Drugs used in Nervous System Disorders-Central Nervous System

Drugs that affect the CNS

Causes depression or stimulation and are thought to generate these changes by altering nerve impulse transmissions between the spinal cord and the brain or within the brain itself

Altering transmissions within the thalamus

Could prevent messages regarding painful stimuli from reaching interpretation centers within the cerebrum

Interfering with impulses within the reticular activating system

Could alter levels of consciousness or wakefulness

Categories of CNS drugs

• Tranquilizers

• Barbiturates

• Dissociatives

• Opioid/antagonists

• Neuroleptanalgesics/antagonists

• Drugs to prevent or control seizures

• Inhalants

• Misc. CNS drugs

• Euthanasia agents

Tranquilizers uses

To calm patients, produce muscle relaxation, decrease the dose of anesthetic requirements, ease the placement of an IV catheter, and promote smooth induction and recovery

Tranquilizers

Decrease anxiety without causing excessive sedation or drowsiness; animals are usually aware of their surrounding but don’t appear to care

Tranquilizers don’t

Provide analgesia

Sedatives

Used to suppress brain activity and awareness to prevent movement for some short medical procedures; animals are usually unaware of their surroundings and are drowsy, which offers some analgesia

Phenothiazine derivatives tranquilizers

Produce sedation and allay fear and anxiety without producing significant analgesia, an antiemetic effect by depressing the chemoreceptor trigger sone in the brain and have a mild antipruritic effect. They also reduce the tendency of epinephrine to induce cardiac arrhythmias

Clinical uses of phenothiazine derivatives tranquilizers

Used for prevention or treatment of vomiting, relief of mild pruritus, and sedation/tranquilization

Dosage forms of phenothiazine derivatives tranquilizers

• Acepromazine maleate (PromAce)

• Chlorpromazine hydrochloride (Thorazine-human label)

• Promazine hydrogen chloride (HCI)

• Prochlorperazine

Adverse side effects of phenothiazine derivative transquilizers

Can cause hypotension and hypothermia through their vasodilator effects (alpha blockade)

Benzodiazepine derivatives (diazepam)

This drug produces sedation, muscle relaxation, appetite stimulation (especially in cats), and anticonvulsant activity. It’s very useful for treating a seizure in progress.

Diazepam used in combination with ketamine

To induce short-term anesthesia

Clinical uses of benzodiazepine derivatives

Sedation, relief of anxiety and behavioral disorders, treatment of seizures, and appetite stimulation. Can be used as an injectable anesthetic

Dosage forms of benzodiazepine derivatives

• Diazepam (Valium, Diastat)

• Midazolam (Versed)

• Zolazepam (Telazol)

• Alprazolam (Xanax)

Adverse side effects of benzodiazepine derivatives

These are limited when used as directed. Dogs can exhibit excitement. An overdose may cause excessive CNS depression

Diazepam

Should be stored at room temp and protected from light, shouldn’t be stored in plastic syringes, shouldn’t be mixed with other meds or solutions, painful if administered IM,

Alpha-2 agonists

Sedative analgesics they provide sedation, analgesia, muscle relaxation, and antianxiety

The CNS effects of alpha-2 agonists

Can be antagonized by alpha-2 receptor antagonists such as yohimbine, tolazoline, and atipamezole

Xylazine Hydrochloride

Is an alpha-2 agonis with sedative, analgesic, and muscle relaxant properties and is antagonized by yohimbine

Xylazine hydrochloride produces

Effective analgesia in horses and is often used for treating the pain associated with colic and for sedation for minor procedures

Xylazine hydrochloride used in combination with ketamine

For short-term field procedures in horses, such as castration and suturing of extensive wounds, because this combination usually produces 15 to 20 minutes of recumbency

Xylazine used in cats and dogs

As a tranquilizer and in combination with other injectable agents for surgical procedures

Clinical uses xylazine

Sedation, analgesia, short-term anesthesia (when combined with other agents), and induction of vomiting

Dosage forms of xylazine

• Rompun

• AnaSed

• Sedazine

• Cervizine (deer and elk)

Adverse side effects of xylazine

Bradycardia, hypotension, respiratory depression, and increased sensitivity to epinephrine, resulting in cardiac arrhythmias. An overdose increases the potential for these effects

Yohimbine used as

The reversal agent for xylazine

Detomidine Hydrochloride clinical uses

Sedative/analgesic for horses

Atipamzole used as

The reversal agent for detomidine

Dosage form of detomidine hydrochloride

• Dormosedan injectable

• Dormosedan gel (for sublingual administration)

Adverse side effects of detomidine hydrochloride

Sweating, muscle tremors, penile prolapse, bradycardia, and heart block

Medetomidine

An alpha-2 adrenergic agonist labeled for use as a sedative and analgesic in dogs older than 12 weeks

Atipamazole (Antisedan) used as

Reversal agent for medetomidine

Clinical uses for medetomidine

Facilitating clinical exam, minor surgical procedures, and minor dental procedures that don’t require intubation

Dosage form for medetomidine

• Domitor (not currently available in the U.S. market)

Adverse side effects of medetomidine

Bradycardia, atrioventricular heart block, decreased respirations, hypothermia, urination, vomiting, hyperglycemia, and pain at the injection site

Dexmedetomidine

An alpha-2 adrenergic agonists labeled for use as a sedative and analgesic in dogs and cats

Clinical uses of dexmedetomidine

Used as a sedative, preanesthetic, and analgesic in dogs and cats

Dosage form of dexmedetomidine

• Dexdomitor

Adverse side effects of dexmedetomidine

Bradycardia, hypertension, vomiting, atrioventricular block, muscle tremors, and others

Dexmedetomidine shouldn’t be used in

Dogs or cats with cardiovascular, respiratory, kidney, or liver disease or in patients with shock or severe debilitation or stress due to heat, cold, or fatigue

Romifidine

An alpha-2 adrenergic agonist labeled for use in horses

Romifidine clincal uses

Used as a sedative to facilitate handling, exam, and treatment and as premedication before general anesthesia

Dosage forms of romifidine

Sedivet

Barbiturates

Used in vet med as sedatives, anticonvulsants, general anesthetics, and euthanasia agents. They’re cheap to administer

Why do barbiturates have great potential for complications?

Because of their potent depressing effects on the cardiac and pulmonary systems (especially in cats) and because they’re nonreversible and must be metabolized by the liver before elimination can occur

Barbiturates are classified according to…

Their duration of action is long-acting, short-acting, and ultrashort-acting, and the chemical side chain on the barbituric acid molecule is an oxybarbiturate or a thiobarbiturate

Oxybarbiturates

The long- and short-acting barbiturates have a side chain that is connected by oxygen

Thiobarbiturates

They have a side chain connected by a sulfur, highly soluble in fat and tend to move rapidly out of the CNS into the fat stores of the body, ultrashort activity

Clinical uses of barbiturates

The prevention and treatment of seizures, as well as sedation, anesthesia, and euthanasia

Long-acting barbiturates (Oxybarbiturates, 8 to 12 hours)

Phenobarbital is used primarily as an anticonvulsant and is the drug of choice for long-term control of epileptic seizures, administered by the oral route, and is a Class IV controlled substance

Short-acting barbiturates (Oxybarbiturates, 45 minutes to 1.5 hours)

Pentobarbital is given IV and provides 1-2 hours of general anesthesia, it’s primarily used for controlling seizures in progress and as a euthanasia agent, and is a Class II

Ultrashort-acting barbiturates (thiobarbiturates, 5 to 30 minutes)

Are very alkaline (especially at the higher concentrations) and must be given IV to avoid necrosis and subsequent sloughing of tissue. They’re redistributed into the fat stores of the body.

Dosage forms of barbiturates

• Thiobarbiturates (thiamylal and thiopental) are currently not available in the U.S.

• Methohexital

Adverse side effects of barbiturates

Excessive CNS, depression, paradoxical CNS excitement, severe respiratory depression, and cardiovascular depression. Tissue irritation may occur when they’re injected perivascularly

Recovery from pentobarbital

Often prolonged, and dogs exhibit padding limb movements during this time

Thiobarbiturates shouldn’t

Be used in sighthounds or in any very thin animal

Dissociative agents

Belong to the cyclohexylamine family, which includes phencyclidine, ketamine, and tiletamine

Characterizations of dissociative anesthesia

Involuntary muscle rigidity (catalepsy), amnesia, and analgesia. Pharyngeal/laryngeal reflexes are maintained, and muscle tone is increased

Dissociative drugs produce

Minor cardiac stimulation, and respiratory depression can occur with higher doses and they act by altering neurotransmitter activity, causing depression of the thalamus and cerebral cortex, and activating the limbic system

Clinical uses of dissociative agents

Sedation, restraint, analgesia, and anesthesia

Dosage forms of dissociative agents

• Ketamine HCI (ketaset)

• Increased salivation

• Tiletamine HCI

• Phencyclidine

Ketamine HCI

Tranquilizers are often used concurrently with this to enhance muscle relaxation and to deepen the level of anesthesia. Oral, ocular, and laryngeal reflexes are maintained when used alone

Increased salivation with ketamine

Can be controlled or prevented with the use of atropine or glycopyrrolate. An ophthalmic lubricant should be used because cat’s eyes remain open after administration

Tiletamine HCI (Telazol [tiletamine plus zolazepam HCI])

Should only be used for restraint and minor procedures of short duration requiring mild to moderate analgesia. Ocular lubrication should be used in cats. Class III controlled substance

Phencyclidine

No longer available. It was originally used as an immobilizing agent for nonhuman primates

Adverse side effects of dissociative agents

Are usually associated with high doses and include spastic jerking movement, convulsions, respiratory depression, burning at the IM injection site, and drying of the cornea

Opioid agonists

Any compound derived from opium poppy alkaloids and synthetic drugs with similar pharmacologic properties. They produce analgesia and sedation (hypnosis) while reducing anxiety and fear

Opioid receptors 4 classes

• Mu

• Kappa

• Sigma

• Delta

Mu

Found in pain-regulating areas of the brain; contribute to analgesia, euphoria, respiratory depression, physical dependence, and hypothermic actions

Kappa

Found in the cerebral cortex and spinal cord; contribute to analgesia, sedation, depression, miosis

Sigma

May be responsible for struggling, whining, hallucinations, and mydriatic effects

Delta

Modify mu receptor activity; contribute to analgesia

Opioids are used as

Preanesthetic or postanesthetic because of their sedative and analgesic properties. Sedation is more pronounced at higher dose. Sometimes used alone or in combination with tranquilizers as anesthetic for surgical procedures, for relief of colic pain in horses, and for restraint/capture of wild/zoo animals

Low doses of opioids

They have antitussive (cough suppression) properties because of depression of the cough center in the brain; they also have antidiarrheal action because of a reduction in peristalsis or segmental contractions

Clinical uses of opioids

For analgesia, sedation, restraint, anesthesia, treatment of coughing, and treatment of diarrhea

Naturally occurring narcotics

• Opium (laudanum-10% opium) pregoric

• Morphine sulfate (Duramorph)

Opium (laudanum-10% opium) pregoric

Also called camphorated tincture of opium, has been used for longer than 100 years for the treatment of diarrhea. It has been used in vet med for treating diarrhea, primarily in calves and foals

Morphine sulfate (Duramorph)

An opium derivative used to treat severe pain. Used as a preanesthetic or anesthetic agent. Also used to relieve anxiety associative with acute congestive heart failure

Synthetic Narcotics

• Meperidine (Demerol)

• Oxymorphone (Numorphan and Opana)

• Butorphanol tartrate (Torbutrol, Torbugesic)

• Fetanyl (Recuvyra, Sublimaze, and Duragesic-Human labels)

• Hydrocodone bitartrate

• Etorphine

• Pentazicine

• Diphenoxylate

• Apomorphine

• Methadone

• Codeine

• Carfentanil

• Buprenorphine (Buprenex)

• Buprenorphine (Simbadol)

• Tramadol

Oxymorphone (Numorphan and Opana)

A semisynthetic opiod that’s a mu agonist. Used primarily in dogs for restraint, for diagnostic procedures, and for minor surgical procedures

Butorphanol tartrate (Torbutrol, Torbugesic)

A synthetic, opioid agonist/antagonist. Its opioid agonist activity is exerted on kappa and sigma receptors, while its antagonist activity occurs at the mu receptor. Shouldn’t be used as the only analgesic agent

Fentanyl

An opioid agonist that has approximately 100 times the analgesic properties of morphine

Adverse side effects of opioid agonists

Respiratory depression, excitement (cats and horses), nausea, vomiting, diarrhea, defecation, panting, and convulsions. Overdose causes profound respiratory depression

Opioid Antagonists

They block the effects of opioids by binding opiate receptors, displacing narcotic molecules already present, and preventing further narcotic binding at the sites

Dosage forms of opioid antagonists

• Naloxone

• Nalorphine

• Butorphanol

Adverse side effects of opioid antagonists

Nalorphine may include respiratory depression. Naloxone usually has few if given in he correct dose

Neuroleptanalgesics

A combination of an opioid and a tranquilizer. They produce a state of reduced awareness and analgesia in which the patient may or may not remain conscious

Clinical uses of Neuroleptanalgesics

For sedation, restraint, and anesthesia. Commonly used in patients undergoing short procedures including wound suturing, porcupine quill removal, and radiographs

Dosage forms of Neuroleptanalgesics

Fentanyl and droperidol, and any combination of an opioid analgesic

Adverse side effects of Neuroleptanalgesics

Panting, flatulence, personality changes, increased sound sensitivity, and bradycardia. An overdose may cause severe depression of the CNS, respiratory system, and cardiovascular system

Reasons for seizures include but are not limited to

Unknown (idiopathic), infectious (postdistemper), traumatic (head injury), toxic (strychnine poisoning), and metabolic (heatstroke) factors

Prolonged seizures

In progress require emergency action with IV therapy

Periodic, recurring seizures

Require preventative oral medications

Drugs given to prevent or control seizures

• Diazepam (Valium)

• Pentobarbital (Nembutal and generic products)

• Phenobarbital (Lumical, Solfoton, generic formulations)

• Primidone (Mylepsin and Neurosyn)

• Bromide

• Gabapentin (Neurontin)

• Levetiracetam (Kappra)

• Zonisamide

Diazepam (Valium)

A tranquilizer with potent antiseizure properties. It’s administered IV and has a 3-4 hour duration of action

Pentobarbital (Nembutal and generic products)

A short-acting barbiturate that’s effective for controlling seizures. Given IV and has 1-3 hour duration

Phenobarbital (Luminal, Solfoton, generic formulations)

An effective antiseizure drugs that’s available in oral and parenteral formulations. Oral route to dogs and cats. Injectable form used in horses. Drowsiness is a potential side effect. Class IV

Adverse side effects of anti-seizure medications

May include drowsiness, CNS depression, anxiety, agitation, polydipsia, and hepatoxicity (phenobarbital and primidone)