Pharm exam 3 - Nervous system

Drugs and conditions

Analgesics

Drugs that relieve or block pain

Tranquilizers

Drugs that produce a relaxed state without significant analgesia

Anxiolytic, calms the patient

Sedatives

Drugs that produce a relaxed state without significant analgesia

Makes the animal sleepy without reduction of anxiety

Anesthetics

Produce a state of no sensation to temperature, pressure, touch or pain

Stimulants

Respiratory stimulation

Transduction

Physical stimulus converted into excitation or depolarization of pain receptor (Nociceptor)

Blocked with local anesthetics which prevent depolarization, opioids, NSAIDs and corticosteroids

Transmission

Depolarization wave from nociceptor to sensory nerve (peripheral receptor to spinal cord)

Blocked by local anesthetic injected near sensory nerve (Nerve block)

Modulation

Depolarization wave amplified or suppressed by neurons in the spinal cord or lower brain

Inhibited by local anesthetics, opioids, NSAIDs, anticonvulsants

Perception

Animal is conscious of pain impulses reaching higher areas of the brain

Inhibited by general anesthetics and opioids

Hyperalgesia

Process by which the sensitivity to pain increases

Decreasing the inflammatory process shortly after trauma or injury decreases the nocicepotrs sensitivity to reduce or avoid pain

Wind-up pain

Loss of the dampening effect of the spinal cord on pain impulse transmissions

Resulting in increasing perception of pain by the brain

Occurs in conscious and unconscious patients

Prevention of win-up pain is critical to controlling post-op pain

Opioids

Most potent veterinary analgesic

Produce analgesia and sedation (Used as preanesthetic and pain reliever)

Bind to opioid receptors

• 3 major types

• Located throughout CNS, brain, CRTZ, GI, Urinary tract and smooth muscle

In general, they are better for dull pain than sharp pain

Mu

Primary pain receptors in the CNS

Responsible for profound analgesia, narcosis, respiratory depression and euphoria

Kappa

Milder analgesia and less respiratory depression than Mu

Delta

Spinal cord analgesia

minimal use

Full/pure agonist

Full opioid receptor activity

Morphine, oxymorphone, meperidine, hydromorphone, fentanyl

Partial agonist

Incomplete opioid effect

Weak agonist

Buprenorphine, butorphanol

Mixed agonist/antagonist

Agonistic effect at one receptor and antagonist effect at another

Buprenorphine, butorphanol

Antagonist

Block opioid receptor activity

Naloxone

Hydrocodone

Low dose opioid

Cough suppression

Lopermide

Low dose opioid

Anti-diarrheal

Potency

Dose required to achieve desired effects

Efficacy

Maximum effect expressed

Pain relief, sedation

Euphoria

Pleasant hallucination or feelings

Dysphoria

State of uneasiness, anxiety, or agitation

Most common in cats and horses

Morphine

Predominantly Mu agonist

Used for visceral and somatic pain

Schedule II drug

Will stimulate CRTZ at low doses given IM or SQ

IV dosing will depress the emetic center before reaching the CRTZ

Oxymorphone and Hydromorphone

Mu agonist

Schedule II

Similar efficacy to morphine

• 10x more potent than morphine

• Less likely to induce vomiting

Fentanyl

Mu receptor agonist

Schedule II

Short lived potent analgesic

• Need to deliver with CRI to maintain Efficacy

100x more potent than morphine

Injectable or patch

Butorphanol

Partial and mixed Mu antagonist, kappa agonist

30-90 minute duration

Rapid onset

Often used in combination with other analgesics

• More sedation than analgesia

Reverses some respiratory suppression with strong Mu agonist

• Stronger affinity than pure agonist

Cough suppression

Buprenorphine (Buprenex)

Partial Mu agonist, Kappa antagonist

Schedule III controlled drug

20-50 times more potent than morphine

Longer duration

• Lasting 4-8 hours

• Slow onset - 20 minutes

Low incidence of adverse effects

Readily absorbed across mucous membranes

Tramadol

Classified as an opioid

Complete MOA is not fully understood

Central acting analgesic

Also has sedative properties

Dogs experience decreasing analgesic effects with
long-term use
• Must be metabolized to M1 metabolite for optimum efficacy
Dogs are unable to fully metabolize to the M1 stage, providing mild to moderate analgesia
Cats are able to better metabolize to the M1 stage, providing more profound analgesia
Contraindicated in animals also taking behavioral modification medications inhibiting serotonin uptake
Serotonin syndrome includes an altered mental state, dilated pupils, seizures, tremors, CNS sedation or stimulation

Naloxone

Opioid antagonist
Competes for Mu and Kappa receptors

Narcotic antagonist

Reserve for use in opioid overdose

Not to be used for reversal of opioid anesthesia

Pain perception will be sudden and severe

Partial reversal can be achieved with partial agonist/antagonist (Butorphanol)

Acepromazine

Phenothiazine tranquilizer

Produces sedation without analgesia

Blocks dopamine receptors resulting in a decrease in anxiety, CNS depression, lower BP, lower HR

Blocks CRTZ and emetic receptors providing antiemetic properties

Commonly used in anesthesia premed or to calm animals for transport or exam

Does it lower seizure threshold?

Assumed to, although starting to be challenged in research

Answer for boards – Acepromazine may lower seizure threshold

Diazepam (Valium)

Benzodiazepine tranquilizer

• -pam ending

Schedule IV drug

Sedation and muscle relaxation – no analgesia

• By enhancing GABA

• Attaches to GABA receptors (responsible for inhibiting or reducing nerve impulses)

• Also makes Benzos effective anticonvusants – can be administered rectally

Appetite stimulation in felines

• Potential for liver damage with prolonged use

Commonly used with ketamine in preanesthetic cocktails

Sensitive to light

Can cause nausea and mild respiratory depression

Midazolam

Schedule III

Benzodiazepine tranquilizer

• -epam ending

Calming and muscle relaxer – no analgesia

• Greater potency & affinity to GABA receptor – more effect with less dose

Appetite stimulation in felines\

• Potential for liver damage with prolonged use

Commonly used in preanesthetic cocktails

Sensitive to light

Mild respiratory depression

Alprazolam (Xanex)

Schedule IV

Benzodiazepine tranquilizer

Anti-anxiety, sedative, suppression of seizure activity (supplement with seizure medications)

Sent home with owners for thunderstorm phobia

• Off label

Sedation, increased hunger side effects

Sensitive to light

Alpha-2 Agonists

Block release of norepinephrine

• Norepi = F or F, alertness, memory, focus, restlessness, anxiety, increase systolic BP, increase HR

Sedation and short-lived analgesia (20 min)

• Skeletal muscle relaxation

Difference in species sensitivity

• Ruminants > Equine > Dogs/Cats > Pigs - most receptive to least

• 1000 lb steer would receive 1/10th the dose of a horse

• A horse would receive half the canine dose (if they were equivalent weights)

Side effects

• Vomiting (dogs & cats), hypotension (secondary to hypertension/vasoconstriction), bradycardia, hyperglycemia

Xylazine (Rompun)

Oldest drug in class

Vomiting in cats is common – stimulates CRTZ receptors

• Drug of choice to induce vomiting in cats after toxicity ingestion

Also used as sedative

• Particularly in large animals

Currently uncontrolled and cheap

Detomidine (Dormosedan)

Sedation in equine
More selective for alpha 2 receptors than xylazine, less effects on the heart

Alpha-2 Agonists

Medetomidine (Domitor)

Alpha-2 Agonists

Dexmedetomidine (Dexdomitor)

Common premedication cocktail or sedation for short-term procedures
• SILEO
• Reversed with Antesedan
• Alpha-2 antagonist

Alpha-2 Antagonists

Reversals for alpha-2 agonists

General anesthesia

Reversible loss of sensations associated with unconsciousness

Local Anesthesia

Reversible loss of sensation in a regional area, without loss of consciousness

-caine suffix
Administered via local infiltration - Blocks
Block perception of pain to brain, patient remains conscious
Loss of function is related to dose amount
Pain < Temperature < Touch < Pressure < Motor Function

Lidocaine (+/- Epi)

Most commonly used – Safe for most ROAs (antiarrhythmic)
Intermediate duration
Blocks signals at nerve endings - All signals, including pain

Bupivacaine

Long duration
• Epidural
Blocks the generation and conduction of nerve impulses - All impulses, including pain
Cardiotoxic if administered IV – Causing severe myocardial depression

Barbiturates

Injectable Anesthetics

Increase amount of time chloride channels are open, depressing/inhibiting the CNS
Classified based on duration

Onset 10-15 min, 3-4 hour duration

Thiopentol

Ultra-short – < 1 hour
Anesthetic induction agent
Old medication
Very irritating if administered outside of the vein causing tissue necrosis and sloughing
Not recommended in sight hounds due to slow drug metabolism
No longer available in the United States
On the FDAs ‘Discontinued Drug’ list, 10+ years ago

Pentobarbital

Previously used as anesthetic agent in short surgical procedures

Narrow therapeutic index

Used today in euthanasia agents
Beuthanasia, Fatal Plus, Sleep Away

Controlled substance

Overdose leads to respiratory and cardiovascular depression quickly progressing to coma, apnea, and death

Also used as an Anticonvulsant medication for seizures - long acting version (30-60 mins, 10-16 hour duration)

Propofol

Chemically unrelated to barbiturates
• Similar anesthetic properties

Hypnotic agent, injectable anesthetic

Short-acting – up to 20 minutes

Used for induction of anesthesia

Providing effective sedation and anesthesia

Questionable analgesia

Injected slowly (apnea & hypotension) and given to effect

Use of additional opioids increases risk of apnea

Minimal residual effects
White opaque color

Propofol, Propoflo, Propoflo-28

Dissociative agents

Ketamine and Tiletamine

NDMA receptor antagonists

Primary excitatory neurotransmitter receptors in the brain

Antagonists bind to receptor site

Hallucinations, agitation, anesthesia, muscle rigidity (ketamine)

Used in combination with diazepam to reduce muscle rigidity
Short acting - ~1-4 hours

Animal feels dissociated (apart-from) their body

Catalepsy – appear awake, but unable to respond to stimuli