Applied Pharmacology Nervous System Modulators
40 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which class of drugs targets axonal voltage-gated ion channels?

  • Antihistamines
  • Antidepressants
  • β-blockers
  • Calcium channel blockers (correct)

What is the main effect of phenytoin on voltage-gated sodium channels?

  • It increases the firing rate of action potentials.
  • It activates calcium influx through the channels.
  • It stabilizes the Nav channels that are inactivated. (correct)
  • It enhances synaptic release of glutamate.

Which voltage-gated sodium channel is NOT expressed in the nervous system?

  • Nav1.5
  • Nav1.6
  • Nav1.4 (correct)
  • Nav1.1

Which option correctly describes the mechanism of action of carbamazepine?

<p>It acts as a non-specific sodium channel blocker. (C)</p> Signup and view all the answers

What does TTX-sensitive mean in the context of voltage-gated sodium channels?

<p>The channel is blocked by tetrodotoxin. (C)</p> Signup and view all the answers

What is the primary medical indication for phenytoin?

<p>Epilepsy following trauma (B)</p> Signup and view all the answers

What type of voltage-gated ion channel primarily determines the threshold for firing an action potential?

<p>Voltage-gated sodium channels (B)</p> Signup and view all the answers

Which of the following drugs does NOT target monoaminergic neurotransmitters?

<p>Beta-agonists (B)</p> Signup and view all the answers

What component of the voltage-gated sodium channel acts as a voltage sensor?

<p>S4 segment (A)</p> Signup and view all the answers

What is the role of the β-subunit in voltage-gated sodium channels?

<p>Regulates α-subunit kinetics and localization. (D)</p> Signup and view all the answers

What is the primary medical indication of Ethosuximide?

<p>Treatment of absence seizures (B)</p> Signup and view all the answers

Which type of calcium channel is mainly found in the brain and peripheral nervous system?

<p>N-type (D)</p> Signup and view all the answers

What effect does Retigabine have on voltage-gated potassium channels?

<p>It binds to Kv7 channels and increases K+ ion outflow. (C)</p> Signup and view all the answers

How does Buspirone act on 5-HT1A receptors?

<p>It is a partial agonist that decreases further serotonin release. (C)</p> Signup and view all the answers

What is the role of the α2δ subunit in voltage-gated calcium channels?

<p>It acts as a stabilizing agent for α1 subunit. (D)</p> Signup and view all the answers

What is a medical indication for the use of CGRP/substance P modulators?

<p>Acute cluster headache (B)</p> Signup and view all the answers

Which of the following best describes the physiological effect of voltage-gated potassium channels?

<p>Hyperpolarize the neuron and decrease action potential probability. (B)</p> Signup and view all the answers

What is the primary action of Ondansetron and Granisetron?

<p>Antagonize 5-HT3 receptors (C)</p> Signup and view all the answers

What neurological function is primarily associated with the 5-HT pathways projecting to the limbic forebrain?

<p>Memory (C)</p> Signup and view all the answers

What does Gabapentin primarily target in treatment?

<p>α2δ calcium channel subunit (D)</p> Signup and view all the answers

Which condition is Haloperidol NOT used to treat?

<p>Acute cluster headache (B)</p> Signup and view all the answers

Which receptors do Metoclopramide antagonize?

<p>Dopamine D2 and 5-HT3 receptors (B)</p> Signup and view all the answers

Which type of calcium channel is known for its transient characteristics and is involved with pacemaker activity in certain cells?

<p>T-type (A)</p> Signup and view all the answers

Which statement correctly describes the role of voltage-gated sodium channels?

<p>They help in the generation of action potentials. (C)</p> Signup and view all the answers

What is a common indication for the use of 5-HT3 receptor modulators?

<p>Antiemetic for cancer treatment (C)</p> Signup and view all the answers

What effect do antagonists of dopamine D2 receptors have on the chemoreceptor trigger zone?

<p>Block neuronal activation (A)</p> Signup and view all the answers

Which statement is true about the action of Metoclopramide?

<p>It blocks both dopamine D2 and 5-HT3 receptors. (C)</p> Signup and view all the answers

Which neurotransmitter's receptors are targeted by Haloperidol for its antipsychotic effect?

<p>Dopamine (D)</p> Signup and view all the answers

Which of the following is NOT a characteristic of 5-HT3 receptors?

<p>They require a second messenger. (A)</p> Signup and view all the answers

What is the role of CGRP and substance P in the context of migraine management?

<p>They induce vasoconstriction. (B)</p> Signup and view all the answers

What is the main medical indication for using agonists of the 5-HT4 receptor?

<p>Prevention and treatment of postoperative nausea and vomiting (B)</p> Signup and view all the answers

Which receptors do risperidone primarily antagonize to alleviate symptoms in schizophrenia?

<p>Dopamine D2 and serotonin 5-HT2A receptors (B)</p> Signup and view all the answers

What is the role of 5-HT1A receptors in the action of SSRIs?

<p>They inhibit firing of serotonin neurons. (A)</p> Signup and view all the answers

Which of the following best describes the mechanism of action for selective serotonin reuptake inhibitors (SSRIs)?

<p>Blocking the reuptake of serotonin at synaptic clefts. (B)</p> Signup and view all the answers

What is a common treatment duration necessary before SSRIs manifest clinical effects?

<p>2-4 weeks (C)</p> Signup and view all the answers

Which condition is NOT among the medical indications for SSRIs?

<p>Schizophrenia (C)</p> Signup and view all the answers

What is one significant outcome of blocking 5-HT2A receptors with risperidone?

<p>Reduced negative symptoms by enhancing dopamine release (C)</p> Signup and view all the answers

What is the primary effect of selective serotonin reuptake inhibitors on serotonin transporters?

<p>They block the serotonin transporter, SERT. (B)</p> Signup and view all the answers

What effect does decreased 5-HT1A receptor activity have on serotonin neurotransmission?

<p>It leads to increased release of serotonin. (B)</p> Signup and view all the answers

Which of the following drug classes does risperidone belong to?

<p>Second-generation antipsychotic drugs (C)</p> Signup and view all the answers

Flashcards

Voltage-gated sodium channels (Nav)

Ion channels in axons that open and close in response to changes in membrane potential, crucial for action potential generation.

Action potential

Rapid, temporary changes in membrane potential that propagate along the axon, allowing communication between neurons.

Phenytoin

A drug that blocks voltage-gated sodium channels, used to treat epilepsy.

Sodium channel blocker

A drug that inhibits the activity of voltage-gated sodium channels.

Signup and view all the flashcards

Epilepsy

A neurological disorder characterized by recurrent seizures.

Signup and view all the flashcards

Refractory period

The time after an action potential when a neuron cannot fire another action potential.

Signup and view all the flashcards

Voltage-gated potassium channels (Kv)

Channels that allow potassium ions to flow across the membrane, contributing to repolarization in action potentials.

Signup and view all the flashcards

Neurotransmitter release

The process by which neurotransmitters are released into the synaptic cleft.

Signup and view all the flashcards

Axonal Terminal

The end of an axon where neurotransmitters are stored and released.

Signup and view all the flashcards

Carbamazepine

A drug that blocks voltage-gated sodium channels, also used to treat epilepsy.

Signup and view all the flashcards

Voltage-gated calcium channels (Cav)

Cells use these channels to regulate various signaling pathways. They open when the cell membrane becomes more positive, allowing calcium to enter.

Signup and view all the flashcards

Cav subtypes

There are different types of calcium channels (L, N, P, R, T) with varying functions in the body.

Signup and view all the flashcards

Ethosuximide's function

This drug blocks T-type calcium channels, reducing neuronal excitability.

Signup and view all the flashcards

Gabapentin's mechanism

By binding to calcium channel's α2δ subunit, this drug reduces calcium channel activity and neurotransmitter release.

Signup and view all the flashcards

Voltage-gated potassium channels

These channels open in response to cell depolarization, allowing potassium to leave the cell and causing hyperpolarization.

Signup and view all the flashcards

Retigabine's action

This drug increases potassium channel activity, prompting more potassium to leave the cell, which reduces excitability.

Signup and view all the flashcards

Serotonergic neurons

Neurons that use serotonin as their neurotransmitter.

Signup and view all the flashcards

5-HT1A receptors

These are serotonin receptors found on neurons that release serotonin (auto-receptors).

Signup and view all the flashcards

Buspirone mechanism

This drug activates serotonin auto-receptors, reducing serotonin release which helps reduce feelings of anxiety.

Signup and view all the flashcards

Sumatriptan's target

This drug specifically affects 5-HT1B/D receptors, involved in pain response, often used to treat migraines.

Signup and view all the flashcards

5-HT4 Receptor Agonist

A medication that stimulates the 5-HT4 receptor, increasing gastrointestinal motility and speeding up stomach emptying.

Signup and view all the flashcards

Antiemetic Drug

Medication used to prevent or reduce nausea and vomiting, often used for chemotherapy or post-surgery.

Signup and view all the flashcards

Dopamine D2 & 5-HT Receptor Modulators

Drugs that affect both dopamine D2 and serotonin (5-HT) receptors in the brain, influencing mood, behavior, and brain activity.

Signup and view all the flashcards

Risperidone

A second-generation antipsychotic that blocks dopamine D2 and serotonin 5-HT2A receptors, helping manage psychosis and other mental health conditions.

Signup and view all the flashcards

Serotonin Reuptake Inhibitor (SSRI)

A type of antidepressant that blocks the reabsorption of serotonin in the brain, increasing its levels and improving mood.

Signup and view all the flashcards

SSRIs and 5-HT1A Receptors

SSRIs also affect 5-HT1A receptors, initially stimulating them but eventually causing downregulation, leading to increased serotonin release.

Signup and view all the flashcards

Sertraline & Fluoxetine

Two examples of SSRIs (selective serotonin reuptake inhibitors) that increase serotonin levels in the brain by blocking its reuptake.

Signup and view all the flashcards

Bulimia Nervosa

An eating disorder characterized by periods of binge eating followed by self-induced purging behaviors.

Signup and view all the flashcards

Obsessive-Compulsive Disorder (OCD)

A mental health condition characterized by persistent intrusive thoughts and repetitive behaviors.

Signup and view all the flashcards

Why Do SSRIs Take Time to Work?

While SSRIs immediately increase serotonin levels, the full therapeutic effects take 2-4 weeks because of the complex adaptations the brain undergoes in response to increased serotonin.

Signup and view all the flashcards

CGRP/Substance P

These peptides are involved in migraine pain and cause vasoconstriction to relieve pain.

Signup and view all the flashcards

5-HT3 Receptor Antagonists

Drugs like Ondansetron and Granisetron block 5-HT3 receptors, which are found in the vagal nerve and vomiting center.

Signup and view all the flashcards

Dopamine D2 Receptor Antagonist

Haloperidol blocks dopamine D2 receptors in the chemoreceptor trigger zone and the striatum.

Signup and view all the flashcards

Metoclopramide's Action

This drug works as both a dopamine D2 and 5-HT3 receptor antagonist.

Signup and view all the flashcards

Migraine Treatment

CGRP/substance P antagonists are used to relieve migraine pain.

Signup and view all the flashcards

Antiemetic Drugs - Mechanism

Ondansetron & Granisetron block 5-HT3 receptors in the vomiting center to prevent nausea and vomiting.

Signup and view all the flashcards

Haloperidol: Use Cases

This drug is used to treat nausea, vomiting, schizophrenia, and manic episodes.

Signup and view all the flashcards

Chemoreceptor Trigger Zone

This area in the medulla is involved in triggering nausea and vomiting.

Signup and view all the flashcards

Striatum

This brain region is associated with movement control and is affected in schizophrenia.

Signup and view all the flashcards

Dopamine D2 Blockade - Effect

By blocking dopamine D2 receptors, Haloperidol reduces nausea and helps manage schizophrenia symptoms.

Signup and view all the flashcards

Study Notes

Applied Pharmacology of the Nervous and Endocrine System - Modulators of Neuronal Excitability

  • The course covers modulators of neuronal excitability, including drugs targeting axonal voltage-gated ion channels and monoaminergic neurotransmitters.
  • Learning objectives include identifying drug classes targeting these elements and their mechanisms of action in affecting neuronal activity.
  • Clinical indications for these drugs are also a focus.

Drugs that will be covered in this lecture

  • Drugs targeting axonal voltage-gated ion channels are a subject of the lecture
  • Drugs targeting monoaminergic neurotransmitters are also included in the lecture.
  • The lecture will contain diagrammatic representations of neuronal structures and their components.

Types of voltage-gated ion channels

  • Voltage-gated sodium (NaV) channels
  • Voltage-gated potassium (Kv) channels
  • Voltage-gated Calcium (CaV) channels
  • Abundant in axon initial segment (AIS)
  • Determine threshold for action potential firing
  • Calcium influx pivotal for neurotransmitter release

Voltage-gated sodium channels (detailed)

  • 10 different Nav subtypes in mammals
  • Classified based on α-subunit differences
  • Some are CNS-specific (Nav1.1-Nav1.3, Nav1.5, Nav1.6)
  • Others are PNS-specific (Nav1.7-Nav1.9)
  • α-subunit (260 kDa) forms the pore
  • 4 homologous transmembrane domains (I-IV)
  • Each domain includes 6 transmembrane segments (S1-S6)
  • S4 is the voltage sensor, related to activation
  • TTX sensitive or resistant based on subtype
  • Multiple intracellular loops
  • Auxiliary β-subunits (33-36 kDa)
  • Four subtypes (β1-β4) regulate α-subunit function.

Modulators of voltage-gated sodium channels

  • Phenytoin: non-specific sodium channel blocker, stabilizes inactivated ion channels, prolongs neuronal refractory period.
  • Medical indication: epilepsy/seizures.
  • Carbamazepine: non-specific sodium channel blocker that affects other ion channels, stabilizes inactivated ion channels, prolongs neuronal refractory period.
  • Medical indication: epilepsy, trigeminal neuralgia, mania.

Voltage-gated calcium channels (detailed)

  • Ca²⁺: a second messenger for many cellular regulations
  • Voltage-gated calcium channels (Cav) are activated by membrane depolarization and mediate calcium influx for action potentials and sub-threshold depolarisations.
  • Five subunits
  • a1: pore-forming; has 4 homologous I-IV domains and 6 transmembrane segments
  • a20: disulfide-linked glycoprotein dimer, drug target for gabapentinoids
  • β: intracellular subunit, stabilizes a1 conformation
  • γ: transmembrane glycoprotein subunit
  • Five types of CaV channels: L, N, P, R, and T.

Modulators of voltage-gated calcium channels

  • Ethosuximide: Blocks T-type calcium channels; Effective for treating absence seizures
  • Gabapentin: Modulates a₂δ subunit, lowers synaptic transmission and neuronal excitability, reducing neurotransmitter release.
  • Medical indications: epilepsy, neuropathic pain, multiple sclerosis.

Voltage-gated potassium channels

  • Form from six transmembrane helices (S1-S6)
  • S1-S4 are the voltage sensors, and S5-S6 is the pore
  • K⁺ ions leave the cells upon depolarisation
  • Decrease the probability of action potentials
  • Reduces neuronal activity.

Modulators of voltage-gated potassium channels

  • Retigabine: binds to Kv7 potassium channels, increases conductance of K⁺ ions, increases hyperpolarisation, reduces action potential frequency to decrease neuronal excitability, effective in treatment of epilepsy.

5-Hydroxytryptamine (5-HT) pathways

  • Behavior effects, mood, perception, memory, aggression.
  • CNS effects, motor control, sleep, CNS vascular tone, temperature regulation.
  • Central serotonergic drugs: SSRIs, tricyclic antidepressants, MAOIs, atypical antipsychotics, triptans.

Serotonin receptors

  • GPCR coupled to, Gi/o, Gq, or Gs (types 1, 2, 4, 5, 6, and 7)
  • Ligand-gated ion channel (type 3)

Modulators of 5-HT receptors

  • Buspirone: partial agonist of 5-HT1A receptors, decreases further 5-HT release (auto-receptors are activated)
  • Medical indication: short-term use for anxiety.
  • Sumatriptan: agonist of 5-HT1B/D receptors affecting trigeminal nerve endings and decreasing CGRP/substance P.
  • Medical indication: acute migraine, cluster headaches.
  • Ondansetron & Granisetron: antagonists of 5-HT3 receptors; block vagal afferents and chemoreceptor trigger zone, used as antiemetics.

Modulators of dopamine D2 receptors

  • Haloperidol: antagonist of dopamine D2 receptors, blocks dopamine D2 receptors in chemoreceptor trigger zone and striatum.
  • Medical indication: schizophrenia, mania, and aggression (moderate-severe Alzheimer's disease).
  • Metoclopramide: antagonist of dopamine D2 receptors and 5-HT3 receptors.
  • Medical indication: antiemetic and prevention/treatment of post-operative nausea and vomiting.
  • Risperidone: antagonist of dopamine D2 receptors AND 5-HT2A receptors; blocks dopamine release and reduces positive symptoms; blocks negative symptoms from over-active serotonergic activity.
  • Medical indication: schizophrenia, mania, and aggressive behaviors (moderate-severe Alzheimer's patients).

Selective serotonin reuptake inhibitors (SSRIs)

  • Sertraline & Fluoxetine: selectively inhibit serotonin reuptake by binding to serotonin transporter (SERT) increasing synaptic serotonin.
  • Medical indication: Major depression, bulimia nervosa, and obsessive-compulsive disorder (OCD).

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Lect 4 Modulators of Neuronal excitability PDF

Description

This quiz focuses on the modulators of neuronal excitability, specifically drugs that target axonal voltage-gated ion channels and monoaminergic neurotransmitters. You will explore their mechanisms of action and clinical applications. Diagrammatic representations of neuronal structures will also be included to enhance understanding.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser