Drugs Affecting Gaba System
Summary
TLDRThis educational module delves into anti-epileptic drugs targeting the GABA system, focusing on enhancing inhibitory neurotransmission. It covers four main drug groups: GABA agonists like benzodiazepines and barbiturates, GABA analogs such as gabapentin and pregabalin, GABA transporter inhibitors exemplified by tiagabine, and GABA transaminase inhibitors like vigabatrin. Each group's mechanism, clinical uses, and side effects are discussed, providing a comprehensive understanding of managing seizures through GABA modulation.
Takeaways
- đ§ GABA (gamma-aminobutyric acid) is a crucial inhibitory neurotransmitter in the brain, and its imbalance can lead to conditions like epilepsy.
- đ Anti-epileptic drugs targeting the GABA system aim to increase inhibitory synaptic activity, thereby reducing the frequency of seizures.
- đ There are two main types of GABA receptors: GABA A, which is concentrated in the brain and opens chloride channels, and GABA B, found in the spinal cord and involved in muscle relaxation.
- đĄ Drugs affecting the GABA system can be categorized into four groups: GABA agonists, GABA uptake inhibitors, GABA transaminase inhibitors, and GABA analogs.
- đŒ GABA agonists, such as benzodiazepines and barbiturates, enhance GABA's effect by increasing the frequency or duration of chloride channel opening.
- đ« Barbiturates like phenobarbital have multiple mechanisms, including blocking AMPA receptors and voltage-gated sodium and calcium channels, but can cause sedation and behavioral abnormalities.
- đ± Benzodiazepines are used for emergency control of seizures but have drawbacks like sedative effects and tolerance development with long-term use.
- đ GABA analogs like gabapentin and pregabalin increase GABA concentration in the brain and are also used for neuropathic pain and anxiety disorders.
- đ« Tiagabine, a GABA uptake inhibitor, increases GABA concentration in the synaptic cleft by inhibiting its reuptake, but can cause side effects like dizziness and tremor.
- đ Vigabatrin, a GABA transaminase inhibitor, irreversibly inhibits the enzyme responsible for GABA metabolism, leading to increased GABA levels, but can cause visual side effects and weight gain.
Q & A
What is the primary function of GABA in the nervous system?
-GABA, or gamma-aminobutyric acid, is an important inhibitory neurotransmitter that plays a crucial role in decreasing neuronal excitability throughout the nervous system.
How do GABA A receptors contribute to the inhibitory synaptic activity?
-GABA A receptors are concentrated in the brain and contribute to inhibitory synaptic activity by opening chloride channels, leading to hyperpolarization of the neuron and thus inhibiting its activity.
What are the two main types of GABA receptors discussed in the script?
-The two main types of GABA receptors discussed are GABA A receptors and GABA B receptors. GABA A receptors are mainly found in the brain and are involved in inhibitory synaptic activity, while GABA B receptors are primarily located in the spinal cord and are involved in muscle relaxation.
How does the drug vigabatrin affect the GABA system?
-Vigabatrin is an irreversible inhibitor of the GABA transaminase enzyme, which is responsible for the metabolism of GABA. By inhibiting this enzyme, vigabatrin increases the concentration of GABA in the brain.
What are the adverse effects associated with the use of phenobarbital?
-Phenobarbital can cause sedation, behavioral abnormalities, impairment in learning and memory, hyperactivity in children, and mental confusion. These adverse effects are particularly relevant in clinical settings.
Which drug is commonly used as a first-line treatment for emergency control of convulsions?
-Diazepam is commonly used as a first-line treatment for emergency control of convulsions, particularly in status epilepticus.
What is the mechanism of action of benzodiazepines in the context of epilepsy treatment?
-Benzodiazepines act as GABA agonists, increasing the frequency of GABA-mediated chloride channel opening, which enhances inhibitory synaptic activity and helps control seizures.
How do GABA analogs like gabapentin and pregabalin affect the GABA system?
-GABA analogs like gabapentin and pregabalin do not directly act as GABA agonists. Instead, they modulate the release of GABA by binding to the alpha2delta subunit of voltage-gated calcium channels, thereby increasing GABA concentration in the brain.
What is the primary use of tiagabine, a GABA transporter inhibitor?
-Tiagabine is primarily used in the treatment of complex partial seizures, with or without generalization, by inhibiting the GABA transporter and increasing the concentration of GABA in the synaptic area.
What are the visual side effects associated with vigabatrin?
-Vigabatrin is known to cause visual side effects, which is a significant drawback of the drug. These effects are commonly asked about in entrance exams and are a clinical consideration when prescribing the medication.
Outlines
đ Introduction to GABA-Affecting Anti-Epileptic Drugs
This paragraph introduces the module on anti-epileptic drugs that target the GABA system, which plays a crucial role in inhibitory neurotransmission. The paragraph explains the imbalance between excitatory and inhibitory neurotransmitters as a key factor in epilepsy. The learning objectives include understanding drugs that affect GABA levels, their adverse effects, and contraindications. GABA acts through two main receptors: GABA A, concentrated in the brain and involved in chloride channel opening, and GABA B, present in the spinal cord and related to muscle relaxation. The synthesis of GABA from glutamate by glutamic acid decarboxylase is discussed, along with its termination through action on postsynaptic receptors, metabolism by GABA transaminase, or reuptake by GABA transporters. Four groups of drugs affecting the GABA system are mentioned: GABA agonists (e.g., benzodiazepines, barbiturates, tiagabine, stiripentol), GABA uptake inhibitors (e.g., tiagabine), GABA transaminase inhibitors (e.g., vigabatrin), and GABA analogs (e.g., gabapentin, pregabalin). The paragraph also discusses the mechanism of phenobarbital, which enhances GABA receptor-mediated synaptic inhibition and blocks AMPA receptors at higher doses.
đ Benzodiazepines and Barbiturates as GABA Agonists
This paragraph delves into the specifics of benzodiazepines and barbiturates as GABA agonists. Benzodiazepines increase the frequency of GABA-mediated chloride channel opening, leading to a sedative effect, while barbiturates like phenobarbital increase the duration of opening. The paragraph discusses the drawbacks of benzodiazepines, such as sedation and tolerance to anti-convulsant action over the long term. Specific drugs like diazepam, clobazam, and lorazepam are highlighted for their use in emergency seizure control, absence seizures, and status epilepticus, respectively. The adverse effects of benzodiazepines, including behavioral abnormalities and motor disturbances, are mentioned, along with their availability in tablet and injection forms. The paragraph concludes with a discussion of GABA analogs, which do not directly act as GABA agonists but modulate GABA release by binding to calcium channels.
đ GABA Analogs and Their Clinical Applications
The final paragraph focuses on GABA analogs, such as gabapentin and pregabalin, which are used not only for epilepsy but also for neuralgias, migraine prophylaxis, and anxiety disorders. These drugs increase GABA concentration in the brain and inhibit certain types of calcium channels, modulating neurotransmitter release. The paragraph addresses the common side effects of drowsiness and dizziness associated with these drugs. Gabapentin is used as a second-line treatment for partial seizures and is available as a tablet, often started at night to manage side effects. Pregabalin, a newer congener with less sedation, is also used for neuropathic pain. The paragraph concludes with a mention of tiagabine, which inhibits the GABA transporter, leading to increased GABA concentration in the synaptic area and facilitating inhibitory neural transmission. The side effects of tiagabine include dizziness, fatigue, tremor, and confusion. Vigabatrin, which inhibits GABA transaminase, is also discussed, with its side effects such as visual disturbances, weight gain, and psychiatric symptoms. The paragraph summarizes the module on drugs affecting the GABA system, covering GABA agonists, analogs, transporter inhibitors, and metabolism enhancers.
Mindmap
Keywords
đĄGABA
đĄGABA A receptor
đĄGABA B receptor
đĄAnti-epileptic drugs
đĄBenzodiazepines
đĄBarbiturates
đĄGABA analogs
đĄGABA transporter inhibitor
đĄGABA transaminase inhibitors
đĄPharmacokinetics
Highlights
Introduction to anti-epileptic drugs affecting the GABA system.
GABA is an inhibitory neurotransmitter with two main receptors: GABA A and GABA B.
GABA A receptors are concentrated in the brain and are the primary target for anti-epileptic drugs.
GABA B receptors are involved in muscle relaxation and are used in centrally acting muscle relaxants.
GABA is synthesized from glutamate by glutamic acid decarboxylase.
GABA's action is terminated by acting on postsynaptic receptors or by being metabolized or re-uptaken.
There are four groups of drugs affecting the GABA system: GABA agonists, uptake inhibitors, transaminase inhibitors, and analogs.
Benzodiazepines and barbiturates act as GABA agonists, enhancing chloride channel opening frequency or duration.
Phenobarbital enhances GABA receptor-mediated synaptic inhibition and blocks AMPA receptors.
Phenobarbital is a potent enzyme inducer and can develop tolerance with long-term use.
Adverse effects of phenobarbital include sedation, behavioral abnormalities, and cognitive impairments.
Benzodiazepines are used for emergency control of seizures but have drawbacks like sedative effects and tolerance.
GABA analogs like gabapentin and pregabalin increase GABA concentration and inhibit certain calcium channels.
GABA analogs are used for resistant partial seizures and neuralgic pain, but can cause drowsiness and dizziness.
Tiagabine inhibits the GABA transporter, increasing GABA concentration in the synaptic area.
Vigabatrin irreversibly inhibits GABA transaminase, leading to increased GABA levels and potential visual side effects.
Vigabatrin is used for partial seizures and is known for its unique side effect profile, including visual disturbances.
Module conclusion summarizing the key points on drugs affecting the GABA system.
Transcripts
welcome students to the next module of
anti-epileptic drugs that is the drugs
affecting gaba system
so we have already discussed the drugs
affecting calcium channels drugs
affecting sodium channels and now we are
discussing the drugs affecting gaba
system as we all know it is mainly the
imbalance between the anxiety chain
inhibitory neurotransmitter so in this
we are going to concentrate mainly how
to you know increase the inhibitory
synaptic activity or inhibit increase
the inhibitory transmissions so learning
objectives will be enumerated drugs
which acts by affecting gaba levels and
discuss the user's adverse effect and
contraindications as we all know gaba is
an important inhibitory neurotransmitter
it mainly acts by two receptor gaba a
receptor and gaba b receptor gaba a
receptor is mainly concentrated in the
brain which mainly acts through chlor
you know chloride channel opening and
that is the one which is the main target
for our anti-epileptic drugs whereas the
gaba b receptors are mainly present in
the spinal cord and they belong to a g
protein couple type of receptors and
they are mainly involved in muscle
relaxation so which we use it as a
centrally acting muscle relaxants
so before we start up what is the drugs
affecting gaba
let's uh see how the gaba is synthesized
and how it is transported as we all know
it is the glutamate which is a precursor
molecule for gaba which gets converted
to gaba by glutamic acid decarboxylase
once this gaba is synthesized it is
stored in the vesicles and it is
released whenever there is a
depolarization or there is a impulse
conduction in the pre-synaptic neuron
the released gaba has two ways for its
action to gets terminated one is it acts
on the postsynaptic receptor
after that either it will get
metabolized by
gaba trans a minus enzyme or it will be
re-uptaken back by
a gaba transporter so when we are
talking of the drugs which are affecting
the gaba system
there are mainly four groups of drugs
one group which are acting as gaba
agonist we have mainly drugs like
benzodiazepine barbiturates genocide and
stirripintol
gabari uptake inhibitors like tiago bean
gaba trans aminos inhibitors like vigor
battery and gaba analogs like
gabapentine and pregabal here gaba
analogs may not be directly acting as
gaba agonist or gaba mimetics they
mainly act by modulating the release of
gaba how is it we will discuss later
now as i discussed s it is the vigor
battery which inhibits the gaba
transient mnas along with that sodium
valproate which i said a broad spectrum
anti-epileptic can also inhibit the
gamma transaminase
and tiago bean is a drug which inhibits
the gaba transporters you see in the
picture benzodiazepine and barbiturates
act as gaba agonist
now discussing on each group mainly
phenobarbitone and
benzodiazepine let's discuss first
phenobabatone enhances the gaba receptor
mediated synaptic inhibition along with
that it has a
other mechanism of blocking ampa
receptor
but when you give it a high dose it also
has other mechanisms like blocks
voltage-gated uh sodium channels and
calcium channels so there are multiple
mechanisms for phenobarbital but the
main mechanism is enhancement of gaba
receptor mediated synaptic inhibition
and coming to pharmacokinetic property
it is a potent enzyme inducer which
develops tolerance to sedative action on
a long term usage
and adverse effects yes phenobabatone
you all know it is one of the drugs
which is used as a sedative and hypnotic
yes the common adverse effect is
sedation but the important adverse
effect mainly which comes in into
clinical relevance is a behavioral
abnormalities if you are using in a
children that is a reason the use of
phenobarbitone in febrile seizure as a
prophylaxis treatment has been abandoned
nowadays
impairment in the learning and memory
hyperactivity in children and mental
confusion
where do we use this drug we use this
drug in all types of seizures you see
generalized on a clonic seizure simple
partial seizure complex partial seizure
and profile axis of febrile seizure yes
it was being used for the prophylaxis of
febrile seizure but nowadays we have
reduced the use and it is only the
diazepam which is being used because of
its
behavioral abnormality and impairing the
learning and memory in children and it
is the second line drop in the status
epileptic what is it we will discuss in
the next module
it's available as injections and in the
tablet form so depending on whether it's
adult or children the dose can be
adjusted
the next group of drugs which act as
gabo against so we said two groups of
drugs which act as gaba agonist one is
benzodiazepine the other one is
barbiturates otherwise phenobarbitude so
we discussed phenobarbitude now coming
to the benzodiazepine how does this drug
act it this drug acts mainly by you can
see in the picture
increasing the frequency of gaba
mediated chloride channel opening see in
the picture it increases the frequency
of gaba mediated chloride channel
opening whereas the phenobarbital
increases the duration of opening
whereas the benzodiazepine increases the
frequency of opening but what is the
drawback the drawback is that it has a
sedative effect yes because this is one
of the sedative drugs which is being
used for anti-epileptic purpose
tolerance to anti-convulsant action so
this is one of the main drawback when
you are using it for a long term that's
the reason the use of benzodiazepine for
long-term use in anti-epileptic purposes
come down
because of its tolerance action in
benzodiazepine we have different drugs
but what is used for anti-epileptic
purpose we have
four drugs that is dizzy power clan as
the pack clobazam and laura zepa now
dicey pump
it's a first line draw for emergency
control of conversion any patient you
say convulsing diazepam can be given 10
milligram intravenously in status
epilepticus the first choice is
larizepam nowadays but previously it was
diazipa
tetanus patient is convulsing because of
tetanus you can give diazepam
eclampsia eclampsia is
a state in pregnancy where the pregnancy
induced hypertension will
lead to a seizure manifestation their
diazepam can be given and drug poisoning
if a there is a epilepsy due to drug
poisoning we can give the diazepa the
second use is the febrile seizures
febrile's teacher yes diazepam is a drug
of choice and it is given per rectally
in a child and febrile suture is nothing
but seizure in the children below the
five years of age when there is a
episode of fever
but what are the adverse effects when we
give it an emergency obviously we give
it through intravenous route it causes
falling blood pressure it causes
respiratory depression and it leads to
thrombophlebitis
it is available as tablets and induction
yes we don't use it for a long term view
so most of the time what we use for
emergency is in an injection form the
next drug is clobaza so it is a potent
long-acting drug which can be used in
absence seizures and even as an adjuvant
in myoclonic and
a kinetic epilepsy that is atonic
epilepsy
but what are the adverse effects lack of
concentration irritability behavior
abnormality motor disturbance ataxia
salivation this is the reason that's the
reason why benzodiazepines are not being
preferred that commonly as the other
drugs because of their central nervous
system adverse effects yes it's
available as capsules and it can be you
know
those can be titrated depending on the
response
clonazepam
it's less sedative compared to other
drugs long acting
again used in partial secondary
generalized tonic cloning seizures
secondary generalized tonic-clonic
seizure that means it is
where the onset was a partial seizure
later seizure activity progressed to
become a secondary generalized
tonoclonal seizures absences or atomic
seizures it is mainly used as an
adjuvant drug so it's not a wastelander
it's used as an adjuvant drug
it is also available in different
strains and the dose can be adjusted
depending on the response the another
important and the life-saving drug in
benzodiazepine group which is the drug
of choice in status epilepticus that is
lorazepam so larazepam is a drug of
choice for status epilepticus and
emergency control of convulsion what's
the advantage compared to diazepam there
is a less thrombophlebitis and the
action is sustained so it is available
in tablets and injection form what we
use is the injection form what we give
is four milligram iv whenever there is a
seizure episode
so that completes one group of drugs
that is gaba agonist which two drugs
there that's benzodiazepines and
phenobarbital the next group of drugs is
gaba analogues now what do we understand
by gaba analogs are they really acting
like gaba no as i said
see here in the picture
uh they are mainly trying to bind to a
calcium channel where there is alpha to
delta subunit in the calcium channel you
can see in the enlarged picture in the
box there
the drug tries to bind to that alpha to
delta subunits and tries to modulate the
release of the neurotransmitter
so the drugs are gabapentine and
pregabalin so coming to the easter these
drugs most commonly nowadays not just
use for anti-epileptic purpose they are
the one of the drugs used in the
neuralgias also so how do they act they
increase the gaba concentration in the
brain by increasing the release and
synthesis along with that it
inhibits the end type of calcium channel
that's what i was telling and it
modulates the release of
neurotransmitters
but
the problem with this drugs is
drowsiness
and dizziness this is one of the main
problem majority of the patient starts
facing when you start the patient on
gabapentin and they try to discontinue
it
where do we use this gaba pentane i said
it is used in resistant partial seizure
that means we have already tried the
first line drugs like carbamazepine and
other drugs and the patient is not
responding then we can try gabapentine
otherwise this drugs that is both gaba
pentene and priy gabalin are a first
line drugs in neuralgic pain especially
in diabetic neuropathy
the other use is prophylaxis in migraine
alternative to phobic state and it is
used in generalized anxiety disorders
and
postherpetic neuralgia available as
tablet most of the time this tablet is
started in the night time so that if the
dizziness all that effects is taken care
but might need to increase the dose
depending on the response
the second drug again pregabalin which
is the newer congenital same mechanism
of action advantage compared to gaba
pentane is less sedation and uses in
neuropathic pain
so we finished uh the second group of
drugs which affect the gaba system that
is the gaba analogues gabapentine and
pregabalin coming to the third which
inhibits the gaba transporter you can
see in the picture tiago bean is
inhibiting the gaba transporter mainly
highlighted in the orange there so it
inhibits the gaba uptake in the neuronal
and glial cells through gaba so what
happens the concentration in the gaba in
the synaptic area is increased which
facilitates the inhibitory neural
transmission so advanced effect is
dizziness fatigue tremor and confusion
so where do we use we use it in complex
partial seizures with or without
generalization
the last group of drugs in gaba uh drugs
affecting gaba system is the drugs which
inhibits the gaba transaminase enzyme
that is vigor battering so it is an
irreversible inhibitor of gaba
transaminase so it irreversibly inhibits
so for the metabolism of the gaba then
the fresh synthesis of enzyme has to
happen
the problem with vigor pattern is it has
a particular type of side effect which
is the most commonly asked in your all
entrance exam that is a visual side
effect which is an anti-epileptic drug
which has a visual side effect as its
drawback that is vigor battery other
than that it causes weight gain
behavioral changes depression and
psychosis most of the time these drugs
are used in partial seizures with or
without generalization
so that ends the module on the drugs
affecting gaba system so we have studied
four drugs gaba agonist gaba analogs
gaba transporter inhibitor and
drugs which increases the metabolism of
gaba that is vigor bacteria
i think that completes the whole module
on the drugs affecting gaba and thank
you all
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