NSAIDS & Opioids

Question 1

What type of drug is Aspirin?

Answer 1

Salicylates

Question 2

What are NSAIDS used to treat

Answer 2

Treatment of gout.

Question 3

ASPIRIN MOA

Answer 3

● Aspirin is a weak organic acid that irreversibly acetylates and, thus, inactivates cyclooxygenase.
● Acetylation of COX-1 and COX-2 results in decreased prostaglandin secretion Anti Inflammatory action:
● Inhibition of cyclooxygenase diminishes the formation of prostaglandins and, thus, modulates aspects of inflammation mediated by prostaglandins
Analgesic action:
● PGE2 is thought to sensitize nerve endings to the action of bradykinin, histamine, and
other chemical mediators released locally by the inflammatory process.
● Thus, by decreasing PGE2 synthesis, the sensation of pain can be decreased.
● As COX-2 is expressed during times of inflammation and injury, it is thought that
inhibition of this enzyme is responsible for the analgesic activity of NSAIDs. Antipyretic action:
● Fever occurs when the set-point of the anterior hypothalamic thermoregulatory center is elevated.
● This can be caused by PGE2 synthesis, which is stimulated when endogenous fever-producing agents (pyrogens), such as cytokines, are released from WBCs that are activated by infection, hypersensitivity, malignancy, or inflammation.
● The NSAIDs lower body temperature in patients with fever by impeding PGE2 synthesis and release, resetting the “thermostat” back toward normal.
● This rapidly lowers the body temperature of febrile patients by increasing heat dissipation through peripheral vasodilation and sweating

Question 4

ASPIRIN USE

Answer 4

● Analgesic
● Antipyretic
● anti inflammatory (high dose)
● antithrombotic (minor effect apart from aspirin which has more)
● closure of ductus arteriosus in the newborn
● Osteoarthritis
● Rheumatoid arhtritis

Question 5

ASPIRIN SIDE EFFECTS

Answer 5

● GI toxicity
● Nephrotoxicity
● Increased bleeding time
● Bronchoconstrictor reaction due to increased leukotriene
● Tinnitus
● Hyperventilation
● Metabolic acidosis
● Hyperthermia
● Coma in overdose

Question 6

ASPIRIN CONTRAINDICATION

Answer 6

Only use in pregnancy if no other choice

Question 7

What type of drug is Celecoxib?

Answer 7

COX-2 inhibitor.

Question 8

Celecoxib MOA

Answer 8

● significantly more selective for inhibition of COX-2 than COX-1
● inhibition of COX-2 is reversible
● Selective reversible inhibition of COX-2 resulting in decreased prostaglandin synthesis

Question 9

Celecoxib USES

Answer 9

● Rheumatoid arthritis
● osteoarthritis, and
● acute pain
● Pain relief

Question 10

Celecoxib SIDE EFFECTS

Answer 10

● Headache
● dyspepsia
● diarrhea and
● abdominal pain
● Nephrotoxicity
● Greater risk to thrombosis

Question 11

Celecoxib CONTRAINDICATIONS

Answer 11

● Gastric ulcer

● Cardiovascular patients

Question 12

What is paracetamol also known as

Answer 12

Acetaminophen

Question 13

Acetaminophen MOA

Answer 13

● inhibits prostaglandin synthesis in the CNS, leading to antipyretic and analgesic effects.
● Acetaminophen has less effect on cyclooxygenase in peripheral tissues (due to
peripheral inactivation), which accounts for its weak anti-inflammatory activity.
● Acetaminophen does not affect platelet function or increase bleeding time.
● N-acetylcysteine is an antidote in cases of overdose

Question 14

Acetaminophen USES

Answer 14

● treatment of fever
● relief of pain
● gastric complaints/risks
● children with viral infections or chickenpox (due to the risk of Reye syndrome with
aspirin).

Question 15

Acetaminophen ADVERSE EFFECTS

Answer 15

● Hepatic necrosis

● hepatotoxicity

Question 16

Acetaminophen CONTRAINDICATIONS

Answer 16

● Patients with hepatic disease, viral hepatitis, or a history of alcoholism are at higher risk of acetaminophen-induced hepatotoxicity

● severe hepatic impairment.

Question 17

Strong opioid agonist EXAMPLES

Answer 17

Morphine 
Fentanyl 
Hydromorphone 
Meperidine 
Methadone 
Oxymorphone

Question 18

Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone

MOA

Answer 18

● Strong mu agonist
● Variable delta and kappa agonist
● exert analgesic effects by interacting stereospecifically with opioid receptors.
● Morphine is somewhat selective to the μ opioid receptor but has some affinity for the κ and δ
receptors.
● inhibits the release of many excitatory transmitters from nerve terminals carrying nociceptive
(painful) stimuli.

Question 19

Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone

USE

Answer 19

● Analgesia: Morphine and other opioids relieve pain by raising the pain threshold at the spinal cord level and by altering the brain’s perception of pain.
● Euphoria: Morphine produces a powerful sense of contentment and well-being. Euphoria may be caused by disinhibition of the dopamine-containing neurons of the ventral tegmental area.
● Respiration: dose dependent respiratory depression ↓ sensitivity of respiratory centre to CO2 → most common cause of death in acute opioid overdose
● Miosis: the pinpoint pupil(constriction) caused by activation of Mu and Kappa receptors
● Emesis: - morphine→ chemoreceptor trigger zone in the area postrema/medulla ( causing nausea)
● GI tract: ↓Gastric motility and emptying → leading to constipation
● Histamine release: from mast cells→ leading to vasodilation → hence
hypotension
● Labor: prolongs 2nd stage of labour by acutely ↓ strength & duration &
frequency of uterine contraction.

Question 20

Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone

USES

Answer 20

● Analgesia (pain in trauma, cancer & severe pain)
● Diarrhoea
● Relief of cough (Codeine)-depression of cough centre in medulla
● Acute pulmonary
● Anastasia
● Post-operative pain

Question 21

Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone

SIDE EFFECTS

Answer 21

● Sedation
● constipation
● urinary retention
● potential for addiction
● respiratory depression
● nausea
● hypotension
● bradycardia
● tolerance
● Withdrawal symptoms: dysphoria, anxiety, diaherra

Question 22

List and evaluate the 2 partial opioid agonists

Answer 22

Codeine
● Lower efficacy
● Lesser toxicity compared to morphine
● Used along with acetaminophen or nsaids

Hydrocodone
● Lower efficacy
● Lesser toxicity compared to morphine

Question 23

Codeine
Hydrocodone

MOA

Answer 23

● Strong mu agonist but lower efficacy
● Variable delta and kappa agonist but lower efficacy
● inhibits the release of many excitatory transmitters from nerve terminals carrying nociceptive
(painful) stimuli.

Question 24

Codeine
Hydrocodone

USES

Answer 24

● For mild to moderate pain

● Cough relief

Question 25

Codeine
Hydrocodone

SIDE EFFECTS

Answer 25

Weaker than strong agonist
● Sedation
● constipation
● urinary retention
● potential for addiction
● respiratory depression
● nausea
● hypotension
● bradycardia
● tolerance
● Withdrawal symptoms: dysphoria, anxiety, diaherra

Question 26

List the two mixed opioid agonists

Answer 26

Buprenorphine

Nalbuphine

Question 27

Buprenorphine

Answer 27

● Partial mu agonist and kappa antagonist
● Longer duration of action due to high affinity to opioid receptor
● provides ceiling effect causing less euphoric and lower abuse potential.
● Adverse effects: cardiovascular factors, chance of addiction.

Question 28

Nalbuphine

Answer 28

● mu agonist and kappa antagonist
● Used in severe headaches
● Does not affect heart or increase BP
● Provides ceiling effect for respiratory depression.

Question 29

TRAMADOL, ANOTHER ANALGESICS

Answer 29

● Weak mu agonist
● Weakly inhibits serotonin and norepinephrine uptake
● Used for pain control
● Adverse effects: anaphylactic reaction, seizures
● CI: seizures

Question 30

Naloxone: Opioid Antagonist

Answer 30

● competitive antagonist at μ, κ, and δ receptors, with a 10-fold higher affinity for mu than for kappa receptors.

● can also be administered intramuscularly, subcutaneously, and intranasally, with a slightly longer onset of 2 to 5 minutes

Question 31

Naltrexone: Opioid Antagonist

Answer 31

● it has a longer duration of action
● Naltrexone in combination with clonidine (and, sometimes, with buprenorphine) is used
for rapid opioid detoxification
● Adverse effect: hepatotoxicity

Question 32

MOA & USE of Opioid Antagonists

Answer 32

Mechanism Of Action:
● Antagonist to all opioid receptors

Therapeutic uses: ● Opioid overdose

Question 33

Antitussives: Examples

Answer 33

Codeine

Dextromethorphan

Question 34

Codeine

Answer 34

● Lower efficacy
● Lesser toxicity compared to morphine
● Used along with acetaminophen or nsaids

Question 35

Codeine
Dextromethorphan

MOA

Answer 35

● Weak mu agonist

● Inhibits norepinephrine and 5-HT transporters

Question 36

Codeine
Dextromethorphan

USES

Answer 36

● Acute debilitating cough