Opioids

Question 1

what are the therapeutic uses of opioids in animals?

Answer 1

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

Question 2

what is opium composed of?

Answer 2

many alkaloids
morphine
codeine
papaverine
thebaine

Question 3

what are endogenous opioids?

Answer 3

naturally occurring opioid peptides that interact with opioid receptors

Question 4

what are the endogenous opioids?

Answer 4

Leu-enkephalin
Met-enkephalin
dynorphin A
beta-Endorphin

Question 5

what are the opioid receptors?

Answer 5

Mu: Mu1 and Mu2
Delta: delta 1 and delta 2
Kappa: K1, K2, K3

Question 6

what are the receptor actions of the delta opioid receptor?

Answer 6

analgesia (spinal and supraspinal)
increase appetite
immunomodulation

Question 7

what are the receptor actions of the kappa opioid receptor?

Answer 7

analgesia
decrease gastrointestinal motility and secretions
increase appetite
sedation
diuresis
miosis/mydriasis
nausea/vomiting or antiemetic

Question 8

what is an agonist in opioids?

Answer 8

a chemical that binds to the receptor and activates it

Question 9

what is a mixed agonist/antagonist in opioids?

Answer 9

depends on the conditions: can be either agonist or antagonist

Question 10

what is an antagonist in opioids?

Answer 10

binds to the receptor to block or dampen a biological response

Question 11

what are some opioid agonists?

Answer 11

morphine
codeine
etorphine
methadone

Question 12

what are some opioid mixed agonists/antagonists?

Answer 12

buprenorphine
butorphanol

Question 13

what are some opioid antagonists?

Answer 13

naloxone
naltrexone

Question 14

where do opioid agonists have effects?

Answer 14

CNS and peripheral

Question 15

what are the CNS effects of morphine (and most opioid agonists)?

Answer 15

analgesia
sedation/excitation
respiratory suppression
cough suppression
nausea/vomiting
convulsions
thermoregulatory changes

Question 16

how do opioids exert their primary analgesic effects?

Answer 16

bind to spinal and supraspinal receptors

Question 17

what is the mechanism for spinal analgesia with opioids?

Answer 17

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

Question 18

what opioid receptors are in the dorsal horn and dorsal root ganglion?

Answer 18

presynaptic mu, delta, and kappa in dorsal horn
postsynaptic mu in dorsal root ganglion

Question 19

how does supraspinal opioid analgesia work?

Answer 19

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)

Question 20

what fibers are impacted by systemic opioid administration?

Answer 20

pain transmission neurons, primarily C fibers: dull aching pain
A delta fibers are minimally affected

Question 21

what fibers do epidural opioids impact?

Answer 21

both C and A delta fibers

Question 22

what species experience excitement with opioids?

Answer 22

horses
pigs
cats

Question 23

what species experience sedation with opioids?

Answer 23

human
primates
dogs

Question 24

what mediates respiratory depression with opioids?

Answer 24

mu receptor
dose dependent

Question 25

why does respiratory depression occur with opioids and is it worrisome?

Answer 25

decreased response to increases in carbon dioxide partial pressures well tolerated in healthy animals, monitor with concurrent anesthesia or other respiratory depressing agents

Question 26

what does the respiratory depression with opioids cause?

Answer 26

cerebral vasodilation increased intracranial pressure bronchoconstriction in dogs

Question 27

in what cases are opioids contraindicated?

Answer 27

head injury emphysema asthma bronchitis

Question 28

what species is especially sensitive to opioids causing vomiting?

Answer 28

dogs

Question 29

how does morphine impact vomiting?

Answer 29

stimulates chemoreceptor trigger zone

Question 30

high doses of morphine produce _____________ while very high doses can produce ______________

Answer 30

excitement convulsions

Question 31

what species are prone to excitement with morphine?

Answer 31

cats horses other large animals

Question 32

what are the mechanisms for convulsions with morphine?

Answer 32

stimulate pyramidal cell inhibit GABA release by interneuron

Question 33

how do you reverse convulsions from morphine?

Answer 33

naloxone (not anticonvulsants)

Question 34

what species have an increased temperature from morphine?

Answer 34

cats goats horses

Question 35

what species have a decreased temperature from morphine?

Answer 35

dogs monkeys

Question 36

what systems does morphine impact?

Answer 36

cardiovascular gastrointestinal genitourinary eye immune

Question 37

what cardiovascular impacts do opioids have?

Answer 37

most have minimal on cardiac output coronary vasoconstriction, bradycardia minimal vascular effects

Question 38

what gastrointestinal impacts do opioids have?

Answer 38

decreased motility increased intrabiliary pressure: prevents bile from entering duodenum

Question 39

how do opioids produce decreased gastrointestinal motility?

Answer 39

slows gastric emptying decreases fluid secretion increases intestinal fluid absorption reduces propulsive motility increases pyloric and other sphincter tone increases smooth muscle tone

Question 40

how does morphine impact the genitourinary system?

Answer 40

decreases urine output increases urinary retention prolongs labor

Question 41

how does morphine decrease urine output?

Answer 41

increases antidiuretic hormone

Question 42

what does morphine do to the eyes?

Answer 42

miosis (primates) mydriasis (cats, horses) none in dogs

Question 43

how does morphine impact the immune system?

Answer 43

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

Question 44

what is tolerance to opioids dependent on?

Answer 44

length of use dose frequency of administration

Question 45

what is the pharmacokinetics of morphine?

Answer 45

well absorbed from gastrointestinal tract, subcutaneous, or intramuscular sites high first-pass metabolism: morphine oral bioavailability is 25% polar metabolites/urinary excretion

Question 46

what is the distribution of morphine like?

Answer 46

well distributed bound to plasma proteins lipophilic: weak bases, intracellular accumulation

Question 47

how are opioids metabolized?

Answer 47

metabolized to more polar compounds and excreted in urine or bile

Question 48

what reactions metabolize opioids?

Answer 48

conjugation primarily cytochrome P450

Question 49

what is the primary opioid conjugate in most species?

Answer 49

glucuronide not cats

Question 50

what are the therapeutic applications of opioids?

Answer 50

analgesia preanesthetic medication cough suppression antidiarrheal emetic immobilization of wild animals

Question 51

what are the adverse effects of opioids?

Answer 51

respiratory depression nausea and vomiting constipation tolerance physical dependence/withdrawal

Question 52

what are the precautions of opioids?

Answer 52

hypothyroidism severe renal insufficiency adrenocortical insufficiency

Question 53

what are the contraindications of opioids?

Answer 53

head trauma/increase CSF pressure CNS dysfunction history of seizures strychnine toxicity compromised respiratory functions

Question 54

what is the primary indication for an opioid antagonist?

Answer 54

treatment of opioid agonist overdose

Question 55

is opioid antagonist or agonist longer-acting?

Answer 55

agonist

Question 56

what are the pure opioid antagonists?

Answer 56

naloxone naltrexone diprenorphine

Question 57

what are the therapeutic applications of opioid antagonists?

Answer 57

reversal of opioid agonist effects (respiratory depression, immobilizing side effects) management of stereotypic behavior +/- treatment of shock

Question 58

how does tramadol act?

Answer 58

its metabolite is the active one

Question 59

in what species does tramadol have a higher effect?

Answer 59

cats

Question 60

which receptor mediates respiratory depression?

Answer 60

mu

Question 61

which drugs are antitussive?

Answer 61

codeine dextromorphan