Week 7 Flashcards by Gabrielle Garrett

three main useful effects of opioids:

– Analgesia
– Antitussive (cough suppressant)
– Treatment of diarrhea (decreased GI motility)

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Opioid Side-effects

Respiratory depression– source of overdose death
• Sedation
• Confusion
• dysphoria
• euphoria– psychological addiction
• miosis (pinpoint pupils)– diagnostic indicator
• constipation
• urinary retention

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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

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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

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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

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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

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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

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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

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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

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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

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naloxone (Narcan)

Opioid pure antagonist used to lessen adverse
effects of narcotic overdose
– Especially respiratory depression
• Available IV, SC, IM

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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

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loperamide (Imodium)

OTC anti-diarrheal medication
• Opioid, but not absorbed,
only affects GI tract
• Lessens GI motility

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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

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Benzocaine:

strictly topical (OTC creams etc)
– pKa = 3.5 –neutral at blood pH (7.4)

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Lidocaine, articaine:

injected
– Dentistry, stitches, minor surgeries
– pKa = 7.7 –mix of neutral + charged forms
– Often mixed with epinephrine to cause local
vasoconstriction, keep anesthetic from spreading
• Epinephrine may cause tachycardia when injected

Local anesthetic drugs

All have “-caine” endings to their generic names

cocaine

• Schedule II, has vasoconstrictor properties as well as
local anesthesia
– Works well for oral/nasal surgeries but almost never used
due to abuse potential
– Insufficient blood supply can cause tissue necrosis with
chronic use
• Also has CNS stimulant effect, via dopamine receptors
• Free base form (“crack” cocaine) rapidly absorbed
(especially via smoking), but has shorter effect
• Side-effects include tachycardia, hypertension, visual
hallucinations, paranoid psychosis

A known side-effect of acetylsalisylic acid in susceptible individuals is

GI bleeding at low dosages through long-term use

lidocaine is often mixed with epinephrine in order to cause

vasoconstriction

lidocaine has a pKa of 7.7, so it is

an injectable local anesthetic that is an equal mix of polar and non-polar forms

Oxycodone is an opioid drug that

has lower frequency of nausea than morphine, and is available in an extended-release pill

Tylenol 3 is a combination drug that contains acetaminophen and

codeine

Hydrocodone is an opioid drug that

has a significant antitussive effect

Codeine is an opioid drug that

has a significant antitussive effect

Vicodin (or Norco) is a combination drug that contains acetaminophen and

hydrocodone

Which of the following is NOT a potential side-effect of most opioid drugs

Heart arrhythmia

Acetylsalicylic acid is

An OTC drug that is often prescribed at low doses to reduce risk of MI

Ketorolac is

A powerful NSAID that is available by prescription only.

Prostaglandins

• Local (paracrine) mediators of inflammation – Short half-life • Synthesized by cyclooxygenase enzyme – From arachidonic acid (a fatty acid) – Makes thromboxane also (platelet aggregation) • Prostaglandins cause: – increased sensitivity of pain receptors – increased body temp (fever) – secretion of cytoprotective mucus in stomach – uterine wall contractions – renal vasodilation

cyclooxygenases

Enzyme that controls prostaglandin production • COX has two isozymes – COX1: mainly affects stomach mucus production – COX2: pain sensitivity, fever, inflammation • Most NSAIDs work by inhibiting cyclooxygenases

Uses of NSAIDs

Baby aspirin to reduce risk of MIs, strokes • osteoarthritis – degeneration of the joints • rheumatoid arthritis – progressive chronic inflammatory disease of the joints – affects > 40 million Americans – due to an autoimmune attack on the joints. • aches and pains • menstrual cramps (primary dysmenorrhea) – aspirin is not particularly effective for dysmenorrhea

NSAID side-effects

stomach ulceration • increased risk of hemorrhage • renal failure at high dosages in predisposed patients: – those with decreased circulation volume due to CHF, liver cirrhosis, renal disease, use of diuretics, elderly • May induce asthma attack in ~ 20% of asthma pts • May reduce efficacy of ACE inhibitor drugs.

Common OTC NSAIDs

acetylsalicylic acid (ASA, Aspirin) – Analgesic, antipyretic, anti-inflammatory – Also inhibits thromboxane production • Lowers MI, ischemic stroke risk – Gastric bleeding with prolonged use is an issue • ibuprofen (Advil, Motrin) q 4 hours – Better than aspirin for primary dysmenorrhea – Less risk of gastric bleeding • naproxen (Aleve) q 8 hours – Similar to ibuprofen, but longer half-life

Ketorolac

``` Most efficacious NSAID • Prescription only • Used post-surgery • IM, IV, opthalmic & oral forms – 6h half-life • Short-term use only (<5 days) – due to risk of stomach ulcers ```

COX2 inhibitors

``` • In principle, specific inhibition of COX2 should cause pain-relief without risk of COX1-related stomach ulcers, bleeding – for long-term arthritis use • celecoxib (Celebrex) is a COX2 inh – does not inhibit platelet aggregation; studies show some increase in mortality due to strokes, MIs ```

Acetaminophen (APAP, Tylenol)

Not actually anti-inflammatory – Analgesic & antipyretic – Works via CNS effects • May be COX2 inhibitor, but only active in CNS, not at sites of inflammation • Does not cause stomach ulcers – Unlike OTC NSAIDs • OTC, but very high doses can cause liver failure – Safe at normal doses Combination with butalbital (barbiturate) for migraines

Migraine drugs

``` Migraines difficult to treat – cause of migraines is not well-understood • Triptan family of drugs – Serotonin agonists? – Work best if taken immediately at migraine onset • SC injection may be best • nasal spray, oral pill also available – sumatriptan (Imitrex) and others • Generic names all end in “–triptan” ```