Central Nervous System Agents

The ability to cause an effect by depressing the CNS activity

What defines a CNS agent

1- Major tranquilizers / Phenothiazines (sedative-hypnotic agents / tranquilizers)

2- Minor tranquilizers / Benzodiazepines (sedative-hypnotic agents / tranquilizers)

3- Barbiturates (tranquilizers - but not major or minor)

4- A2 Adrenergic Receptors

5- Opioids

6- Injectable Anesthetics

7- Inhalant Anesthetics

8- Behavior Drugs

How many drug classes are there that are considered CNS agents? Name them

Sedative - An agent that acts on the CNS by decreasing motor activity, causing the animal to be calm and quiet

Hypnotic - An agent that produces drowsiness and facilitates the onset and maintenance of sleep

Tranquilizers - An agent that provides a tranquil and calming effect. A Sedative-Hypnotic agent

What is a Sedative? What is a Hypnotic? What does that make a Tranquilizer (another name)?

Phenothiazines / Sedative-Hypnotic Agent

What is another name for Major Tranquilizers

MOA - Antagonizes D receptor in Brain / Blocks D & A1 in PNS / Blocks D in CRTZ / Blocks histamine receptor / Mild anti-cholinergic

Used for - A STRONG initial tranquilizer / Vasodilation / Antiemetic / Antipruritic / decrease GI motility

Contraindication - Hypovolemia / Hypotension / Hx of seizures (caution)

Bc of A1 block it can cause: Hypothermia / Headrush (due to arterial dilation → decrease BP & venodilation → ORTHOSTATIC Hypotension)

Adverse effect - Paraphimosis (Prolapse of P.) in horses / Ace eyes / General CNS stim / Develop aggression

NO ANALGESIA = NO PAIN RELIEVE

Acepromazine is

Considered a Neuroleptic drug / Bc it causes a sedative-hypnotic effect by DEPRESSING activity between the brain stem and cerebral cortex

Acepromazine is also considered a (what type of drug) why?

Benzodiazepines / Sedative-Hypnotic Agent

What is another name for Minor Tranquilizer

NO

Can Benzodiazepines cause medullary paralysis by itself?

GABA / Gamma - amino - butyric - acid

What is the major inhibitor for Minor Tranquilizers?

MOA - Enhances GABA activity / Binds to GABA → OPENS Cl channels → Cl rushes in leading to HYPERPOLARIZATION & inhibition of neurotransmission

Used for - Tranquilization / Muscle relaxation / Anticonvulsant (give CRI) / Sedation / Appetite stim for Valium trial in cats (if cat eats = can go home BUT if cat does not eat = Systemic problem)

Give SLOW IV

Notes - Controlled drug / Rapid IV = hemolysis & irritation / Mixed with Ketamine used immediately / Mixed with other drugs cause Precipitation / Absorbed thru plastic / light sensitive

Adverse effects - Paradoxical excitement (Hyperactive) / liver dysfunction in cats in chronic use / aggression inhibition

Diazepam (Valium) is

MOA - GABA enhances

Used for - Induction (by sedate)

Notes - can be used in IV, IM, IN, SQ / is a CONTROLLED drug

Adverse effects - Paradoxical Excitement / Dysphoria / restlessness / vocalization

Midazolam is

MOA - GABA agonist

Used for - Acute tx for seizures / Muscle relaxation / anxiolytic (most used for)

Notes - CONTROLLED drug

Adverse effects - Sedation / tolerance

Alprazolam (Xanax) is

ANTAGONIST

MOA - Competitive Reversal of Benzodiazepines

Used for - Reverse BZD effects (paradoxical excitement / Dysphoria / Aggression)

Notes - NO ANALGESIC / Injectable ONLY / high 1st pass

Adverse effects - Abstinence syndrome (restlessness) / extravasation on local tissue (necrosis)

Flumazenil is

Tranquilizers (but not Major or Minor) / Euthanasia

Another name for Barbiturates? What is the MOST COMMON use for this drug class

LONG ACTING 8-12hrs

MOA - GABA agonist

Used for - Tranquilizer / COMMON USE Anticonvulsant (long term use) to prevent or control sz in IDOPATHIC sz / Euth

Notes - CONTROLLED drug 4

Adverse effects - PU/PD / polyphagia / ataxia / Chronic use dogs = increase liver enzymes = Liver toxicity / Decrease T4

Phenobarbital is

SHORT ACTING 45-90 mins

MOA - GABA agonist

Used for - COMMON USE euth / Anticonvulsant for intractable sz / not for anesthetic

Notes - CONTROLLED drug 2

Adverse effects - Fast IV = Cardiac Arrest / Dose dep CNS depression / very NARROW safety margin / decrease CO

Pentobarbital is

ULTRA SHORT ACTING 5-30mins

MOA - GABA agonist / LIPID SOLUBLE = in and out of CNS FAST

Used for - induce anesthesia

Notes - IV ONLY / Controlled drug 3 / Don’t use for sighthounds

Adverse effects - Sight hounds = Glucose effect & Slow Biotransformation / Cardiac arrhythmia / Apnea - Respiratory depression

Sodium thiopental

Glucose Effect = Occurs when Sodium Thiopental is used as an anesthetic, binds with glucose making it SLOW to metabolize

Slow Biotransformation = Sighthounds have a lack of oxidized enzymes which also cause a DECREASE in metabolism and also has a LOW fat amount.

So when sodium thiopental or Alfaxalone is used it will redistribute after the brain to the storage fat but since sighthounds don't have much fat it just keeps going and gets recycled throughout the body, keeping them in an anesthetized state

Explain the Glucose Effect and the Slow Biotransformation in Sight hounds

Peripheral A2 receptor (Excitatory) / Central A2 receptor (Excitatory)

Where are 2 places that the A2 receptors are located? Excitatory or Inhibitory?

Decrease CO by 60%

Synergistic effect w/ opioids = decreased tolerance to opioids & decreased adverse effects

What are 2 factors that ALL A2 adrenergic receptors cause

Biphasic CV response

What is a RISK that can occur to the Cardiac

Phase 1: A2 receptor on PERPHIAL act. = vasoconstriction on VESSELS → increased PVR → Baroreceptors want DECREASED BP → Decreased HR (Bradycardia)

Phase 2 = since there is a DECREASED PVR (vasodilate) → Baroreceptor will want increased BP but there will be a PERSISTANT Bradycardia (Ca binds to NORE = Closes Ca channels = therefore no NOREPINEPHRINE release)

Explain the phases of the Biphasic CV response

MOA - A2 Receptors on adrenergic neurons will bind to norepi→ complex proteins release, bind to calcium channels and close them

Used for - Tranquilize in LARGE animals / CNS effects / Emetic agents for CATS and dogs / ANAGESIA

Notes -Controlled drug 4 / LONG acting 8 - 12 hrs / Less selective for A2 compared to Dex and Med

Adverse effects - Bradycardia (phase 1 Bip CV) / AV block

Xylazine

Yohimbine & Tolazoline

Can be given IM, IV

A2 : A1 ratio match = 160 : 1

Adverse effect - Abrupt stop of effect / Removes ANALGESIA give other analgesia agent before giving this agent

What is the reversal for Xylazine?

MOA - A2 Receptors on adrenergic neurons will bind to norepi→ complex proteins release, bind to calcium channels and close them

Used for - Sedation / Emetic agent for CATS / ANALGESIA / anxiolytic

Notes - Commonly used for small animals / KITTY magic = combo w/ Dex + opioid + Ketamine

Adverse effects - Bradycardia (phase 1 Bip CV) / AV block / Absorbed by skin, mouth, eyes

Dexmedetomidine is

MOA - A2 Receptors on adrenergic neurons will bind to norepi→ complex proteins release, bind to calcium channels and close them

Used for - A precursor for Dex (NO longer use)

Medetomidine is

Atipamezole

Give as CRI, IM

A1 : A2 ratio must match = 1620 : 1

Adverse effect - Abrupt stop of effect / Removes ANALGESIA give other analgesia agent before giving this agent

What is the reversal for Dexmedetomidine and Medetomidine

Its BOTH agonist and antagonist to A2 receptors

(Vatinoxan)(NO BBB) Antagonist for Peripheral A2 = no vasoconstriction

(CROSSES BBB) Agonist for Central A2 therapeutic effect

What makes Zenalpha unique?

Its BOTH agonist and antagonist to A2 receptors

Which means that the (Vatinoxan)(NO BBB) Antagonist for Peripheral A2 WILL CAUSE NO vasoconstriction → No increase PVR → No baroreceptor triggered

Why does Zenalpha decrease the Biphasic CV effect

Mu / Kappa / delta

What are the 3 receptors of Opioids?

Mu better for Analgesia (Pain relief)

Kappa better for Sedation

Mu is better for …..

Kappa is better for …

Adverse Effects

Pain Relief (Analgesia)

Pure mu will have the MOST…. but ….MOST

MOA - FULL mu agonist

Notes - 4-6 hr duration / Controlled drug 2 / DO NOT USE in hypovolemic / ORIGINAL 1ST

Used for - Analgesia (best for) / Decrease use of Gas Anesthetics / Diarrhea / antitussive

Adverse Effects - Histamine release (Rapid IV) / Respiration depression / Depression of laryngeal reflex / DYSPHORIA / HYPER THERMIA / constipation w/ long use / BRADYCARDIA

Morphine is

MOA - FULL mu agonist

Notes - 8x potent / 4-6 hr duration / controlled drug 2

Used for - Analgesia (best for) / Decrease use of Gas Anesthetics / Sedation

Adverse Effects - Respiration depression / Depression of laryngeal reflex / DYSPHORIA / HYPER THERMIA / constipation w/ long use / BRADYCARDIA

Hydromorphone is

MOA - FULL mu agonist

Notes - 8x potent / 4-6 hr duration / controlled drug 2

Used for - Respiration depression / Depression of laryngeal reflex / DYSPHORIA / HYPER THERMIA / constipation w/ long use / BRADYCARDIA

Oxymorphone

MOA - FULL mu agonist

Notes - 100x potent / CRI / 30 min duration / Controlled drug 2

Used for - Analgesia (best for) / Decrease use of Gas Anesthetics / Sedation

Adverse Effects - Respiration depression / Depression of laryngeal reflex / DYSPHORIA / HYPER THERMIA / constipation w/ long use / BRADYCARDIA

Fentanyl is

MOA -FULL mu agonist / NMDA antagonist

Notes - 3x potent / LEAST to cause vomit / Controlled drug 2

Used for - Analgesia (best for) / Decrease use of Gas Anesthetics / Sedation

Adverse Effects - Respiration depression / Depression of laryngeal reflex / DYSPHORIA / HYPER THERMIA / constipation w/ long use / BRADYCARDIA

Methadone is

MOA - Competitive mu antagonist / Metabolized by Glucuronidation (careful w/ CATS)

Notes - Rapid onset w/ IV 1-2min / IM 5 min / 45 - 90 min Duration

Adverse Effects - Analgesia REVERSAL = PAIN WILL RETURN

Naloxone is

MOA - kappa AGONIST & mu ANTAGONIST

Notes - Duration 30-90min (Dogs) / Duration 3-4hrs (CATS) / Controlled drug 4

Used For - SEDATION (best for) / mild pain relief

Adverse Effects - Minimal cardio / resp effects

Butorphanol

MOA - PARTIAL mu AGONIST & kappa ANATGONIST

Notes - HIGHEST AFFINITY / Rapid onset IV (1-2min) IM (5mins) / Duration 45-90mins (dose dependent) / Controlled drug 3

Common use in CATS - IV, SQ, IM, Transmucosal and Transdermal for CATS

Used For - Moderate analgesia / POOR SEDATION

Adverse Effects - Minimal cardio / resp effects

Buprenorphine

Minimum Alveolar Concentration (MAC) - minimum concentration needed in the alveoli Lower MAC = HIGH Potency

Partition Coefficient - Solubility of the agent to the blood / LOWER # = FASTER agent (means that less amt of the agent gets dissolved in blood and MORE can reach the BRAIN)

Vapor Pressure - how VOLATILE (becomes to gas) the agent is

HIGH # = GREATER volatility (more becomes into GAS)

What are the 3 characteristics of Inhalant Anesthetics? Explain them

NOT REALLY, but because the patient is UNCONCIOUS, they CANNOT perceive the pain (pain is there but cannot act upon it)

Does Inhalant Anesthetics cause analgesia?

MOA

MAC = 1.3% (DOG) 1.6% (CAT) /

Partition Coefficient = 1.45%

Volatility = 240

Used for - Produce and Maintain GA / unconsciousness / analgesia / muscle relaxation

Notes - Biotransformation enter and exit through LUNGS / SLOW induction than Sevo

Adverse Effects - Decrease vital organ function / Decrease renal blood flow and GFR / dysrhythmias / depression of liver function

Isoflurane is

MOA

MAC = 2.4%

Partition Coefficient = 0.74%

Volatility = 160

Used for - Produce and Maintain GA / unconsciousness / analgesia / muscle relaxation

Notes - Biotransformation enter and exit through LUNGS / FASTER induction than Iso

Adverse Effects - Decrease vital organ function / Decrease renal blood flow and GFR / dysrhythmias / depression of liver function

Sevoflurane is

RESPIRTORY STIMULANT - NOT an INHALANT

MOA - Stimulate all CNS levels / Acts directly on CHEMORECEPTORS in aorta & carotid arteries

Notes - DO NOT use for CRI

Used for - Lapar challenge

Adverse effect - arrhythmias / hypertension / seizures

Doxapram is

When the patient is given an injectable anesthetic (Propofol or Alfaxalone) / get an endoscope to watch the Arotinoids / Give Doxapram to see if the Laryngeal moves when breathing

Laryngeal moves = NO laryngeal paralysis

Explain the Lapar Challenge

Propofol and Alfaxalone

What are the 2 INJECTABLE anesthetics

MOA - Decreases GABA rate by INCREASING hyperpolarization DECREASING CNS nerve impulse transmission

Used for - Sed - hyp / Induction & maintenance GA / Give IV slowly 60-90 sec

Notes - MILKY appearance / IV only / NOT CONTROLLED / Short duration / SLOW RECOVERY in Sighthounds

Adverse effects - Rapid admin = apnea (make sure to OXYGENATE) / Vasodilate / Propylene Glycol (careful w/ CATS)

Propofol is

MOA - binds GABA INCREASING hyperpolarization DECREASING CNS nerve impulse transmission

Used for - Sed - hyp / Induction & maintenance GA

Notes - NO ANALGESIA / IM OR IV / CONTROLLED DRUG 4 / give minimum at 12 weeks of age

Adverse effects - Hypotension (Give FLUIDS)

Alfaxalone is

CYCLOHEXAMINE

Another name for DISSOCIATIVE ANESTHETIC

NO, Instead it affects the NMDA receptor

Does Cyclohexamine cause their effects through GABA?

MOA - NMDA antagonist (decrease spinal wind-up)

Used for - ANALGESIA / Sedation / Maintenance for anesthesia

Notes - Controlled drug 3 / Skeletal muscle rigidity (eye lube)

Adverse effects - Hyperthermia / Emergence phenomena / Apneustic breathing / INCREASED secretions

Ketamine is

MOA - NMDA antagonist (decrease spinal wind-up)

Used for - ANALGESIA / Sedation / Maintenance for anesthesia

Notes - Controlled drug 3 / Skeletal muscle rigidity (eye lube)

Adverse effects - Hyperthermia / Emergence phenomena / Apneustic breathing / DO NOT use in head trauma patients

Tiletamine is

Hyperalgesia - OVER sensitive reaction to pain

Allodynia - Mistakens simple TOUCH as PAIN

What can Spinal Wind Up cause and explain what they are

When there is repetitive noxious stimulate, glucamate WILL BIND to NMDA receptors causing Spinal wind up

Explain Spinal Wind up

TRANSDUCTION - Noxious Stimulus (thermal, chemical, mechanical) (occurs in periphery) → Turns ELECTRICAL

TRANSMISSION - Nerve impulses along the Axon of the Peripheral Neurons

MODULATION - Signal gets transmitted to the Thalamus → gets AMPLIFIED thru Excitatory synapse along the AXON → Then gets DIMMED down

CONCIOUS PERCEPTION - Pain mediator happening to the cortex

Explain the steps of the Process of Nociception

Influences MODULATION

Normally, the NMDA is CLOSED → so when Gluconate binds w/ NMDA → OPENS channel → IMPOSSIBLE to reach ACTION POTENTIAL (cannot continue synapse)→ NO PAIN CAUSED

What does the NMDA receptor influence and how?

BENZODIAPINES (Minor tranquilizer)

What can be added with Injectable Anesthetics to DECREASE muscle rigidity effect?

OPIOIDS and CYCOHEXAMINES (Dissociative anesthetics)

What other drug class does HYPERTHERMIA occur to? other than Inj. Anesthetics

Agents used to help behaviors

What are MISCELLANEOUS DRUGS for?

MOA - BINDS to Ca channels → DECREASE Ca influx → Inhibits the excitatory neurotransmitter release

Used for - Decrease Anxiety in CATS / Analgesia for lesions in neurology

Notes - Can cause sedation / ataxic / SHORT TERM - behavior prblms

Adverse Effects - Sedation / Ataxia

Gabapentin is

PART OF SSRI

MOA - Selective Serotonin Reuptake Inhibitor / Direct Serotonin Antagonist

Used for - Commonly used in DOGS / Anxiolytic / Anti compulsive

Notes - Short time use for nail trims and sx post op

Adverse Effects - GI / sedation / Disinhibition of behaviors

Trazadone is

MOA - A2 Agonist

Used for - Noise Aversion / Storms / fireworks / before the clinic

Notes - FDA approved to treat noise / TRNSMUCOSAL form

Sileo (Dexmedetomidine) is

Minor Tranquilizers - which mean they function by ENHANCING GABA

Another name for Benzodiazepines

MOA - Enhances GABA / Binds to GABA → OPENS Cl channels → Cl rushes in leading to HYPERPOLARIZATION & inhibition of neurotransmission

Used for - SHORT TERM / Phobia / Storms / Owner leaving / Anxiolytic

Notes - RAPID onset / Use as needed

Adverse Effects - Paradoxical excitement (OPPOSITE of SED)

Alprazolam (Xanax) is

MOA - Enhances GABA

Used for - SHORT TERM / Phobia / Storms / Owner leaving / Anxiolytic

Notes - RAPID onset / Use as needed

Adverse Effects - Paradoxical excitement (OPPOSITE of SED)

Diazepam (Valium) is

MOA - Enhances GABA

Used for - SHORT TERM / Phobia / Storms / Owner leaving / Anxiolytic

Notes - RAPID onset / Use as needed

Adverse Effects - Paradoxical excitement (OPPOSITE of SED)

Clonazepam is

Selective Serotonin Reuptake Inhibitor - Causing the levels of Serotonin to INCREASE

This process takes 4-8 weeks to cause effect

What does SSRI mean

MOA - Decrease Serotonin Reuptake inhibitor → INCREASE Serotonin

Used for - Anxiety / Fear / URINE marking / Compulsive disorders / Anx-fear aggression

Notes - FDA for DOGS / OFFLABEL CATS

Adverse Effects - GI / SHORT sedation / CATS urine retention / SEROTONIN SYNDROME

Fluoxetine is

MOA - Decrease Serotonin Reuptake inhibitor → INCREASE Serotonin

Used for - Anxiety / Fear / URINE marking / Compulsive disorders / Anx-fear aggression

Adverse Effect - SEROTONIN SYNDROME

Sertraline is

MOA - Decrease Serotonin Reuptake inhibitor → INCREASE Serotonin

Used for - Anxiety / Fear / URINE marking / Compulsive disorders / Anx-fear aggression

Adverse Effect - SEROTONIN SYNDROME

Paroxetine is

SS - When there is a HIGH amount of Serotonin causing Fever / Muscle spasm / Vomit / Autonomic Dysfunction

DO NOT USE W/ SSRI, TCA, MAOI

What is Serotonin Syndrome? Which combinations of drugs should you not use bc it can cause SS

Tricyclic Antidepressant

What is TCA

MOA - INHIBIT serotonin reuptake and norepinephrine reuptake

Similar to SSRI effects and adverse effects

Notes - FDA approved in DOGS - OFFLABEL w/ CATS / Takes 4-8 weeks to cause effect

Clomipramine is

MOA - INHIBIT serotonin reuptake and norepinephrine reuptake

Similar to SSRI effects and adverse effects

Notes - used on CATS for INAPPROPRIATE URINATION / 4-8 weeks to cause effect

Amitriptyline is

Monoamine Oxidase Inhibitors

What does MAOI mean

MOA - MAO B selective / Inhibits oxidase (enzyme) that catabolizes CATECOLAMINES (specifically Dopamine)

Used for - Cognitive Dysfunction Syndrome in OLDER Dogs and Cats

Notes - FDA approved in DOGS and OFFLABEL in CATS

Adverse Effect - GI / Restlessness / Agitation / DECREASED Hearing

Selegiline is