Opiods

Front 1

What two mu opiod agonists are similar to Fentanyl but are short duration and given parenterally?

Back 1

• Alfentanil
• Remifentanil

mne: Alf ramps it up in the rump (rump for injection/parenteral)

Front 2

What mu opiod agonist has medium oral potency and duration of 2-4 hours?

Back 2

• Meperidine

Front 3

What mu opiod agonist has good oral potency (can also be given parenterally) and has a long duration of action (> 6 hours)?

Back 3

• Methadone

Think! Used for heroin addicts, long duration ↓ highs & lows associated w/ heroin, helps wean off addition.

Front 4

What strong mu agonist is similar to Fentanyl but also has some action at the δ and ƙ receptors?

Back 4

Sufentanil

Front 5

What mu opiod agonist has antimuscarinic action & is contraindicated in pts using MAO inhibitors? Why is this?

Back 5

• Meperidine
• Blocks serotonin reuptake. With MAO-I there's risk of Serotonin syndrome.

Front 6

What mu opiod agonist also has MAO inhibition & blocks NMDA receptors (therefore can be used for neuropathic pain)?

Back 6

• Methadone

Front 7

What class of drugs has the following possible side-effects:
• Extension of therapeutic and organ system effects
• Tolerance, physical and psychologic dependence.
• Dysphoric reactions
• Respiratory depression
• Nausea & vomiting
• ↑ intracranial pressure and postural hypotension
• Constipation & urinary retention
• Itching around nose, urticaria
• Partial agonists may precipitate explosive abstinence in addicts

Back 7

Opioids

Front 8

What are the drug interaction risks that are associated w/ Opioid use?

Back 8

• Sedative hypnotics: ↑ CNS depression
• Antipsychotic tranquilizers: ↑sedation, ↑CV effects
• MAO inhibitors: *Meperidine in particular - CONTRAINDICATED* Hyperpyrexic (extreme elevation of temperature) coma & hypertension (Serotonin syndrome)

Front 9

How do opiods affect the uterus during labor? What are the associated neuroendocrine effects?

Back 9

• Opiods prolong labor
• ↑ the release of prolactin, ADH, & somatotropin
• ↓ release of luteinizing hormone

Front 10

How do opiods impact the GI & GU system?

Back 10

• GI: Constipation & biliary collic
• GU: ↓ Renal fxn

Front 11

What opiods has action at the ƙ receptor but also at the Mu receptor because 10% is metabolized to morphine?

Back 11

• Codeine
• Oxycodone
• Dihydrocodeine
• Hydrocodone

Front 12

What opiod that has medium action at the ƙ receptor and mild action at the Mu receptor also has high oral potency and a duration of 3-4 hours?

Back 12

Codeine

Front 13

What opiod that has action at both ƙ & mu receptors has both analgesic and mild antitussive effects?

Back 13

Codeine

Front 14

What opiod is approximately 1/2 as potent as codeine?

Back 14

Proxyphene

Front 15

What morphinan opiod has a high abuse potential? By what route of administration is it given? At what receptor does it act?

Back 15

• Levorphanol
• Mu receptor (Most drugs that act stronly on the mu receptor have high abuse potential)
• High ORAL potency

Think! Addicts get High ≈ Levatate ≈ Levorphanol

Front 16

Drugs that bind to which receptor have a high abuse potential? What are the names of those drugs?

Back 16

• Mu receptor
• Fentanyl, Sufentail, Alfentanil, Remifentanil, Meperidine, Methadone, Morphine, Hydromorphine, Oxymorphone, & Levorphanol

Front 17

What two drugs can be used for detox and maintenance Tx in heroin abusers?

Back 17

Methadone & Buprenorphine

Front 18

This opiod that is a parital agonist at the mu receptor, can only be given parenterally or sublingually, and has a duration of action of > 8 hrs (long T1/2).

Back 18

Buprenorphine
Think! Long duration of action means good for heroin detoxification and maintenance therapy.

Front 19

What opiod that has partial mu-receptor activity and activity at the ƙ receptor can not be given subcutaneously because of irritation?

Back 19

Pentazocine

Front 20

What opiod that has partial activity at the Mu receptor is the only one to also have action at the δ receptor?

Back 20

Dezcocine

Front 21

What drugs are opiod antagonists?

Back 21

• Nalaxone
• Naltrexone
• Nalmefen

Front 22

What opiod antagonist can only be given IV? What is unique about it?

Back 22

• Nalmefen
• Long t1/2

Front 23

What opiod antagonist has long duration? What is unique about it?

Back 23

• Naltrexone
• Extensive first pass metabolism

Front 24

What opiod antagonist has a short duration of action? What is unique about it?

Back 24

• Nalaxone
• Poor oral potency

Front 25

What opiod antagonist is used for acute opioid overdose?

Back 25

• Nalaxone

Front 26

What opiod antagonist is used for maintenance in addict treatment programs and may ↓ craving for EtOH

Back 26

• Naltrexone

Front 27

What two opiods are used for the treatment of diarrhea? Do they have analgesic or CNS effects?

Back 27

• Diphnoxylate (Lomotil) & Loperamide (Immodium)
• No CNS effects, minimal analgesic effects

Front 28

What opiod is used as an anti-tussive?

Back 28

• Dextromethorphan (syzzzrup)

Front 29

What opiod's main action is to blcok serotonin uptake?
What is its use?
What drug interaction is of concern?

Back 29

• Tramadol
• Neuropathic pain (antidepressant effects), or as adjunct with other opioids for pain
• Risk of interaction w/ MAO-i --> serotonin syndrome.

Front 30

Tramadol is used for what? What is its 1º MOA?

Back 30

• Neuropathic pain (antidepressant effects), or as adjunct with other opioids for pain
• Blocks serotonin uptake (concern of Serotonin syndrome when used w/ MAO-i's)

Front 31

What are the names of the endogenous opiods?
What is their chemical stucture & how are they derived?
Where are they found in the body?

Back 31

• Enkephalins, Endorphins, Dynorphins
• Opiod PEPTIDES derived from larger precursor protein
• Found in: brain & sppinal column (efferent pain modulation + afferent perception), adrenal medulla & neural plexuses of the gut

Front 32

What kind of receptors are the mu, ƙ, & δ receptors? What is the net effect in the cell?

Back 32

• G-protein receptors (Gi)
• Gi = inhibitory, means it ↓ Adenyl cyclase & ↓ cAMP. Also ↓ Ca++ influx, ↑ K+ efflux (hyperpolarization) ∴ impeding neuronal firing/NT release

Front 33

Mu receptors bind which endogenous opiod most strongly? δ ? ƙ?

Back 33

• Mu binds b-endorphin most strongly
• δ binds Enkephalin most strongly
• ƙ binds Dynorphins most strongly

mne: Most familiar is endorphins, bind to most familiar receptor - mu (recall abuse potential). δ binds enKephalin while ƙ binds D*ydnorphin: δ binds w/ the one that has a K, ƙ binds w/ the D.

Front 34

What are the two mechanisms by which opiods reduce nociceptive signaling?

Back 34

• Spinal: ↓ AFFERENT stimulation to the brain, via inhibitory interneuron in Dorsal Horn (regional analgesia)
↓ in sensory afferent nociceptive signals via direct inhibition of pre and post synaptic nociceptive relay neurons by opioids
• Supraspinal (CNS): ↑ "pain-inhibitory" neuronal EFFERENTS (brain modulation of incoming pain)

Front 35

What is neurotransmitter released by the inhibitory interneurons in the Dorsal horn which ↓ afferent stimulation to the brain?

Back 35

• Inhibitor interneurons release ENKEPHALINS

Front 36

Which receptor is found on both pre-synaptic and post-synaptic neurons?

Back 36

• Mu (most clinically useful)

Front 37

What is the mechanism by which opiates ↓ respiratory fxn?

Back 37

Via mu receptors in the medulla

Front 38

Since analgesia, means pain relief (both sensory + emotional response), whoat does this imply about the location of mu receptors?

Back 38

• Mu receptors are located on sensory neurons
• AND limbic activation (highest density of receptors), amygdala, & locus ceruleus

Front 39

What sign is diagnostic of opiod overdose even in tolerant addicts?
Theoretically how could this sign be blocked?
What other signs may be observed?
What other sign can one not build tolerance to?

Back 39

• Pinpoint pupils (miosis) mediated by parasympathetic pathways
• Blocked by atropine or opiod antagonists (Nalaxone, Naltrexone, Nalmefen)
• Truncal rigidity, nausea & vomiting
• No tolerance to constipation.

Front 40

What is the method my with opiates are metabolized in the liver (w/ strong first-pass effect)?

Back 40

• Glucuronidation of hydroxyl groups (morphine, levophanol)
--> Esters are hydrolyzed then conjugated
--> Glucuronides are excreted in the urine (Morphine-6-glucuronide is more potent than parent molecule)
• N-demythlation in the liver (minor pathway, metabolite nor-meperidine is active)

Front 41

Which opiods are extensively oxidized by CYP3A4

Back 41

• Fentanyl, meperidine (phenylpiperidines)

Front 42

Which opiods are metabolized by CYP2D6 to active metaboolites (i.e. morphine)?

Back 42

Codeine, oxycodone, hydrocodone

Front 43

What opiod can be used to relieve dyspnea due to left ventricular failure (Acute pulmonary edema)? What additional relief is helpful?

Back 43

• IV morphine
• Also helps to reduce anxiety/perception of SOB

Front 44

What is the mechanism by which opiods act as antitussants?
Which drugs have this action?
What is a potential concern?

Back 44

• Action is on CNS to suppress cough reflex (at lower than analgesic doses)
• Dextromorphan & Codeine
• Risk of interaction with MAO-i (Serotonin syndrome)

Front 45

What opiod is often used as an anesthetic during cardiovascular surgery to avoid cardiovascular depression?

Back 45

• Fentanyl

Front 46

Why can opiods be used in epidurals?

Back 46

• Analgesia only, no impairment of motor, autonomic or other sensory fxns (♀ can still push!)

Front 47

What opiod can be given as a lollipop? In addition to yumminess what is another benefit? What is the benefit of rectal suppositories?

Back 47

• Fentanyl citrate lollipol (buccal transmucosal - no first pass effect!)
• Rectal administraton eliminates 1/2 of the first pass metabolism

Front 48

What cellular changes occur in physiological dependence?

Back 48

• Chronic use ↑ intracellular Ca++ content.
• Receptor recycling
• Downregulation of opiod receptors
• Uncoupling of receptor to G-protein

Front 49

What three side-effects do not change w/r/t tolerance to opiods?

Back 49

Miosis, Constipation, Convulsions

Front 50

What anesthetic drug can block tolerance to opiods?
What does this mean about how toleracnce is developed?

Back 50

• Ketamine
• Tolerance is mediated by NMDA receptors (where Ketamine binds)

Front 51

In what 4 situations are opiods contraindicate? Why?

Back 51

• Head injury: respiratory depression ---> ↑ CO2 --> cerebral vasodilation --> LETHAL if intracranial pressure is ↑
• Pregnancy: crosses placenta, chronic use makes fetus depedent --> w/drawal symptoms after birth --> baby won't breathe (take a good Hx!!!)
Tx in pregnancy is diazepam (mild), methadone (severe)
• Imparied pulmonary fxn: opiods cause ↓ respiration
• Endocrine disease: ↑ responses in Addison's disease & hypothyroidism.

Front 52

What are the drug interactions b/w opiods & sedative hypnotics?

Back 52

↑ respiratory and CNS depression

Front 53

What are the drug interactions b/w opiods & antipsychotics?

Back 53

↑ sedation and ↑ anti-muscarinic effects

Front 54

What can result from the interaction of opiods and MAO-i's? Which drug in particular?

Back 54

• Hyperpyrexic coma (Serotinergic syndrome)
• Meperidine is the biggest culprit

Front 55

Which opiods are strong mu agonists?

Back 55

M*eperidine, M*ethadone, M*orphine, HydroM*orphone, OxyM*orphone, ALL Fentanyls

Front 56

What can catalyze explosive abstinence syndrome?

Back 56

Mixing the use of a full opiod agonist w/ a parital or mixed agonist-antagonist