Download Adjunct to anesthesia One of a number of drugs or techniques used

Adjunct to anesthesia
One of a number of drugs or techniques used to enhance anesthesia but that
are not classified as anesthetics.
Adjuncts to anesthesia include:
- Pre-anesthetic medication
- Muscle relaxants
Preanesthetic medications help both anesthetist and animal because it makes
induction and maintenance of anesthesia easier for the anesthetist, safer, and
comfortable to the patient.
It's given usually before anesthesia but sometimes at/or immediately after
the induction of anesthesia.
1.
2.
3.
4.
5.
6.
Pre-anesthetic medication groups
Anticholinergics
Antiemetics
Antihistamines
Barbiturates
Benzodiazepines
Opioids
1.
2.
3.
4.
5.
Anticholinergics
Tranquilizers drugs
Narcotics drugs.
Sedative drugs and adrenergic agonist.
Neuroleptanalgesics
1.
2.
3.
4.
5.
6.
Anticholinergics
Tranquilizers
Opioids
Alpha2-Adrenergic Agonists
Alpha2-Adrenergic Antagonists
Tranquilizer-Opioid combinations
Or
Or
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Examples:
Anticholinergics
Atropine Sulfate
Glycopyrrolate (Robinul – V)
Tranquilizers
Acepromazine Maleate
Droperidol
Diazepam (Valium)
Midazolam (Versed)
Flumazenil (Romazicon)
Opioids
Morphine Sulfate
Alpha2-Adrenergic Agonists
Xylazine Hcl (Anased, Rumpun)
Detomidine (Dormosedan)
Medetomidine (Dormitor)
Alpha2-Adrenergic Antagonists
Yohimbine (Yobine)
Tolazoline (Priscoline)
Atepmizole (Antisedan)
Tranqulizer-Opioid combinations
Fentanyl Citrate – Droperidol (Innovar – vet)
Etrophine – Acepromazine (Immobilon LA) and
Etrophine – Methotrimeperazine (Immobilon SA)
Meperidine Hcl (Demerol, Pethidine)
Methadone Hcl (Methadone, Dolophine)
Oxymorphone Hcl (Numorphan)
Fentanyl Citrate (Sublimaze)
Carefentanil Citrate (Wildnil)
Sufentanil and Alfentanil (Sufenta and Alfenta)
Etrophine Hcl (M – 99)
Agonist – Antagonist Opioids
Butorphanol Tartrate (Torbutrol, Torbugesic)
Bupernorphine (Buprenex, Temgesic)
Pentazocine Lactate (Talwin)
Groups of pre anesthetic drugs
1. Anti cholinergic drugs.
2. Tranquilizers drugs.
3. Narcotics drugs.
4. Sedative drugs and adrenergic agonist.
5. Neuroleptanalgesics
Aims of Pre-medications:
1- To relieve anxiety, fear and resistance to anesthesia.
2- To decrease unwanted side effect of anesthetic agents. These effects may require
modification depend on the species of animal and on the drugs used they include:Vomiting (mainly in dogs and cats), poor quality of recovery, bradycardia,
salivation and excessive muscle tone.
3- To reduce the dose of anesthetic in many but not in all cases, drug combination
may have a lower side effect than a high dose of anesthetic.
4- To provide extra analgesia.
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So: Preanesthetic drugs are used to prepare patient for induction and contribute to
maintenance and smooth recovery from anesthesia. Specifically, these drugs are
chosen to:
1- Calm the patient.
6- Decrease gastric fluid and acidity.
2- Induce sedation
7- Suppress or prevent vomiting or
regurgitation.
3- Provide analgesia and muscle 8- Decrease anesthetic requirements.
relaxation.
4- Decrease airway secretion and 9- Promote smooth induction and
salivation.
recovery from anesthesia.
5- Obtund autonomic reflex responses.
Anticholinergic drugs
An anticholinergic agent is a substance that blocks the neurotransmitter
acetylcholine in the central and the peripheral nervous system. Anticholinergics
inhibit parasympathetic nerve impulses by selectively blocking the binding of the
neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the
parasympathetic system are responsible for the involuntary movement of smooth
muscles present in the gastrointestinal tract, urinary tract, lungs, etc.
Anticholinergics are divided into three categories in accordance with their specific
targets in the central and/or peripheral nervous system: antimuscarinic agents,
ganglionic blockers, and neuromuscular blockers.
Anticholinergics are classified according to the receptors that are affected:
 Antimuscarinic agents operate on the muscarinic acetylcholine receptors.
The majority of anticholinergic drugs are antimuscarinics.
 Antinicotinic agents operate on the nicotinic acetylcholine receptors. The
majority of these are non-depolarizing skeletal muscle relaxants for surgical
use that are structurally related to curare. Several are depolarizing agents.
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Examples of common anticholinergics:
Atropine
Anti-Muscarinic agents
Ipratropium (Atrovent)
Benztropine (Cogentin)
Orphenadrine
Biperiden
Oxitropium (Oxivent)
Chlorpheniramine
(Chlor-Trimeton)
Oxybutynin (Ditropan,
Driptane, Lyrinel XL)
Dicyclomine (Dicycloverine)
Tolterodine (Detrol,
Detrusitol)
Dimenhydrinate(Dramamine) Tiotropium (Spiriva)
Diphenhydramine (Benadryl,
Sominex, Advil PM, etc.)
Doxylamine (Unisom)
Glycopyrrolate (Robinul)
Hydroxyzine (Atarax,
Vistaril)
Anti-Nicotinic agents
Bupropion (Zyban,
Wellbutrin) - Ganglion
blocker
Dextromethorphan Cough suppressant and
ganglion blocker
Doxacurium Nondeplorizing skeletal
muscular relaxant
Hexamethonium Ganglion blocker
Mecamylamine Ganglion blocker and
occasional smoking
cessation aid
Tubocurarine Nondepolarizing skeletal
muscular relaxant
Trihexyphenidyl
Scopolamine
Solifenacin
Tropicamide
The most common plants containing anticholinergic alkaloids are:
 Atropa belladonna (Deadly Nightshade), source of atropine
 Brugmansia species (Brugmansia)
 Datura species (Datura)
 Hyoscyamus niger (Henbane)
 Mandragora officinarum (Mandrake)
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Drug: Atropine
Class: Anticholinergic
MOA: Competitive blockade of muscarinic receptors
DOA: 60–90 min (some species variation)
ROA: (IV, I M, SC)
Effect: Parasympatholytic: increased heart rate, decreased salivation/secretions,
dilated pupils; gastrointestinal stasis, increases physiologic dead space
(bronchodilation)
Adverse: Tachycardia, arrhythmias, colic (equine)
Approved: Dogs, cats, cattle, horses, sheep
Note:
 Atropine should not be given to ruminants because it makes their secretion
more viscid and therefore more difficult to remove from the mouth and
respiratory tract.
Drug: Glycopyrrolate (Robinul)
Class: Anticholinergic
MOA: Blocks effect of acetylcholine at muscarinic receptors
DOA: 2–4 hr
ROD: (IV, IM, SC)
Effect: Parasympatholytic: increased heart rate, decreased respiratory secretions,
increases physiologic dead space (bronchodilation), does not cross placental or
blood-brain barrier
Adverse: Ileus, sinus tachycardia
Approved: Dog, cat
Other anticholinergic agents:
Dosage forms
- Scopolamine (hyoscine) (levo-duboisine)
- Methscopolamine
- Aminopentamide (Centrine)
- Propantheline (Pro-Banthine)
- Pralidoxime (Protopam, 2-PAM)
Main usage
- it is used in antidiarrheal medications
- It is used to control diarrhea.
- it is used to control vomiting and diarrhea
in dogs and cats
- it is used to treat diarrhea
- it is used to treat urinary incontinence
- It is used to treat bradycardia.
- It is used to reduce colonic peristalsis in
horses to allow rectal examination.
- It is used to treat Organophosphate
intoxication.
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Tranquilizers drugs:
Tranquilizers agents: drugs that cause a state of behavioral change in which
the patient is relaxed and unconcerned by his surroundings.
 Phenothiazine Derivatives
Mechanism of action on CNS is not well understood. It has been proposed that
they are Dopamine blockers.
- They approved for use in wide variety of animals, and for administration by
almost any rout.
- They are relatively safe drugs to use when administered appropriately.
- They should be given with care when used with other CNS depressants because
of the additive effect.
- Most phenothiazine derivatives are metabolized by the liver and excreted by the
kidneys.
- They can cause hypotension and hypothermia because of their vasodilator effect
(alpha blockade).
- They also can induce seizures (by lowering the seizure threshold) in epileptic
animals.
- They should not be used within 1 month of worming with organophosphate
anthelmintic.
- The tranquilizing effect may be reduced in an excited animal.
Example:
* Acepromazine maleat (Acepromazine, Promace)
* Chlorpromazine HCl (Thorazine)
* Promazine HCl
* Prochlorperazine /isopropamide (Darbazine, Compazine)
* Propionylpromazine
* Methotrimeprazine
* Promethazine
Drug: Acepromazine (Promace; Acetylpromazine)
Class: Phenothiazine tranquilizer (major)
MOA: Antiadrenergic, anticholinergic, antihistaminic, antidopaminergic
DOA: Dose dependent; 2–3 hr (prolonged in hepatic-compromised, geriatric, and
pediatric patients)
ROA: (IV, IM, SC, PO)
Effect: Calming effect; decreased motor activity; antiemetic; no analgesia
Adverse: Hypotension, penile paralysis (equine), decreased seizure threshold,
prolonged duration with liver disease; anecdotal reports of profound respiratory
and cardiovascular depression in Boxers
Approved: Horses, cats, dogs.
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 Benzodiazepine derivatives
Mode of action: (a) Exert many of their pharmacologic effects by enhancing the
activity of CNS inhibitory neurotransmitters and opening chloride channel, thereby
hyperpolarizing memberanes; also produce their effects by combining with CNS
benzodiazepines receptors (BZ1, BZ2).
Effects can be antagonized by the benzodiazepines antagonist Flumazenil.
(b) Depress the limbic system, thalamus, and hypothalamus (reducing sympathetic
output), thereby inducing a mild calming effect.
(c) Reduce polysynaptic reflex activity, resulting in muscle relaxation.
(d) Cause minimal CNS depression and produce anti-convulsant effects in most
animals; may cause disorientation and agitation after rapid IV administration,
particularly in cats.
(e) Stimulate appetite and pica.
Example
*Diazepam (Valium, Vazepam)
* Midazolam
Drug: Diazepam (Valium)
Class: Benzodiazepine tranquilizer (minor)
MOA: Activates CNS benzodiazepine receptors, which increase inhibitory
neurotransmitters (i.e., GABA, glycine)
DOA: <3 hr
ROA: (IV, IM, PO)
Effect: Mild sedation, muscle relaxation, enhances effect of concurrently used
agents
Adverse: Excitement in some species (horses, dogs), hepatoxicity has been
reported with PO administration in cats
Approved: Dog
Drug: Midazolam (Versed; Hypnovel):
Class: Benzodiazepine tranquilizer (minor)
MOA: Activates CNS benzodiazepine receptors, which increase inhibitory
neurotransmittors (i.e., GABA, glycine)
DOA: <2 hr (duration is slightly less than diazepam)
ROA: (IV, IM, SC)
Effect: Mild sedation, muscle relaxation; works well IV or IM
Adverse: Excitement in some species, respiratory depression
Approved: None
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Drug: Flumazenil (Romazicon)
Class: Benzodiazepine receptor antagonist
MOA: Competes with benzodiazepines for receptor
DOA: 2–3 hr.
ROA: (IV)
Effect: Specific reversal of benzodiazepine tranquilizers
Adverse: Rare
Approved: None.
 Alpha2-Adrenergic Agonists
Mode of action: produce CNS depression by stimulating both presynaptic alpha2adrenoreceptors in the CNS and peripherally.
- decreasing nor-epinephrine release centrally and peripherally reducing ascending
nociceptive transmission.
The net result is a decrease in CNS sympathetic outflow and a decrease in
circulating catecholamines and other stress-related substances; the CNS effects of
alpha2-agonists can be antagonized by aplha2-receptor antagonists.
Example
* Xylazine (Rompun)
* Detomidine
* Medetomidine
Drug: Xylazine (Rompun; Ansed)
Class: Alpha2 agonist
MOA: Activates CNS alpha2 receptors, which inhibit neurotransmitter release in
brain
DOA: Dose and species dependent; 15–30 min (analgesia); 1–2 hr (sedation)
ROA: (IV, IM, SC)
Effect: Sedation, analgesia, muscle relaxation
Adverse: Bradycardia, conduction disturbances, hypotension, respiratory
depression, hypoxia
Approved: Horses (10% formulation); dogs
Drug: Medetomidine (Dormitor)
Class: Alpha2 agonist
MOA: Activates CNS alpha2 receptors, which inhibit neurotransmitter release in
brain
DOA: Dose and species dependent; 60–120 min
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ROA: (IV, IM, SC)
Effect: Sedation, analgesia, muscle relaxation
Adverse: Bradycardia, conduction disturbances,
depression, hypoxia
Approved: Dogs.
hypotension,
respiratory
Drug: Romifidine (Sedivet)
Class: Alpha2 agonist
MOA: Activates CNS alpha2 receptors, which inhibit neurotransmitter release in
brain
DOA: Dose dependent; >120 min
ROA: (IV, IM, SC)
Effect: Sedation, analgesia, muscle relaxation
Adverse: Bradycardia, conduction disturbances, hypotension, respiratory
depression, hypoxia
Approved: Not currently approved in the United States, but studies have been
published for dosages in dogs and horses.
Drug: Tolazoline (Tolazine)
Class: Alpha1 and alpha2 receptor antagonist
MOA: Occupies and antagonizes alpha2 receptors (least specific for the alpha2
receptor)
DOA: 2 hr
ROA: (IV, IM)
Effect: Reverses effects of alpha2 agonists
Adverse: Hypotension with rapid injection due to vasodilatory effect, excitement,
tremors, salivation, tachypnea
Approved: Horses
Drug: Yohimbine (Yobine)
Class: Alpha2 antagonist
MOA: Blocks alpha2 receptors; also has antiserotonin activity
DOA: <1 hr
ROA: (IV, IM)
Effect: Reverses effects of alpha2 agonists
Adverse: Hypotension with rapid injection due to vasodilatory effect, excitement,
tremors, salivation, tachypnea
Approved: Dogs
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Narcotic analgesic
Narcotic agents (drugs): - a drug that produce state of sleep accompanied by
analgesia.
Narcotic analgesic
Act by reversible combination with one or more specific receptors in the
brain and spinal column
- Produces a variety of effects
 Analgesia
 Sedation
 Dysphoria
 Euphoria
 excitement
- Act as an agonist or antagonist
• Pure agonists stimulate all receptors – morphine, fentanyl and oxymorphone
• Mixed agonists/antagonists block one type of receptor and stimulate another
• Pure antagonists such as naloxone will reverse the effects of pure and mixed
agonists with very little clinical effect on their own
Also classified according to their analgesic activity and their addiction potential
Pure agonists are more effective for severe pain in order of decreasing potency
they are: Fentanyl ; Oxymorphone ;Buprenorphine ; Meperidine ; Pentazocine
Commonly used as an analgesic in premedication, as an induction agent or
can be used for balanced anesthesia and post-operative pain control. Provides some
sedation and may potentiate the action of the sedative that it is given with has a
synergistic effect.
Fentanyl, sufentanil and oxymorphone are often part of a balanced anesthetic
regimen.
Fentanyl is available as a transdermal patch in various sizes for long-term
analgesia used as neuroleptanalgesia in combination with tranquilizer.
Morphine can be injected epidurally or sub-arachnoidally for regional analgesia.
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Other narcotic analgesic: Pethidine; Methadone; Etorphine; Fentnyl
Opioids Agonists
Naturally occurring Narcotics
* Opium
*Morphine sulphate (Duramorph)
Synthetic Narcotics
* Meperidine (Demerol)
* Oxymorphone (Numorphan)
* Butorphanol tartrate (Torbutrol, Torbugesic)
* Fentanyl (Sublimaze)
* Hydrocodone bitartrate (Hycodan, Tussigon)
* Etorphine (M-99)
* Pentazocine (Talwine, Takwin-V)
* Diphenoxylate (Lomotil)
* Apomorphine
* Methadone (Dolophine)
* Codeine
*Carfentanil (Wildnil)
* Buprenorhine (Buprenex)
Opioid Antagonists
Classified in to:
- Pure antagonists
- Partial antagonists (may have some agonist
activity).
* Nalaxone (Nalaxone HCl, Naracan)
* Nalorphine (Nalline
Moe of action: Act by reversible combination
with one or more specific receptors (i.e. μ, κ,
δ) in the brain and spinal cord to produce a
variety effects including analgesia, euphoria,
dysphoria,, and excitement.
The opioids are used as preanesthetic or postanesthetic because of their sedative and
analgesic properties.
Clinical uses: Opioid agonists are used for
analgesia, sedation, restraint, anesthetics,
treatment of coughing, and treatment of
diarrhea.
Adverse side effects: these can include
respiratory depression, excitement (cat and
horses), nausea, vomiting, diarrhea,
defecation, panting, and convulsion, Overdose
causes profound respiratory depression
They block the effects of Opioids by binding
with opiate receptors, displacing narcotic
molecules already present, and preventing
further narcotic binding at the site
*Note: Opioids: the term opioids is refer to all exogenous and synthetic
compounds that bind to specific subpopulation of opioid receptors.
Opioid receptors
• Mu found in pain - regulating areas of the brain.
Contribute to:
• analgesia
• Euphoria
• Respiratory depression
• Physical dependence
• Hypothermic action
• Kappa found in the cerebral cortex and spinal cord
Contribute to:
• Analgesia
• Analgesia
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• Sedation
• And miosis
• Sigma may be responsible for struggling, whining, hallucination and
mydriatic effects.
• Delta modify Mu receptor activity.
* Note: Sequential analgesia: is term introduced to describe the use of partial
agonist subsequent to pure agonists (usually Fentanyl) in an attempt to reverse
residual respiratory depression whilst maintaining analgesia.
Drug: Morphine (Duromorph)
Class: Opioid agonist
MOA: Activates μ opioid receptors in CNS and other organs
DOA: 4 hr.
ROA: (IM, SC, PO)
Effect: Analgesia, sedation, alleviates pulmonary edema by increasing venous
capacitance; provides 10–24 hr of analgesia as far forward as the thoracic limbs
when administered epidurally.
Adverse: Respiratory depression, flatulence, constipation, histamine release with
IV administration; excitement possible in horses and cats
Approved: None
Note: should be used under strict supervision because of its potential for abuse.
Morphine and its substitutes:
1. It has a potent analgesic and sedative action due to depression of the sensory
area of cerebral cortex.
2. It has a potent respiratory depression and hypotension action.
3. It stimulate vomiting center and gastrointestinal tract for that it is
contraindicated in intestinal obstruction.
Contraindications
• Previous history of opioid excitement.
• Morphine has a higher incidence of producing vomiting so should be
avoided in cases of GI obstruction and diaphragmatic hernia.
• Morphine has both excitement and depression effect the final effect depend
on three factors: 1-Species of animal.
2-Dose.
3- Rate of administration
• Excitement occurs if given rapidly IV.
• Horse and cat are particularly susceptible to excitatory effects .
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• Dogs generally show sedation although hypnosis can be seen in higher doses
in sick animals.
• Dogs that are not in pain may show excitement
Excitement symptom: - mydriasis, nausea and convulsion.
Sedation symptom: - miosis, respiratory depression, bradycardia, hypothermia.
• Morphine causes excitement in cat and pig and sheep in horse it may cause
sedation and sometime excitement.
Drug: Meperidine (Demerol; Pethidine):
Class: Opioid agonist
MOA: Activates μ receptors in CNS and other organs
DOA: <2 hr
ROA: (IM, SC)
Effect: Analgesia, sedation, increases venous capacitance
Adverse: Respiratory depression, flatulence, constipation, bradycardia, can cause
histamine release with rapid IV injection, excitement possible in cats, horses
Approved: None
Notes:
 It also may be combined with a tranquilizer for use as an anesthetic agent
(neuroleptanalgesic).
 Naloxone is the preferred antagonist.
Drug: Oxymorphone (Numorphan):
Class: Opioid agonist
MOA: Activates μ receptors
DOA: 2–6 hr
ROA: (IV, IM, SC)
Effect: Analgesia, sedation
Adverse: Respiratory depression, bradycardia, excitement in some species
Approved: Dogs, cats.
Notes
 It is approximately 10 times more potent analgesic than Morphine.
 This drug used primarily in dogs for restraint, for diagnostic procedures, and
for minor surgical procedures.
 It may be combined with a tranquilizer for use as an anesthetic agent
(neuroleptanalgesic.
 Naloxone is the antagonist.
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Drug: Butorphanol (Torbugesic; Torbutrol):
Class: Opioid agonist/antagonist
MOA: Activates (k) and blocks (μ) opioid receptors in brain and spinal cord
DOA: 1–2 hr
ROA: (IV, IM, SC, PO)
Effect: Analgesia, sedation
Adverse: Respiratory depression (less than with pure opioids), bradycardia,
flatulence, defecation, hypothermia
Approved: Horses, dogs.
Notes:
 Torbugesic is approved for treatment of the pain associated with colic in
horses.
 It is also used in combination with other sedative / tranquilizer in horses,
dogs, and cats as a preanesthetic for minor surgical procedure.
Drug: Fentanyl (Sublimaze)
Class: Opioid agonist
MOA: Activates μ opioid receptors
DOA: <1 hr;
ROA: used as constant rate infusion (IV) or transdermal patch
Effect: Analgesia, sedation, 75–125 times as potent as morphine
Adverse: Respiratory depression, bradycardia, excitement in some species
Approved: None.
Note:
 Fentanyl transdermal patches are sometimes used in animals to control sever
pain.
Hydrocodone bitartrate (Hycodan, Tussigon): it is an opioid agonist; it is used
as antitussive agents in dogs.
Drug: Etorphine (M-99)
Class: Opioid agonist
MOA: Activates μ opioid receptors
DOA: <2 hr
ROA: (IV, IM)
Effect: Sedation, analgesia, immobilization, 80–1,000 times as potent as morphine
Adverse: Profound respiratory depression, bradycardia, hypertension
Approved: Animal use only: exotic animal immobilization.
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Notes:
 It is an opioid that produces analgesic effects 1000 times those of morphine.
 It is restricted to use by veterinarians in zoo or exotic animal practice.
 It is lethal to people accidently inject themselves (it is also can be absorbed
through intact skin) if the antagonist (Diprenorphine) is not administered
immediately.
Drug: Pentazocine (Talwin)
Class: Opioid agonist/antagonist
MOA: Activates (k) and blocks (μ) opioid receptors in brain and spinal cord: low
potency
DOA: <2 hr
ROA: (IM, SC)
Effect: Analgesia, sedation; 0.1–0.3 times potency of morphine
Adverse: Respiratory depression (less than with pure opioids), bradycardia,
flatulence, defecation, hypothermia
Approved: Horses, dogs.
Diphenoxylate (Lomotil): Synthetic opioid agonist combined with atropine for
use as an antidiarrheal agent.
Apomorphine - generic Labeling: it is an opioid with the principle effect of
inducing vomiting by stimulating the chemoreceptor trigger zone in the brain. This
drug is often administered by placing a portion of a tablet in the conjunctival sac
for absorption.
Methadone (Dolophine): it is a synthetic opioid that was developed as a treatment
for Morphine and Heroin addiction in humans. It is primarily use in veterinary
medicine is in the treatment of colic pain in horses.
Codeine - generic labeling or in combination: it is an opioid that is available in
humans - label products for use as an antitussive in dogs.
Drug: Carfentanil (Wildnil) (requires DEA special user’s permit)
Class: Opioid agonist
MOA: Activates opioid μ receptors
DOA: Prolonged if not reversed
ROA: (IM)
Effect: Analgesia, sedation, immobilization
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Adverse: Hypoventilation, excitement (some species), hypothermia, muscle
fasciculations
Approved: Animal use only, reserved for use in immobilization of wildlife and
exotic species
Note:
 Carfentanil (Wildnil) is used to induce wildlife anesthesia. It has 10.000
times the potency of Morphine.
Drug: Buprenorphine (Buprenex; Temgesic; Vetergesic)
Class: Opioid partial agonist
MOA: Activates opioid receptors in brain and spinal cord
DOA: 6–12 hr
ROA: (IV, IM, SC)
Effect: Analgesia; minimal sedation
Adverse: Respiratory depression (less than with pure opioid agonists), bradycardia,
flatulence, defecation, hypothermia; may be more difficult to reverse due to high
receptor affinity
Approved: None
Drug: Alfentanil (Alfenta; Rapifen)
Class: Opioid agonist
MOA: Activates μ opioid receptors
DOA: <30 minutes; used as constant rate infusion;
ROA :( IV)
Effect: Analgesia, sedation
Adverse: Respiratory depression, bradycardia, excitement in some species
Approved: None; rarely used in veterinary medicine
Drug: Diprenorphine (Revivon, M50-50)
Class: Opioid agonist/antagonist
MOA: Blocks opioid receptors
DOA: Short (renarcotization following reversal of potent opioids has been
reported);
ROA: (IV, IM).
Effect: Used to antagonize etorphine
Adverse: Opioid sedation and respiratory depression may persist with overdose
Approved: Animal use only, for reversal of etorphine in wildlife and exotic species
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Opioid antagonist
Are used to antagonize the effect of opioid agonist.
Drug: Naloxone (Narcan)
Class: Opioid antagonist
MOA: Antagonizes all opioid receptors
DOA: 30–45 min
ROA: (IV, IM, SC)
Effect: Reverses the effects of opioid agonists, including respiratory depression and
analgesia; has been used in the treatment of hemorrhagic shock
Adverse: Stimulates sympathetic nervous system: potential for cardiac arrhythmias
Approved: None
Drug: Nalbuphine (Nubain)
Class: Opioid agonist/antagonist
MOA: Antagonizes μ receptor, activates kappa receptors
DOA: 2–3 hr
ROA: (IV, IM, SC)
Effect: Analgesia, sedation
Adverse: Minimal respiratory depression
Approved: None
Drug: Nalmefene (Revex)
Class: Opioid antagonist
MOA: Antagonizes all opioid receptors
DOA: Longer acting than naloxone
ROA: (IV, IM, SC)
Effect: Reverses effects of opioid agonists, including respiratory depression and
analgesia
Adverse: Stimulates sympathetic nervous system; potential for cardiac arrhythmias
Approved: None
Drug: Naltrexone (Trexonil)
Class: Opioid antagonist
MOA: Antagonizes all opioid receptors
DOA: Longer acting than naloxone
ROA: (IV, IM,SC)
Effect: Reverses the effects of opioid agonists, including respiratory depression and
analgesia; available as an oral preparation for humans.
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Adverse: Stimulates sympathetic nervous system: potential for cardiac arrhythmias
Approved: Used for reversal of carfentanil in exotic species.
Sedative drugs and adrenergic agonist.
Sedative is defined as a drug, which relieves anxiety and as a result tends to
make it easier for the patient to rest or sleep – in fact, they are usually associated
with drowsiness. Many drugs fall into the sedative and the hypnotic categories, the
differentiation usually being related to dose.
They are best considered as one group, exemplified by chloral hydrate or xylazine
where low doses cause drowsiness and higher doses cause sleep. So sedation mean
calming due to mild degree of depression of central nervous system and most
sedative cause drowsiness.
So sedative and anxiolytic premedication decrease anxiety, fear and stimulation of
CNS, so it is useful to decrease the dose of anesthetic agents they include:
1-Phenothiazine
(Aceprmazine)
(Proponylpromazine)
(Promethazine)
(Chlorpromazine).
2- Butyrophenones (Tranquilizers, anti-emetic).
3- Azaperon (in horses).
4- Benzodiazepines
5- α2 adrenoreceptor agonists: Xylazine, Clonidine, Detomidine, Medetomine and
romifidine.
Neuroleptanalgesics
Any combination of an analgesic and a tranquilizer
(i.e. oxymorphone and acepromazine) ( Acepromazine + Fentanyl)
(Droperidol + fentanyl)
Or combination between
Sedative + Narcotic analgesic
Like
(Xylazine + Morphine)
(Xylazine + Butorphenol)
So:
1- Fentanyl and Droperidol
2- Acepromazine and Morphine
Acepromazine and Oxymorphone
Acepromazine and Butorphanol
(Innovar - vet): the only commercially
available Neuroleptanalgesic
may be prepared by a clinician
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Clinical uses:
They are used for:
 Sedation :Heavier sedation (depending on dose) for short procedures (i.e.
wound suturing, porcupine quill removal)
 Cardiac or shock cases
 Restraint
 And to produce anesthesia.
Adverse side effects: these can include:
 Panting (May hyperventilate, or pant a lot )
 Flatulence
 Animal may defecate or vomit
 Personality changes
 Increased sound sensitivity (Animal may become hyperactive to auditory
stimuli)
 And bradycardia
 Over dose may cause severe depression of CNS, Respiratory system and
cardiovascular system.
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Adjunct to anesthesia: Muscle Relaxants
Muscle relaxant: The drugs which causes relaxation of voluntary muscles by
acting on the neuromuscular junction or spinal cord.
Indication: 1. To produce good muscle relaxation during surgical operation i.e. orthopedics
or deep abdominal surgery.
2. To facilitate end tracheal intubations.
3. To facilitate ventilation in thoracic surgery.
4. To facilitate correction of dislocated joint.
5. To decrease the doses of general anesthesia.
Contraindication: 1. In animal with respiratory, liver or kidney diseases.
2. In animals suffering from glaucoma.
3. In animals, being recently (30 days) treated with any antibiotics the name
which ends in mycin or with organophosphorus compound because these
drugs increase the intensity of paralysis and prolong the recovery period.
4. Muscle relaxant drug should not be used without general anesthesia.
Release of acetylcholine from neurons at the neuromuscular junction
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Mechanism of skeletal muscle relaxation evoked by interference with normal
peripheral neuromuscular function:
1. At presynaptic sites
A. Inhibition of ACh synthesis (e.g hemicholinium blocks choline uptake)
B. Inhibition of Ach release
1. CA++ deficiency, Mg++ increases
2. Procaine
3. Tetracycline and aminoglycoside antibiotics.
4. Some ᵦ - blockers.
5. Botulinum toxin
2. At posynaptic sites
A. Persistent depolarization with an agonist that has a longer duration of action
than ACh (e.g., succinylcholine chloride).
B. Competitive block of ACh receptors causing non-depolarizing blockade (e.g.,
curare, pancuronium).
Types of neuromuscular blocks
I. Phase I block: depolarizing block (succinylcholine).
II. Phase II block: nondepolarizing block (pancuronium)
III. Mixed block: any combination of II and I.
IV. Dual block: excessive amounts of depolarizing agents producing phase II
block.
V. Nonacetylcholine block (procaine, botulinum, decreased Ca++, increased Mg++,
decreased K+).
Sequence of muscle of muscle relaxation
1- Oculomotor m.
Palpebral m.
Fascial m.
Tongue
and
pharynx
jaw and tail
limbs
pelvic m.
Caudal
abdominal m.
Cranial abdominal m.
Intercostal m.
Larynx
diaphragm
A. The sequence of motor blockade is highly variable in clinical patients.
B. Motor activity to the limbs may appear to return (twitching, jerking) before
the diaphragm is fully functional.
2. Intercostal and diaphragmatic muscles are thought to be affected last.
3. Recovery is generally in the reverse order of paralysis.
4. It is possible but difficult to titrate the specific neuromuscular blocking drugs
(NMBDs) to paralyze the muscles of the eye while maintaining diaphragmatic
function.
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Specific neuromuscular blocking drugs (NMBDs)
I. Depolarizing drug act like ACh
A. Succinylcholine chloride (Sucostrin, Anectine, Quillicine, suxamethonium)
II. Nondepolarizing drugs; competitive blocking drugs
A. D-Tubocurarine chloride (curare, Metubine)
B. Gallamine triethiodide (Flaxedil)
C. Pancuronium bromide (Pavulon)
D. Vecuronium bromide (Norcuron)
E. Atracurium besylate (Tracrium)
F. Mivacurium chloride (Mivacron)
G. Doxacurium chloride (Nuromax)
H. Pipecuronium (Arduran).
Drug: Guaifenesin (Guailaxin; Glycerol guaiacolate)
Class: Central-acting muscle relaxant
MOA: Depresses internuncial neuron transmission; central-acting muscle relaxant
DOA: Dose dependent; 30 min
ROA: (IV)
Effect: Muscle relaxation, sedation
Adverse: Very safe although overdose can occur, which manifests as forelimb
rigidity followed by respiratory paralysis
Approved: Horses
Note:
 Internuncial neuron: a connecting neuron in a neural pathway, usually
serving as a link between two other neurons.
Drug: Succinylcholine (Anectine; Sucostrin; Scoline)
Class: Depolarizing noncompetitive neuromuscular blocker
MOA: Depolarizes nicotinic receptors on muscle motor end plate and prevents
neuromuscular transmission.
DOA: <15 min;
ROA: (IV)
Effect: Nonreversible (short-duration) skeletal muscle paralysis
Adverse: Respiratory paralysis (necessary equipment to provide mechanical
ventilation should be available if this drug is used); prolonged effect with hepatic
compromising diseases due to dependency on metabolism by the liver-derived
enzyme, pseudocholinesterase; muscle fasciculations; hyperkalemia; known trigger
of malignant hyperthermia
Approved: None
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Drug: Tubocurarine (Curare)
Class: Competitive nondepolarizing neuromuscular blocker
MOA: Competitive blockade of acetylcholine receptors of neuromuscular junction
DOA: <30 min
ROA: (IV)
Effect: Reversible skeletal muscle relaxation
Adverse: Respiratory paralysis (must control respiration), causes histamine release
that results in hypotension and bronchoconstriction
Approved: None
Drug: Gallamine (Flaxedil): currently not available commercially
Class: Nondepolarizing neuromuscular blocker
MOA: Competitive blockade of acetylcholine receptors of neuromuscular junction;
prevents muscle contraction
DOA: <30 min
ROA: (IV)
Effect: Reversible skeletal muscle relaxation
Adverse: Respiratory paralysis, tachycardia, hypertension
Approved: None (has been used in reptiles for immobilization)
Drug: Pancuronium (Pavulon)
Class: Competitive nondepolarizing neuromuscular blocker
DOA: 30–45 min
ROA: (IV)
MOA: Competitive blockade of acetylcholine receptors of neuromuscular junction
Effect: Reversible skeletal muscle paralysis
Adverse: Respiratory paralysis (must control ventilation), minimal cardiovascular
effects although may cause transient tachycardia; prolonged effect in renal- and
hepatic-compromised patients
Approved: None
Drug: Vecuronium (Norcuron)
Class: Competitive nondepolarizing neuromuscular blocker
MOA: Competitive blockade of acetylcholine receptors of neuromuscular junction
DOA: <30 min
ROA: (IV)
Effect: Reversible skeletal muscle relaxation
Adverse: Respiratory paralysis (must control respiration), minimal cardiovascular
effects; significant hepatic dysfunction will prolong effect
Approved: None
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Drug: Atracurium (Tracrium**)
Class: Competitive nondepolarizing neuromuscular blocking agent
MOA: Competitive blockade of acetylcholine receptors at neuromuscular junction
DOA: <30 minutes (undergoes Hofmann elimination: spontaneous nonenzymatic
degradation at body pH; also metabolized by esterases)
ROA: (IV)
Effect: Reversible skeletal muscle relaxation
Adverse: Respiratory paralysis (must support respiration), minimal cardiovascular
effects, may cause histamine release
Approved: None
Drug: cis-Atracurium (Nimbex)
Class: Competitive nondepolarizing neuromuscular blocking agent
MOA: Competitive blockade of acetylcholine receptors of neuromuscular junction
DOA: <20–30 min (undergoes Hofmann elimination: spontaneous nonenzymatic
degradation at body pH)
ROA: (IV)
Effect: Reversible skeletal muscle relaxation
Adverse: Respiratory paralysis (must control respiration), minimal cardiovascular
effects
Approved: None
Drug: Neostigmine (Prostigmine; Stiglyn)
Class: Acetylcholinesterase inhibitor
MOA: Inhibits acetylcholinesterase and allows accumulation of ACh, enhances
ACh release, induces repetitive firing of the motor nerve terminal
DOA: Onset of action is 7–10 min; duration of action is relatively short
ROA: (IV)
Effect: Antagonize nondepolarizing neuromuscular blockers to restore
neuromuscular transmission, onset of action is rapid
Adverse: Parasympathetic stimulation including bradycardia, airway constriction,
increased secretions
Approved: None
Drug: Pyridostigmine (Regonol)
Class: Acetylcholinesterase inhibitor
MOA: Inhibit acetylcholinesterase and allow accumulation of ACh, enhance ACh
release, induce repetitive firing of the motor nerve terminal
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DOA: Onset of action is 12–16 min and duration 40% longer than neostigmine and
Edrophonium
ROA: (IV)
Effect: Antagonize nondepolarizing neuromuscular blockers to restore
neuromuscular transmission
Adverse: Parasympathetic stimulation, including bradycardia, airway constriction,
increased secretions
Approved: None
Drug: Edrophonium (Tensilon)
Class: Acetylcholinesterase inhibitor
MOA: Inhibits acetylcholinesterase and allows accumulation of ACh, enhances
ACh release, induces repetitive firing of the motor nerve terminal
DOA: Onset of action is rapid (1–2 min); duration relatively short
ROA: (IV)
Effect: Antagonize nondepolarizing neuromuscular blockers to restore
neuromuscular transmission
Adverse: Parasympathetic stimulation: bradycardia, airway constriction, increased
secretions
Approved: None
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