-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? 

Drugs that will affect the metabolism of the Pill are Perampanel, phenobarbitone, phenytoin, carbamazepine and oxcarbazepine. They all decrease the effectiveness of the Pill and will lead to an increase in pregnancies and also an increase in teratogenic effects in the pregnancies.

Drugs that are safe to use in combination with the Pill is Lamotrigine, Valproate, Gabapentin, Leviteracetam and Vigabatrin.

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

Yes, oral contraceptives can decrease the serum levels of drugs such as Lamotrigine and Valproate.

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

Neonates metabolises the drugs slower, thus they should have lower dosages. Kids and children have a faster metabolism and they metabolise the drugs faster, thus they should receive a higher dosage. Geriatric patients have slower metabolism and decreased renal function that is why they should receive lower dosages.

-In which cases is plasma blood level monitoring indicated?   

Where protein binding takes place, this can also be in diseases that affect protein binding. It can include liver diseases, hypoalbuminemia, burns, pregnancy and malnutrition.

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

There can be changes or adjustments in the central nervous system due to the constant exposure on the receptors or secondary messengers.

There can be an increase in the MEOS system when alcohol in chronically used.

There can be an increase in the metabolism of ethanol and also clearance of other drugs in the body that are eliminated by cytochrome P450 enzymes.

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

Liver diseases like hepatitis, cirrhosis or liver failure may happen since the tissues of the liver will be damaged when alcohol is chronically consumed. The damage to the tissue is because of the effects of ethanol and acetaldehyde.

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

It is a syndrome that is because of neuropathy. The characteristics of this syndrome is the paralysis of the external eye muscles, ataxia, confusion and coma that can lead to death. It is associated with a thiamine deficiency and parenteral thiamine is given to patients with chronic alcohol effects. Even though the syndrome can’t always be reversed, the thiamine is given to prevent permanent damage to the brain.

-What is foetal alcohol syndrome? Explain. :

Foetal alcohol syndrome is caused by alcohol consumption when the mother is pregnant. The alcohol that is consumed then causes teratogenic effects. If someone is exposed to alcohol in the uterus, it may cause developmental disabilities and cognitive/behavioural defects because it causes damage to the developing neurons. Foetal alcohol syndrome is presented as mental retardation, growth deficiency, microcephaly and underdevelopment of the middle facial area.

-How do the pharmacokinetic interactions of acute alcohol consumption differ from chronic alcohol consumption:

Acute alcohol consumption decreases the metabolism of drugs, which causes the drugs to accumulate and cause central nervous system suppression. Drugs include: tricyclic anti-depressants, phenothiazines and other sedative-hypnotics.

Chronic consumption of alcohol increases the metabolism of drugs so that means the drug has a shortened duration of action.

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

Phenothiazines, tricyclic anti-depressants and other sedative hypnotic’s metabolism will be decreased with acute alcohol consumption due to a decrease in enzyme activity and liver blood flow. Vasodilators and hypoglycaemic drugs also react with acute alcohol consumption which causes a vasodilatory effect in the body (lower blood pressure, decreased heart rate). Alcohol also increases the anti-platelet effect of aspirin.

-What types of kinetics applies for alcohol in the body? Also explain the clinical significance of this:

There are two types of kinetics that applies for alcohols in the body namely: The Alcohol Dehydrogenase system and the MEOS system

The Alcohol Dehydrogenase system metabolizes alcohol by means of zero-order kinetics at a rate of 7-10g/hour. Only low to moderate amounts of alcohol because there is a limited amount of NAD (co-enzyme) that saturates the system.

The MEOS system (Mixed Function Oxidase System) metabolizes higher concentrations of alcohol, the significance of this is that with chronic alcohol users this system’s activity increases, thus more alcohol is metabolized per time unit and in that way tolerance is created.

-Give a brief summary of the metabolic pathways of ethanol metabolism:

Ethanol is metabolized and acetaldehyde is formed as an end product. Acetaldehyde is converted by the enzyme aldehyddehidrogenase to acetate which is then converted to carbon dioxide and water us excreted.

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

Disulfiram

Cephalosporins

Metronidazole

Hypoglycaemic drugs.

These drugs affects the conversion of acetaldehyde to acetate by blocking the action of the enzyme aldehyddehidrogenase.

A lot of other alternative medicines are used for the treatment of conditions such as anxiety and insomnia. A lot of patients believe that it is better to use medicines of natural origin for these conditions since a lot of the medicines that can be prescribed for these conditions can lead to dependency and has other unwanted side effects. Here is a list of alternative medicines used for these conditions: 

Anxiety:

- Amino Acids such as L-tryptophan and L-tyrosine which are precursors for neurotransmitters such as serotonin, dopamine and norepinephrine. 

-Minerals such as Magnesium and Selenium.

-VItamin C,E and D. 

-St. John's Wort can be used as an anti-depressant since it increases the levels of serotonin in the brain. 

-Gingko Biloba which is a herb with anti-inflammatory and rejuvenating qualities. 

Insomnia: 

-Hops

-Lemon Balm

-Lavendar

-Melatonin

 

Alramadhan, E., Hanna, MS., Goldstein, TA., Avila, SM., Weeks, BS. 2012. Dietary and Botanical anxiolytics.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560823/. 8 March2021. 

Taibi, DM., Landis, CA. 2009. Valerian and Other CAM Botanicals in treatment of sleep disturbances. https://www.sciencedirect.com/science/article/pii/B9780123742285000044. 8 March 2021. 

 

 

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

The rate of absorption is determined by the lipophilicity of the drugs, the higher the lipophilicity the faster the onset of action and distribution of the drug and its central nervous system effects (the faster it will work in on the patient’s body). The lower the lipophilicity the slower the absorption and distribution.

What is meant by redistribution and what is the significance thereof?

• Redistribution happens from the brain to the rest of the body. Drugs that are very lipophilic are absorbed and distributed to the brain fast and is then redistributed to other parts of the body like the heart,kidneys and lungs where the drugs can have a depot preparation and thus be released systemically in time.
• How are BD’s metabolized?

1. Dealkylation
2. Oxidation
3. Conjugation

• Which BD’s are converted to active metabolites and what is the significance thereof?

1. Diazepam
2. Chlorazepate
3. Prazezam
4. Chlordiazepoxide
5. Ketazolam

These drugs are converted to active metabolites because they are metabolized by the hepatic microsomal enzymes (CYTP450) they undergo oxidation and conjugation. This active metabolite contributes to the drug effect. These drugs can however be dangerous when it is not metabolized in patients that receive therapy of CYTP450 inhibitors like patients with impaired liver enzyme function, the elderly and neonates.

• Which BD’s are not dependent on the cytochrome P450 oxidative enzymes for metabolism? What are the advantages thereof?

1. Oxazepam
2. Lorazepam
3. Temazepam
4. Lormetazepam

• These drugs are not affected or metabolized by CYTP450, thus they can be given to patients with liver cirrhosis, elderly and neonates because they are not affected by cytochrome P450 and is the drug of choice for these patients.
• 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 when the drug causes an increase in the metabolism of  specific enzymes that increase the metabolism of the drug. This causes a decrease in the amount of drug that circulates in the body and thus means that there will be a decrease in the effect that the drug should have on the body. Enzyme induction usually takes place in barbiturates like phenobarbitone and meprobamate.

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

Anterograde amnesia is a decreased ability to retain new information, you can experience it difficult to make new memories and this can affect your daily life. Drugs that can cause anterograde amnesia is benzodiazepines, like tremazepam and triazolam.

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

Sedative hypnotic drugs decreases the time it takes to fall asleep and increases the duration of the sleep in patients who normally sleep less than six hours a night. A person should preferably not use sedative hypnotic drugs for longer than one to two weeks otherwise the chances (in the case of benzodiazepines) the person could develop a dependency of the drug. A patient could also become tolerant to the effects that the drug has and in then has to increase the dosage of the drug in order to experience the same effects as previously.

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

BD’s like diazepam,midazolam and are included in the anaesthesia regime because it disturbs cognitive and motor function that leads to memory loss which is helpful to forget unnecessary trauma a patient might experience.

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

Benzodiazepines are used as anticonvulsants. Like Chlordiazepoxide,Clonazepam,Clobazam,Diazepam,Lorazepam,Phenobarbital

 

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

The carbamates and benzodiazepines induce skeletal muscle relaxation by inhibiting their presynaptic reflexes.

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

The sedative-hypnotic drugs work in on the medulla which then causes medullar depression which means that respiratory and cardiovascular systems also become depressed by die drugs. That is why the drugs should not be used in patients with prior respiratory or cardiovascular diseases because the depression of these systems could lead to death.

1. Which types of ion channels are found on the nerve cell membranes:

The two types of ion channels are the voltage-gated ion channel and the ligand-gated ion channel.

2. Name 3 differences between voltage-gated and ligand-gated ion channels:

The voltage-gated ion channel responds to when there are changes in the membrane potential of the cell, where the ligand-gated ion channel responds to the binding of a neurotransmitter/ligand to the ion channel. The voltage-gated channel’s gating is controlled by the voltage sensor component of the protein and the ligand-gated channel’s gating is controlled by binding of the neurotransmitter to the ionotropic channel. Voltage-gated channels are responsible to transmit the signal from the cell body to the nerve terminal whereas the Ligand-gated channel is only responsible for fast synaptic transmission typical of hierarchical pathways in the central nervous system. Examples of the voltage-gated ion channels are Sodium channels, Potassium channels and Calcium channels where the ligand-gated ion channels are ionotropic receptors which consist of multiple subunits, which forms part of a receptor complex.

3. Compare ionotropic and metabotropic receptors

Ionotropic receptors are part of the transduction system and they convert extracellular signals to intracellular effects through the opening of ion channels, where Metabotropic receptors convert the extracellular signals to intracellular effects through metabolic changes.

4. Classify the CNS receptors into ionotropic and metabotropic and know the transduction mechanism of each receptor: Receptors that are ionotropic are GABA(y-amino butyric acid) , Nicotinic receptor(acetylcholine) ,EAA(glutamate) and 5-HT3(serotonin). The metabotropic receptors are the 7 Transmembrane G protein coupled receptors and their 2^nd messengers that formed that are grouped as the Adenylyl cyclase system (Beta 1,2/Dopamine 1/Serotonin 1a,b/Muscarinic2) and the Phospholipase C system (alpha 1, serotonin 2 , Muscarinic1,Histamien1).
5. Explain the difference between an EPSP and an IPSP and give examples of each: EPSP is the Excitatory Post Synaptic Potential which has a depolarizing effect (+) and causes the membrane potential to be closer to the threshold of excitation, which gives it a better chance to trigger an action potential, example Glutamate is the main excitatory neurotransmitter. ISPS is Inhibitory Post Synaptic Potential and it has a hyperpolarizing effect (-) which leads the membrane potential further away from the threshold of excitation, example – GABAa is the main inhibitory neurotransmitter.
6. What is the role of calcium in the development of a synaptic potential?: Neurotransmitters like Glutamate opens Calcium and Sodium channels and causes an EPSP, this means that the cell membrane will be much closer to be triggered for an action potential since the value is then closer to the threshold of excitation.