P20: Neuroleptanalgesics & Opioids

What are sedatives?

induce sedation by reducing irritability or excitement

Why are sedatives used?

relax animals for procedures such as trimming nails, taking x-rays, drawing blood, pre-medication

How are sedatives administered?

IM, IV

Neuroleptanaglgesia

state of sedation and pain control induced for medical procedure by a combination of opioid analgesics and neuroleptics

Neuroleptanaesthesia

general anaesthesia induced by the intravenous administration of neuroleptic drugs in combination with inhalation of a weak anaesthetic

What are groups are sedatives divided into?

phenothiazines, α2-adrenergic agonists, benzodiazepines, butyrophenones, Rauwolfia alkaloids

What are examples of phenothiazines?

acepromazine, chlorpromazine, promazine

What are examples of α2-adrenergic agonists?

xylazine, detomidin, medetomidin, dexmedetomidin, romifidin

What are examples of benzodiazepines?

diazepam, zolazepam, midazolam, clonazepam

What are examples of butyrophenones?

azaperone, droperidol, haloperidol, fluanisone

What are examples of Rauwolfia alkaloids?

reserpine, metoserpate

Which regions does chlorpromazine affect?

subcortical regions

What must be used in combination with chlorpromazine if used at surgical operations, and why?

local anaesthetic; chlorpromazine has no analgesic effect

What effects does chlorpromazine have?

myorelaxation, parasympathetic, adrenolytic, antihistaminic, antiemetic

Which drug has chlorpromazine been largely replaced with?

acepromazine

Why is chlorpromazine mainly used in small animals?

inhibits apomorphine-induced emesis in dogs (not cats); inhibits emetic effect of morphine dogs (not cats)

What effects does acepromazine have?

antianxiety, CNS depression, drop in heart rate and blood pressure

What is oral acepromazine used for?

anti-motion sickness; sedation for office visits, nail trimming or grooming

What drug is acepromazine used with as a pre-medication?

atropine

Which breeds of dog are sensitive to acepromazine?

giant breeds, greyhounds

What does the dose of sedalin (acepromazine) depend on?

degree of sedation

What is sedalin (acepromazine) used for?

premedication, tranquilising, symptomatic treatment of stress, spontaneous vomiting

What is xylazine classified as?

α2 adrenergic agonist sedative/analgesic with muscle relaxant properties

Which species are sensitive to xylazine?

ruminants

Which animals does xylazine have a strong emetic effect?

carnivores

Which drugs are used with xylazine for neuroleptanaesthesia?

atropine (prem-med), (xylazine IM), ketamine

What is detomidine classed as?

sedative with analgesic properties

What is detomidine used for?

handling for examination, minor surgical procedures, manipulations

What drug can detomidine be used with or without?

butorphanol

What does butorphanol do when used with detomidine?

increases analgesic effect

What is medetomidine classed as?

sedative with analgesic

What is medetomidine used for?

sedation, premedication, general anaesthetic

What drugs are used with medetomidine to induce general anaesthesia?

butorphanol and ketamine

What is dexmedetomidine classed as?

sedative and analgesic

Which animals is dexmedetomidine used on?

small animals (cats and dogs)

What procedures is dexmedetomidine used for?

clinical examinations, clinical procedures, minor surgical procedures, minor dental procedures, preanaesthetic

What are benzodiazepines used for?

minor tranquilisers, anxiolytic, anaesthesia, premedication, sedation, anticonvulsants

What class of drugs are butyrophenones similar to?

phenothiazines

What effects does azaperone have?

tranquilisation, sedation, anti-emetic, reduces motor activity

What is azaperone used for?

control of aggressiveness in swine

What drugs are used with azaperone for anaesthesia?

xylazine, tiletamine, zolazepam

When are neuroleptic antagonists used?

overdose; cancel effects of neuroleptics

What drug is used as an antagonist for α2 adrenergic antagonists?

atipamezole

Which drugs is atipamezole used to counteract?

dexmedetomidine, medetomidine

What are anaglesics?

supress the sense of pain by affecting the corresponding parts of the CNS (hypothalamus, thalamus, brain cortex)

What are the groups of analgesics?

opioids, non-opioids

What are examples of opioid analgesics?

morphine, codeine, heroine, pethidine, methadone, thiamorphine, and its synthetic compounds

What are opioid analgesics commonly used in veterinary medicine, and why?

etorphine, fentanyl; possess stronger analgesic action

What activities do non-opioid analgesics have?

antipyretic, analgesic

What are examples of non-opioid analgesics?

acetyl-salicylate, salicylate, phenylbutazone, ibuprofen, flunixin, meloxicam

What substances can be obtained from opium?

morphine, codeine, papaverine, thebaine, noscapine

What non-narcotic alkaloids can be obtained from opium?

papaverine, thebaine, noscapine

What can opium alkaloids be derivatives of?

phenanthrene, isoquinoline

What are examples of phenanthrene derivatives?

morphine, codeine, thebaine

What are examples of isoquinoline derivatives?

papaverine, noscapine, narcetine

What are the primary pharmacologic effects of morphine?

analgesia, antitussive, respiratory depression, sedation, emesis, physical dependence, intestinal effects

What are the secondary pharmacologic effects of morphine?

CNS: euphoria, sedation, confusion;
cardiovascular: bradycardia due to central vagal stimulation, alpha-adrenergic receptors may be depressed resulting in peripheral vasodilation;
urinary: increased bladder sphincter tone can induce urinary retention

Which drug is the standard against which strong analgesic drugs are compared?

morphine

Which species may develop excitement after morphine injections?

horses, cattle, swine, cats

Which species may defecate after morphine?

dogs

Which species may develop miosis after morphine?

dogs, humans

Which species may develop mydriasis after morphine?

cats and other species

Which species does morphine increase reflex irritability of the spinal cord?

mice

What is Straub's phenomenon?

when morphine increases reflex ability of the spinal cord resulting in typical spasms of the tail muscles even at extremely small doses; demonstrated by the vertical S-curved erection of the mouse tail

What centre does morphine have an affinity for?

respiratory centre

What effect does morphine have on the respiratory centre?

decrease excitability (dyspnoea, cough)

What are examples of analgesic opiates (other than morphine)?

hydromorphone, oxymorphone, codeine, fentanyl, sufentanil, alfentanil, remifentanil, buprenorphine, butorphanol, pentrazocine

Describe hydromorphone

morphine derivative with similar duration of effect;
produces less emetic effect than morphine, but emesis and nausea occur frequently

Describe oxymorphone

morphine derivative with 10 times the potency;
produces less emesis, nausea, and sedation than morphine and hydromorphone on cats and dogs;
causes less histamine release in dogs

Describe codeine

naturally occurring alkaloid with similar structure to morphine;
antitussive drug;
weak analgesic for mild pain;
rarely used in veterinary medicine

Describe fentanyl

synthetic opioid;
very potent opiate agonist (IV, transdermal);
transdermal patches used in dogs and cats;
used for adjunctive control of postoperative care;
parenteral solution contains droperidol (butryphenon[sedative]) induces considerable neuroleptanalgesia

What do sufentanil, alfentanil, and remifentanil have in common?

fentanyl derivatives that exhibit similar pharmacodynamic effects

Compare sufentanil to fentanyl

5-7 times more potent; eliminated in a metabolically similar way

Compare alfentanil to fentanyl

less potent; eliminated in a metabolically similar way

Describe remifentanil

undergoes non-hepatic metabolism (muscle and intestinal) resulting in short half-life (30 mins) and rapid clearance in dogs

Describe buprenorphine

synthetic, partial opiate agonist;
30 times as potent as morphine;
produces dose-related analgesia;
exhibits many of the same actions as opiate agonists

Describe butorphanol

synthetic partial opiate agonist;
related structurally to morphine but exhibits pharmacologic actions similar to other partial agonists;
more potent than morphine, pentazocine, meperidine;
antitussive

Describe pentazocine

similar pharmacologic effects as butorphanol;
effective for mild to moderate pain with 1-3 hour effect;
less sedation compared to other opioids;
can cause excitement and tremors at high doses