy. Abnormalities that are characterized with this syndrome includes intrauterine growth retardation, microcephaly, poor coordination, underdevelopment of midfacial region, minor joint anomalies. In severe cases, patients present with congenital heart defects and mental retardation. Ethanol crosses the placenta and reaches concentrations in the fetus similar to those in the maternal blood. The fetal liver does not have ADH activity thus the fetus relies on the enzymes in the maternal blood to eliminate alcohol.  

Name 4 drug interactions with alcohol where the pharmacological effects of the other drugs are potentiated by alcohol. 

• Alcohol potentiates the pharmacological effects of many non-sedative drugs including vasodilators and oral hypoglycemic agents. 

• Chronic consumption of alcohol increases the risk of hepatotoxicity due to toxic levels of acetaminophen as a result of increased P450-mediated conversion of acetaminophen to reactive hepatotoxic metabolites. 

• Acute alcohol use can inhibit metabolism of some drugs due to reduced liver blood flow. These drugs include phenothiazines, tricyclic antidepressants and sedative-hypnotic drugs. 

• CNS depression can occur when alcohol is consumed with other CNS depressants such as sedative-hypnotics. 

What type of kinetics applies for alcohol in the body? Also, explain the clinical significance of this. 

Peak alcohol levels are reached within 30minutes and distribution happens very fast. The presence of food in the stomach delays the absorption of alcohol. In the CNS, the concentration of ethanol rises quickly because the brain receives the most blood and ethanol readily crosses biologic membranes. 

More than 90% of alcohol consumed is oxidized in the liver, the rest is excreted by the lungs and in the urine. The rate of oxidation follows zero-order kinetics thus it is independent of time and concentration of the drug. An adult can metabolize 7-10g (150-220ml) of alcohol per hour which is approximately 300ml beer or 105ml wine   

Give a brief summary of the metabolic pathways of ethanol metabolism. 

1. Alcohol dehydrogenase pathway: the primary pathway of alcohol metabolism involves the enzyme called ADH which catalyzes the conversion of alcohol to acetaldehyde. These enzymes are usually found in the liver and small amounts are found in the stomach and brain. Thus, metabolism can occur in the stomach, more in men than in female. 

2. Microsomal ethanol-oxidizing system: this system is also known as the mixed function oxidase system and uses the co-factor NADPH in the metabolism of ethanol. It consists primarily of cytochrome P450 2E1, 1A2 and 3A4. If alcohol is being misused/ chronically consumed, MEO system is induced. 

3. Acetaldehyde metabolism:   much of acetaldehyde is oxidized in the liver in a reaction catalyzed by mitochondrial NAD-dependent aldehyde dehydrogenase (ALDH). Acetate is the product of this reaction and is further metabolized to CO2 and water. 

Which drugs can affect this metabolism and what are the effects thereof? 

Alcohol dehydrogenase are inhibited by the drug Fomepizole, which blocks the metabolism of ethanol. 

Oxidation of acetaldehyde is inhibited by Disulfiram. Acetaldehyde accumulates and causes the person to experience nausea, vomiting, dizziness and headache. 

Drugs such as metronidazole, trimethoprim and cefotetan inhibit ALDH and has the same reaction as disulfiram.