Zusammenfassung der Ressource
Anxiety
- A normal & essential human response to impending or percieved
danger. Response includes activation of the autonomic system
(fight or flight). In contrast to fear which is a response to a known
threat. It becomes a clinical issue when the anxiety has no
reasonable cause & interferes with normal functioning
- Serotonin
- ligands acting as antagonists at other
5-HT receptors (not 1A) eg ondansetron
also have anxiolytic properties
- Activation of postmen serotonin receptors
(5-HT2A, 2C, 3) increases anxiety.
Activation of presyn serotonin receptors
(5-HT 1A) reduces 5-HT release &
therefore reduces anxiety
- GAD- muscle tension, restlessness,
autonomic effects: sweating, frequent
urination, dizziness, difficulty in
concentrating, insomnia, irritability
- Post traumatic disorder-past
events stop you from living your life
- Panic disorder with or without
agoraphobia-palpitations, nausea, fear
of dying with no apparent cause
- Sedatives- reduce alertness-can relieve
anxiety & in higher doses, producing sleep
- Hypnotics- induce sleep-triggers sleep response
- Anxiolytics- relieve anxiety & stress. Ideal anxiolytics have no
sedative effect-sometimes referred to as 'minor tranquillisers'
- Treatment for anxiety
includes not only
anxiolytics but also
psychological
approaches & use of
antidepressants
- Historical- Belladonna alkaloids-atropine,
scopolamine & opiates- opium, morphine,
diamorphine. Both still used as element of
general anaesthesia and in eye drops
- Historical- early 20th century ones included bromide,
chloral hydrate, urethane (still used for animal anaesthesia)
& thalidomide (treats morning sickness during pregnancy)
& barbiturates-seatives/hypnotics- eg amobarbital,
phenobarbital-no longer used as sedatives because of
harmful side effects (Phenobarbital is used as
anti-convulsant & thiopental as iv anaesthetic)
- Current
- Benzodiazepines- anxiolytics,
sedatives, hypnotics,
anticonvulsants eg. diazepam,
nitrazepam, flurazepam - now used
as anxiolytics in acute cases only.
Some compounds therapeutically
selective-action at diff GABA A
receptor subtypes may underlie this
eg Zolpidem is a hypnotic,
clonazepam is an anticonvulsant.
Act at benzodiazepine (BDZ) site of
GABA A receptors to increase the
receptors affinity for GABA-
- Azapirones (anxiolytics)-none of the other side effects
e.g..buspirone, ipsapirone-effectiveness develops over
1-3 weeks. Agonists/partial agonists at 5-HT1A
receptors (which are presynaptic & thir activation by
azapirones inhibits serotonin release via inhibition of
adenylate cyclase)-their therapeutic effects are
delayed (suggests complex mech of action). Buspirone
also binds to DA receptors but anxiolytic effect due to
action @ 5HT1A
- Barbiturates- their sedative & anxiolytic actions are thought to
arise from their binding to GABA A receptors where they
potentiate GABAergic signalling- dont bind where GABA binds,
bind else where and increase GABA signalling
- Other anxiolytics
- The calcium channel blocker pregabalin has
been recently approved to treat GAD (also an
anticonvulsant & pain killer). Anti-depressants
& anti-psychotics are also used to treat panic
disorder. beta adrenoceptor antagonists eg
propanolol are used in some cases to treat
the symptoms of anxiety
- Other receptor systems
- In addition to GABA & 5-HT others are thought to
be involved= NA & neuropeptides (CCK &
substance P). There are currently no anxiolytic
drugs acting at neuropeptide receptors
- GABA A receptor
- Ionotropic receptor permeable to
chloride ions=hyperpolarises,
action therefore inhibitory.
Endogenous agonist is GABA. 5
subuunits
- Side effects
- Benzodiazepines & barbiturates- sedation, resp
depression (particularly with alcohol)-can be
treated with an antagonist eg flumazenil), tolerane
& dependence (not addiction), increased anxiety,
dizziness & nausea on cessation of treatment,
paradoxical effects of benzodiazepines eg
aggression, depression, confusion.
- Azapirones- much less side
effects- relatively minor:
principally nausea, dizziness,
headaches