1839903
Description
Flashcards by rachel-chads, updated more than 1 year ago
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Created by rachel-chads
over 9 years ago
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| Question | Answer |
| What are the different types of anxiety disorders? | - General anxiety - Panic disorder - Phobias - Post traumatic stress disorder - Obsessive compulsive disorder |
| What are the two excitatory amino acid neurotransmitters? | Glutamate and asparate |
| What are the two inhibitory amino acid neurotransmitters? | GABA and glycine |
| Which is the GABA receptor that is metabotropic? | GABA-B (GABA-A is ionotropic) |
| Is it GABA-A or GABA-B which mediates fast inhibitory transmission? | GABA-A (GABA-B is slow transmission) |
| Which ion is GABA-A selective for? | Chloride ions (Cl-) |
| How many subunits are in each GABA-A ion channel receptor? | 5 It is pentramic. 5 proteins come together to form one channel |
| What is the orthosteric site (for GABA-A R)? | It is the site to which an agonist binds and causes the channel to open |
| What are the agonists and antagonists at the orthosteric site on the GABA-A receptor? | Agonist - muscimol Antagonists - bicuculline and picrotoxin |
| What is the allosteric site? | A site in which an allosteric binds but doesn't open the channel. Instead it modifies the opening of the channel to an agonist at the orthosteric site. |
| What are examples of allosteric agonists and antagonists for GABA-A receptors? | Allosteric agonist = diazepam (a benzodiazepine) Antagonist = flumazenil |
| What is an inverse agonist for a GABA-A receptor? | A drug which stabilises the inactive (~= closed) receptor Beta carbolines are an example. They prevent the receptor from spontaneously opening. |
| Do orthosteric and allosteric agonists increase or decrease inhibitory neurotransmission in the brain? | They increase inhibitory neurotransmission. |
| Which type of G protein is the GABA-B (metabotropic) receptor coupled with? | It is a Gi/o protein coupled receptor. |
| What is an example of an agonist and antagonist at GABA-B receptors? | Agonist = baclofen Antagonist = phaclofen |
| How do post-synaptic GABA-B receptors produce inhibition? | - Activate K+ channels (GIRK) - Hyperpolarised the neurone - Fire less action potentials - Produces post-synaptic inhibition |
| How do pre-synaptic GABA-B receptors produce inhibition? | - Inhibit voltage gated Ca2+ channels - Prevents release of neurotransmitters - Produces pre-synaptic inhibition |
| What are the physiological effects of benzodiazepines? | - Sedation/anxiolytic - Hypnosis - Anterograde amnesia - Anti-convulsant - Reduction of muscle tone |
| How do benzodiazepines affect GABA-A receptors? | They are positive allosteric regulators of GABA-A receptors. They don't open GABA-A receptors themselves. They increase the activity of the GABA-A receptor, by increasing the frequency of the opening of channels in the presence of an agonist. |
| Do benzodiazepines have a high or low lipid solubility? | High. They pass the BBB easily and usually have a rapid onset of action. But this does mean they do accumulate in body fat. |
| What are the pharmacokinetics of the benzodiazepine Zoipidem? | - Half life = 2.5 hours - No active metabolites - Ultrashort duration of action (<6 hours), therefore used as a hypnotic. |
| What are the pharmacokinetics of the benzodiazepine diazepam? | - Half life = 20-40 hours - Has an active metabolite (which has a half life of 60 hours) - Long duration of action (24-48 hours), therefore useful as an anxiolytic |
| What are the pharmacokinetics of the benzodiazepine Clonazepam? | - Half life = 50 hours - No active metabolite - Long duration of action (so not useful as a hypnotic) - Useful for someone suffering from anxiety (especially mania) - Also useful as an anti-convulsant for epileptics |
| What is status epilepticus and which benzodiazepine is used? | Intravenous diazepam is used to treat status epilepticus, a seizure that lasts for more than 30 minutes or more. |
| What are the adverse effects of benzodiazepine agonists? | - Sleepiness/drowsiness - Impaired psychomotor function - Amnesia - Has additive effects with other CNS depressants (fatal in overdose) - Tolerance - Subject to misuse - Physical dependence characterised b y withdrawal symptoms |
| What are some examples of barbiturates? | Thiopentone Phenobarbital |
| How do barbituates affect the nervous system? | At low concentrations they are positive allosteric regulators of GABA-A (increase inhibition and have sedative properties.) At high concentrations they begin to act as agonists and open channels all over the CNS --> widespread depression across the CNS leading to death due to the inhibition of respiratory system. |
| What can be non-genetic causes of epilepsy? | - Head injury - Local lesion (eg. small blood clot) - Tumours - Infection |
| What is the main mutation that causes inherited/familial epilepsy? | Mutations in the voltage gated Na+ channel, SCN1A |
| What are the characteristics of epilepsy? | High frequency discharge of electrical activity. Unprovoked seizures. |
| What different problems result during a seizure due to the affected areas of the brain? | Motor cortex - convulsion (not necessarily the whole body) Hypothalamus - autonomic discharge; salvate, urinate etc. Reticular formation - loss of conciousness |
| What can be triggers for epilepsy? | - Altered blood glucose or pH - Stress - Fatigue - Flashing lights - Loud noises |
| What method is used to diagnose epilepsy? | EEG (Electrodes are placed on the head to see abnormal neurone firing patterns) |
| What is a generalised (grand mal) epileptic seizure? | - Tonic-clonic seizure type - Rhythmic seizures involving the whole body - Electrical firing pattern spread and mirrored over the whole brain - High frequency firing then rhythmic firing - Always associated with loss of conciousness |
| What is a generalised (petit mal) seizure? | - Absence seizure type - No convulsion - Temporary loss of awareness - More common in children |
| What is a partial seizure? | - Electrical firing starts in one place and doesn't spread - Doesn't include the whole brain - Symptoms depend on which area is affected |
| In what ways can GABA transmission be increased? | 1. By the use of benzodiazepines/barbiturates 2. By the use of uptake inhibitors 3. By the use of metabolic inhibitors |
| How to uptake inhibitors help increase GABA (inhibitory) transmission? | They increase the amount of GABA in the brain by decreasing the uptake of GABA by the pre-synaptic neurones. So there is more GABA around for longer action. An example of an uptake inhibitor is tiagabine. |
| What is GABA synthesised from? And what enzyme is required? | GABA is synthesised from glutamate by the enzyme GAD (glutamic acid decarboxylase). (Glutamate is synthesised from glutamine or alpha-ketoglutarate from Krebs' Cycle). |
| How is GABA metabolised? | GABA is metabolised in a two step process. GABA --> succinate semialdehyde (GABA transaminase) Succinate semialdehyde --> succinate (succinate semialdehyde dehydrogenase) |
| How do anti-epileptic drugs work on excitatory synapses? | They limit excitatory transmission, by decreasing the amount of glutamate being released. Mainly work by blocking Na+ channels to limit action potential firing. |
| What are the typical symptoms of depression? | - Low mood - Anhedonia -> not enjoying things that normally would do - Negative thoughts, pessimism, low self esteem, feelings of worthlessness/guilt - Sleep disturbances -> insomnia or over sleeping - Severe loss/gain of weight/appetite |
| Is there a genetic component to depression? | To a certain extent. There is no single gene that puts you at risk of depression. But there is a genetic risk of ~40%. In addition, women are twice as likely to have depression in comparison to men. |
| What is Iproniazid? | It was the first specific antidepressant. It is an MAOI (inhibitor of the MAO enzyme family) |
| What does Reserpine do? | It produces depression and Parkinson-like symptoms by depleting stores of monoamine transmitters. |
| What are the three main classes of antidepressants? | 1) Selective serotonin reuptake inhibitors (SSRIs) 2) Classical tricyclic antidepressants (TCAs) 3) Monoamine oxidase inhibitors (MAOIs) |
| Is it MAOI type A or B which are good antidepressants? | MAOI type A |
| Why can MAOIs cause problems? | They can cause problems in the peripheral nervous system because noradrenaline is used in the sympathetic NS. |
| What is the synthesis pathway involving dopamine, NA and adrenaline? | Tyrosine --> DOPA --> Dopamine --> Noradrenaline --> Adrenaline |
| What is the 'cheese effect' in relation to MAOIs? | The same enzyme breaks down tyramine and noradrenaline. If you eat lots of cheese or other foods that contain the amino acid tyramine, it causes the displacement of NA from its vesicles. It can lead to issues such as high blood pressure. |
| What population of neurones is the main area of serotonin release? | The Ralphe nuclei are a cluster of nuclei found in the brainstem. Their main function is to release serotonin to the rest of the brain. |
| What are the functions of serotonin? | - Hallucinations - Sleep and wakefulness - Mood and emotion - Feeding behaviour - Sensory pathways and nociception - Body temperature - Vomiting |
| How does BDNF relate to depression? | Brain derived neurotrophin factor is a neurotrophin and stabilises synapses. Decreased levels of BDNF are seen in some parts of the brain of patients with depression. Antidepressants increase BDNF and therefore help restabilise the connections between synapses. However this can take weeks, which is why there is a delay seen from when antidepressants are first taken to when a clinical difference is seen. |
| What approaches/treatments are taken for bipolar disorder/depression? | - Lithium. - Antiepileptic drugs are sometimes used as mood stabilisers. - Electroconvulsive shock therapy. - Electromagnetic therapy. - Deep brain stimulation. - Vagus stimulation. |
| Electroconvulsive shock therapy (ECT) | - Used in severe depression. - Is a very refined technique now, specific/selective for particular areas of the brain. - Effects expression levels of monoamine transmission. |
| What does dopamine do? | Dopamine is implicated in numerous body functions: - Movement - Attention - Learning - Reward and reinforcement (addictive drugs) |
| What are the dopaminergic pathways in the CNS? And what are they involved in? | 1) Nigrostriatal (Fine motor control) 2) Mesocortical and mesolimbic (behaviour, pleasure/reward, compulsion) 3) Tuberhypophyseal (pituitary hormone secretion) 4) Medullary chemoreceptor trigger zone (nausea and vomiting) |
| What is the cellular pathway of D1 type (D1 and D5) dopamine neurones? | Gs coupled protein, Activation of adenylate cyclase, Increased cAMP, Increase PKA, Alter protein phosphorylation. |
| What is the cellular pathway of D2 type (D2, D3 and D4) dopamine neurones? | Gi protein (inhibition), Inhibition of adenylate cyclase, Decreased cAMP levels, Inhibits Ca2+ channels and activates K+ channels. |
| How do amphetamines and cocaine affect dopamine transmission? | They increase dopamine (and noradrenaline) transmission. |
| How do amphetamines affect DA? | They stimulate the secretion of dopamine and noradrenaline: - Inhibit MAO and the metabolism of DA and NA - Displace DA and NA from vesicles - Cause re-uptake transporters to work in reverse. |
| What are amphetamine-like drugs used to treat? | - Narcolepsy (stimulate wakefulness) - ADHD (increase concentration) |
| What is the prevalence of schizophrenia? | - The prevalence rate is approximately 1.1% of the adult population. - 250,000 diagnosed cases in the UK. - As many as 51 million people worldwide suffer from schizophrenia. |
| What are the negative symptoms of schizophrenia? | - Blunting of emotions - Anhedonia - Withdrawal from social contacts, reluctance to engage - Language deficits - Lack of energy (Quite similar to depression) |
| What are the positive symptoms of schizophrenia? | - Hallucinations, delusions, voices in head - Thought disorders (irrational/wild) - Speech disturbed - Paranoia - Bizarre behaviour, including stereotyped behaviour - Aggression - Deficit in selective attention |
| How is schizophrenia observed in animal models? | Negative: - Stop grooming, - Stop keeping cage clean, - Loss of appetite, - Facial expressions (drooping of ears/whiskers) Positive: - stereotyped behaviour (eg. move/spin in circles, moving in a nonsensical way) |
| What are some of the structural differences between schizophrenic and normal brains? | Schizophrenic brains don't have the same number of synapses in some areas of the brain. Schizophrenic brains tend to have larger lateral ventricles and a smaller volume of tissue in the left temporal lobe. |
| What is a side effect of antipsychotic drugs? | Chronic drug administration is tardative dyskinesia - disturbance of motor control (extrapyramidal effects) and muscular twitches. Changes become irreversible. |
| What are the signalling pathways associated with the D2 receptor? | D2 receptor Inhibitory G protein Inhibit adenylate cyclase Decreased cAMP |
| What is the schizophrenia Dopamine Hypothesis? | Excessive dopamine action (D2-like receptor signalling). Treated by D2 dopamine receptor antagonists. |
| What is the relation between dopamine and Parkinson's disease? | Due to death of pigmented cells in the substantia nigra and a decrease in dopamine action in this region. Treated by drugs that increase dopamine levels eg. L-DOPA and MOA-B inhibitor (Selegiline) |
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