Opioids & antagonists: the actual drugs

Question 1

Morphine: action, use, administration, metabolism, dosing

Answer 1

STIMULATES ALL OPIOID receptors
STRONG agonist, produces ALL the effects of opioids

USEFUL IN SEVERE PAIN

oral, parenteral, rectal, intrathecal, epidural
-more effective when injected than oral due to HIGH-FIRST PASS METABOLISM (~75%)
SHORT T1/2, extended release long-acting oral prep used in chronic/terminal pain

STANDARD THERAPEUTIC DOSE=10 mg SC or IM, all other analgesic drugs are composed to this drug

Question 2

Hydromorphone (Dilaudid): use, admin, comparison

Answer 2

very strong analgesic, MORE POTENT THAN MORPHINE
VERY effective in moderate to severe pain
-metabolites don’t accumulate so GOOD IF RENAL DYSFXN
-less likely to cause histamine release & itching than morphine

Oral, SC, IV, rectal, IM

similar duration of action as morphine

Question 3

Methadone (Dolophine): activity

Answer 3

LONG t1/2 & duration of action
*stimulates MU receptors
may block NMDA receptors & inhibit NE/5-HT reuptake

trad use: maintenance treatment of addicts

• low doses used to prevent withdrawal sxs
• withdrawal thought to be milder, but very prolonged

Now commonly used in LONG-TERM PAIN CONTROL

effective in hard-to-tx types of pain

-LOWER INCIDENCE OF TOLERANCE TO ANALGESIA

Question 4

Meperidine (Demerol)

Answer 4

DIFFERENT FROM OTHER Opioids
Mu agonist
-can cause EUPHORIA
don’t use for more than 48 hours, in high doses or in renal failure b/c accumulation of metabolite, NORMEPERIDINE CAN CAUSE SEIZURES
anticholinergic: TACHYCARDIA, PUPIL DILATION
NO COUGH SUPPRESSION
Ob:less resp depression in baby
less constipation/urinary retention than morphine
N/V may be less, or worse, than morphine
also inhibits NE/5-HT reuptake=SEROTONIN SYNDROME W/MAOIs

Question 5

Fentanyl (Sublimaze): characteristics, use, admin, SEs, metabolism, things like it

Answer 5

very lipid soluble & highly potent
short duration of action and half-life; HIGH ABUSE POTENTIAL!!! (ANESTHESIOLOGISTS)

use: SHORT SURGICAL PROCEDURES< w/midazolam

may cause TRUNCAL RIGIDITY if give RAPIDLY IV
-available in TRANSDERMAL PATCHES or LOLLIPOPS

metabolized by CYP3A4-drug intrxns likely

Alfentanil, sulentanil, remifantanil similar, w/shorter half-lives, durations of action

Question 6

Hydrocodone

Answer 6

used for MODERATE TO SEVER PAIN
often combined w/ acetaminophen, but not recommended now

sometimes combined w/homatropin to decrease abuse potential

(U) given PO, well absorbed
relatively short half-life, duration of action

conversion by CYP2D6 neded for some of the analgesic effect, so doesn’t work as well if pt on SSRIs esp. fluoxetine & paroxetine

Schedule II alone or III w/acetaminophen (Vicodin)
often abused

Question 7

Oxycodone (Oxycontin)

Answer 7

Moderate to sever pain

also used for Tourette’s & restless leg syndrome

metabolism by CYP2D6 increases analgesic effectiveness, so fluoxetine decreases effectiveness

t1/2 abt 4 hours unless extended release

Schedule II, often abused

Oxymorphone is similar to oxycodone, also extended release & schedule II

Question 8

Codeine

Answer 8

good COUGH SUPPRESSANT, doses lower than for analgesia

mild-to-moderate pain

must be metabolized by CYP2D6 to be active, inhibited by fluoxetine

converted to morphine

oral admin, (U) combined w/acetaminophen or ASA

some abuse potential, don’t use in small kids

schedule II if alone, III when combined, or IV in cough suppressants

Question 9

Effect of genetic differences in CYP2D6

Answer 9

poor metabolizers won’t get much relief

ultrametabolizers OD easily

Question 10

Penatazocine (Talwin)

Answer 10

KAPPA receptor AGONIST
MU recept PARTIAL AGONIST
moderate pain, oral or injected
may be less sedating than other opioids
-may have less resp depression, GI effects (all mediated by mu)
-may cause less DYSPHORIA (kappa)
-may cause withdrawal iin pts dependent on opioids, partial mu agonist
-low abuse potentialpschedule IV

Question 11

Buprenorphine

Answer 11

PARTIAL AGONIST on mu & maybe kappa
-ceiling effect=not much euphoria
-low abuse potential
-now used for maintenance tx of opioid addiction, decreases drug craving
can be: injected, sublingual or intranasal
COMBINED w/ NALOXONE: if you inject it, it won’t work but sublingual admin will

Question 12

Tramadol: Activity, SEs, intrxns, abuse potential

Answer 12

mild to moderate pain
WEAK MU AGONIST
inhibits NE/5-HT reuptake, contributes to analgesic effects
mild SEs: dizziness, sedation, constipation, nausea
COMBO w/ANTIDEPRESSANTS=SEIZURES
COMBO W/MAOIs, TCSa, SSRIs may cause serotonin syndrome
LOW abuse potential
tapentadol is similar but a schedule II drug

Question 13

Dextromethorphan: Use, intrxns, SEs, concerns

Answer 13

NOT an analgesic-COUGH SUPPRESSANT
frequently combined w/guafenisen (expectorant)
-not likely to cause constipation
-DECREASES 5-HT REUPTAKE: serotonin syndrome w/MAOIs
-BLOCKS NMDA receptors: abuse potential, drug of abuse in teens
OTC: cough syrup, tablet/internet concentrated form without rx
{HAS CAUSED SOME DEATHS IN TEENS}

Question 14

Naltrexone (ReVia): admin, duration, use, SEs

Answer 14

effective orally & long acting (24 hours)
-used in tx of opioid addicts, esp health care professionals
-WILL PRECIPITATE WITHDRAWAL
decreases craving in recovering alcoholics
may cause LIVER TOXICITY when used chronically
Nalmefene is similar to naloxone with a slightly longer duration for action & less liver toxicity