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

Fenotiasienderivate:

• Alifatiese syketting (verbinding): Chloorpromasien

Lae potensie, dus min ekstrapiramidale steurnisse (EPS).

Erge sedasie

Sterk anticholinerge effekte

Sterk alfa-litiese effekte, het postural hipotensie tot gevolg

Kardiotoksisiteit

• Piperidien syketting (verbinding): Perisiasien

Lae potensie, dus min ekstrapiramidale steurnisse.

Erge sedasie

Sterk anticholinerge effekte

Sterk alfa-litiese effekte, het postural hipotensie tot gevolg

Kardiotoksisiteit

• Piperasien syketting (verbinding): Flufenasien

Hoë potensie, dus meer EPS

Minder sedasie

Swakker anticholinerge newe-effekte

Swakker alfa-litiese effekte

Minder kardiotoksies (KVS newe-effekte) (Brand, 2021)

Watter reseptore word veral deur die tipiese antipsigotiese middels blokkeer?

Dopamien

Muskariene

Alfa

Histamien

Serotonien (Brand, 2021)

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

Tipiese middels: Blokkeer mesolimbiese dopamien-2 reseptore

Atipiese middels: Blokkeer serotonien-2A reseptore meer as wat dit die dopamien-2 reseptore blokkeer (Brand, 2021).

Watter van die reseptore wat blokkeer word deur die ouer middels verminder die risiko vir ekstrapiramidale newe effekte?

Muskariene

Alfa

Histamien

Serotonien (Brand, 2021)

Watter van die ouer middels het ‘n hoë insidensie van ekstrapiramidale effekte?  Wat is die rede?

Piperasienderivate: Flufenasien, Perfenasien, Trifluoperasien, Prochloorperasien

Haloperidol (Butirofenoonderivaat)

Pimosied (Difenielbutielpiperidien)

Rede: Hierdie middels is potente D2 blokkers, dus is daar ‘n hoë voorkoms van EPS (Brand, 2021).

A.g.v. watter reseptorblokkade het die alifatiese groep middels ‘n hoë insidensie van outonome newe effekte?

Alfa-1 reseptore (Brand, 2021)

Bronne

Brand, L. 2021. Pharmacology FKLG312 2021 Antipsigotiese middels en litiumsoute. Leergeenheid 9. [PDF]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

Brand, L. 2021. Pharmacology FKLG312 2021 Antipsigotiese middels en litiumsoute. Leergeenheid 9. [Video]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

• Watter anti-epileptiese middels beïnvloed die Pil (orale kontrasepsie) se metabolisme en wat is die implikasies hiervan?  Watter middels is veilig om saam met die Pil te gee?

Die volgende anti-epileptiese middels verlaag die Pil (orale kontrasepsie) se effektiwiteit.

• Fenitoïen
• Fenobarbitoon
• Karbamasepien
• Okskarbasepien
• Topiramaat

Die implikasies hiervan kan ‘n onbeplande swangerskap wees (Brand, 2021)

Leviterasetam, Valproaat, Vigabatrin, Gabapentin en Lamotrogine is veilig om saam met die Pil te gee (Brand, 2021).

• Hoe word die kinetika van hierdie middels deur ouderdom beïnvloed (vanaf neonate tot by bejaardes)?

• Neonate: metabolisme vind stadiger plaas.
• Babas en kinders: metabolisme vind vinniger plaas as by volwassenes.
• Bejaardes: metabolisme vind stadiger plaas, laer dosisse moet gegee word aangesien lewerfunksie nie meer optimaal is nie (Brand, 2021).

• In watter gevalle is plasmabloedvlakmonitering aangedui?

• Vir die assessering van pasiëntmeewerkendheid.
• Om te bepaal of die newe-effekte en geneesmiddel vlakke verwant aan mekaar is.
•  Om ‘n terapeutiese konsentrasie omvang te vestig wanneer die pasiënt in remissie is.
• Tydens swangerskap .
• Wanneer ‘n middel wat interaksies (kan) veroorsaak bygevoeg of van die pasiënt se regime verwyder word.
• Indien deurbraak toevalle voorkom.
• Indien die middel se formulering verander (Katzung, 2018).

Bronne

Brand, L. 2021. Pharmacology FKLG312 2021.  Leereenheid 4 [PDF]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

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

• 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.

• Watter tipe kinetika ondergaan etanol in die liggaam?  Verduidelik ook wat die kliniese betekenis hiervan is.

Zero-orde kinetika- daar is ‘n beperkte hoeveelheid ko-ensiem NAD teenwoordig in die liggaam wat veroorsaak dat die alkoholdehidrogenase ensiemsisteem versadigbaar is. Dus sal dit slegs lae en matige hoeveelhede alkohol kan hanteer (Brand, 2021). Indien die alkohol te veel is, kan toksiese newe-effekte ontstaan as gevolg van die opeenhoping.

By vlakke etanol wat gewoonlik in die bloed bereik word, volg die tempo van oksidasie zero-orde kinetika, dit wil sê dit is onafhanklik van tyd en konsentrasie van die middel (Katzung, 2018:397).

• Gee ‘n kort opsomming van die metaboliese weë van etanolmetabolisme.
• Give a brief summary of the metabolic pathways of ethanol metabolism.

Alcohol Dehydrogenase Pathway

This is the primary pathway for alcohol metabolism. Cystolic enzymes catalyze the conversion of alcohol to acetaldehyde mainly in the liver (also brain and stomach). The genetic variation in ADH enzymes affects the rate of ethanol metabolism and can also alter vulnerability to alcohol-abuse disorders. Conversion of ethanol by ADH to acetaldehyde takes place, and a hydrogen ion is transferred from ethanol to the cofactor nicotinamide adenine dinucleotide (NAD+) to form NADH. Alcohol oxidation generates an excess of reducing equivalents in the liver (NADH) as net result. This can contribute to metabolic disorders that accompany chronic alcoholism and lactic acidosis and hypoglycemia that regularly accompany acute alcohol poisoning (Katzung, 2018:397).

This is the metabolism for low and moderate amounts of alcohol. There is a restricted amount of NAD involved  and zero-kinetics are followed.(Brand, 2021).

Microsomal Ethanol-Oxidizing System (MEOS)

Also known as mixed function oxidase system. It uses NADPH as a cofactor in ethanol metabolism and consists primarily of cytochrome P450.

With chronic consumption of alcohol, MEOS activity is induced. This causes a significant increase in ethanol metabolism and clearance of other drugs eliminated by CYP450’s that constitute the MEOS system and in generation of the toxic byproducts of cytochrome P450 reactions (toxins, free radicals, H2O2) (Katzung, 2018:397-398).

The increased MEOS activity (metabolism for higher concentrations of alcohol bigger than 100mg/dl) can be partly responsible for tolerance. As in Alcohol Dehydrogenase Pathway, the end product is also acetaldehyde (Brand, 2021).

• Watter geneesmiddels kan hierdie metabolisme beïnvloed en wat is die effekte daarvan?
• Which drugs can affect this metabolism and what are the effects thereof?

Fomepizole- inhibits alcohol dehydrogenase. It prevents the conversion of methanol and ethylene glycol to toxic metabolites (Katzung, 2018: 406)

Cephalosporins, metronidazole, disulfiram and hypoglycemic drugs  can inhibit Aldehyde dehydrogenase. When these drugs are given with alcohol, aldehyde enzyme activity can be reduced, causing accumulation of acetaldehyde in the body (Brand, 2021).

Disulfiram inhibits oxidation of acetaldehyde and is used to stop drinking by patients with alcohol dependence. When ethanol is used with disulfiram, acetaldehyde accumulates and causes facial flushing, nausea and vomiting, dizziness, and headache.

Metronidazole, cefotetan, trimethoprim – these drugs inhibit ALDH and can cause disulfiram-like reactions in combination with ethanol (Katzung, 2018:398).

Reference list

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.

Some botanicals are effective in treating anxiety and/or insomnia. These botanicals or herbs have less harsch effects than anxiolytic medicines and those used to treat insomnia:

St. John’s wort (Hypericum perforatum): It increases levels of serotonin in the brain and normalizes the HPA-axis by reducing both inflammatory and oxidative stress (anxiolytic effect) (Almaradhan et al., 2012)

Ginkgo biloba: Acts like benzodiazepines, activates GABA pathways and reduces anxiety in patients with General Anxiety Disorder (GAD) (Almaradhan et al., 2012)

Ashwagandha (Withania somnifera): Reduces Anxiety and has anti-inflammatory and rejuvenating qualities (Almaradhan et al., 2012).

Kava kava: This is used as treatment against anxiety. Consists of six psychoactive kavalactones that bind to GABA- dopamine and opiate receptors and uncouple sodium potassium channels. Impulses to muscles are reduced, thus it is a muscle relaxant (Almaradhan et al., 2012).

Valerian (Valeriana officiaonalis): Valerian root components increase GABA synthesis and decrease GABA reuptake at synapses. It also activates glutamic acid decarboxylase. This enzyme is involved in GABA synthesis. The active Valerian root extract (valernic acid) also acts as a GABA agonist and binds to GABA receptors. These Valerian root extracts can reduce anxiety (Almaradhan et al., 2012). Valerian root may also help with onset of sleep and sleep maintenance (insomnia) (WebMD, 2020).

GABA: This neurotransmitter occurs naturally in herbs and plants. It is the main inhibitory neurotransmitter and reduces the excitability of a neural network, thus functioning as a brake on the neural circuitry during stress (Almaradhan et al., 2012)

Theanine: This amino acid is found in green tea. It crosses the blood-brain barrier and increases GABA and dopamine production. Thus theanine lowers anxiety (Almaradhan et al., 2012).

Hops, Lemon Balm, Skullcap, Passionflower and Chamomile: Extracts from these plants also reduce anxiety. Lemon balm increases synaptic GABA. Skullcap components are GABA receptor agonists (Almaradhan et al., 2012). Hops, lemon balm, passionflower and chamomile can also reduce symptoms of insomnia (WebMD, 2020).

Melatonin: This can have sedative-hypnotic effects. It improves sleep onset, duration and quality (Katzung, 2018:1143).

References

Almaradhan, E., Hanna, M.S., Goldstein, T.A., Avila, S.M. & Weeks, B.S.  2012.  Dietary and Botanical Anxiolytics.  Medical Science Monitor, 18(4).  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560823/  Date of access: 4 Mar. 2021.

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

WebMD.  2020.  Alternative Treatments for Insomnia.  https://www.webmd.com/sleep-disorders/alternative-treatments-for-insomnia  Date of access: 4 Mar. 2021.

What factors may affect the absorption and distribution of sedative-hypnotic drugs? What is the clinical significance thereof?

Lipophilicity is a factor that affects the rates of oral absorption of sedative-hypnotics. For example, triazolam’s absorption is very rapid, and the absorption of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, which is a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam) by acid hydrolysis in the stomach. Most of the barbiturates and older sedative-hypnotics, as well as eszopiclone, zaleplon and zolpidem (newer hypnotics) are absorbed fastly into the blood after oral administration.

Lipid solubility plays a big role in determining the rate at which a certain sedative-hypnotic enters the CNS. This property causes a rapid onset of effects of triazolam, thiopental and newer hypnotics.

All the sedative-hypnotics cross the placenta barrier during pregnancy. If they are given during the predelivery period, they can cause depression of neonatal vital functions. They are also detectable in breast milk and can cause depressant effects in the nursing infant (Katzung, 2018: 388).

What is meant by redistribution and what is the significance thereof? / Wat beteken herdistribusie en wat is die belang daarvan?

Herdistribusie van die brein na ander weefsel vind plaas. ‘n Middel soos tiopentoon wat hoogs lipiedoplosbaar is en as induksie narkose middel gebruik word, beweeg baie vinnig va die bloed na die brein; beweeg dan ook weer baie vinnig uit die brein uit. Dit word nie dadelik geëlimineer nie, maar kan versprei na vetweefsel waar dit ‘n depot kan veroorsaak en vandaar vrygestel word (Brand, 2021).

How are the BDs metabolized? Name the various steps in the process.

Biotransformation by hepatic microsomal enzymes (step-by-step):

Step 1: Dealkylation – active metabolites are formed

Step 2: Oxidation – (Cytochrome P450) active metabolites are formed

Step 3: Conjugation (Phase II) of oxidised metabolite with glucuronic acid takes place and inactive metabolite is formed (Brand, 2021).

Which BDs are converted to active metabolites? What is the significance thereof?

• Diazepam
• Chlorazepate
• Prazepam
• Chlordiazepoxide
• Ketazolam

Active metabolites cause an extended duration of action and cumulative effects can occur with multiple doses (Brand, 2021).

Which BDs are not dependent on the cytochrome P450 oxidative enzymes for metabolism? What are the advantages thereof?

• Lorazepam
• Oxazepam
• Lormetazepam
• Temazepam

When Cytochrome P450 activity is reduced, these are the drugs of choice and can be used for older patients, neonates, liver cirrhosis and therapy with P450 enzyme inhibitors like cimetidine, ketoconazole, erythromycin and fluvoxamine (Brand, 2021).

What is enzyme induction? Which of the sedative hypnotic drugs are known for this?. What is the clinical significance of enzyme induction?

Enzyme induction is the enhancement of the rate of its synthesis or the reduction in its rate of degradation (Katzung, 2018:59).

The following sedative hypnotic drugs are affected by enzyme-inducers:

• Flurazepam and zolpidem (Some inducers= barbiturates, carbamazepine, glucocorticoids, phenytoin...) (Katzung, 2018:63).

Induction leads to accelerated substrate metabolism and usually in a decrease in the pharmacologic action of the inducer and also of co-administered drugs. When drugs are metabolically transformed to reactive metabolites, enzyme induction may intensify metabolite-mediated toxicity (Katzung, 2018: 59).

References

Brand, L. 2021. Pharmacology FKLG312 2021 Inleiding. Leergedeelte 1.1. [PDF]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

Brand, L. 2021. Pharmacology FKLG312 2021 Inleiding. Leergedeelte 1.1. [Video]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

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

What does anterograde amnesia mean and which drugs can cause this effect?

Anterograde amnesia  is the inability to remember what happened during the duration of action of the drug and it is caused by benzodiazepines (Katzung, 2018:388).

Name the effects of the sedative-hypnotic drugs on the normal sleep pattern and explain their significance to the patient.

The effects of older sedative-hypnotic drugs and benzodiazepines on normal sleep patterns are:

• the time to fall asleep  (latency of sleep onset)  is decreased
• stage 2 NREM (non-rapid eye movement) sleep duration is increased
• REM (rapid eye movement) sleep duration is decreased
• stage 4 NREM slow-waved sleep duration is decreased

Latency is decreased to persistent sleep by new hypnotics.

Zolpidem decreases REM sleep but do not have a big effect on slow-wave sleep.

Zaleplon decreases the latency of sleep onset but do not have a big effect on total sleep time, NREM or REM sleep.

Eszopiclone increases the total sleep time mostly by increases in stage 2 NREM sleep, but do not have a big effect on sleep patterns at low doses. It decreases REM sleep at the highest recommended dose.

Suvorexant decreases the time to persistent sleep and also increases the total time of sleep.

Clinically useful effects are more rapid onset of sleep and stage 2 prolongation. The deliberate interruption of REM sleep leads to anxiety  as well as irritability  that is followed by a rebound increase in REM sleep.  A similar pattern to this rebound increase in REM sleep can occur after abrupt cessation of drug treatment with older sedative-hypnotics, especially high doses of short duration of action drugs (like triazolam). There is not much evidence  of REM rebound when zolpidem and other new hypnotics are discontinued after use of recommended doses. However, higher doses of zolpidem and zaleplon can cause rebound insomnia. Except for reductions that may occur in slow-wave sleep, there are no reports of disturbances in the secretion of pituitary or adrenal hormones when barbiturates or benzodiazepines are used as hynotics. Sedative-hypnotics that are used for more than 1 to 2 weeks lead to some tolerance to their effects on sleep patterns (Katzung, 2018: 388).

Which of the sedative-hypnotic drugs are used as a supplementary therapy in anaesthesia?  Can you explain why?

• Benzodiazepines (diazepam, lorazepam, midazolam) – these drugs are used intravenously in anesthesia and often in combination with other agents. When benzodiazepines are given in large doses as a supplementary therapy anaesthesia, it can contribute to a persistent postanesthetic respiratory depression. This might be related to their relatively long half-lives ond the formation of active metbolites. These actions can usually be reversed with flumazenil (Katzung, 2018:389).
• Barbiturates (thiopental and methohexital) – these are very lipid–soluble, thus these drugs penetrate brain tissue rapidly after intravenous administration. This caracteristic favours their use for the induction of anesthesia. Fast tissue redistribution accounts for the short duration of action of these drugs, which is useful in recovery from anesthesia (Katzung, 2018:388).

Which of the sedative-hypnotic drugs are used as anticonvulsants?

• Benzodiazepines useful in the management of seizures (clonazepam, nitrazepam, lorazepam, diazepam) (Katzung, 2018:389).
• Barbiturates useful in the treatment of generalized tonic-clonic seizures, but not the drugs of first choice (phenobarbital, metharbital) (Katzung, 2018:389).

What is the mechanism of the muscle-relaxing effects of some of the carbamates and the BDs?

These drugs have inhibitory effects on polisynaptic reflexes and internuncial transmission. At high doses, these drugs can depress transmission at the skeletal neuromuscular junction. This leads to muscle relaxation (Katzung, 2018:389).

Discuss the effects of the sedative-hypnotic drugs on the respiratory and cardiovascular systems.

When hypnotic doses of sedative-hypnotics are given to healthy patients, their effects on respiration are comparable to changes during natural sleep. At therapeutic doses, sedative-hypnotics can cause respiratory depression in patients with pulmonary disease. These are dose-related effects on respiration . Depression of the medullary respiratory center is usually the cause of death due to overdose of sedative-hypnotics (Katzung, 2018:389).

When doses up to those causing hypnosis are given to healthy patients, no significant effects on the cardiovascular system are observed.

However, in hypovolemic states, in patients with heart failure and other diseases that impair cardiovascular function, normal doses of hypnotics can lead to cardiovascular depression, probably as a result of actions on the medullary vasomotor centers. When toxic doses are given, myocardial contractility and vascular tone may both be depressed by central and peripheral effects, possibly by facilitation of the actions of adenosine that leads to circulatory collapse.

Respiratory and cardiovascular effects are more marked when sedative-hypnotics are administered intravenously (Katzung, 2018:389).

References

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

Reza Kuhn

31787215

FKLG 312

Naam van Blog: Blog #1

• Watter tipe ioonkanale word op senuselmembrane gevind?

Voltage gated (Potensiaalafhanklik)

Ligandbemiddelde ioonkanale (Brand, 2021)

• Noem 3 verskille tussen potensiaalafhanklike en ligandafhanklike ioonkanale.

• Vergelyk ionotropiese en metabotropiese reseptore.

• Klassifiseer die SSS reseptore in ionotropiese en metabotropiese reseptore en ken die transduksiemeganisme van elke reseptor.

Ionotropiese reseptore:

GABA-A (y-amino bottersuur)

Nikotinies (Asetielcholien)

EAA (Glutamaat)

• NMDA
• AMPA
• Kaїnaat

5-HT3 (Serotonien)

Metabotropiese reseptore:

1. Adrenergies

∝1 (fosfolipase C)

∝2 (adenielsiklase)

ß (1+2) (adenielsiklase)

ß3

2. Dopamienergies

D (1+2) (adenielsiklase)

3. Serotonienergies

5-HT1A + 5-HT1B (adenielsiklase)

5-HT2 (fosfolipase C)

4. Cholienergies

Muskarien-

M1 (fosfolipase C)

M2 (adenielsiklase)

M3

5. GABA

GABA-B (adenielsiklase)

6. Eksitatoriese Aminosuur reseptore

mGluR1 – mGluR8

7. Bensodiasepien

BD

8. H1 (fosfolipase C)

(Brand, 2021)

• Verduidelik die verskil tussen 'n EPSP en 'n IPSP en gee voorbeelde van elk.

• Wat is die rol van kalsium in die ontwikkeling van 'n sinaptiese potensiaal?

‘n Aksiepotensiaal wat beweeg na die akson van die presinaptiese neuron gaan die sinaptiese terminaal binne en aktiveer potensiaal (voltage)-sensitiewe kalsium-kanale in die terminaal se membraan. Die verhoging in die intraterminale kalsium konsentrasie bevorder die samesmelting van sinaptiese vesikels met die presinaptiese membraan. Die neuro-oordragstof binne die vesikels word vrygestel in die sinaptiese spleet en versprei om aan die reseptore van die postsinaptiese membraan te bind, wat veroorsaak dat kanale oopgemaak word en ‘n vinnige verandering in membraangeleiding van die postsinaptiese sel vind plaas (Katzung, 2018: 371).

Bronnelys

Brand, L. 2021. Pharmacology FKLG312 2021 Inleiding. Leergedeelte 1.1. [PDF]. Ongepubliseerde lesing notas op eFundi, FKLG312. Potchefstroom: NWU.

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