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

Mixed function oxidases increase with chronic alcohol use and can therefore cause tolerance

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

Toxic effects are cirrhosis decrease in liver function, increase enzyme activity of the liver and hepatitis.

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

It is a syndrome characterized by a decrease in thiamine caused by alcohol abuse and it is treated with vitamin b 1

Fully explain the foetal alcohol syndrome.

Foetal alcohol syndrome occurs when a mother consumes alcohol while she is pregnant this causes the baby to have growth abnormalities and most commonly retardation is seen mostly in the first trimester of pregnancy

How do the pharmacokinetic interactions of acute alcohol consumption differ from that of chronic alcohol consumption?

Chronic alcohol consumption has allot more negative effects as chronic ethanol increases metabolic transformation of drugs and acute alcohol decreases the metabolism of drugs

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

Vasodilators, hypoglycaemic drugs, aspirin and benzodiazepines.

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

There are many factors that can affect the absorption and distribution of drugs like the more lipid soluble a drug is the faster the rate of adsorption will be and faster redistribution to the CNS. Other factors like drugs that inhibit CYT P450 enzymes has an effect on the elimination half-life of highly lipophilic BD which has a rapid onset of action so you should be careful to administer these drugs with impaired CYT P450 enzymes.

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

Redistribution occurs when highly lipophilic drugs is redistributed from the cns to fatty tissues and muscles so it will increase its elimination half-life.

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

BD are metabolized by

Dealkylation then by oxidation followed by conjugation

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

It is significant as it increases the drugs duration of action examples of these drugs are diazepam, chlorazepate, prazepam chlordiazepoxide and ketazolam

• Which BDs are not dependent on the cytochrome P450 oxidative enzymes for metabolism?

What are the advantages thereof?

(BOLT)

Bromazepam, oxazepam, Lorazepam and Temazapam.

It is advantageous as it can be used in patients who have impaired CYT P450 enzyme function.

• 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 increased rate of hepatic metabolism leading to increased metabolism of the drug. Drugs in this category are barbiturates like phenobarbitone

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

Inability to remember evets occurring during drugs duration of action. Drugs that cause this eg is midazolam diazepam lorazepam ect.

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

Long term use of BD can decrease the time taken to fall asleep and increase a patient’s duration of sleep who do not get more than 6hrs of sleep per night

Low doses of BD have a small effect on REM sleep but Highers doses decrease REM sleep.

BD increase the duration of phase 2 NREM but decrease the duration of phase 4 NREM sleep.

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

Barbiturates, Midazolam diazepam and lorazepam is used as it induces anterograde amnesia so patient will remember nothing while using the medication.

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

Diazepam lorazepam phenobarbitone, clonazepam and clobazam

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

They induce skeletal muscle relaxation by inhibiting polysynaptic reflexes.

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

Can cause respiratory depression in high doses due to depression of medullary respiratory centre.

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

Voltage gated channels

Ligand gated channels

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

• Voltage gated works by reaction to changes in membrane potential whereas ligand gated works by ligand binding to ion channel that has affinity for it.
• Voltage gated ion channels initiates fast all or nothing action potential which propagates down neuron where ligand gated consists of many subunits and when stimulated a brief opening of the channel which causes a fast synaptic transmission.
• Voltage gated channels are ion specific whereas ligand gated channels are not

Compare ionotropic and metabotropic receptors.

Ionotropic channels or ligand gated channels consists of multiple subunits and when a neurotransmitter binds to it directly opens the channels. They are directly responsible for fast synaptic transmissions whereas metabotropic receptors are G protein coupled and when binding occurs on receptor it does not result in direct opening of gate but  the initiation of a pathway that gives rise to a secondary messenger .

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

Ionotropic receptors: nicotinic, Cl, Na, EAA(glutamate), GABAa

Metabotropic receptors are divided into 2 groups

• Adenylyl cyclase system

Neurotransmitters can bind positively (R+) to adenylyl cyclase 1&2 and dopamine which causes increased AMP formation

Negative binding (R-) means it is negatively bound therefore decrease in AMP formation

• Phospholipase system

All receptors are positively bound meaning increased enzyme activity IP3 and DAG

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

EPSP- excitatory post synaptic potential

This happens due to the opening of sodium and calcium channels when a neurotransmitter binds, this causes increased permeability to cations that causes depolarization and in turn causes threshold to be reached and an action potential forms.

Examples of receptors that will bring this to effect: 5-HT3, Nicotinic, EAA, BD

IPSP- inhibitory post synaptic potential

This happens when an action potential is stopped by hyperpolarization of the post synaptic membrane which is achieved by potassium and chloride channels opening when a neurotransmitter GABAa binds

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

Ca is very important as it stimulates the release of neurotransmitters from the axon terminal as the action potential reaches membrane calcium flows into the synaptic vessel stimulating the release of neurotransmitters.