DRUGS ACTING ON NERVOUS SYSTEM-PART I (BSc. NURSING)

 

DRUGS ACTING ON NERVOUS SYSTEM

PREPARED BY MR. ABHIJIT DAS

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

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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

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USES:

1.     Anxiety disorders

2.     Insomnia

3.     Muscle relaxation

4.     Seizure disorders

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

SKELETAL 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.

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

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

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.

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 (additional) treatment for partial seizures in adults.