Opioids And Non-opioid Analgesics

Question 1

What are the 4 steps in the pain pathway?

Answer 1

Transduction
Transmission
Modulation
Perception

Question 2

Which step converts a chemical soup signal into an action potential?

Answer 2

Transduction

Question 3

What drugs target transduction?

Answer 3

NSAIDS
Local anesthetics
Steroids
Antihistamines
Opioids

Question 4

What step allows a pain signal to be relayed through the three-neuron afferent pathway along the spinothalamic tract?

Answer 4

Transmission

Question 5

Where are first order pain neurons?

Answer 5

Periphery to dorsal horn

Question 6

Where are second order neurons?

Answer 6

Dorsal horn to thalamus

Question 7

Where are third order neurons?

Answer 7

Thalamus to the cerebral cortex

Question 8

What drugs target transmission?

Answer 8

Local anesthetics

Question 9

Which section of the pain pathway allows a signal to be modified (inhibited or augmented)?

Answer 9

Modulation

Question 10

Where is the most important site of modulation?

Answer 10

Substantia gelatinosa in the dorsal horn (rexed Lamina 2 and 3)

Question 11

What drugs target modulation?

Answer 11

Neuraxial opioids
NMDA antagonists
Alpha 2 agonists
AchE inhibitors
SSRIs
SNRIs

Question 12

What aspect of the pain pathway describes the processing of the afferent pain signals ~ how we “feel” about pain?

Answer 12

Perception

Question 13

What drugs target perception?

Answer 13

Opioids
General anesthetics
Alpha 2 agonists

Question 14

What are the endogenous ligand for the opioids receptors?

Answer 14

Endorphins = Mu
Enkephalins = Delta
Dynorphins = Kappa
Nociceptin = NOP

Question 15

How does opioid stimulation affect the presynaptic neuron

Answer 15

Decreased cAMP
Reduces calcium conductance —> reducing neurotransmitter release

Question 16

How does opioid receptor stimulation affect the post synaptic neuron?

Answer 16

Increase potassium conductance —> hyperpolarizes the cell

Question 17

What are some aspects about the Mu receptor?

Answer 17

Resp: depression
Cardio: bradycardia
CNS: sedation, euphoria, hypothermia
Pupil: miosis
GU: urinary retention
GI: N/V, decrease peristalsis, and ^ biliary
Pruritus: yes
Antishivering: 0

Question 18

What are some aspects about the delta receptor?

Answer 18

Resp: depression
Cardio: 0
CNS: 0
Pupil: 0
GU: urinary retention
GI: 0
Pruritus: yes
Antishivering: 0

Question 19

What are some aspects about the kappa receptor?

Answer 19

Resp: depression??
Cardio: 0
CNS: sedation, dysphoria, hallucinations
Pupil: miosis
GU: 0
Pruritus: 0
Antishivering: yes

Question 20

What do opioids do to the CO2 response curve?

Answer 20

Right —> this reduces ventilatory response to CO2

Reduces RR increase TV

Question 21

What aspect of the pupil do opioids stimulate?

Answer 21

Edinger Westphal nucleus —> pupil constriction

Question 22

How do opioids affect biliary pressure? How do you relieve this?

Answer 22

Contraction of the sphincter of Oddi —> increases biliary pressure

Tx: glucagon and naloxone

Question 23

What are naturally occurring opioids?

Answer 23

Phenantherene derivatives:

Morphine
Codiene

Question 24

What are some semisynthetic opioids?

Answer 24

Morphine derivatives:

Hydromorphone, heroin, naloxone, naltrexone

Thebaine derivatives: oxycodone

Question 25

What are some synthetic opioids?

Answer 25

Piperidines: meperidine Phenylpiperidines: fent, sufentanil, Remi, alfentanil Diphenylpropylamines: methadone

Question 26

What is the relative potency for all the opioids? And their potency compared to 10 mg morphine

Answer 26

Sufentanil (1000) > Fentanyl (100) > Remifentanil (100) > alfentanil (10) > hydromorphone (7) > Morphine (standard) > meperidine (0.1)

Question 27

What occurs when a person taking a drug goes through withdrawals upon discontinuation?

Answer 27

Dependence

Question 28

What occurs when a patient requires higher doses of a drug to achieve a given effect?

Answer 28

Tolerance

Question 29

What occurs when tolerance to one drug produces tolerance to another drug that has similar effects?

Answer 29

Cross-tolerance

Question 30

What is considered a disease state where a person cannot stop using a drug despite negative consequences?

Answer 30

Addiction

Question 31

What are the two exceptions to tolerance?

Answer 31

Miosis Constipation

Question 32

What would be the peak hours of withdrawal for a patient addicted to fent/meperidine?

Answer 32

6-12 hours

Question 33

What would be the peak hours of withdrawal for a patient addicted to morphine/heroin?

Answer 33

36-72 hrs

Question 34

What would be the peak hours of withdrawal for a patient addicted to methdone?

Answer 34

3-21 days

Question 35

Which opioids have an active metabolite?

Answer 35

Morphine (morphine-3-glucuronide) AND (morphine-6-glucuronide) Meperidine (normeperidine)

Question 36

Why is normeperidine so bad?

Answer 36

Reduces seizure threshold Increase CNS excitability Avoid in renal patients and Elderly

Question 37

What is Remifentanil dosed at?

Answer 37

Lean body weight.

Question 38

What drugs must you avoid with Meperidine for risk of serotonin syndrome?

Answer 38

Demerol is a weak serotonin reuptake inhibitor Avoid in MOAS (phenelzine, isocarboxazid, tranylcypromine)

Question 39

Why does Meperidine exhibit anticholinergic effects?

Answer 39

Structurally related to atropine (has atropine-like ring) Tachycardia, mydriasis, dry mouth

Question 40

Which opioid has the fastest onset of action?

Answer 40

Alfentanil This is due to its low pKa (more of the drug is in an unionized form)

Question 41

What type of procedures is alfentanil beneficial in?

Answer 41

Tracheal intubation Retrobulbar block

Question 42

What is the maintenance infusion of Remifentanil?

Answer 42

0.1-1.0 mcg/kg/min

Question 43

What can Remifentanil cause following discontinuation?

Answer 43

Hyperalgesia This can be attenuated by ketamine and magnesium

Question 44

What are the three MOAs of methadone?

Answer 44

Mu agonism NMDA antagonism MOA reuptake inhibition

Question 45

How does methdone affect the heart?

Answer 45

It can increase QT interval ~ this can lead to Torsades

Question 46

What is Oliceridine?

Answer 46

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

Question 47

What can rapid administration of opioids cause?

Answer 47

Skeletal muscle rigidity More common with sufentanil, fentanyl, Remi, and alfentanil

Question 48

What is the treatment for opioid-induced skeletal rigidity

Answer 48

Paralysis and intubation Also naloxone, but nobody wants that. Haha

Question 49

What are some complications of stiff chest?

Answer 49

Resp: (hypoxia, hypercapnia, ^ O2 consumption, decrease compliance, decreases FRC) Card: ^ CVP, PAP, PVR

Question 50

What are some partial opioid agonists?

Answer 50

Buprenorphine (high affinity Mu agonist) Nalbuphine (kappa agonist, Mu antagonist) Butorphanol (kappa agonist, Mu antagonist ~ weak)

Question 51

What is the dose for Nalxone?

Answer 51

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

Question 52

Which opiate reversal agent doesn’t cross the BBB thus making it beneficial for opioid induced bowel dysfunction?

Answer 52

Methylnaltrexone

Question 53

What is considered the “gold standard” for postoperative opioid delivery?

Answer 53

IV PCA

Question 54

What are the programmable components to IV PCA

Answer 54

Initial loading dose Demand dose Lockout interval Basal infusion rate