Applied Pharmacology Nervous System Modulators

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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?

It acts as a non-specific sodium channel blocker. Signup and view all the answers

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

The channel is blocked by tetrodotoxin. Signup and view all the answers

What is the primary medical indication for phenytoin?

Epilepsy following trauma Signup and view all the answers

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

Voltage-gated sodium channels Signup and view all the answers

Which of the following drugs does NOT target monoaminergic neurotransmitters?

Beta-agonists Signup and view all the answers

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

S4 segment Signup and view all the answers

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

Regulates α-subunit kinetics and localization. Signup and view all the answers

What is the primary medical indication of Ethosuximide?

Treatment of absence seizures Signup and view all the answers

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

N-type Signup and view all the answers

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

It binds to Kv7 channels and increases K+ ion outflow. Signup and view all the answers

How does Buspirone act on 5-HT1A receptors?

It is a partial agonist that decreases further serotonin release. Signup and view all the answers

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

It acts as a stabilizing agent for α1 subunit. Signup and view all the answers

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

Acute cluster headache Signup and view all the answers

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

Hyperpolarize the neuron and decrease action potential probability. Signup and view all the answers

What is the primary action of Ondansetron and Granisetron?

Antagonize 5-HT3 receptors Signup and view all the answers

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

Memory Signup and view all the answers

What does Gabapentin primarily target in treatment?

α2δ calcium channel subunit Signup and view all the answers

Which condition is Haloperidol NOT used to treat?

Acute cluster headache Signup and view all the answers

Which receptors do Metoclopramide antagonize?

Dopamine D2 and 5-HT3 receptors 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?

T-type Signup and view all the answers

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

They help in the generation of action potentials. Signup and view all the answers

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

Antiemetic for cancer treatment Signup and view all the answers

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

Block neuronal activation Signup and view all the answers

Which statement is true about the action of Metoclopramide?

It blocks both dopamine D2 and 5-HT3 receptors. Signup and view all the answers

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

Dopamine Signup and view all the answers

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

They require a second messenger. Signup and view all the answers

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

They induce vasoconstriction. Signup and view all the answers

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

Prevention and treatment of postoperative nausea and vomiting Signup and view all the answers

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

Dopamine D2 and serotonin 5-HT2A receptors Signup and view all the answers

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

They inhibit firing of serotonin neurons. Signup and view all the answers

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

Blocking the reuptake of serotonin at synaptic clefts. Signup and view all the answers

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

2-4 weeks Signup and view all the answers

Which condition is NOT among the medical indications for SSRIs?

Schizophrenia Signup and view all the answers

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

Reduced negative symptoms by enhancing dopamine release Signup and view all the answers

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

They block the serotonin transporter, SERT. Signup and view all the answers

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

It leads to increased release of serotonin. Signup and view all the answers

Which of the following drug classes does risperidone belong to?

Second-generation antipsychotic drugs Signup and view all the answers

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

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).

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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.