Week 7 Flashcards
three main useful effects of opioids:
– Analgesia
– Antitussive (cough suppressant)
– Treatment of diarrhea (decreased GI motility)
Opioid Side-effects
Respiratory depression– source of overdose death • Sedation • Confusion • dysphoria • euphoria– psychological addiction • miosis (pinpoint pupils)– diagnostic indicator • constipation • urinary retention
morphine (morphine sulfate salt)
Effective for serious pain
– Post-surgical, terminal cancer, post-MI
• Schedule II, high potential for addiction
• Available orally, IV, IM, rectal suppository
– MS-Contin (sustained-release pill) has 12h half-life
• Initial exposure may cause nausea,
hallucinations, dysphoria
heroin
More lipophilic than morphine
– Enters brain more quickly than morphine when
smoked or given IV
– More intense “rush”
• Schedule I in U.S.
– Legal narcotic in UK, other countries
• Withdrawal symptoms include:
– diarrhea, intestinal cramping, nausea, vomiting
– profuse cold sweating with hair standing on end
(hence the term “going cold turkey”)
– Withdrawal symptoms treated with methadone,
clonidine
hydromorphone
Dilaudid
Higher potency than morphine • Possibly less side effects than morphine – Nausea, vomiting, sedation • Available orally, SC, IM, or IV • Heroin, hydromorphone, others are chemically related to morphine – Codeine, hydrocodone, oxycodone too
codeine
Metabolized into morphine by CYP 2D6
– 7% of Americans lack the CYP 2D6 enzyme
– Also inhibited by some SSRI’s: Prozac, Paxil
• Good antitussive effect
– without conversion to morphine
– Present in low dosages in some cough syrups
• Moderate opioid
– Often effective for dental pain
– Plateau in efficacy ~60mg / dose
• Usually combined with acetaminophen (Tylenol II, III, IV)
– synergistic effect
• Schedule II on its own,
III-V (depending on dosage) in combination products
hydrocodone
Usually combined with acetaminophen – Vicodin, Norco – 142M prescriptions in 2012 in U.S. • CYP 2D6 converts it to hydromorphone – Same drawbacks as with codeine • Antitussive properties also useful • Oct 2014: hydrocodone combo products (including Vicodin) reclassified as Schedule II – No refills on prescriptions, no phone prescriptions
oxycodone
Lower frequency of nausea & vomiting than
morphine
– Constipation may still be a problem
• Oxycodone + acetaminophen = percocet
• Extended release form: Oxycontin (bid)
– Reformulated into an abuse-resistant polymer in 2010
– previously, grinding Oxycontin pills up would allow rapid release
fentanyl
Short-acting (1-2hrs) when given IV – Used for serious childbirth pain – Other breakthrough pain too • 3-day transdermal patch (Duragesic) – Helpful at home for patients who can’t swallow or who experience chronic vomiting • [buccal lozenges Abstral, Actiq for breakthrough cancer pain] • Schedule II • Synthetic opioid – Chemical structure unlike morphine, but same receptors – 80-100x higher potency than morphine
methadone
Used to suppress withdrawal symptoms of opioid
addiction, eg from heroin
– Still produces euphoria and psychological dependence
– Oral admin avoids dirty needle problems
• Also used as an analgesic [to replace oxycodone?]
• Action is relatively slow, can lead to repeated
dosing for greater effect, which in turn can lead
to respiratory depression and death
naloxone (Narcan)
Opioid pure antagonist used to lessen adverse
effects of narcotic overdose
– Especially respiratory depression
• Available IV, SC, IM
dextromethorphan
Robitussin
Cough suppressant, no analgesic effect – Chemically related to morphine – I think of it as “an orphan” in terms of how its action relates to other opioids • Available OTC – Syrup, tablet, gel capsules • “robo-tripping” can produce hallucinations at large doses
loperamide (Imodium)
OTC anti-diarrheal medication
• Opioid, but not absorbed,
only affects GI tract
• Lessens GI motility
Local anesthetics
Block sodium channels, block all nerve
conduction in nerves where they are dissolved
– Must dissolve through membrane, block channel
from the inside
• Amine chemistry: water-soluble when charged
(with H+
, lower pH), lipid-soluble when neutral
– pKa matters
Benzocaine:
strictly topical (OTC creams etc) – pKa = 3.5 –neutral at blood pH (7.4)