Drugs For Treating Pain

Question 1

Aspirin/NSAIDs

Answer 1

• Aspirin/NSAIDs inhibit/bind the COX-1 and COX-2 enzymes
  ~ The results in a reduction of PG which
  is one of the chemical mediators for
  inflammation that initiate a pain
  response
  > Less PG = less pain

Question 2

Acetaminophen

Answer 2

• APAP: N-acetyl-P-aminophenol (chemical name)
  ~ Non-aspirin
  ~ Tylenol (trade name)

Question 3

Acetaminophen: Action

Answer 3

• Not well understood
  ~ Derived from Cinchona tree bark
  ~ Appears to be selective for nervous
  system tissues
  > Doesn’t have strong effects in
  other tissues
  > Weak inhibitor of COX enzymes
  outside the nervous system
  > Doesn’t have large effects on
  edema formation or blood clotting
• Used to treat pain and fever

Question 4

Acetaminophen: Analgesic Action

Answer 4

• Doesn’t have all the same effects as aspirin/NSAIDs so probably not the same mechanism in pain reduction
  ~ Theorized that there may be a COX-3
  enzyme in Nervous tissue for which
  acetaminophen is selective, but small
  evidence in animal studies
  ~ May inhibit pain afferents

Question 5

Acetaminophen: Antipyretic Action

Answer 5

• Inhibits COX enzymes in the brain
  ~ Reduces PGE2 production

Question 6

Acetaminophen: Side Effects

Answer 6

• Fewer than aspirin/NSAIDs since it is only a weak inhibitor of COX pathway outside the nervous system
  ~ No bleeding
  ~ No GI tract irritation

Question 7

Acetaminophen: Hepatotoxicity

Answer 7

Liver damaged by toxin that is normally produced in the metabolism of acetaminophen

Question 8

Acetaminophen: Hepatotoxicity Dosage

Answer 8

• Dosage of >4000 mg/24 hours, begins hepatotoxicity. (illness)
  ~ Death
  • > 7500 mg/24 hours
• Alcohol use accentuates this effect.
  ~ Same enzymes metabolize both.
  ~ Increases toxic metabolites.
  ~ > 3 drinks/day should consult a
  physician before use.
• Maximum dosage including OTC goes up to 4000 mg/day
  ~ 1000 mg every 6 hours

Question 9

Acetaminophen: Hepatotoxicity S&S

Answer 9

• Nausea
• Vomiting
• Drowsiness
• Abdominal pain
• Common cause of accidental overdose
  ~ Mostly since acetaminophen is found
  in combination products for: cold and
  pain

Question 10

Opioid Agonist: Opioid Receptors

Answer 10

• Types
  ~ Mu Opioid Receptors (MOR)
  ~ Delta Opioid Receptors (DOR)
  ~ Kappa Opioid Receptors (KOR)
• Distributed throughout the body especially in the central and peripheral nervous systems, but also found in the skin and organs.
• When stimulated close sodium channels.
  ~ Sodium can’t enter cell
  > Inhibits nerve depolarization
  (won’t tell you about pain)

Question 11

Opioid Agonist Actions: Analgesia

Answer 11

• Stimulated receptors inhibit pain afferents in the peripheral and CNS
  ~ Mostly the MOR are responsible for
  acute pain reduction so drugs that
  target this receptor are most
  effective.
  ~ Activation of MOR also causes feeling
  of euphoria due to increased
  dopamine release, which can
  contribute to the decrease in pain.

Question 12

Opioid Agonist Actions: Antitussive/Cough Suppression

Answer 12

• Activated receptors inhibit nerves in the brain and or airway/GI tract
  ~ Stops the cough reflex arc

Question 13

Opioid Agonist Side Effects: Sedation

Answer 13

• Induces Calm/Relaxation
  ~ Could be seen as a therapeutic
  action, but not used in this way due
  to abuse potential and side effects.
  ~ Mechanism not well understood:
  > Decreased sensory input
  > Decreased arousal

Question 14

Opioid Agonist Side Effects: Respiratory Depression

Answer 14

• Depresses activity of chemoreceptors in the carotid arteries
  ~ Chemoreceptors sensitive to O2 and
  CO2 levels inhibited
  > Respiratory rate not adjusted to
  reduce CO2 or O2 levels in the
  blood
• Depresses activity of respiratory control centers of the brain
  ~ Neurons controlling respiratory
  rhythm inhibited
  ~ Neurons sensing changes in pH
  inhibited
  > Respiratory rate not adjusted to
  compensate for pH changes
• CO2 affects pH making it important for the body to excrete it

Question 15

Opioid Respiratory Depression

Answer 15

• Main cause of death with opioid overdose
  ~ Combining with CNS depressants
  worsens this effect
• CNS depressants
  ~ Alcohol
  ~ Sedatives
  ~ Anticonvulsants
  ~ Hypnotics
  ~ Muscle relaxers
  ~ Anti-Anxiety meds

Question 16

Signs of Opioid Induced Respiratory Depression

Answer 16

• Unconsciousness/Inability to Awaken
• Slow or Shallow Breathing
• Choking or Gurgling Sounds
• Cyanosis of Lips and Fingernails
• Opioid antagonists can be used to reverse effects of overdose
  ~ Drug administered to block binding of
  opiate agonists to opiate receptors
  > Naloxone (Narcan)
  > Push to have this drug available
  to first responders and families
  of addicts

Question 17

Opioid Agonist Side Effects: Constipation

Answer 17

• Opioid receptors inhibit afferents lining the bowel
  ~ Decreased motility/contractility
  ~ Decreased intestinal secretion

Question 18

Local Injectable Anesthetics

Answer 18

• Parenteral administration by a physician or nurse
• Action
  ~ Binds directly to sodium channels
  > Sodium can’t enter cell
  > Inhibits nerve depolarization
  ~ Local anesthetic often paired with a
  vasoconstrictor to prolong
  effectiveness
  > Epinephrine
• Anesthetics include
  ~ Novocain
  ~ Lidocaine
  ~ Marcaine

Question 19

Local Injectable Anesthetics: Guidelines for Use

Answer 19

• Only in facilities equipped to handle any allergic reaction or cardiopulmonary emergency.
• Only when risk of administration is fully explained to the patient.
• Only when no/minimal risk of increased injury.

Question 20

Local Injectable Anesthetics: Side Effects

Answer 20

• CNS
  ~ Seizures
  ~ Tremors
  ~ Dizziness
  ~ Lightheadedness
• Depressed electrical conduction of the myocardium.