DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM
PREPARED BY MR. ABHIJIT DAS
ANAESTHETICS
Anaesthetics are substances
used to induce a reversible loss of sensation,
typically to prevent pain during medical procedures. There are two main types:
1.
General
Anaesthetics: These induce
a state of controlled unconsciousness and a
lack of sensation over the entire body.
2.
Local
Anaesthetics: These numb a
specific part of the body, allowing a
patient to remain conscious.
GENERAL
ANAESTHETICS
STAGES OF ANAESTHESIA:
1.
Stage
1: Analgesia
·
Onset: Begins with the administration of the anaesthetic.
·
Symptoms: The patient starts to feel drowsy, experiences a reduction in pain perception, and may remain
conscious.
2.
Stage
2: Excitement (Delirium)
·
Onset: Starts with the loss of consciousness.
·
Symptoms: The patient may exhibit irregular
breathing, increased heart rate and increased blood pressure. This stage can be marked
by agitation or delirium.
3.
Stage
3: Surgical Anaesthesia
·
Onset: Begins as the patient stabilizes into a regular pattern of breathing and relaxation.
·
Symptoms: This stage is characterized by the absence of reflexes, relaxed
muscles, and adequate depth of anaesthesia for
surgical procedures. Breathing is steady, and the patient's eyes may
become fixed.
4.
Stage
4: Overdose
·
Onset: Begins if the
anaesthetic depth is too great.
·
Symptoms: Characterized by severe depression
of the central nervous system, including the
respiratory and cardiovascular systems. This stage can lead to respiratory arrest, cardiovascular
collapse, and can be fatal if not
promptly corrected.
CLASSIFICATION
OF GENERAL ANAESTHETICS:
§ Inhalational Anaesthetics:
1.
Gas:
Nitrous Oxide
2.
Volatile
Liquid: Isoflurane, Sevoflurane, Desflurane, Ether, Halothane
§ Intravenous (IV) Anaesthetics: Propofol, Thiopental, Etomidate, Ketamine, Midazolam
NITROUS
OXIDE
MOA:
Nitrous oxide (N2O)
works by entering the neuron and causing disturbances
within the cell membrane. This process, known as membrane fluidization, alters the physical properties of the
lipid bilayer of the neuron.
As a result, the ion channels
embedded in the membrane, particularly those for sodium ions (Na+),
are affected. The fluidization of the membrane prevents
the normal influx of Na+ ions into the neuron, thereby inhibiting the generation and propagation of
action potentials.
This disruption of neuronal
signaling leads to a lack of sensation and contributes to the anaesthetic and
analgesic effects of nitrous oxide.
ADVERSE
EFFECTS:
1.
Respiratory
depression
2.
Nausea
and vomiting
3.
Hypotension
USES:
1.
Surgical
procedures
2.
Sedation
for medical procedures
3.
Management
of acute pain
DOSE AND
ROUTE:
Dose: For general anaesthesia: Usually
administered in concentrations ranging from 50% to 70%, mixed with oxygen.
Route of Administration: Inhalation
CONTRAINDICATIONS:
1.
Pneumothorax: Nitrous oxide can expand trapped air, worsening the
condition.
[NOTE: Pneumothorax
is a medical condition characterized by the presence of air or gas in the
pleural cavity, the space between the lung and the chest wall.]
2.
Middle
ear blockage: Nitrous
oxide can cause further pressure build-up in these areas.
[NOTE:
Middle Ear Blockage occurs when the Eustachian tube, which connects the middle
ear to the back of the nose and throat, becomes blocked or swollen.]
3.
Pregnancy: Nitrous oxide is contraindicated in the first
trimester due to potential teratogenic effects.
SEDATIVES AND HYPNOTICS
Sedatives are a group of drug that slow down brain
activity without inducing sleep. These drugs
are prescribed to help patients calm down, feel more relaxed and get better
sleep.
Hypnotics are a group of drugs that induce sleep and reduce wakefulness during sleep.
Sedatives and hypnotics are very commonly prescribed
drugs because anxiety and insomnia are very common problems.
Often, a drug which at lower doses, produces sedation,
causes hypnosis or even anaesthesia coma, and death in sufficiently higher
doses. For example barbiturates at lower doses produce sedation, and at higher
doses produce hypnosis.
ANXIETY
The person, without any reason, develops an episode of
panic which is characterized by palpitation
(rapid and irregular heart beat), fear of unknown, sweating, dyspnea (shortness
of breathing) etc.
INSOMNIA
The person take too much time
after retiring into bed for falling asleep or inability to stay in sleep
that means the person’s sleep is broken repeatedly.
CLASSIFICATION:
BARBITURATES
LONG ACTING: Phenobarbitone
SHORT ACTING: Butobarbitone, Phentobarbitone
ULTRA-SHORT-ACTING: Thiopentone, Methohexitone
BENZODIAZEPINES
HYPNOTIC: Diazepam, Flurazepam, Nitrazepam,
Alprazolam, Temazepam, Triazolam
ANTIANXIETY: Diazepam, Chlordiazepoxide, Oxazepam,
Lorazepam, Alprazolam
ANTICONVULSANT: Diazepam, Lorazepam, Clonazepam,
Clobazam
NEWER NONBENZODIAZEPIN HYPNOTICS: Zopiclone, Zolpidem, Zaleplon
BARBITURATES:
MOA:
Barbiturates act by binding to GABA receptors, enhancing the inhibitory effect of
GABA neurotransmitter, which opens chloride
channels. This results in hyperpolarization
(No Depolarization) of neurons, leading to sedation and inhibition of neuronal
activity.
ADVERSE
EFFECTS:
1.
Respiratory
depression
2.
Dependence
and tolerance
3.
CNS
depression leading to drowsiness or coma
4.
Hypotension
USES:
1.
Sedation/anesthesia
induction
2.
Antiepileptic
therapy
3.
Treatment
of insomnia
BENZODIAZEPINES:
MOA:
Benzodiazepines act by binding
to GABA receptors, enhancing the inhibitory
effect of GABA neurotransmitter, which opens
chloride channels. This results in hyperpolarization
(No Depolarization) of neurons and inhibition of neuronal activity.
ADVERSE
EFFECTS:
1.
Drowsiness/fatigue
2.
Memory
impairment
3.
Respiratory
depression
4.
Dependence
and withdrawal symptoms
USES:
1.
Anxiety
disorders
2.
Insomnia
3.
Muscle
relaxation
4. Seizure disorders
ANTICONVULSANTS
Anticonvulsants are medications
that help control or prevent seizures, which
are sudden, uncontrolled electrical activity in the brain.
They work by stabilizing this
abnormal activity, reducing the likelihood of seizures occurring.
CLASSIFICATION:
1. SODIUM CHANNEL BLOCKERS:
·
Examples: Phenytoin, Carbamazepine, Lamotrigine.
·
MOA: They block voltage-gated
sodium channels, reducing neuronal excitability and preventing the
spread of abnormal electrical activity.
·
Adverse
Effects: Possible adverse effects
include dizziness, drowsiness, ataxia (loss of coordination), and skin rash
(especially with Lamotrigine).
·
Uses: Treatment of epilepsy and bipolar disorder.
2. CALCIUM CHANNEL BLOCKERS:
·
Examples: Ethosuximide, Valproate.
·
MOA: They block calcium
channels, thereby inhibiting neuronal activity.
·
Adverse
Effects: Adverse effects may include
gastrointestinal disturbances, weight gain, liver toxicity (especially with
Valproate).
·
Uses: Primarily used to treat seizures and also used for mood stabilization
(Valproate).
3. GABA ENHANCERS:
·
Examples: Benzodiazepines (e.g., Diazepam, Lorazepam),
Barbiturates (e.g., Phenobarbital).
·
MOA: They enhance the
activity of gamma-aminobutyric acid (GABA),
which is an inhibitory neurotransmitter, leading to activation
chloride (Cl-) channels (so, no
Depolarization).
·
Adverse
Effects: Adverse effects can include
sedation, cognitive impairment, respiratory depression (especially with high
doses), and physical dependence.
·
Uses: Acute (severe) seizure management (e.g., status
epilepticus), adjunctive therapy (or additional therapy) for various types of
seizures.
4. GLUTAMATE INHIBITORS:
·
Examples: Topiramate, Felbamate.
·
MOA: They inhibit glutamate
release, reducing excitatory neurotransmission.
·
Adverse
Effects: Potential adverse effects
include cognitive impairment, weight loss, kidney stones (especially with
Topiramate)
·
Uses: Treatment of epilepsy, including partial seizures.
5. POTASSIUM CHANNEL OPENERS:
·
Examples: Ezogabine (also known as Retigabine).
·
MOA: They selectively activate
potassium channels on post synaptic neurons (so efflux
of K+), which can hyperpolarize neurons (no depolarization), reducing their excitability.
·
Adverse
Effects: Adverse effects may include dizziness,
urinary retention, and potential for retinal abnormalities.
·
Uses: Adjunctive treatment for partial seizures in adults.
ANTIANXIETY DRUGS
Antianxiety drugs are
medications used to alleviate symptoms of anxiety disorders by calming the nervous
system.
ANXIETY:
Anxiety is a natural response
to stress or perceived threats, but when it becomes chronic or overwhelming, it
can be considered pathological anxiety. Pathological anxiety involves excessive
worry or fear that interferes with daily life. It often involves a hyperactive sympathetic nervous system, which is
responsible for the body's "fight or flight" response, leading to symptoms like increased
heart rate, sweating, and tremor.
CLASSIFICATION
OF ANTIANXIETY DRUGS:
1. SEDATIVES AND HYPNOTICS:
·
Examples: Benzodiazepines (e.g., diazepam, lorazepam), Z-drugs
(e.g., zolpidem, zaleplon)
·
Mechanism
of Action (MOA): Enhance the
activity of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain,
leading to a calming effect.
·
Adverse
Effects: Drowsiness, dizziness,
confusion, risk of dependence and withdrawal symptoms with long-term use.
·
Uses: Short-term relief of anxiety, insomnia, and acute
agitation.
2. ANTIDEPRESSANTS:
·
Examples: Selective Serotonin Reuptake Inhibitors (SSRIs)
(e.g., sertraline, escitalopram), Serotonin-Norepinephrine Reuptake Inhibitors
(SNRIs) (e.g., venlafaxine, duloxetine)
·
Mechanism
of Action (MOA): SSRIs
increase serotonin levels in the brain, while SNRIs increase both serotonin and
norepinephrine levels, helping to regulate mood and reduce anxiety.
·
Adverse
Effects: Nausea, headache, insomnia,
increased risk of suicidal thoughts (especially in young adults).
·
Uses: Treatment of generalized anxiety disorder (GAD),
panic disorder, social anxiety disorder
3. BETA BLOCKERS:
·
Examples: Propranolol, atenolol
·
Mechanism
of Action (MOA): Block the
effects of adrenaline (epinephrine) on beta-adrenergic receptors, reducing the
physical symptoms of anxiety such as rapid heartbeat, sweating and trembling.
·
Adverse
Effects: Fatigue, dizziness, decreased
heart rate, cold extremities.
·
Uses: Management of performance anxiety (e.g., public
speaking), treatment of physical symptoms of anxiety such as palpitations and
tremors.
ANTIDEPRESSANTS
Antidepressant drugs are
medications prescribed to help alleviate symptoms of depression and improve
mood by influencing the levels of certain chemicals in the brain called
neurotransmitters.
CLASSIFICATION
1. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS):
EXAMPLES:
Fluoxetine, Sertraline,
Paroxetine, Escitalopram, Citalopram.
MOA:
Selective Serotonin Reuptake
Inhibitors (SSRIs) work by blocking the reabsorption (reuptake) of serotonin in
the brain. Serotonin is a neurotransmitter, a chemical that helps transmit
signals between nerve cells. By inhibiting the reuptake of serotonin, SSRIs
increase the concentration of serotonin in the synapses (gaps between nerve
cells), which can enhance neurotransmission and alleviate symptoms of
depression and anxiety. In simple terms, SSRIs help keep more serotonin
available in the brain, positively affecting mood regulation.
ADVERSE
EFFECTS:
a)
Insomnia
b)
Nausea
c)
Dry
mouth
d)
Headache
USES:
a)
Depression
b)
Anxiety
Disorders
c)
Panic
Disorders
d)
Post-Traumatic
Stress Disorder (PTSD)
2. SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS
(SNRIS):
EXAMPLES:
Venlafaxine, Duloxetine,
Desvenlafaxine.
MOA:
Serotonin-Norepinephrine
Reuptake Inhibitors (SNRIs) work by blocking the reabsorption (reuptake) of
both serotonin and norepinephrine in the brain, helping to increase the levels
of these neurotransmitters. This enhanced presence of serotonin and norepinephrine
in the synapses can positively impact mood and alleviate symptoms of depression
and anxiety.
ADVERSE
EFFECTS:
a)
Nausea
b)
Insomnia
c)
Increased
Heart Rate
d)
Dry
Mouth
e)
Dizziness
USES:
a)
Major
Depressive Disorder
b)
Generalized
Anxiety Disorder
c)
Chronic
Pain Management
3. MONOAMINE OXIDASE INHIBITORS (MAOIS):
EXAMPLES:
Amitriptyline, Nortriptyline,
Imipramine, Doxepin, Clomipramine.
MOA:
Monoamine Oxidase Inhibitors
(MAOIs) work by blocking the action of an enzyme called monoamine oxidase. This
enzyme normally breaks down neurotransmitters such as serotonin,
norepinephrine, and dopamine. By inhibiting monoamine oxidase, MAOIs increase
the levels of these neurotransmitters in the brain. This elevation in
neurotransmitter levels can help improve mood and alleviate symptoms of
depression.
ADVERSE
EFFECTS:
a)
Hypertensive
Crisis (Severe Increase in Blood Pressure)
b)
Weight
Gain
c)
Drowsiness
d)
Dizziness
USES:
a)
Major
Depressive Disorder
b)
Atypical
Depression
c)
Social
Anxiety Disorder
d)
Panic
Disorder
ANTIPSYCHOTICS
Antipsychotics are medications
primarily used to manage symptoms of psychosis, which can include
hallucinations, delusions, and disordered thinking. They work by affecting
certain neurotransmitters in the brain to help alleviate these symptoms.
CLASSIFICATION:
1.
Typical
(First-Generation) Antipsychotics:
·
Examples:
Chlorpromazine, Haloperidol, Fluphenazine
2.
Atypical
(Second-Generation) Antipsychotics:
·
Examples:
Risperidone, Olanzapine, Quetiapine, Aripiprazole
TYPICAL
ANTIPSYCHOTICS
MOA:
Typical (first-generation)
antipsychotics work by blocking dopamine receptors
in the brain, which helps to reduce symptoms of psychosis like hallucinations
and delusions.
ADVERSE
EFFECTS:
1.
Drowsiness
2.
Dizziness
3.
Blurred
vision
4.
Dry
mouth
USES:
1.
Treatment
of schizophrenia
2.
Management
of acute psychotic episodes
3.
Control
of agitation and aggression in certain conditions
ATYPICAL
ANTIPSYCHOTICS
MOA:
Atypical antipsychotics work by blocking dopamine and serotonin receptors in
the brain, which helps to reduce symptoms of psychosis.
ADVERSE
EFFECTS:
1.
Drowsiness
2.
Dizziness
3.
Dry
mouth
4.
Blurred
vision
USES:
1.
Schizophrenia
2.
Acute
psychotic episodes
3.
Agitation
and aggression management
NOOTROPIC AGENTS
Nootropic agents, also known as cognitive enhancers or
"smart drugs," are substances that enhance cognitive function,
particularly memory, creativity, and motivation, without producing significant
side effects. These agents can include natural compounds, such as caffeine and
ginkgo biloba, or synthetic compounds, such as racetams and modafinil. While
some nootropic agents are available over the counter, others are available only
by prescription and should be used under the guidance of a healthcare provider.
CLASSIFICATION OF NOOTROPIC AGENTS
1.
Stimulants: Examples include
caffeine, modafinil, and methylphenidate.
2.
Racetams: Examples include
piracetam, aniracetam, and oxiracetam.
3.
Cholinergics: Examples include
choline, acetylcholine precursors, and acetylcholinesterase inhibitors.
4.
Herbal and natural supplements:
Examples include ginkgo biloba, bacopa monnieri, and ashwagandha.
5.
Other miscellaneous agents:
Examples include creatine, L-theanine, and phosphatidylserine
CENTRALLY ACTING MUSCLE RELAXANTS
A centrally acting skeletal
muscle relaxant is a medication that targets the brain or spinal cord to reduce
muscle contraction, easing muscle spasms and stiffness.
CLASSIFICATION:
1.
GABAergic
Agents:
·
Baclofen
·
Gabapentin
2.
Antispastic
Agents:
·
Tizanidine
·
Diazepam
(less common due to concerns about tolerance and dependency)
BACLOFEN
MOA:
1.
Binding
to GABA-B Receptors on Upper Motor Neurons:
·
Baclofen
binds to GABA-B receptors located on the
terminals of upper motor neurons in the
spinal cord.
·
This
binding inhibits the release of excitatory
neurotransmitters such as glutamate by blocking calcium (Ca++) channels.
·
By
reducing the release of excitatory neurotransmitters, baclofen decreases the
excitability of upper motor neurons and inhibits the signals that contribute to
muscle spasticity.
2.
Binding
to GABA-B Receptors on Lower Motor Neurons:
·
Baclofen
also binds to GABA-B receptors located on
the soma (cell body) of lower motor neurons.
·
This
binding leads to the opening of potassium (K+)
channels and subsequent efflux of potassium
ions from the neuron.
·
The
efflux of potassium ions hyperpolarizes the neuron, making it less likely to
reach the threshold for depolarization and action potential firing.
·
By
hyperpolarizing lower motor neurons, baclofen further inhibits the transmission
of signals to muscles, contributing to muscle relaxation.
ADVERSE
EFFECTS:
1.
Drowsiness
2.
Dizziness
3.
Weakness
4.
Fatigue
USES:
1.
Muscle
spasms relief
2.
Treatment
of muscle rigidity and pain associated with certain neurological disorders.
TIZANIDINE
MOA:
- Tizanidine binds to alpha2-adrenergic
receptors located on the terminals of upper motor neurons in the
spinal cord.
- By binding to these receptors, tizanidine inhibits the release of excitatory
neurotransmitters such as glutamate.
- This inhibition reduces the excitability of upper
motor neurons and decreases the transmission
of signals that contribute to muscle contraction.
OPIOID ANALGESICS
Opioid analgesics are drugs primarily used to relieve pain. They work by binding to opioid receptors in the brain, spinal cord, and
other areas of the body, reducing the perception of pain.
- Opium:
Opium is a natural substance derived from the sap of the opium poppy plant
(Papaver somniferum). It contains various alkaloids, including morphine
and codeine, which have pain-relieving properties.
·
Opioids: Opioids are
substances that includes natural, semi-synthetic, and synthetic drugs that act
on the body's opioid receptors. They can be derived from opium (like morphine
and codeine), semi-synthesized from opium alkaloids (like heroin), or entirely
synthetic (like fentanyl and pethidine).
CLASSIFICATION
1.
Natural opioids:
Morphine, Codeine
2.
Semi-synthetic opioids:
Oxycodone, Hydrocodone, Heroin
3.
Synthetic opioids:
Fentanyl, Methadone, Pethidine
MORPHINE
MOA:
Morphine's mechanism of action involves blocking calcium channels on presynaptic neurons, which in turn blocks the release of neurotransmitters such as substance P.
Additionally, morphine opens
potassium ion channels on postsynaptic
neurons, leading to repolarization (no
depolarization) and preventing further signal transmission.
PHARMACOLOGICAL ACTIONS:
1.
Central Nervous System (CNS):
·
Reduces visceral pain
·
Induces drowsiness
·
May produce a pleasurable floating
sensation
2.
Respiration:
·
Depresses the respiratory center
·
Overdose can lead to respiratory
depression, morphine poisoning, and potentially death
3.
Cardiovascular System:
·
Causes vasodilation
·
Reduces blood pressure (BP)
·
May result in bradycardia (slow heart
rate)
·
Reduces cardiac work
4.
Gastrointestinal Tract (GIT):
·
Reduces gastrointestinal motility
·
Reduces gastrointestinal secretion
5.
Smooth Muscle:
·
Can cause bronchoconstriction (contraction
of bronchial smooth muscle)
·
Induces contraction of the urinary bladder
ADVERSE EFFECTS:
1.
Respiratory depression, which can lead to
death in cases of morphine overdose.
2.
Mental confusion and sedation.
3.
Hypotension (low blood pressure).
4.
Development of tolerance and dependence
with prolonged use.
5.
Allergic reactions, though these are
relatively rare, they can include symptoms such as rash, itching, and
difficulty breathing.
THERAPEUTIC USES:
1.
Analgesics:
Used for moderate to severe pain relief.
2.
Preanesthetics:
Can alleviate anxiety and provide pain relief before anesthesia.
3.
Antitussive agents:
Used to suppress severe coughing.
4.
Treatment of diarrhea:
Sometimes used for severe cases when other medications fail.
CONTRAINDICATIONS:
1.
Respiratory depression: Patients with
compromised respiratory function, such as severe asthma or chronic obstructive
pulmonary disease (COPD).
2.
Acute or severe bronchial asthma: Morphine
can worsen respiratory function in these patients.
DOSE AND ROUTE:
The typical dose of morphine ranges from 5 to 30 milligrams, administered orally or via injection (IV, IM & SC), every 4 hours as needed for pain relief.
ADVERSE
EFFECTS:
1.
Drowsiness
2.
Dizziness
3.
Dry
mouth
4.
Weakness
USES:
1.
Muscle
spasticity relief
2.
Management
of symptoms associated with conditions such as multiple sclerosis or spinal
cord injuries.