Neuroscience Chapter on Neurotransmitters

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Questions and Answers

Which neurotransmitter is NOT listed as one of those in the central nervous system?

Serotonin

Cortisol (correct)

Norepinephrine

Dopamine

What characteristic of a drug enhances its ability to cross the blood-brain barrier (BBB)?

Lipid solubility (correct)

Ionized at CSF pH

Large molecular size

High protein binding

What role do second messengers play in neurotransmitter action?

They block neurotransmitter receptors.

They degrade neurotransmitters in the synapse.

They amplify and sustain the cellular response. (correct)

They convert neurotransmitters into hormones.

In what situation is the permeability of the blood-brain barrier likely to increase?

In the presence of inflammation Signup and view all the answers

Which of the following is NOT typically a therapeutic effect of drugs acting on the central nervous system?

Increased muscle mass Signup and view all the answers

Which of the following is NOT an adverse effect associated with bromide treatment in cats?

Hypothermia Signup and view all the answers

What effect does abrupt discontinuation of gabapentin have?

Seizures Signup and view all the answers

In which species has valproic acid not been clinically evaluated for usefulness?

Cats Signup and view all the answers

Which of the following is a mechanism of action for gabapentin?

Inhibition of voltage dependent Ca2+ channels Signup and view all the answers

Which of the following adverse effects is specific to the administration of valproic acid in dogs?

Liver failure Signup and view all the answers

What is a primary therapeutic use of levetiracetam?

Adjunctive therapy for refractory canine epilepsy Signup and view all the answers

Which adverse effect is associated with gabapentin?

Ataxia Signup and view all the answers

Which condition can bromide treatment precipitate in cats?

Asthma Signup and view all the answers

What is an indication of toxicity related to bromide?

Constipation Signup and view all the answers

What is the primary reason diazepam is limited in its use as a maintenance anticonvulsant in dogs?

The development of tolerance occurs rapidly due to drug metabolism. Signup and view all the answers

Which benzodiazepine has a shorter elimination half-life in dogs compared to diazepam?

Midazolam Signup and view all the answers

What severe adverse effect can cats experience when administered diazepam?

Acute fatal hepatic necrosis Signup and view all the answers

Which of the following therapeutic uses is not associated with midazolam?

Long-term maintenance anticonvulsant Signup and view all the answers

How does lorazepam hypothesized to function in raising the seizure threshold?

By allowing Br− entry through Cl− channels Signup and view all the answers

Which side effect is not commonly associated with clonazepam?

Kidney failure Signup and view all the answers

In what way is the mechanism of action for benzodiazepines like diazepam highlighted in their therapeutic use?

They enhance GABA-gated Cl− channel activity. Signup and view all the answers

What is the primary mechanism of action for levetiracetam?

Interaction with synaptic vesicle protein 2A Signup and view all the answers

Which adverse effect is associated with felbamate in dogs?

Liver dysfunction Signup and view all the answers

Doxapram primarily acts on which part of the body to stimulate respiration?

Medullary respiratory centers Signup and view all the answers

What is a significant limitation in the use of zonisamide?

Cost of the drug Signup and view all the answers

Which combination of mechanisms of action does felbamate exhibit?

Blockade of NMDA receptors and inhibition of voltage-dependent Na+ channels Signup and view all the answers

Which adverse effects are commonly associated with the use of zonisamide?

Minimal adverse effects are reported Signup and view all the answers

Which of the following is NOT an adverse effect of levetiracetam?

Hyperactivity Signup and view all the answers

What is a key characteristic of felbamate compared to other anticonvulsants?

Useful for focal and generalized seizures Signup and view all the answers

What care should be taken when discontinuing levetiracetam?

It must be withdrawn slowly Signup and view all the answers

Which neurotransmitter is associated with sedative effects in the central nervous system?

γ-aminobutyric acid (GABA) Signup and view all the answers

Which property of drugs enhances their ability to penetrate the blood-brain barrier?

Lipid solubility Signup and view all the answers

Which statement accurately describes the role of receptors in the central nervous system?

They alter membrane potential via neurotransmitter binding. Signup and view all the answers

What effect does inflammation have on the blood-brain barrier?

It increases permeability. Signup and view all the answers

Which of the following is not typically a mechanism of action through which drugs affect the central nervous system?

Directly altering neurotransmitter production Signup and view all the answers

What is a common adverse effect associated with the use of phenobarbital in dogs?

Sedation Signup and view all the answers

How does phenobarbital primarily function in relation to seizure management?

Activating GABA-gated Cl− channels Signup and view all the answers

What differentiates primidone from phenobarbital in terms of metabolism in cats?

Primidone to phenobarbital metabolism is slower Signup and view all the answers

Which drug has therapeutic uses related to terminating seizures at anesthetic doses?

Pentobarbital Signup and view all the answers

What is a potential risk following the abrupt discontinuation of anticonvulsant drugs?

Increased seizure frequency Signup and view all the answers

What is a reported side effect of using primidone in dogs after prolonged use?

Hypoproteinemia Signup and view all the answers

What is the unique characteristic of phenobarbital compared to other barbiturates regarding dosage and sedation?

It produces effects at lower doses than required for sedation Signup and view all the answers

What is the primary mechanism of action for zonisamide in treating epilepsy?

Inhibition of voltage-dependent Na+ and Ca2+ channels Signup and view all the answers

Which adverse effect is rarely seen with the administration of felbamate in dogs?

Keratoconjunctivitis sicca Signup and view all the answers

What precaution should be taken during the withdrawal of levetiracetam?

Reduce dosage progressively to avoid withdrawal seizures Signup and view all the answers

What is a notable therapeutic use of doxapram in veterinary medicine?

Arousing animals from anesthesia or overdose Signup and view all the answers

What common side effect is associated with the use of levetiracetam?

Gastrointestinal disturbances Signup and view all the answers

What aspect of felbamate makes it particularly useful for dogs with brain tumors?

It does not induce sedation at clinical doses Signup and view all the answers

Which of the following correctly lists the mechanisms of action for felbamate?

Blockade of NMDA receptors and Na+ channel inhibition Signup and view all the answers

What is a significant challenge in using zonisamide for treatment in dogs?

The high cost of the drug Signup and view all the answers

What potential adverse effect can occur as a result of felbamate use in dogs?

Generalized tremor Signup and view all the answers

What is a significant adverse effect of diazepam in cats?

Acute fatal hepatic necrosis Signup and view all the answers

Which statement correctly describes the mechanism of action for benzodiazepines?

They activate GABA-gated Cl− channels Signup and view all the answers

Which benzodiazepine has a shorter elimination half-life in dogs compared to diazepam?

Midazolam Signup and view all the answers

Why is clonazepam of limited value as a maintenance anticonvulsant in dogs?

It leads to rapid development of tolerance Signup and view all the answers

What therapeutic use is NOT associated with midazolam?

Chronic pain management Signup and view all the answers

Which of the following adverse effects is most commonly associated with midazolam?

Mild respiratory depression Signup and view all the answers

Which statement concerning the pharmacokinetics of diazepam is accurate?

It is administered IV for status epilepticus in dogs. Signup and view all the answers

What is the primary reason for the rapid development of tolerance to diazepam in dogs?

Metabolism into inactive metabolites Signup and view all the answers

What effect might midazolam have when used in therapeutic settings?

Causes local irritation Signup and view all the answers

Study Notes

Drugs Acting on the Central Nervous System

Drugs can alter CNS function to provide anticonvulsant effects, tranquilization (sedation), and analgesia.
Neurotransmitters in the CNS include dopamine, GABA, acetylcholine, norepinephrine, serotonin, histamine, glutamate, glycine, substance P and many neuropeptides.
Neurotransmitters combine with receptors on the postsynaptic neuron, altering membrane potential.
Receptors for neurotransmitters are the site of action for exogenous drugs.
The neurotransmitter-receptor complex may directly alter the cell membrane permeability by opening or closing ion channels or initiate a sequence of chemical reactions altering ion transport across the membrane to change membrane potential.
Second messenger molecules and systems are generated and sustain and amplify the cellular response to drug-receptor binding.
Many neurotransmitters have G protein-coupled receptors (GPCRs).
Circulating drugs must cross the blood-brain barrier (BBB) to gain access to the neurons in the brain.
Drugs that readily cross the BBB are usually lipid-soluble, small in molecular size, poorly bound to protein, and nonionized at the pH of cerebrospinal fluid (CSF).
The BBB is typically poorly developed in neonates.
The BBB tends to increase permeability at sites of inflammation and tumors.
Only some anticonvulsant drugs available for human use are clinically useful in dogs and cats.
Some drugs are rapidly metabolized in dogs even at high dosages.
Cats generally metabolize drugs more slowly and poorly than dogs.
Anticonvulsant drugs stabilize neuronal membranes directly acting on ion channels inducing hyperpolarization of neuronal membranes.
Anticonvulsant drugs activate GABA-gated CL-channels increasing the frequency of CL-channel opening.
Anticonvulsant therapeutic uses reduce the incidence, severity, and duration of seizures.
Anticonvulsant adverse effects include seizures or status epilepticus following rapid cessation of administration, enzyme induction, and hepatoxicity.

Barbiturates

Phenobarbital is an oxybarbiturate.
Barbiturates activate GABA-gated Cl- channels causing hyperpolarization of the neurons.
Phenobarbital limits the spread of action potentials, increasing seizure threshold.
Often used for long-term seizure control but administration until onset of effect is slow (~20 minutes).
GI absorption is practically complete in all animals, and maximum levels occur in dogs between 4-8 hours.
Common side effects include sedation, polydipsia, polyuria, and polyphagia.
Dogs develop tolerance to sedative effects after 1-2 weeks.

Primidone

Primidone is a deoxybarbiturate (an analog of phenobarbital).
Primidone slowly absorbed in dogs.
Metabolism to phenobarbital is slower in cats.
Prolonged use of Primidone in dogs can cause decreased serum albumin and elevated serum liver enzymes and can ocasionally cause severe liver damage.

Pentobarbital

Pentobarbital is an oxybarbiturate.
Used to terminate seizures, but the therapeutic dose commonly induces anesthesia.
Known for rapid onset (~<1 minute) after IV injection and short duration of action.
Causes CNS depression, irritating when administered perivascularly.

Phenytoin

Phenytoin is a hydantoin derivative.
Phenytoin stabilizes neuronal membranes and limits development and spread of seizure activity.
Its effect includes reduction of Na+ influx during action potential, reduction of Ca2+ influx during depolarization, promotion of Na+ efflux and inhibition of seizure activity.
K+ movement out of the cell during action potential may be delayed, increasing refractory period and decreasing repetitive depolarization.
Phenytoin is used as an anticonvulsant, however, because of its short half-life, its use in dogs may be impractical.
Recommended for treating digitalis-induced ventricular arrhythmias.

Benzodiazepines

Diazepam, midazepam, clonazepam, and lorazepam are used as anticonvulsants.
Effective for status epilepticus (continuous seizure activity).
Used as maintenance anticonvulsant in cats but use is limited in dogs due to rapid drug tolerance development.
Benzodiazepines activate GABA-gated Cl- channels potentiating the channel opening activity of GABA resulting in hyperpolarization of the neurons.
Cats given Diazepam is usually given orally for seizure control, dogs is given IV for status epilepticus and cluster seizures, Diazepam can be used as maintenance anticonvulsant, given that it has a short half-life (2-4 hours).
Common side effects include changes in behavior, depression, and aberrant demeanor.
Cats may develop acute fatal hepatic necrosis.
Midazolam has a shorter elimination half-life (77 minutes in dogs—shorter than Diazepam’s ~3 hours), easily crosses the BBB.
Used for anticonvulsives for status epilepticus, muscle relaxant, tranquilizer and appetite stimulant.
Clonazepam has limited value as a maintenance anticonvulsant because of rapid tolerance development.
Common side effects include GI disturbances (e.g., vomiting, hyper-salivation).
Lorazepam mechanism of action similarly involves activating GABA-gated Cl- channels.
Lorazepam can be used orally (cats) for seizure control, intravenously for status epilepticus and seizures cluster, and as a maintenance anticonvulsant (dogs) due to short half-life (2-4 hours).

Valproic acid and sodium valproate

Valproic acid is a derivative of carboxylic acid and structurally unrelated to other anticonvulsant drugs.
Effective in controlling seizures in dogs when given orally.
Short half-life makes it impractical for long-term use in dogs. It is usually considered a second- or third-line anticonvulsant in dogs.
Potential usefulness as an adjunctive therapy in some dogs.
Use and clinical value in cats not determined.
Potential adverse effects include Gl disturbances, hepatoxicity (including liver failure), central nervous system effects (e.g., sedation and ataxia), dermatologic effects (e.g., alopecia, rash), and hematologic effects (e.g., thrombocytopenia, leukopenia, anemia).

Gabapentin

Gabapentin is a synthetic GABA analog that crosses the BBB affecting anticonvulsant effects.
Its mechanism of action involves increase in GABA content in neurons and inhibition of voltage-dependent Ca2+ channels in neurons; this reduces neuronal Ca2+ levels, which thereby inhibits excitatory neurotransmitter release, e.g., glutamate.
Useful as an adjunct therapy for refractory or complex partial seizures, or for chronic pain treatment in dogs and cats.
Administered orally.
Common side effects include sedation, ataxia, and mild polyphagia.

Levetiracetam

Levetiracetam is used as an adjunct therapy for refractory canine epilepsy and well tolerated in dogs. An initial prospective trial in cats was favorable.
Levetiracetam inhibits hypersynchronization of epileptiform burst firing and propagation of seizure activity.
It binds to synaptic vesicle protein 2A in neurons, and this interaction with neuronal vesicular protein may account for levetiracetam's anticonvulsant effect.
Common side effects include minimal changes in behavior, drowsiness, and Gl disturbances (vomiting and anorexia).
Withdrawal of this drug should be slow in order to prevent "withdrawal" seizures.

Felbamate

Felbamate is a dicarbamate drug used orally to treat refractory epilepsy in dogs.
Felbamate does not induce sedation at clinical doses, useful to control obtunded mental status due to brain tumor or cerebral infarct.
It blocks NMDA receptor-mediated neuronal excitation, and enhances inhibition of GABA-mediated neuronal inhibition and also inhibits voltage-dependent Na+ and Ca2+ channels.
Potential adverse effects include liver dysfunction (hepatotoxicity), reversible bone marrow depression (thrombocytopenia, leukopenia), and keratoconjunctivitis sicca, and generalized tremor effects.

Zonisamide

Zonisamide is a sulfonamide-based anticonvulsant drug or adjunct therapy to control refractory epilepsy in dogs with minimal adverse effects,
It's administered orally (twice daily).
Its mechanism of action involves inhibiting voltage-dependent Na+ and Ca2+ channels of neurons to induce hyperpolarization and decreased Ca2+ influx.
Potential adverse effects are not extensively studied in cats.

CNS Stimulants (Analeptics)

Doxapram is CNS stimulant used to arouse animals from inhalant and parenteral anesthesia or anesthetic overdose.
Doxapram mechanism of action involves directly stimulating medullary respiratory centers, and probably through activation of carotid and aortic chemoreceptors.
Depth of anesthesia is reduced but the effect may be transient.
Doxapram is not effective in reviving seriously depressed neonates and not a good substitute for endotracheal intubation and ventilation.
High doses of doxapram may induce seizures and also cause hypertension, arrhythmias, and hyperventilation leading to respiratory alkalosis.

Tranquilizers, Atacics, Neuroleptics, and Sedatives

These terms are commonly used interchangeably to refer to medications that calm and promote sleep but do not always cause sleep
Neuroleptic means to "take hold of nerves."
Used as pre-anesthetic medications enabling a use of less general anesthetic

Phenothiazine Derivatives

Phenothiazine derivatives include acepromazine, promethazine, chlorpromazine, fluphenazine, prochlorperazine, and trimeprazine.
These drugs affect the CNS at the basal ganglia, hypothalamus, limbic system, brain stem, and reticular activating systems.
They block dopamine, α1-adrenergic, and serotonergic receptors.
CNS effects include tranquilizing effects, decrease in spontaneous motor activity, hypotension due to α1-adrenergic receptor blockade and reflex sinus, antiarrhythmic and inotropic effects.
Respiratory depression, decreased Gl motility, and inhibition of emesis are common.
Effects on blood: decrease in packed cell volume.
Metabolic effects: hypothermia, hyperthermia, hyperglycemia, and hyperprolactinemia are seen.

Opioids

Opioids are used for analgesia (reducing pain), preanesthetic medication (reducing anxiety and stress before surgery), and induction/maintenance of anesthesia.
Opioid receptors are located in the brain, spinal cord, urinary tract, GI tract, and vas deferens
There are at least 3 major subtypes of opioid receptors (µ, к, δ).
Mu (µ)-receptors and Kappa (к)-receptors are located throughout the brain/CNS, and deltas (δ)-receptors reside in the limbic system of the brain.
Opioids cause analgesic effects by activating and/or antagonizing these receptors.
Opioids (e.g., morphine) are respiratory depressants decreasing arterial Co2 tension and arterial O2 tension, lowering pH.
In dogs, opioids will cause panting in an attempt to regulate temperature.
Cardiovascular effects (e.g., decreased heart rate and hypotension) are often noted.
Analgesia effect lasts less than that of elimination t.
GI effects include antidiarrheal and constipation.
Opioid adverse effects include hyperexcitability, hypotension, cerebral hemorrhage and edema.
Tramadol, Methadone, Oxymorphone, Hydromorphone, Fentanyl, Alfentanil, Sufentanil, Carfentanil.

Opioid partial agonists

Butorphanol is a partial agonist for µ receptors but a full agonist for k-receptors.
Used to reverse μ effects of other opioids such as morphine, and oxymorphone; it maintains some analgesia (k effect) which is 4-7 times more potent than morphine.
Indicated for analgesia, antitussives, and antiemetics
Can induce mild adverse effects such as sedation, ataxia, anorexia and diarrhea in dogs and cats; in horses, includes ataxia, sedation, and increased GI motility and ileus (due to prolonged use).

Opioid agonist-antagonist drugs

Nalbuphine and buprenorphine are opioid agonist-antagonists.
Nalbuphine is an agonist at the к receptor and antagonist at the μ receptor.
Buprenorphine is a partial agonist at the µ receptor and an antagonist at the к receptor.
Naloxone is a long acting μ, κ, and δ receptor antagonist and reverses opioid-induced depression and respiratory depression.
Naltrexone is a long-lasting opioid receptor antagonist and can be given IV or IM to reverse opioid-induced immobilization/depression, especially in wildlife or large animals.
It can also treat certain behavioral problems in dogs such as excessive licking or tail chasing.
Naloxone is relatively free of adverse effects.

Anxiolytic Drugs and Antidepressants

The pages do not contain detailed information for these categories.

α2-Adrenergic Agonists

These drugs act on a2 adrenergic receptors in CNS to produce analgesic/sedative/relaxation
Ruminants, followed by cats, dogs, and horses are most sensitive to a2-agonists; Pigs, least sensitive.
High doses can induce CNS excitation.
Produce skeletal muscle relaxation by inhibiting intraneuronal transmission.
Can induce emesis and cardiovascular effects (bradycardia, hypertension, hypotension).

Xylazine

Approved by FDA for use in cats, dogs, horses, and wildlife.
Common adverse effects include GI stasis leading to bloat, bradycardia with sinus arrhythmia/arrest, hypothermia, or hyperthermia.
Contraindicated in animals with cardiac aberrations, hypotension, shock, renal insufficiency, hepatic impairment, or pre-existing epilepsy

Detomidine

Approved by FDA for use in horses.
Common adverse effects include piloerection, sweating, partial penis prolapse, salivation, muscle tremors, CNS excitation.
IV sulfonamides given in detomidine-treated horses (potentiating fatal dysrhythmias)
Potent α2-agonist
Adverse effects are similar to xylazine.

Medetomidine

Potent and selective a2-agonist—induces a light anesthesia, common in examinations/procedures in some animals.
Adverse effects are similar to xylazine and detomidine

Romifidine

For use in horses, has similar adverse effects that of xylazine and detomidine.

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Test your knowledge on neurotransmitters and their functions within the central nervous system. This quiz examines key concepts related to drug actions, the blood-brain barrier, and therapeutic effects. Assess your understanding of how these elements interact in the realm of neuroscience.

Neuroscience Chapter on Neurotransmitters

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Questions and Answers

Which neurotransmitter is NOT listed as one of those in the central nervous system?

What characteristic of a drug enhances its ability to cross the blood-brain barrier (BBB)?

What role do second messengers play in neurotransmitter action?

In what situation is the permeability of the blood-brain barrier likely to increase?

Which of the following is NOT typically a therapeutic effect of drugs acting on the central nervous system?

Which of the following is NOT an adverse effect associated with bromide treatment in cats?

What effect does abrupt discontinuation of gabapentin have?

In which species has valproic acid not been clinically evaluated for usefulness?

Which of the following is a mechanism of action for gabapentin?

Which of the following adverse effects is specific to the administration of valproic acid in dogs?

What is a primary therapeutic use of levetiracetam?

Which adverse effect is associated with gabapentin?

Which condition can bromide treatment precipitate in cats?

What is an indication of toxicity related to bromide?

What is the primary reason diazepam is limited in its use as a maintenance anticonvulsant in dogs?

Which benzodiazepine has a shorter elimination half-life in dogs compared to diazepam?

What severe adverse effect can cats experience when administered diazepam?

Which of the following therapeutic uses is not associated with midazolam?

How does lorazepam hypothesized to function in raising the seizure threshold?

Which side effect is not commonly associated with clonazepam?

In what way is the mechanism of action for benzodiazepines like diazepam highlighted in their therapeutic use?

What is the primary mechanism of action for levetiracetam?

Which adverse effect is associated with felbamate in dogs?

Doxapram primarily acts on which part of the body to stimulate respiration?

What is a significant limitation in the use of zonisamide?

Which combination of mechanisms of action does felbamate exhibit?

Which adverse effects are commonly associated with the use of zonisamide?

Which of the following is NOT an adverse effect of levetiracetam?

What is a key characteristic of felbamate compared to other anticonvulsants?

What care should be taken when discontinuing levetiracetam?

Which neurotransmitter is associated with sedative effects in the central nervous system?

Which property of drugs enhances their ability to penetrate the blood-brain barrier?

Which statement accurately describes the role of receptors in the central nervous system?

What effect does inflammation have on the blood-brain barrier?

Which of the following is not typically a mechanism of action through which drugs affect the central nervous system?

What is a common adverse effect associated with the use of phenobarbital in dogs?

How does phenobarbital primarily function in relation to seizure management?

What differentiates primidone from phenobarbital in terms of metabolism in cats?

Which drug has therapeutic uses related to terminating seizures at anesthetic doses?

What is a potential risk following the abrupt discontinuation of anticonvulsant drugs?

What is a reported side effect of using primidone in dogs after prolonged use?

What is the unique characteristic of phenobarbital compared to other barbiturates regarding dosage and sedation?

What is the primary mechanism of action for zonisamide in treating epilepsy?

Which adverse effect is rarely seen with the administration of felbamate in dogs?

What precaution should be taken during the withdrawal of levetiracetam?

What is a notable therapeutic use of doxapram in veterinary medicine?

What common side effect is associated with the use of levetiracetam?

What aspect of felbamate makes it particularly useful for dogs with brain tumors?

Which of the following correctly lists the mechanisms of action for felbamate?

What is a significant challenge in using zonisamide for treatment in dogs?

What potential adverse effect can occur as a result of felbamate use in dogs?

What is a significant adverse effect of diazepam in cats?

Which statement correctly describes the mechanism of action for benzodiazepines?

Which benzodiazepine has a shorter elimination half-life in dogs compared to diazepam?

Why is clonazepam of limited value as a maintenance anticonvulsant in dogs?

What therapeutic use is NOT associated with midazolam?

Which of the following adverse effects is most commonly associated with midazolam?

Which statement concerning the pharmacokinetics of diazepam is accurate?

What is the primary reason for the rapid development of tolerance to diazepam in dogs?

What effect might midazolam have when used in therapeutic settings?

Study Notes

Drugs Acting on the Central Nervous System

Barbiturates

Primidone

Pentobarbital

Phenytoin

Benzodiazepines

Valproic acid and sodium valproate

Gabapentin

Levetiracetam

Felbamate

Zonisamide

CNS Stimulants (Analeptics)

Tranquilizers, Atacics, Neuroleptics, and Sedatives

Phenothiazine Derivatives

Opioids