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)
