Opioids And Non-opioid Analgesics Flashcards
What are the 4 steps in the pain pathway?
Transduction
Transmission
Modulation
Perception
Which step converts a chemical soup signal into an action potential?
Transduction
What drugs target transduction?
NSAIDS
Local anesthetics
Steroids
Antihistamines
Opioids
What step allows a pain signal to be relayed through the three-neuron afferent pathway along the spinothalamic tract?
Transmission
Where are first order pain neurons?
Periphery to dorsal horn
Where are second order neurons?
Dorsal horn to thalamus
Where are third order neurons?
Thalamus to the cerebral cortex
What drugs target transmission?
Local anesthetics
Which section of the pain pathway allows a signal to be modified (inhibited or augmented)?
Modulation
Where is the most important site of modulation?
Substantia gelatinosa in the dorsal horn (rexed Lamina 2 and 3)
What drugs target modulation?
Neuraxial opioids
NMDA antagonists
Alpha 2 agonists
AchE inhibitors
SSRIs
SNRIs
What aspect of the pain pathway describes the processing of the afferent pain signals ~ how we “feel” about pain?
Perception
What drugs target perception?
Opioids
General anesthetics
Alpha 2 agonists
What are the endogenous ligand for the opioids receptors?
Endorphins = Mu
Enkephalins = Delta
Dynorphins = Kappa
Nociceptin = NOP
How does opioid stimulation affect the presynaptic neuron
Decreased cAMP
Reduces calcium conductance —> reducing neurotransmitter release
How does opioid receptor stimulation affect the post synaptic neuron?
Increase potassium conductance —> hyperpolarizes the cell
What are some aspects about the Mu receptor?
Resp: depression
Cardio: bradycardia
CNS: sedation, euphoria, hypothermia
Pupil: miosis
GU: urinary retention
GI: N/V, decrease peristalsis, and ^ biliary
Pruritus: yes
Antishivering: 0
What are some aspects about the delta receptor?
Resp: depression
Cardio: 0
CNS: 0
Pupil: 0
GU: urinary retention
GI: 0
Pruritus: yes
Antishivering: 0
What are some aspects about the kappa receptor?
Resp: depression??
Cardio: 0
CNS: sedation, dysphoria, hallucinations
Pupil: miosis
GU: 0
Pruritus: 0
Antishivering: yes
What do opioids do to the CO2 response curve?
Right —> this reduces ventilatory response to CO2
Reduces RR increase TV
What aspect of the pupil do opioids stimulate?
Edinger Westphal nucleus —> pupil constriction
How do opioids affect biliary pressure? How do you relieve this?
Contraction of the sphincter of Oddi —> increases biliary pressure
Tx: glucagon and naloxone
What are naturally occurring opioids?
Phenantherene derivatives:
Morphine
Codiene
What are some semisynthetic opioids?
Morphine derivatives:
Hydromorphone, heroin, naloxone, naltrexone
Thebaine derivatives: oxycodone
What are some synthetic opioids?
Piperidines: meperidine
Phenylpiperidines: fent, sufentanil, Remi, alfentanil
Diphenylpropylamines: methadone
What is the relative potency for all the opioids? And their potency compared to 10 mg morphine
Sufentanil (1000) > Fentanyl (100) > Remifentanil (100) > alfentanil (10) > hydromorphone (7) > Morphine (standard) > meperidine (0.1)
What occurs when a person taking a drug goes through withdrawals upon discontinuation?
Dependence
What occurs when a patient requires higher doses of a drug to achieve a given effect?
Tolerance
What occurs when tolerance to one drug produces tolerance to another drug that has similar effects?
Cross-tolerance
What is considered a disease state where a person cannot stop using a drug despite negative consequences?
Addiction
What are the two exceptions to tolerance?
Miosis
Constipation
What would be the peak hours of withdrawal for a patient addicted to fent/meperidine?
6-12 hours
What would be the peak hours of withdrawal for a patient addicted to morphine/heroin?
36-72 hrs
What would be the peak hours of withdrawal for a patient addicted to methdone?
3-21 days
Which opioids have an active metabolite?
Morphine (morphine-3-glucuronide) AND (morphine-6-glucuronide)
Meperidine (normeperidine)
Why is normeperidine so bad?
Reduces seizure threshold
Increase CNS excitability
Avoid in renal patients and Elderly
What is Remifentanil dosed at?
Lean body weight.
What drugs must you avoid with Meperidine for risk of serotonin syndrome?
Demerol is a weak serotonin reuptake inhibitor
Avoid in MOAS (phenelzine, isocarboxazid, tranylcypromine)
Why does Meperidine exhibit anticholinergic effects?
Structurally related to atropine (has atropine-like ring)
Tachycardia, mydriasis, dry mouth
Which opioid has the fastest onset of action?
Alfentanil
This is due to its low pKa (more of the drug is in an unionized form)
What type of procedures is alfentanil beneficial in?
Tracheal intubation
Retrobulbar block
What is the maintenance infusion of Remifentanil?
0.1-1.0 mcg/kg/min
What can Remifentanil cause following discontinuation?
Hyperalgesia
This can be attenuated by ketamine and magnesium
What are the three MOAs of methadone?
Mu agonism
NMDA antagonism
MOA reuptake inhibition
How does methdone affect the heart?
It can increase QT interval ~ this can lead to Torsades
What is Oliceridine?
IV opioid analgesic that primary selects Mu receptor. Indicated for adults with acute pain or where alternative treatments fail
Loading dose: 1-2 mg
Supplemental doses: 1-3 mg q 1-3 hours
*** should not be used in patients with acute or severe asthma in an unmonitored setting
What can rapid administration of opioids cause?
Skeletal muscle rigidity
More common with sufentanil, fentanyl, Remi, and alfentanil
What is the treatment for opioid-induced skeletal rigidity
Paralysis and intubation
Also naloxone, but nobody wants that. Haha
What are some complications of stiff chest?
Resp: (hypoxia, hypercapnia, ^ O2 consumption, decrease compliance, decreases FRC)
Card: ^ CVP, PAP, PVR
What are some partial opioid agonists?
Buprenorphine (high affinity Mu agonist)
Nalbuphine (kappa agonist, Mu antagonist)
Butorphanol (kappa agonist, Mu antagonist ~ weak)
What is the dose for Nalxone?
Dose: 1-4 mcg/kg ~ try 20 to 40 mcg at a time
Duration: 30-45 mins (** it may be necessary to repeat dose)
Metabolism: liver
Which opiate reversal agent doesn’t cross the BBB thus making it beneficial for opioid induced bowel dysfunction?
Methylnaltrexone
What is considered the “gold standard” for postoperative opioid delivery?
IV PCA
What are the programmable components to IV PCA
Initial loading dose
Demand dose
Lockout interval
Basal infusion rate
