NSAIDS & Opioids Flashcards
What type of drug is Aspirin?
Salicylates
What are NSAIDS used to treat
Treatment of gout.
ASPIRIN MOA
● 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
ASPIRIN USE
● 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
ASPIRIN SIDE EFFECTS
● GI toxicity ● Nephrotoxicity ● Increased bleeding time ● Bronchoconstrictor reaction due to increased leukotriene ● Tinnitus ● Hyperventilation ● Metabolic acidosis ● Hyperthermia ● Coma in overdose
ASPIRIN CONTRAINDICATION
Only use in pregnancy if no other choice
What type of drug is Celecoxib?
COX-2 inhibitor.
Celecoxib MOA
● 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
Celecoxib USES
● Rheumatoid arthritis
● osteoarthritis, and
● acute pain
● Pain relief
Celecoxib SIDE EFFECTS
● Headache ● dyspepsia ● diarrhea and ● abdominal pain ● Nephrotoxicity ● Greater risk to thrombosis
Celecoxib CONTRAINDICATIONS
● Gastric ulcer
● Cardiovascular patients
What is paracetamol also known as
Acetaminophen
Acetaminophen MOA
● 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
Acetaminophen USES
● treatment of fever ● relief of pain ● gastric complaints/risks ● children with viral infections or chickenpox (due to the risk of Reye syndrome with aspirin).
Acetaminophen ADVERSE EFFECTS
● Hepatic necrosis
● hepatotoxicity
Acetaminophen CONTRAINDICATIONS
● Patients with hepatic disease, viral hepatitis, or a history of alcoholism are at higher risk of acetaminophen-induced hepatotoxicity
● severe hepatic impairment.
Strong opioid agonist EXAMPLES
Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone
Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone
MOA
● 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.
Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone
USE
● 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.
Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone
USES
● Analgesia (pain in trauma, cancer & severe pain)
● Diarrhoea
● Relief of cough (Codeine)-depression of cough centre in medulla
● Acute pulmonary
● Anastasia
● Post-operative pain
Morphine Fentanyl Hydromorphone Meperidine Methadone Oxymorphone
SIDE EFFECTS
● Sedation ● constipation ● urinary retention ● potential for addiction ● respiratory depression ● nausea ● hypotension ● bradycardia ● tolerance ● Withdrawal symptoms: dysphoria, anxiety, diaherra
List and evaluate the 2 partial opioid agonists
Codeine
● Lower efficacy
● Lesser toxicity compared to morphine
● Used along with acetaminophen or nsaids
Hydrocodone
● Lower efficacy
● Lesser toxicity compared to morphine
Codeine
Hydrocodone
MOA
● 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.
Codeine
Hydrocodone
USES
● For mild to moderate pain
● Cough relief
Codeine
Hydrocodone
SIDE EFFECTS
Weaker than strong agonist ● Sedation ● constipation ● urinary retention ● potential for addiction ● respiratory depression ● nausea ● hypotension ● bradycardia ● tolerance ● Withdrawal symptoms: dysphoria, anxiety, diaherra
List the two mixed opioid agonists
Buprenorphine
Nalbuphine
Buprenorphine
● 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.
Nalbuphine
● mu agonist and kappa antagonist
● Used in severe headaches
● Does not affect heart or increase BP
● Provides ceiling effect for respiratory depression.
TRAMADOL, ANOTHER ANALGESICS
● Weak mu agonist
● Weakly inhibits serotonin and norepinephrine uptake
● Used for pain control
● Adverse effects: anaphylactic reaction, seizures
● CI: seizures
Naloxone: Opioid Antagonist
● 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
Naltrexone: Opioid Antagonist
● 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
MOA & USE of Opioid Antagonists
Mechanism Of Action:
● Antagonist to all opioid receptors
Therapeutic uses: ● Opioid overdose
Antitussives: Examples
Codeine
Dextromethorphan
Codeine
● Lower efficacy
● Lesser toxicity compared to morphine
● Used along with acetaminophen or nsaids
Codeine
Dextromethorphan
MOA
● Weak mu agonist
● Inhibits norepinephrine and 5-HT transporters
Codeine
Dextromethorphan
USES
● Acute debilitating cough
