Opioids Flashcards
what are the therapeutic uses of opioids in animals?
analgesia
sedation
calming and euphoria
immobilization and chemical restraint
diarrhea, inhibition of gastrointestinal motility
antitussive (decrease cough)
adjunctive use for general anesthesia
increased locomotor activity
what is opium composed of?
many alkaloids
morphine
codeine
papaverine
thebaine
what are endogenous opioids?
naturally occurring opioid peptides that interact with opioid receptors
what are the endogenous opioids?
Leu-enkephalin
Met-enkephalin
dynorphin A
beta-Endorphin
what are the opioid receptors?
Mu: Mu1 and Mu2
Delta: delta 1 and delta 2
Kappa: K1, K2, K3
what are the receptor actions of the delta opioid receptor?
analgesia (spinal and supraspinal)
increase appetite
immunomodulation
what are the receptor actions of the kappa opioid receptor?
analgesia
decrease gastrointestinal motility and secretions
increase appetite
sedation
diuresis
miosis/mydriasis
nausea/vomiting or antiemetic
what is an agonist in opioids?
a chemical that binds to the receptor and activates it
what is a mixed agonist/antagonist in opioids?
depends on the conditions: can be either agonist or antagonist
what is an antagonist in opioids?
binds to the receptor to block or dampen a biological response
what are some opioid agonists?
morphine
codeine
etorphine
methadone
what are some opioid mixed agonists/antagonists?
buprenorphine
butorphanol
what are some opioid antagonists?
naloxone
naltrexone
where do opioid agonists have effects?
CNS and peripheral
what are the CNS effects of morphine (and most opioid agonists)?
analgesia
sedation/excitation
respiratory suppression
cough suppression
nausea/vomiting
convulsions
thermoregulatory changes
how do opioids exert their primary analgesic effects?
bind to spinal and supraspinal receptors
what is the mechanism for spinal analgesia with opioids?
binds to G protein coupled receptor in the dorsal horn of the spinal cord
inhibits adenylyl cyclase
activates receptor linked potassium channels: hyperpolarizes neuron
inhibits voltage gated calcium channels: decreases excitatory neurotransmitter release
antagonizes substance P
what opioid receptors are in the dorsal horn and dorsal root ganglion?
presynaptic mu, delta, and kappa in dorsal horn
postsynaptic mu in dorsal root ganglion
how does supraspinal opioid analgesia work?
opioid receptors in periaqueductal grey region activate to inhibit GABA interneurons
inhibition activates enkephalin-releasing neurons in medullary pain inhibitory pathways that inhibit dorsal horn nociceptors through release of serotonin
other brain regions have activated opioid receptors, which decrease level of pain perception (decrease anxiety and increase well-being)
what fibers are impacted by systemic opioid administration?
pain transmission neurons, primarily C fibers: dull aching pain
A delta fibers are minimally affected
what fibers do epidural opioids impact?
both C and A delta fibers
what species experience excitement with opioids?
horses
pigs
cats
what species experience sedation with opioids?
human
primates
dogs
what mediates respiratory depression with opioids?
mu receptor
dose dependent
why does respiratory depression occur with opioids and is it worrisome?
decreased response to increases in carbon dioxide partial pressures
well tolerated in healthy animals, monitor with concurrent anesthesia or other respiratory depressing agents
what does the respiratory depression with opioids cause?
cerebral vasodilation
increased intracranial pressure
bronchoconstriction in dogs
in what cases are opioids contraindicated?
head injury
emphysema
asthma
bronchitis
what species is especially sensitive to opioids causing vomiting?
dogs
how does morphine impact vomiting?
stimulates chemoreceptor trigger zone
high doses of morphine produce _____________ while very high doses can produce ______________
excitement
convulsions
what species are prone to excitement with morphine?
cats
horses
other large animals
what are the mechanisms for convulsions with morphine?
stimulate pyramidal cell
inhibit GABA release by interneuron
how do you reverse convulsions from morphine?
naloxone (not anticonvulsants)
what species have an increased temperature from morphine?
cats
goats
horses
what species have a decreased temperature from morphine?
dogs
monkeys
what systems does morphine impact?
cardiovascular
gastrointestinal
genitourinary
eye
immune
what cardiovascular impacts do opioids have?
most have minimal on cardiac output
coronary vasoconstriction, bradycardia
minimal vascular effects
what gastrointestinal impacts do opioids have?
decreased motility
increased intrabiliary pressure: prevents bile from entering duodenum
how do opioids produce decreased gastrointestinal motility?
slows gastric emptying
decreases fluid secretion
increases intestinal fluid absorption
reduces propulsive motility
increases pyloric and other sphincter tone
increases smooth muscle tone
how does morphine impact the genitourinary system?
decreases urine output
increases urinary retention
prolongs labor
how does morphine decrease urine output?
increases antidiuretic hormone
what does morphine do to the eyes?
miosis (primates)
mydriasis (cats, horses)
none in dogs
how does morphine impact the immune system?
complex: depends on dose and drug
direct effect on leukocytes
interaction between immune system, sympathetic nervous system, and HPA axis
both immunosuppressive and stimulatory effects have been observed
what is tolerance to opioids dependent on?
length of use
dose
frequency of administration
what is the pharmacokinetics of morphine?
well absorbed from gastrointestinal tract, subcutaneous, or intramuscular sites
high first-pass metabolism: morphine oral bioavailability is 25%
polar metabolites/urinary excretion
what is the distribution of morphine like?
well distributed
bound to plasma proteins
lipophilic: weak bases, intracellular accumulation
how are opioids metabolized?
metabolized to more polar compounds and excreted in urine or bile
what reactions metabolize opioids?
conjugation primarily
cytochrome P450
what is the primary opioid conjugate in most species?
glucuronide
not cats
what are the therapeutic applications of opioids?
analgesia
preanesthetic medication
cough suppression
antidiarrheal
emetic
immobilization of wild animals
what are the adverse effects of opioids?
respiratory depression
nausea and vomiting
constipation
tolerance
physical dependence/withdrawal
what are the precautions of opioids?
hypothyroidism
severe renal insufficiency
adrenocortical insufficiency
what are the contraindications of opioids?
head trauma/increase CSF pressure
CNS dysfunction
history of seizures
strychnine toxicity
compromised respiratory functions
what is the primary indication for an opioid antagonist?
treatment of opioid agonist overdose
is opioid antagonist or agonist longer-acting?
agonist
what are the pure opioid antagonists?
naloxone
naltrexone
diprenorphine
what are the therapeutic applications of opioid antagonists?
reversal of opioid agonist effects (respiratory depression, immobilizing side effects)
management of stereotypic behavior
+/- treatment of shock
how does tramadol act?
its metabolite is the active one
in what species does tramadol have a higher effect?
cats
which receptor mediates respiratory depression?
mu
which drugs are antitussive?
codeine
dextromorphan
