1. Two main groups of drugs that are important in the treatment of Parkinson’s:

• Drugs that increase dopamine activity
• Drugs that decrease Cholinergic activity

2. In what way does Amantadine act as an antiparkinsonism drug:

Amantadine increases DA neurotransmission by increasing the synthesis or release of dopamine ot the inhibition of DA reuptake. It also blocks muscarinic action.

3. MOA of antiparkinsonism drugs that increases DA concentration indicectly:

• Monoamine Oxidase inhibitors selectively inhibits Monoamine Oxidase type B. This is the form of the enzyme that metabolises dopamine.
• COMT inhibitors inhibits the enzyme in both the CNS and peripheral tissues that coverts levodopa to 3-OMD.
• Amantadine enhances neurotransmission involved in the inhibition of dopamine reuptake

4. Which drugs are ergot derivatives and which are not:

Ergot derivatives:

• Bromocriptine

Non-ergot derivatives:

• Pramipexole
• Ropinirole

5. Dopamine receptors stimulated by each agonist:

• Bromocriptine: D2 receptors
• Pramipexole: D3 receptors
• Ropinirole: D2 receptors

6. Drugs classified as neuron protecting drugs and what that means:

Neuroprotective drugs are those which protects the brain from being damaged. These drugs include all MAO-B inhibitors and Pramipexole.

7. Importance of MAO-B inhibitors in the treatment of Parkinson’s:

It increases the DA concentration in the CNS. It can be given as a combination therapy with L-dopa. Safinamide also increases DA activity by inhibiting DA reuptake and decreases glutamate release.

8. How do COMT inhibitors act in Parkinsonism:

COMT metabolizes L-dopa to 3-OMD. A COMT inhibitor therefore extends the duration of action of L-dopa, it decreases peripheral metabolism and improves the bio availability.

9. How does Istradephyllin work:

It is an Adenosine A_2A antagonist. It can be used as an add-on therapy drug to L-dopa/Carbidopa when experiencing off-episodes.

10. Discuss the MOA of Safinamide:

Safinamide has a novel dual mechanism of action. It increases DA activity by inhibiting MAO-B as well as the inhibition of DA reuptake. The second MOA is that Safinamide decreases glutamate release.

1. a) Unmyelinated fibres are more sensitive to local anaesthetics because they are more easily blocked than myelinated fibres.

b) Touch, pressure and motor fibres are influenced by a-type fibres. These fibres are the final fibres that are blocked and therefore they are not sensitive to LA.

2. Local anaesthetics have an effect on both cardiovascular tissues and the Central nervous system tissues.

3. Local anaesthetics are chosen according to the type of procedure for which it is needed as well as the duration of the procedure.

4. Carbon dioxide raises the concentration used effectively of the nonionized form of the LA, this helps as only the nonionized form of the LA can cross the plasma membrane. Therefore the onset of action is faster.

5. Surface active anaesthetics: Benzocaine, Cocaine and Oxybuprocaine.

Compile a table, listing the major effects on every system (cardiovascular, CNS, renal, hepatic and uterus) for all the inhalation anaesthetics. This table is important when it comes to the selection of drugs in certain individuals:

Name the major acute toxic effects of the inhalation drugs:

• Neurotoxicity
• Hepatotoxicity
• Malignant hyperthermia

Reference list: 

Brand, L.Prof.  2021.  Study Unit 5: General Anaesthesia.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

1. The anti-epileptic that interact with oral contraceptives include: phenobarbitone, phenytoin, carbamazepines, oxacarbazepine and topiramate. The implication of these drugs are that it decreases the effectiveness of the oral contraceptives, causing unwanted pregnancies and unregulated hormone levels. The anti-epileptic drugs that doesn’t affect oral contraceptives are valproate, lamotrigine, gabapentin, leviteracetam and vigabatrin.
2. Oral contraceptives can affect the effectiveness of anti-epileptic drugs as well by affecting their serum levels.
3. Anti-epileptic drugs affect Neonates, babies and children, adults and geriatric patients differently. The metabolism of anti-epileptic drugs in neonates is slower than in adults whereas in babies and children, it is faster than in adults. A geriatric patient’s liver doesn’t work as optimally as that of a healthy adult and therefore anti-epileptic drugs are metabolised slower by them than by adults.
4. Plasma blood levels are monitored to ensure that the patient’s renal and liver functions aren’t affected by the drugs they are taking. These tests are also to check for allergies, drug interactions and adverse effects.

1. Like with most neurotransmitters, the more a receptor is stimulated, the more it takes to saturate that specific receptor. Therefore when a person consumes a lot of alcohol it can saturate the ethanol-induced up-regulation that responds to a continuous alcohol consumption.
2. Continued alcohol consumption can have an impact on the liver due to the ethanol oxidation in the liver. The by-products caused by the metabolism of the ethanol is toxic and can cause inflammation.
3. Wernicke-Korsakoff syndrome is caused by thiamine deficiency and can be treated with parenteral thiamine.
4. Foetal alcohol syndrome is a disorder caused by the mother drinking constantly during her pregnancy. The alcohol travels through the placenta until the foetuses alcohol concentration is the same as the mothers. This triggers neurodegeneration and causes neuronal and glial migration. This causes mental retardation and congenital malformations.
5. In acute alcohol consumption the enzymes involved are mostly alcohol dehydrogenase and MEOS whereas with chronic alcohol consumption, mostly MEOS are the active enzymes.
6. Aspirin, Paracetamol, Vasodilators, Hypoglycemic drugs

1. Since Alcohol can only be metabolized once Nicotinamide Adenine Dinucleotide (NAD) enzymes are saturated and you start feeling intoxicated, alcohol metabolizes through zero order kinetics.
2. Alcohol is metabolized through two pathways:

• Alcohol dehydrogenase
• Microsomal Ethanol Oxidising System (MEOS)

3. Disulfiram, Cephalosporins and Hypoglycemics. An excess of Acetaldehyde causes nausea, headaches, hot flashes and fevers and therefore if aldehyde dehydrogenase is inhibited, acetaldehyde can’t be made and you don’t experience the side effects of alcohol intake.

Botanical substances or natural substances are plant based medicines that don't have to go through the rigorous testing that registered medicines do. These substances are therefore dangerous to use without the input of a pharmacist or a doctor as they can still have adverse effects on a patient as well as have a contra-indication or a bad interaction with medicines that are already being used by the patient. These medicines might be considered 'safer' due to the fact that it is a natural product but it is more dangerous because of the information we do not have. 

Botanical substances for use as anxiolytics: Lavender, Valerian, Passion flower, Lemon balm, Linden, Chamomile. 

Botanical substances for uses as hypnotics: Passion flower, Jamaican dogwood, Skullcap, Motherwort, Hops, Californian poppy.  

1. Absorption and distribution of drugs are affected the most by lipid solubility. Lipid solubility helps sedative-hypnotic drugs to be absorbed into the central nervous system. This factor is responsible for how fast the sedative-hypnotic drugs start working. The clinical significance of this is that the more lipophilic a drug is, the faster and better it is absorbed into the patients system. 

2. Redistribution of drugs is when a lipid soluble drug is distributed to the organs of the body and is then distributed again into the fat and tissue. Redistribution is done to lengthen the action of the drug. 

3. The metabolism of BDs happen via biotransformation by hepatic enzymes and in 3 steps: 

• Dealkylation 
• Oxidation 
• Conjugation

4. The benzodiazepines that are converted to active metabolites are:

• Diazepam
• Prazepam 
• Chlorazepate 

By converting BDs to active metabolites, you lengthen the duration of action of the drug. 

5. The BDs that are not dependent on the cytochrome P450 oxidative enzymes are: 

• Oxazepam 
• Lorazepam 
• Temazepam 

These drugs are not metabolised by the CYP450 enzymes. It is therefore the preferred drug for patients with decreased CYP450 enzyme activity.

6. Enzyme induction is when a drug causes an increase in the production of specific enzymes that betters the metabolism of that drug. A drug that causes this include: phenobarbital. Enzyme induction decreases the amount of drugs in the patient's circulation which causes the therapeutic effect to be decreased. 

1. Anterograde amnesia and drugs that can cause this? 

Anterograde amnesia or proactive amnesia is a subset of amnesia where the patient struggles to make new memories from new experiences and information. This is caused by Adco-alzam, Ativan, Azor, Brazepam, Bromaze, CPL Alliance Alprazolam, Demetrin, Lexotan.

2. Benzodiazepines (BD) helps patients to fall asleep faster, which lengthens the time that a patient can sleep. BDs in high dosages decreases REM sleep. These drugs are significant to the patient as it helps with sleeplessness and insomnia. They help a patient sleep longer. 

3.  

• Barbiturates
• Diazepam 
• Lorazepam 

Sedative-hypnotic drugs put patients to sleep and can therefore be used as anaesthesia. Anaesthesia helps the patient because an operation can be traumatic.

4.

• Clonazepam
• Lorazepam 
• Clobazam
• Diazepam  

5. The mechanism of action of the carbamates and the BDs are that they inhibit multiple synaptic reflexes. 

6. Sedative-hypnotic drugs decreases the cardiovascular and respiratory systems. They therefore decrease respiratory and cardiovascular disease.

1. Voltage-gated and Ligand-gated ion channels 

2. Voltage-gated ion channels respond to changes in the membrane potential of a cell, it transmits a signal to the nerve terminal and it includes Ca²⁺, K⁺ and Na⁺ ion channels whereas ligand-gated channels work by binding the ligand neurotransmitter (NT) to the ion channel, is an ionotropic receptor and can be found both presynaptic and postsynaptic.  

3. Ionotropic receptors bind directly to the receptor and opens the ion channels. Metabotropic receptors on the other hand doesn't bind directly to the receptor but is a G-protein-coupled receptor that releases secondary messengers thus opening the ion channels. 

4.  Ionotropic receptors include: GABA_A, Nicotinic, EAA and 5-HT₃ receptors.

Metabotropic receptors work with 2 transduction systems, these are: Adenylyl cyclase systems and Phospholipase C systems. 

In the Adenylyl  Cyclase System, the receptors are positively and negatively bound. The positively bound receptors include: β₁₊₂ and D_1. These receptors stimulates the formation of secondary messengers. The negatively bound receptors, on the other hand, includes: D2, α₂, 5-HT_1A+B and M_2. These receptors suppresses the formation of cAMP. 

In the Phospholipase C system, the receptors are only positively bound. These receptors include: α₁, 5-HT2, M₁, H_1. 

5. EPSP is generated by the opening of Na⁺ or Ca²⁺ channels whereas IPSP is generated by opening of K⁺ or Cl^-. 

6. Calcium causes a change in the action potential of the presynaptic membrane which in turn releases the neurotransmitters needed to cause an effect in the postsynaptic membrane. Thus, calcium is an essential part of producing a synaptic potential.