Analgesics

Question 1

The analgesic properties of the opiates are primarily mediated by what receptor?

Answer 1

Mu receptors

Question 2

What are the drugs in the class of Opioid Analgesics?

Answer 2

Morphine sulfate - MS Contin
Fentanyl - Duragesic
Codeine - T#3, T#4
Tramadol/Ultram

Question 3

Morphine/MS Contin
Class:
Indication:
MOA:

Answer 3

Morphine/MS Contin
Class: Opioid analgesic
Indication: Pain relief
MOA: Opiod agonist (high affinity for mu receptors; raises pain threshold and alters brain’s perception of pain

Question 4

Morphine additional indications

Answer 4

MI: pain relief, decrease anxiety, peripheral vasodilator

Question 5

Morphine
Char:
SE:

Answer 5

Morphine
Char: PO, PR, IM, IV
SE:
(1)respiratory depression (MC cause of death related to morphine use)
(2)Miosis (pin point pupils) due to enhanced parasympathetic stim
(3)Itching: histamine release
(4) N/V
(5) Constipation - decreased GI smooth muscle motility

Question 6

Fentanyl/ Duragesic
Class:
Indication:
MOA:
Char:

Answer 6

Fentanyl/ Duragesic
Class: Opioid analgesic
Ind: Pain relief, anesthesia
MOA: 80X the analgesic property of morphine
Char: IV, transdermal patch, buccal lozenge, sublingual spray, lollypop. Onset within minutes

Question 7

Fentanyl/Duragesic

Duration of action

Answer 7

Fentanyl/Duragesic
Duration of Action:
Single IM dose duration 1-2 hours
Single IV dose 30 min - 1 hour

Question 8

Fentanyl/Duragesic

SE

Answer 8

Fentanyl/Duragesic
SE:
(1) Respiratory depression: life threatening hypoventilation
(2) Beware of use with CYP 450 inhibitors
(3) N/V
(4) Constipation, paralytic ileus

Question 9

Codeine
Class:
Ind:
MOA:
Char:

Answer 9

Codeine
Class: Opioid analgesic
Ind: pain relief, antitussive
MOA: Opioid agonist (converted to morphine in the body but gm for gm is weaker than morphine)
Char: PO, IV, IM, SQ (lower abuse potential)

Question 10

Codeine
Dosing:
DOA:
Pregnancy Cat:

Answer 10

Codeine
Dosing: PO (commonly w/syrup)
DOA: 4-6 hours
Pregnancy Cat: C

Question 11

Codeine:

SE

Answer 11

Codeine:
SE: sedation, constipation, itching, potential for exaggerated response in certain individuals

Question 12

What polymorphism was associated with ultra-rapid metabolism of codeine?

Answer 12

CYP2D6

Caused death in children following tonsillectomy and/or adenoidectomy

Question 13

Tramadol/Ultram
Class:
Ind:
MOA:

Answer 13

Tramadol/Ultram
Class: centrally-acting analgesic
Ind: moderate to severe pain
MOA: agonist action at mu-opioid receptor and affects reuptake at noradrenergic and serotonergic systems

Question 14

Tramadol/Ultram

Char:

Answer 14

Tramadol/Ultram
Char: does not have the common SE of respiratory depression in normal doses

May be effective against depression and anxiety

Question 15

Heroin DEA drug designation

Answer 15

Category I : No accepted medical use

Question 16

Difference between Methadone and Morphine?

Answer 16

Methadone: synthetic, orally effective, equal potency to morphine but less euphoria and longer DOA

Question 17

Naloxone/Narcan
Class:
Ind:
MOA:
Char:

Answer 17

Naloxone/Narcan
Class: Opioid antagonist
Ind: opioid overdose (reverse coma and respiratory depression of opioid overdose)
MOA: Opioid antagonist binds with high affinity to opioid receptors but does not activate the receptor mediated response
Char: IV - rapidly displaces all receptor bound opioid molecules with onset of action w/in 30 seconds, half life 60-100 minutes, PO

Question 18

What other drug is Dextromethorphan related to?

Answer 18

Dextromethorphan is the dextro-isomer of CODEINE.

Question 19

What happens to an individual who not addicted to an opiate analgesic if they take Naloxone?

Answer 19

Nothing

Question 20

What do NSAIDs inhibit synthesis of?

Answer 20

Prostaglandins including thromboxanes and prostacyclins

Question 21

What precursor are prostaglandins synthesized from?

Answer 21

Arachadonic Acid via the cyclooxygenase pathway?

Question 22

What do prostaglandins do in the body?

Answer 22

Promote inflammation, pain and fever

Support clotting function of platelets

Protect the lining of the stomach

Question 23

What enzymes produce prostaglandins?

Answer 23

Cox-1 and Cox-2

Cox-1: production related to platelets and protecting the stomach

Question 24

Aspirin
Class:
MOA:
Ind:

Answer 24

Aspirin
Class: NSAID
MOA: Irreversible inhibition of COX 1 and 2 enzymes. Diminishes pain and sensitivity to pain by blocking prostaglandin E2 (PGE2)
Ind: Inflammation, pain, fever

Question 25

Aspirin SE

Answer 25

GI irritation and PUD N/V Increased risk of bleeding Renal insufficiency

Question 26

Aspirin use is associated with increased risk for what syndrome?

Answer 26

Reye's syndrome

Question 27

What are the signs of salicylsim?

Answer 27

Dizziness, tinnitus, hyperventilation, mental status changes and potential for coma/death.

Question 28

What is treatment for salicylism?

Answer 28

IV hydration, alkalization of urine and dialysis if renal insufficiency occurs.

Question 29

What is a major difference between Aspirin and Ibuprophen?

Answer 29

Ibuprophen is REVERSIBLE while Aspirin IRREVERSIBLY blocks COX-1 and COX-2 enzymes

Question 30

``` Celecoxib/Celebrex IND: MOA: Char: SE: ```

Answer 30

Celecoxib/Celebrex IND: ADENOMATOUS POLYPS, inflammation, pain MOA: Reversible selective COX-2 inhibition Char: Less GI bleeding, no inhibition of platelet agg SE: possible CVD

Question 31

Acetaminophen/Tylenol IND: MOA: Char:

Answer 31

Acetaminophen/Tylenol IND: Pain, fever MOA: Peripheral blockade of prostaglandin synthesis in hypothalamus Char: PO, PR, Metab by liver, no risk of GI bleed, no risk for Reye's syndrome

Question 32

Acetaminophen/Tylenol | Overdose/SE

Answer 32

Overdoes (>7 gm/24 hour) or with alcohol. Hepatic necrosis leading to liver failure, coma, death

Question 33

What is the maximum safe dose of Acetaminophen in an adult w/o underlying liver disease Pregnancy category

Answer 33

4 grms/24 hours Pregnancy category: B

Question 34

What toxic metabolite is acetaminophen metabolized to in the liver via P450?

Answer 34

N-acetyl-p=benzoquinone-imine (NAPQI)

Question 35

What is NAPQI conjugated with under normal conditions?

Answer 35

Glutathione

Question 36

With excess NAPQI what happens?

Answer 36

NAPQI binds to vital proteins and the lipid bilayer of hepatocytes resulting in hepatocellular death and liver necrosis.

Question 37

What are the stages of acetaminophen toxicity?

Answer 37

Stage 1: 12-24 hrs - N/V Stage 2: 24-48 hrs- rising AST/ALT and bilirubin Stage 3: 72-96 hours - peak hepatotoxicity (AST may be > 20,000) Stage 4: > 96 hrs - recovery, need for liver transplant or death

Question 38

What is the antidote to acetaminophen toxicity?

Answer 38

Syrup of ipecac to produce emesis N-acetylcysteine (NAC) - should be administered as early as possible

Question 39

How is acetylcysteine used?

Answer 39

``` Mucolytic (mucomyst) Acetaminophen overdose (Acetadote) ``` Augments glutathione reserves and binds toxic metabolites to protect hepatocytes from NAPQI toxicity.