N: Pharmacology Of Opiates

Front 1

What are the principal neurotransmitters involved in pain modulation?

What are examples of the important neurotransmitters released from primary afferent terminals in the dorsal horn for conveying and sustaining pain messages to 2nd order ST neurons?

Back 1

NE, 5HT, GABA, and endogenous opioid peptides.

Glutamate, Substance P, CGRP, NO

Front 2

What are the three distinct families of endogenous opioid peptides?

Generally speaking, how are they produced, i.e., how are they synthesized?

Back 2

enkaphalins, endorphins, dynorphins

not directly... they are cleaved from a distinct polypeptide precursor (proenkephalin, Proopiomelanocortin (POMC), prodynorphin).

Front 3

The analgesic and reqarding effects of synthetic, semisynthetic, and naturally-occuring opioids is due primarily to ___ receptor (agonism/antagonism).

What are the three major types of opiod receptors?

Back 3

u (mu) receptor agonism

u (mu), d (delta), and k (kappa).

Front 4

What are naloxone and naltrexone?

Back 4

pure antagonists of opioid-induced effects.
- seems to block the placebo effect

Front 5

What is Salvia divinorum?

What is the most potent, naturally occuring hallucinogen?

Doses of which drug can block this drug?

Back 5

the plant from which salvinorin A is derived.

salvinorin A (induces an intense, but shorted lived,
hallucinogenic experience.

naloxone

Front 6

given the following important physiological functions, give both the a) opioid receptors related and b) what effect stim of those receptors has:
- respiration
- feeding
- GI motility
- sedation
- neurotransmitter release of ACh
- DA

Back 6

\u
^ u, k d
\u, k
^u, k
\u
\k

Front 7

How do opoids act supraspinally?

Back 7

they activate "off-cells" (sertonergic or noradrenergic cells held "off" by GABA) indirectly. --> analgesia.

Front 8

What is the PAG? RMN? RVM?

Back 8

PAG = periaqueductal grey region
Raphe's magnus nucleus (RMN)
rostral ventral medulla (RVM)

Front 9

codeine and hydrocodone are used to tx cough. Do they also have high affinity for opioid receptors?

Back 9

no, they have exceptionally low affinities for opioid receptors, thus they do not suppress respiration.

Front 10

What is Dextromethorphan?

Effects of dextromethorphan are mediated by which receptors?

Is it addictive?

SE?

Back 10

dextrorotatory enantiomer and O-methyl derivative
of levorphanol, acts centrally to elevate coughing threshold. The agent does not act through opioid receptors (in contrast to levorphanol!) and is neither analgesic nor addictive. Dextromethorphan produces fewer subjective and gastrointestinal side effects than codeine.

Front 11

Death due to morphine (or morphine-like) opioids is almost always due to what?

Back 11

respiratory depression via reduction in responsiveness of the brainstem respiratory centers to CO2.

Front 12

Morphine and most u and k agonists do what to the pupil? how?

Back 12

constriction of the pupil by an excitatory action on parasympathetic nerve innervating the circular (sphincter) smooth muscle of the pupil. [excitation of the Edinger-Westphal nucleus] Pinpoint pupils (miosis) are characteristic of u-agonist toxicity.

Front 13

pinpoint pupils (miosis) are characteristic of what?

Back 13

u-agonist toxicity.

Front 14

Morphine-like agents induce emesis via action where?

Can they also induce convulsions?

Back 14

chemoreceptor trigger zone (area postrema of the medulla)

yes, infrequently, and usually only at doses far in excess of those required for profound analgesia.

Front 15

What effect does morphine have on histamine?

Does morphine have CV effects?

Back 15

^ release from mast cells --> urticaria, sweating, and vasodilation.
- can cause bronchoconstriction

respiratory depression and CO retention --> cerebral vessel dilation --> ^CSF
- morphine is contraindicated in those with severe brain injury.

Front 16

Can morphine help tx dyspnea caused by pulmonary edema?

Back 16

yes, if it's due to LV failure, possibly owing to it's vasodilatory effects.

Front 17

Does morphine cross the BBB? Do other opioids?

Back 17

not well.
yeah, fentanyl, methadone, and heroin cross quite well.

Front 18

Should morphine be used as an analgesic during labor?

Back 18

no.

Front 19

Note if the following enhance or inhibit the depressant effects of morphine (or the analgesic effects, if applicable):
- hydroxyzine
- MAOI
- tricyclic antiD
- phenothiazines
- amphetamine

Back 19

- enhance analgesia
- enhance depress x 3
- enhance analgesia at SMALL doses.

Front 20

Meperidine
- morphine like?
- any sig CV effects w/oral admin?
- in what other ways does it differ from morphine (re: effects)?
- clinically useful for diarrhea and cough?
- what happens on OD?
- Side effects?

Back 20

- no
- no
- cause DILATION, not pinpoint pupils. This is due to atropine-like action.
- no
- dilated pupils and hyperreflexia
- dry mouth and blurred viz due to antimuscarinic effects.

Front 21

What is the opioid commonly used in obstetrics?

Back 21

meperidine

Front 22

What can happen in you give MAOI and meperidine at the same time?

Back 22

hyperthermia, convulsions.

Front 23

How is methadone different from morphine?
- primarily receptors?
- can it produce dependence?

Back 23

synthetic, orally effective opioid that has approx equal potency but induces less euphoria w/ longer duration.
- still acts primarily on u receptors.
- yes

Front 24

What is chemically related to meperidine, but has 100x the analgesic potency of morphine?

Back 24

Fentanyl.

Front 25

Though often used transdermally, Fentanyl should be avoided being admin in this way post-surgery why?
- does Fentanyl cause pupillary dilation or constriction?

Back 25

life-threatening hypoventilation
- constriction, even though it is chemically related to meperidine.

Front 26

Of the following 3 opioids, rank them for duration and onset:
morphine, meperidine, fentanyl

Back 26

[long] morphine > meperidine > fentanyl [short]

Front 27

Sufentanil, alfentanil, and remifentanil are all related to which opioid? Differences?

Back 27

fentanyl.
sufentanil is even more potent, whereas the other two are even shorter acting (even though fentanyl is already 15-20min for duration).

Front 28

Oxycodone
- how is it excreted?
- what is it?

Back 28

- kidney
- semisynthetic derivative of morphine. orally active. metabolized to products with lower analgesic activity.

Front 29

Codeine
- what are it's analgesic properties due to?
- antitussive effects?

Back 29

- conversion to morphine
- codeine itself

Front 30

What is Propoxyphene?
- what can toxic doses cause in some?
- can these pts be rescued by naloxone?

Back 30

deriviative of methadone. used to relieve mild to moderate pain (dextro), whereas (levo) is used as an antitussive.
- CV toxicity and pulm edema
- only the respiratory depression can be reversed, the CV/pulm edema cannot.

Front 31

agonist-antagonists do what in opiate naive pts?
- pts with opioid dependence?

Back 31

- analgesia
- produce withdrawal sx

Front 32

Pentazocine
- receptor effects?

Back 32

- K agonist, weak antag of u and d.

Front 33

Buprenorphine
- classification?
- effects in pt with opioid dependence?

Back 33

- partial agonist
- can cause withdrawal sx, though not as bad as methadone in that regard.

Front 34

Tramadol
- centrally acting analgesic that binds to which receptor?
- other effects?
- uses?
- analgesia reversible with naloxone?

Back 34

- u
- weakly inhibits reuptake of NE and 5HT.
- management of mod to sev pain
- only partially

Front 35

Naloxone
- effects?
- receptor preference?
+ what might this explain?
- Naltrexone and Nalmefene are different because...

Back 35

- rapidly displaces all receptor-bound opioid molecules.
- u
+ might explain why it reverses the respiratory depression but only minimally reverses the analgesia.
- they have a longer duration of action. They have other diff too, but none that are clinically sig.