Week 7

Question 1

three main useful effects of opioids:

Answer 1

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

Question 2

Opioid Side-effects

Answer 2

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

Question 3

morphine (morphine sulfate salt)

Answer 3

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

Question 4

heroin

Answer 4

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

Question 5

hydromorphone

Dilaudid

Answer 5

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

Question 6

codeine

Answer 6

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

Question 7

hydrocodone

Answer 7

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

Question 8

oxycodone

Answer 8

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

Question 9

fentanyl

Answer 9

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

Question 10

methadone

Answer 10

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

Question 11

naloxone (Narcan)

Answer 11

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

Question 12

dextromethorphan

Robitussin

Answer 12

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

Question 13

loperamide (Imodium)

Answer 13

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

Question 14

Local anesthetics

Answer 14

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

Question 15

Benzocaine:

Answer 15

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

Question 16

Lidocaine, articaine:

Answer 16

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

Question 17

Local anesthetic drugs

Answer 17

All have “-caine” endings to their generic names

Question 18

cocaine

Answer 18

• 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

Question 19

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

Answer 19

GI bleeding at low dosages through long-term use

Question 20

lidocaine is often mixed with epinephrine in order to cause

Answer 20

vasoconstriction

Question 21

lidocaine has a pKa of 7.7, so it is

Answer 21

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

Question 22

Oxycodone is an opioid drug that

Answer 22

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

Question 23

Tylenol 3 is a combination drug that contains acetaminophen and

Answer 23

codeine

Question 24

Hydrocodone is an opioid drug that

Answer 24

has a significant antitussive effect

Question 25

Codeine is an opioid drug that

Answer 25

has a significant antitussive effect

Question 26

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

Answer 26

hydrocodone

Question 27

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

Answer 27

Heart arrhythmia

Question 28

Acetylsalicylic acid is

Answer 28

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

Question 29

Ketorolac is

Answer 29

A powerful NSAID that is available by prescription only.

Question 30

Prostaglandins

Answer 30

• 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

Question 31

cyclooxygenases

Answer 31

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

Question 32

Uses of NSAIDs

Answer 32

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

Question 33

NSAID side-effects

Answer 33

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.

Question 34

Common OTC NSAIDs

Answer 34

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

Question 35

Ketorolac

Answer 35

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

Question 36

COX2 inhibitors

Answer 36

• 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

Question 37

Acetaminophen (APAP, Tylenol)

Answer 37

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

Question 38

Migraine drugs

Answer 38

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”