Opioids Flashcards
Name 7 effects of opioids?
sedation
analgesia
antitussiv
muscle relaxation
control of compulsive behaviour
support or right sided heart function
overresponsiveness to noises or sensory stimuli
Name 2 groups of opioids and their chemical structure?
- Phenanthrenes: morphine
- three-ring nucleus - Benzylisoquinoline derivatives: papaverine
- ring structure with a tertiary amine nitrogen
Levorotatory are much more active agonists than dextrorotary
What is the mechanism of action of opioids?
- bind to stereospecific opioid receptors in CNS + other sites
- Receptor binding activates G proteins as second messengers –> modulates adenylate cyclase activity–> alters transmembrane transport of effectors
- also interfere presynaptically with neurotransmitter release
- receptor affinity correlates well with analgesic potency of pure agonists
These changes result in interruption of the pain message to the brain and a decreased sensation of pain within the brain.
Name 4 opioid receptors in CNS + gut?
- μ-receptor (MOP)
- k-receptor (KOP)
- d-receptor (DOP)
- opiate-like receptor 1 (OLR-1, nociceptin receptor, NOP)
Why can opioids lead to excitatory behaviour?
- results from the effects of the drug on the hypothalamus
- indirect activation of dopaminergic receptors (benzodiazepines and phenothiazines, can block this activation)
How do opioids cause CNS depression?
cerebral cortex
What side effect can arise if opioids are combined with tricyclic antidepressants?
- hypotension.
What side effects can be noted when opioids are combined with monoamine oxidase inhibitors?
- rare but severe and immediate reactions: excitation, rigidity, hypertension, severe respiratory depression
What effects do opioids have on the respiratory system and how are these effects mediated? What patients are of increased risk?
- tachypnea (oxymorphone, hydromorphone)
- respiratory depressants: reduce RR and tidal volume
–> depress pontine and medullary respiratory centers
–> produce a delayed response (altered threshold) and decreased response (altered sensitivity) to arterial CO2 –> retention of CO2 - Bronchoconstriction
- wooden chest
Increased risk:
- critically ill patients
- underlying airway obstruction (e.g., brachycephalic animals) - pulmonary disease
Why can opioid administration cause tachypnea?
- excitation and/or alteration of the thermoregulation center
What cardiovascular effects do opioids cause?
- minimal effects
- vagally mediated bradycardia (responsive to anticholinergics)
- affect ability of vascular system to compensate for positional and blood volume changes
- some (methadone, morphine, meperidine) cause histamine release –> hypotension
How can morphine induced histamine release be minimised?
dilution with saline + given slowly over 10-20 min
Name 2 contraindications for morphine, methadone and meperidine usage and explain why?
- mast cell tumors
- histamine-based diseases
cause histamine release –> hypotension
What effects do opioids have on the GI tract?
initial stimulation (vomiting, defecation) followed by decrease in motility
What effects do opioids have on ADH?
Release of ADH
What effects do opioids have on the urinary tract?
urine retention due to bladder atony
What effects to opioids have on the body temperature and why?
hypothermia + hyperthermia (cats, drug + dosage dependant - buprenorphine did not result in hyperthermia)
thermoregulatory center in the hypothalamus is reset to a lower setting
How are opioids metabolised and excreted?
Matbolisation: hepatic conjugation
Excretion: renal in the urine
Exception: remifentanil - metabolisation through nonspecific plasma esterases
In general: Principal metabolites can be highly active (e.g. morphine)
Why can meperidine cause seizures?
- meperidine’s metabolite normeperidine is a convulsant –> causes neurotoxicity and seizures
What is the pharmacokinetic profile of opioids and how can this change in drug overdose?
- elimination of first order
- Opioid overdoses change kinetics of elimination from first order to zero order by saturating the processes responsible for elimination and thereby greatly prolonging the duration of action
How are potency of opioids measured? What are the potencies of methadone, fentanyl, remifentanyl, buprenorphine, butorphanol, codein, hydromorphone, oxymorphone and meperidine?
- relative potencies of opioids are compared with the potency of morphine on an “equal-analgesic” basis
- pure-agonist opioids: maximum biologic effect (e.g., analgesia or respiratory depression) is relatively dosage-dependent.
methadone: 1
fentanyl: 100-150
remifentanyl: 200-300
buprenorphine: 50-100
butorphanol: 3-5
codeine: 1/10
hydromorphone: 10
oxymorphone: 10
meperidine: 1/5
You choose morphine for an epidural analgesia. What dose would you use and what are your expected pharmacokinetics?
- morphine (0.1 mg/kg)
- onset of action: 30 minutes
- lasting effect: 12 to 24 hours
You want to add a local anaesthetic to your epidural analgesia? What would you choose, what dose would you use and what would be your reasoning behind thi?
- bupivacain: 0.5 mg/kg
- blunting of deleterious postoperative or injury-associated increases in stress hormone levels and the metabolic response to surgery
Name 5 contraindication to epidural injection or catheter placement?
- local infection
- coagulopathy
- neurologic dysfunction
- marked obesity (which increases difficulty)
- hypovolemia with hypotension (avoided unless IVF corrects hypotension)
What are common side effects of morphine?
vomiting, diarrhoea, bradycardia
hypotension + bronchoconstriction (histamine release)
(less common if actually painful)
What is the bioavailability of oral morphine?
- may be effective in some dogs but individual variability in bioavailability
- poorly and erratically absorbed from the GI tract
- –> oral route is not to be recommended
On what receptors does methadone work?
- μ-receptor agonist
- noncompetitive inhibitor of NMDA receptors
What happens if a heat source is applied over a fentanyl patch?
- can greatly increase uptake of the drug (cave: overdose)
What is the onset of analgesia for a fentanyl patch and how long does it last?
- does not occur until 12 to 24 hours after application
- lasts 4 days
What is the difference of long-term fentanyl and remifentanyl infusion and what is the reason for this?
- recovery from fentanyl after long-term CRI is more prolonged than in remifentanil because remifentanil is eliminated by plasma esterases and does not rely on hepatic metabolisation
What is the ceiling effect of butorphanol?
drug reaches a maximum effect and increasing the drug dosage does not increase its effectiveness
Why may butorphanol be of benefit in patients with intracranial hypertension or increased ocular pressure?
- less potential than agonist opioids to cause reflexive increases in intracranial pressure (ICP)
- antitussive effect + less vomiting lead to less increase in ICP
- antiemetic effect
What class of opioids does buprenorphine beolong to?
partial-agonist opioid, with limited agonist activity at μ-receptors
What is the ceiling effect of buprenorphine?
ceiling effect on respiratory depression, but not analgesia, as the dose is increased
Why may buprenorphine be of benefit in patients with intracranial hypertension or increased ocular pressure?
does not stimulate vomiting
Why is analgesic efficacy greater for IV/IM than SC administration of buprenorphine?
slow uptake and resultant low plasma concentration gradient following SC
What is the bioavailability of oral transmucosal buprenorphine in cats and dogs?
50%
What is Simbadol 1.8mg/ml?
- higher concentration buprenorphine injectable
- extended duration (24 hr, repeatable up to 3 days) at doses approximately 10-fold higher than standard doses
What class of opioids does codein belong to?
pure μ-agonist
What is the bioavailability of oral codein in dogs?
- 4% –> very poor bioavailability
Name 3 opioid antagonists and their duration of action?
Name 2 agents useful for partial reversal of pure-agonist opioids? What opioid can be difficult to reverse?
Antagonists:
1. naloxone (very short acting)
2. nalmefene (long-acting)
3. naltrexone (long-acting)
Partial antagonists:
1. butorphano
2. nalbuphine
buprenorphine can be difficult to reverse due to its great receptor affinity
What is the mechanism of action of opioid antagonists?
bind with great affinity to the μ, k, and d opioid receptors, competitively displacing agonists with lesser affinity
What analgesic effects do opioid antagonists have?
- no analgesic activity
- ultra-low doses of naloxone and naltrexone potentiate the antinociception of opioid agonists
In what setting has naloxone been used in research apart from it’s effect as an opioids antagonist?
- treatment of hypovolemic shock in dogs.
- infusion of high doses of naloxone lead to reduction in splanchnic capacitance leading to an improvement in VR, MAP and CO
What effects are reversed by opioid antagonists?
- Sedation
- respiratory depression
- analgesia
