Botanical and herbal medications are available anywhere and no prescription is needed.  Herbal medications however, possess numerous health benefits and low risks of tolerance and dependence developing. There is no guarantee that they are safe and effective. They were not approved by SAHPRA, thus we do not know their side effects or their interaction with other drugs.  If a patient considers taking herbal medication/supplements, they should first consult with a doctor or pharmacist. 

Botanicals / herbal remedies that can be used for anxiety and insomnia are as follows:

 Passion Flower, Ginseng, Valerian root, Lavender, Lemon Balm, Glycine, Magnesium, St. John's Wort and Melatonin. 

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

Rate is determined by lipophilicity, therefore high lipid solubility = rapid absorption from the gastrointestinal tract and good distribution of the drug to the brain. 

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

Redistribution means that the drug goes to the brain and is then distributed to the rest of the tissues. This is significant because it determines the duration of action of the drug.

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

By hepatic microsomal enzymes. This process includes:

• Dealkylation to active metabolites.
• Oxidation by the cytochrome P450 enzymes to an active metabolite.
• Conjugation (Phase II) of the oxidised metabolite with glucuronic acid to form an inactive metabolite.

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

Diazepam, Clorazepate, Prazepam, Chlordiazepoxide and Ketazolam are all examples of benzodiazepines that are converted to an active metabolite. Active metabolites are important because they contribute to the extension of the duration of action.

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

Oxazepam, Lorazepam, Temazepam, Lormetazepam. These drugs benefit patients that suffer from liver cirrhosis, geriatrics, neonates and patients that make use of CYP-P450 inhibitors, due to the drugs not having an effect on the levels of CYP-P450 because it does not require the enzyme to produce an effect.

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

Enzyme induction - when a drug increases the production of an enzyme that will lead to an increase in the rate of metabolism of the drug.

Barbiturates and meprobamate are known for this action and are significant in increasing drug metabolism, therefore a decrease of drug in the systemic circulation causing a decrease in the overall therapeutic effect.

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

Anterograde amnesia - reduced ability of a patient to remember new information or occurring events during the time the drug is effective. Benzodiazepines drugs such as Triazolam, Temazepam, Lorazepam and Midazolam cause this effect.

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

• Decrease in the time it takes to fall asleep.
• Decrease in the duration of REM sleep.
• Increase duration of NREM phase.
• Decrease duration of phase 4 NREM.
• Ultimately increase the sleep duration.

Significance - to help patients who suffer from insomnia to fall asleep and increase the quality of sleep.

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

Diazepam, lorazepam and especially midazolam.

This is due to their anterograde amnesiac effects, sedation and anti-anxiolytic effects.

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

• Diazepam
• Lorazepam
• Clonazepam
• Clobazam
• Phenobarbitone
• Primidone.

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

The mechanism of action is the binding of the drug to the α-γ subunit of the GABA receptor, thus potentiating GABA's effects, this includes prolonged hyperpolarisation (relaxation of smooth muscle).

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

Effects are more noticeable when drugs are given via IV.

• Most sedative-hypnotic drugs: Decrease breathing and heart rate during phase 4 NREM
• Buspirone: Chest pain, tachycardia
• Thiopental: Hypotension, respiratory depression and apnoea, laryngeal and bronchial spasms
• Antihistamines: Tachycardia
• Propranolol: Bradycardia, bronchospasm
• Flumazenil: Cardiac arrhythmias

• Which types of ion channels are found on the nerve cell membranes?

• Voltage-gated ion channels
• Ligand-gated ion channels

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

• Voltage-gated ion channels:

- Controlled by changes in the membrane potential of the cell.

- Transmits signal from cell body to the nerve terminal.

- Na⁺, K⁺ and Ca²⁺ channels.

• Ligand-gated ion channels:

- Binding of a ligand (neurotransmitter) to ion channel.

- Ionotropic receptor

• Compare ionotropic and metabotropic receptors.

IONOTROPIC RECEPTOR:	METABOTROPIC RECEPTOR:
Transmembrane ion channels that open or close in response to binding of a chemical messenger.	7-Transmembrane G-protein coupled receptor
Ion channels	2nd messengers
Open quickly and remain open for only a few milliseconds	Effects last longer (minutes)
Effect occurs only in immediate region of the receptor	Effect is widespread throughout the cell

• Classify the CNS receptors into ionotropic and metabotropic and know the transduction mechanism of each receptor.

• Ionotropic receptors – GABA_A , Nicotinic, EAA and 5-HT₃
• Metabotropic receptors – Adenylyl cyclase system and Phospholipase C system

Phospholipase C – Conversion of PIP₂ to DAG and IP_3,

• Explain the difference between an EPSP and an IPSP and give examples of each.

• EPSP – excitatory postsynaptic potential. The EPSP causes a neuron to be more likely to generate an action potential. Eg. The binding of a acetylcholine to a nicotinic receptor.
• IPSP – inhibitory postsynaptic potential. This is a type of postsynaptic potential that causes a postsynaptic neuron to be less likely to generate an action potential. Eg. GABA receptor located on postsynaptic membranes are stimulated, they then cause an opening of the chloride channels. This results in hyperpolarization.

• What is the role of calcium in the development of a synaptic potential?

• Neurotransmitter is released from synaptic vesicles into the synaptic cleft.