Flashcards in Anxiolytics And Hypnotics Deck (27)
1
Treating anxiety disorders
- CBT
- Applied relaxation
- Medication ( Anxiolytics and hypnotics )
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Anxiolytics
Used to treat anxiety disorders
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Hypnotics
Used to treat insomnia
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Types of insomnia
- Transient (jet lag)
- Short term (illness or stress)
- Chronic (alcohol or drug misuse or dependence)
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What type of drugs are anxiolytics and hypnotics
CNS depressant drugs
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Therapeutic window of CNS depressants
Low dose - Anxiolytics
High dose - Hypnotics ( sedative effect - induce sleep )
Anaesthesia
Toxic dose - coma
Respiratory depression
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What are barbiturates?
- GABAa receptor modulators
- Positive allosteric modulators
- Severe CNS depressants
- Used in treatment of epilepsy, general anaesthesia and capital punishment
- no longer used as anxiety treatment
- Are dirty compounds having other actions at high doses
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How do barbiturates work?
- Bind to GABA A receptor
- Channel is opened more than if GABA bound alone
- Enhances function response
- Increases activity of GABA A receptor
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Effects of barbiturates at high doses
- Direct GABA A agonise
- nAchR and 5-HT3 blockade
- AMPA and Kainate blockade
- Blockade of calcium dependent neurotransmitter release
- Stabilise open channel of glycine receptor
10
What are benzodiazepines?
- GABA A receptor modulators
- Decrease anxiety and induce sleep
- reduction in muscle tone and anticonvulsant effects
- Specific to GABA A receptor so lower dose required
- Antidote available to reduce effects of bzd e.g. flumenazil
- short acting drug so avoid sedative effects during the day
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How do benzodiazepines work?
- Stabilise GABA A receptor binding site for GABA in open configuration
- Increases GABA affinity for its binding site
Only bind to alpha 1, 2, 3 or 5
- BZD bind at alpha gamma interface
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Side effects of benzodiazepines
- Drowsiness
- Confusion
- Forgetfulness
- Loss of motor control
- Combined with alcohol causes respiratory depression
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What are Z Drugs
- Hypnotics only
- GABA A Modulators
- Act on benzodiazepine binding site
- Structurally different time bzd - bzd have Cl attached to aromatic ring
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GABA A receptors
- inhibitory effects
- Ligand gated Cl- channel
- Causes hyperpolarisation
- GABA binds at alpha beta interface
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How is addiction to benzodiazepines caused?
1.) More glutamate receptors than GABA
2.) Benzodiazepines restore balance between GABA and glutamate
3.) Body develops tolerance to drug and neuroadaptation takes place
4.) More glutamate receptors are trafficked leading back to imbalance
5.) Withdrawal from drug causes severe lack of GABA
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Using benzodiazepine to treat alcohol dependence
1.) Balance between glutamate and GABA activity in healthy person
2.) More GABA activity in an alcoholic
3.) Withdrawal from alcohol causes neuroadaptation where more glutamate receptors are trafficked
4.) Benzodiazepine restores imbalance between GABA and glutamate
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What is a 5-HT1A agonist?
- metabotropic (GPCR)
- Used to treat GAD e.g. buspirone
- Less tolerance and withdrawal symptoms
- Does not induce sleep
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How do 5-HT1A agonists work?
- Activate pre-synaptic 5-HT1A autoreceptots
- are auto inhibitory and initially decrease serotonin levels
- Induce desensitisation of 5-HT1A autoreceptor causing enhanced release of serotonin in the long term
- Reduces noradrenergic neuron activity and decreases arousal
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What are beta adrenoceptor antagonists?
- Treat some forms of anxiety e.g. propranolol
- Metabotropic receptor (GPCR)
- Reduce some of the peripheral manifestations of anxiety and do not have an effect on CNS
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What does beta-1 and beta-2 do?
Beta 1 increases heart rate, contraction and ejection fraction
Beta 1 and 2 increases renin release by juxtaglomerular cells
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What are antihistamines?
- used to treat allergic conditions e.g. hay fever
- found in some cold remedies
- only hypnotics due to sedative effect
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How do antihistamines work?
Histamine H1 receptor are responsible for wakefulness
- Using antihistamines overcome this
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Benzodiazepine drug examples
- Lorazepam
- Temazepam
- Clonazepam
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Z Drug examples
- Zolpidem
- Zopiclone
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5-HT1A receptor agonist drug examples
- Buspirone
- Tandospirone
- Flesinoxan
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Beta adrenoceptor antagonist drug examples
- Propanolol
- Metoprolol
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