• Watter moontlike meganismes is ter sprake by die ontstaan van toleransie teenoor chroniese alkoholinname?

1) SSS aanpassing as gevolg van chroniese blootstelling aan alkohol (op reseptor of 2de boodskapper vlak word kompensatoriese aanpassings gemaak) (Brand, 2021).

2) Metaboliese tempo verhoog met chroniese alkoholgebruik. By die MEOS (Microsomal Ethanol-Oxidizing System) sisteem –by  hoër konsentrasies alkohol kan ensieme geïnduseer word met chroniese gebruik en kan sodoende meer alkohol per tydseenheid afbreek (Brand, 2021).

Toleransie kan ontstaan as gevolg van etanol geïnduseerde op-regulering van hierdie sisteem (Katzung, 2018:400).

GABA neurotransmissie speel ook ‘n groot rol in toleransie en onttrekking aangesien sedatiewe hipnotikums wat GABA-ergiese neurotransmissie bevorder, alkohol kan vervang tydens onttrekking. GABA-A gemedieerde response kan afreguleer met chroniese alkoholgebruik (Katzung, 2018:400).

• Watter toksiese effekte het chroniese alkoholgebruik op die lewer en lewermetabolisme? What are the toxic effects of chronic alcohol consumption on the liver and hepatic metabolism?

Alcoholic fatty liver can progress to alcoholic hepatitis and then progress to cirrhosis and liver failure. Simultaneous infection with hepatitis B or C virus can increase risk of severe liver disease. Cirrhosis can lead to elevated portal blood pressure as well as esophageal and gastric venous varices. The varices can cause severe bleeding when ruptured.

Alcoholic liver disease’s pathogenesis is a multifactorial process that includes methabolic repercussions of ethanol oxidation in the liver, dysregulation of fatty acid oxidation and synthesis, and also the activation of innate immune system. This is the cause of direct effects of ethanol and its metabolites and bacterial endotoxins that access the liver as a result of ethanol-induced changes in the intestinal tract. Tumor necrosis factor alfa plays a crucial role in the progression of alcoholic liver disease and can be a good choice of therapeutic target (Katzung, 2018:400).

Gluconeogenesis is another toxic effect on the liver as it can decrease with chronic alcohol consumption. This can be caused by hypoglycemia and fat accumulation as well as nutrient deficiencies. There is also an increased activity of MEOS enzymes that can cause tolerance to alcohol  (Brand, 2021).

• Wat is Wernicke-Korsakoff-sindroom en hoe word dit behandel? What is Wernicke-Korsakoff-syndrome and how is it treated?

This relatively uncommon syndrome is characterized by paralysis of the external eye muscles, ataxia, and a confused state that can lead to coma and death. It is connected to thiamine deficiency and is uncommon in the abscenece of alcoholism. Therapy consists of administration of thiamine (Katzung, 2018:400).

• Wat is die fetale alkoholsindroom?  Verduidelik volledig. Fully explain the foetal alcohol syndrome.

Chronic alcohol abuse by a mother while pregnant can cause teratogenic effects. The alcohol can cause mental retardation and congenital malformation. The abnormaities in a person with fetal alcohol syndrome are:

• Intrauterine growth retardation
• Microcephaly
• Poor coordination
• Underdevelopment of midfacial area
• Minor joint abnormalities
• Congenital heart defects and mental retardation in severe cases

The mechanism of teratogenic effects is unknown. Ethanol speedily crosses the placenta and reaches concentrations in the fetus similar to those in maternal blood. The fetus’sliver has little or no alcohol dehydrogenase activity , thus the fetus must rely on maternal and placental enzymes for alcohol elimination.

Neurological abnormalities are that ethanol triggers apoptotic neurodegeneration and also causes abnormal neuronal and glial migration in the developing nervous system. In tissue culture systems, ethanol can cause a big reduction in neurite outgrowth (Katzung, 2018:401).

• Hoe verskil die farmakokinetiese interaksies van akute en chroniese alkoholgebruik? How do the pharmacokinetic interactions of acute alcohol consumption differ from that of chronic alcohol consumption?

Chronic consumption of alcohol without damage to the liver can enhance the metabolic biotransformation of other drugs.

Acute consumption of alcohol can inhibit metabolism of other drugs because of decrease in activity of enzymes or decreased liver blood flow (Katzung, 2018:402) like Phenothiazines, TAD’s (tricyclic antidepressants) and other sedative-hypnotics (Brand, 2021).

• Noem 4 geneesmiddelinteraksies met alkohol waar die farmakologiese effekte van die ander middels deur alkohol gepotensieer word. Name 4 drug interactions with alcohol where the pharmacological effects of the other drugs are potentiated by alcohol.

Potensieer effekte van:

Parasetamol

Vasodilatore

Hipoglisemiese middels

Aspirien (anti-kleefbaarheidseffekte) (Brand, 2021)

Acetaminophen

Inhibit metabolism of other drugs

Phenothiazines

Tricyclic antidepressants

Sedative hypnotic drugs (Katzung, 2018:402)

Reference list

Brand, L. 2021. Pharmacology FKLG312 2021.  Leereenheid 3 [Video]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

Brand, L. 2021. Pharmacology FKLG312 2021.  Study unit 3 [PDF]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU.

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14th ed. New York: McGraw-Hill Education.