Pharmacology I: Lecture 6 - Opioids/NSAIDs Flashcards

Question

Morphine Names and History

Answer 1

Duramorph MS Cotin DepoDur Astramorph First isolated in 1804 by a German pharmacist Named after Morpheus, the Greek god of dreams Cause of “Soldier’s Disease” during the American Civil War Heroin was derived from morphine in 1874

Answer 2

Prototype opioid agonist Effects: Analgesia Euphoria **Sedation** Diminished ability to concentrate **Relieves continuous, dull pain more effectively than intense sharp pain (somatic)**

Answer 3

Poor penetration of BBB increases effect site equilibration time because…. Relatively poor lipid solubility High degree of ionization Highly protein bound Hepatic conjugation with glucuronic acid Active metabolite: morphine-6-glucuronide (M6G) >>> M3G

Answer 4

Morphine-6-glucuronide (M6G)

Answer 5

Cardio: ↓HR,↓BP, depression Resp: Ventilation depression -↓RR,↑TV (slow and deep) CNS: ↓CBF with ↓ICP... ...sedation conversely↑PaCO2 → ↑ ICP (this will ultimately overtake the decrease effects)

Answer 6

Slow onset (15 – 20 min) and offset IV DOA: 3 – 4 hrs Active metabolite – M6G Histamine release Cough suppression Skeletal muscle rigidity Biliary spasm Miosis Decreased gastric emptying Constipation Nausea and vomiting Free placental transfer

Answer 7

Commercial preparation 0.1% morphine sulfate Duramorph®: PF Epidural: 1 mg/cc Spinal: 0.2 mg/cc Dosing IVP: 1 – 2 mg - Peds IVP 0.1 mg Intravenous: 0.05 – 0.2 mg/kg Epidural: 2 mg Spinal: 0.2 mg Used the most in C-Sections during neuroaxial anesthesia, because it doesnt pass easily through lipid barrier/BBB, won't diffuse out of the space as easy and wont pass to baby as easy

Answer 8

Synthetic Mu agonist derived from phenylepiperidine Prologue of many opioids Shares structural similarity: Local anesthetics Amine, ester, phenyl Atropine Weak antimuscarinic effect Antispasmodic effect

Answer 9

Well absorbed from the GI tract Extensive hepatic metabolism Demethylation to normeperidine Ester Hydrolysis to meperidinic acid Renal excretion

Answer 10

Analgesia Labor & delivery Post-surgery PCA Peds Post-operative shivering (decreases it)

Answer 11

Cardio: ↓BP,↑HR, myocardial depression Resp: ventilatory depression CNS: delirium, seizures Other: Free placental transfer Mydriasis Dry mouth **Toxic with MAOI – Serotonin Syndrome**

Answer 12

Commercial preparation 50 mg/cc meperidine hydrochloride Dosing IVP 50 – 100 mg Peds IVP 10 mg 0.5 – 2 mg/kg

Answer 13

Synthesized in 1960s in Belgium Recreational use at “China White” in 70s

Answer 14

Phenylpiperidine-derivative 75-125x more potent than morphine Rapid onset and short duration of action due to extremely lipophilic

Answer 15

Rapid onset and high potency reflect high lipid solubility Large tissue reservoir extend duration of action High first pass pulmonary uptake Hepatic P450 demethylation to norfentanil metabolites (inactive)

Answer 16

Analgesia Operative IV SAB Epidural Intranasal Chronic pain Transmucosal Transdermal

Answer 17

Cardio: ↓HR, mild ↓CO Resp: depression CNS: mild ↑ICP Other: Profound synergism with benzodiazepines Reflex coughing Skeletal muscle rigidity

Answer 18

Commercial preparation 50 mcg/cc fentanyl citrate Duragesic©: 12.5 – 100 mcg/hr Dosing IVP: 1 mcg/kg or 50 – 100 mcg Peds IVP: 5 mcg Intravenous: 0.5-2 mcg/kg Intrathecal: 5-25 mcg Sublingual: 5-20 mcg/kg Infusion: 1.5 – 3 mcg/kg/hr

Answer 19

75-125 times more potent than morphine

Answer 20

Thienyl analogue of fentanyl 10x potency as fentanyl

Answer 21

Rapid onset and redistribution reflect the high degree of lipid solubility of sufentanil Significant first pass pulmonary effect (60%) Same Elimination 1/2 time Lipid solubility = rapid crossing of BBB & onset Less accumulation compaired to fentanyl (in adipose tissue) Hepatic dealkylation and demethylation to desmethyl sufentanil

Answer 22

Commercial preparation 50 mcg/cc sufentanil hydrochloride DOA: 10 – 20 min Dosing IVP: 5 – 10 mcg IV: 0.05 – 0.2 mcg/kg Infusion: 0.1 – 0.4 mcg/kg/hr

Answer 23

Analgesia with 10x potency compared to Fentanyl

Answer 24

Analogue of fentanyl 20% potency of fentanyl 30% duration of fentanyl

Answer 25

Rapid effect-site equilibration due to↓pK **Vd = fentanyl > sufentanil > alfentanil > remifentanil** 90% of drug exists as non-ionized which can cross the BBB **Interaction with erythromycin will ↓ metabolism** Hepatic metabolism via dealkylation Piperidine to noralfentanil

Answer 26

Commercial preparation 500 mcg/cc alfentanil hydrochloride Dosing IV: 15 – 30 mcg/kg Infusion: 15 – 25 mcg/kg/hr

Answer 27

**Chemically related to fentanyl of phenylpiperidine, but with a unique ester linkage** Potency equal to fentanyl Duration equal to alfentanil Selective Mu opioid agonist

Answer 28

Brevity of action Precise Rapidly titratable Non-cumulative effect **Rapid recovery** **Great of infusions or short stimulations** **Continued infusion causes hyperalgesia** (great for procedures that are 40-60 minutes to avoid this, but then flip side for long surgeries you know they will wake up) ## Footnote Used at every teaching facility across the US, because very forgiving if the students mess up

Answer 29

Small Vd and extremely rapid clearance Dealkylation metabolism by non-specific plasma and tissue esterases (when metbolized by esterases, off set is quick) 99.8% of remifentanil is eliminated in less then six minutes Minimum accumulation seen no matter how long infusion is running Prolonged infusion results in hyperalgesia

Answer 30

Commercial preparation 2 mg/cc remifentanil hydrochloride Dosing IV: 0.25 mcg/kg Infusion: 0.1 – 0.5 mcg/kg/min

Answer 31

Is a derivative of morphine A semi-synthetic Mu agonist Structure change increases its lipid solubility and ability to cross the BBB 3 – 4x as potent but shorter DOA Hepatic metabolism by CYP 450 Rapid elimination and redistribution

Answer 32

Commercial preparation 1 mg/cc or 2 mg/cc Dosing IVP: 0.5 – 1 mg Often used in post op PCA pump

Answer 33

Carfentanil, an opioid 10,000 times more powerful than morphine and 100 times more powerful than fentanyl Used in Veterinary medicine in an injection form On October 26, 2002, Russian Special Forces deployed an aerosol form of carfentanil and remifentanil against Chechen terrorists to rescue hostages in the Dubrovka theatre. Caused 125 deaths through respiratory failure. Carfentanil is a considered a weapon by the Chemical Weapons Convention.

Answer 34

It is 10,000 times more powerful than morphine and considered a weapon

Answer 35

3-methylmorphine

Answer 36

3-4 times as potent as morphine

Answer 37

Selective Mu opioid agonist with a rapid onset and non-cumulative effect

Answer 38

Metabolites are excreted in the urine

Answer 39

* Analgesia * Euphoria * Sedation * Diminished ability to concentrate

Answer 40

It criminalized narcotic possession

Answer 41

* Cardiovascular effects: ↓BP, ↑HR * Respiratory: ventilation depression * CNS: delirium, seizures

Answer 42

1 mcg/kg or 50 – 100 mcg

Answer 43

Limits 1st pass hepatic metabolism ## Footnote This modification affects the metabolism of morphine, influencing its pharmacological properties.

Answer 44

90% ## Footnote Norcodeine is considered an inactive metabolite of morphine.

Answer 45

Codeine – 100mg Morphine – 10 mg Dilaudid – 1 mg (to 2mg depends on text) Fentanyl – 100 mcg Sufentanyl – 10 mcg

Answer 46

Natural-occurring phenanthrene Results from a methyl group substituted for an alcohol at C #3 of morphine This limits 1st pass hepatic metabolism de-Methylation in liver  Morphine 10% 90% is norcodeine – inactive Oral antitussive, IM analgesic

Answer 47

Add a alcohol to hydromorphone 10X as potent as morphine More N/V Physical dependence

Answer 48

Oxy Contin has a high abuse potential Rapid and powerful opioid effects

Answer 49

Vicodan High abuse potential

Answer 50

Synthetic opioid agonist Highly effective by oral route Used for suppression of w/drawl symptoms in dependent (heroin addict) Substitute for morphine but 1/4th the dose

Answer 51

5-10X less potent than morphine Mix of two enantiomers, one inhibits NE the other acts on mu receptors Metabolized by hepatic P450 to desmethyltramadol

Answer 52

Is a synthetic opioid activated by acetylation to morphine It rapidly enters the brain and is hydrolyzed to active metabolites monoacetylmorphine and morphine Heroin has a rapid onset, lack of N/V effect and high dependency

Answer 53

10X as potent as morphine ## Footnote Oxymorphone is derived from hydromorphone and has increased side effects, including nausea and vomiting.

Answer 54

Oral analgesic with high abuse potential ## Footnote Oxy Contin is a formulation of oxycodone known for its rapid and powerful opioid effects.

Answer 55

Synthetic opioid agonist used for withdrawal symptom suppression ## Footnote Methadone can be used as a substitute for morphine, typically at a quarter of the dose.

Answer 56

Bind to Mu receptors to produce limited (partial agonist) or no effects (competitive antagonist) Similar side effects Advantages = produce analgesia w/ limited depression of ventilation and low dependence due to ceiling effect Commonly given to treat withdrawal symptoms

Answer 57

Naloxone (Narcan) Pure opioid receptor antagonist at μ receptors Displaces agonist and binds to receptors Onset: < 60 seconds Duration: 30 – 45 minutes

Answer 58

Associated N/V after rapid IV administration (slow push) Cardiovascular stimulation Neonatal withdrawal Commercial preparation 0.4 mg/cc nalaxone hydrochloride Dosing 1 – 4 mcg/kg IVP 40 mcg q 60s Infusion: 5 mcg/kg/hr

Answer 59

Aspirin protypical NSAID Hippocrates wrote about using powder from willow bark for pain and fever in 5th century BC 20th Century Bayer scientist acetylsalicylic acid and marketed Aspirin for pain/fever Anti-inflammation Analgesic Anti-pyretic Treatment of gout Prophylaxis of heart disease (MI and stroke) Prophylaxis of colorectal cancer Treatment of Alzheimer’s Dz

Answer 60

COX activity is associated with two isoenzymes COX-1 Found in gastric mucosa, renal parenchyma, and platelets Essential in platelet agg., GI mucosal integrity, and renal function COX-2 Inducible Expressed mainly at sites of injury Mediates inflammation, fever, pain

Answer 61

All-encompassing classification of drugs possessing analgesic, anti-inflammatory, and anti-pyretic (fever) effects Categorization Non-specific COX inhibitors Aspirin & NSAIDs COX-2 selective inhibitors Beneficial effects Pain relief Attenuation of inflammatory processes No dependence or addiction potential Synergistic effects with opioids No ventilatory depression No associated N/V

Answer 62

Adverse side-effects ↓platelet aggregation Gastric ulceration Renal dysfunction ↑asthmatic bronchospasm

Answer 63

Irreversibly acetylates COX Clinical indications Analgesia (low-intensity pain) Anti-pyretic Anti-platelet for prevention of MI Clinical considerations GI intolerance and ulceration Anticoagulant effects Aspirin-induced asthma

Answer 64

Clinically used agents Ibuprofen (Advil®, Motrin®) Naproxen (Alleve®) Tiaprofenic acid (Surgam®) Diclofenac (Voltaren®) Clinical considerations Extensive plasma albumin binding

Answer 65

Proprionic acid derivative Dosing: 30 mg IV or IM Analgesic equivalent to 10 mg of MSO4 Clinical considerations Inhibition of platelet aggregation Cross-tolerance with aspirin Life-threatening bronchospasm in aspirin-induced asthma Old studies show renal damage but now no indication of renal toxicity

Answer 66

Not a true NSAID, but exhibits strong central inhibition of prostaglandin synthesis Analgesic and antipyretic effects, but no anti-inflammatory mechanisms Clinical considerations No anticoagulant effects Chronic use can lead to renal medullary ischemia Hepatotoxicity IV acetaminophen (Ofirmev®) Old drug new use Dosage & Preparation Peds: 10 – 15 mg/kg IV or suppository IV: 1 g q 6 hrs max dose 4 g Comes in 1000 mg in 100 ml Given over 15 min

Answer 67

Exhibit analgesic efficacy, w/o effects on platelets and GI tract Commonly used agents Celecoxib (Celebrex®) Rofecoxib (Vioxx®) Valdecoxib (Bextra®) Meloxicam (Mobic®) Indications for clinical use Osteoarthritis Rheumatiod arthritis Acute gout Dysmenorrhea Post-operative pain Prevention of Alzheimer’s disease*

Answer 68

Imbalance between the prothrombotic and vasoconstricting activity of thromboxane A2 (TXA2), and the antithrombotic and vasodilatory effects of prostacyclin (PGI2), thereby favoring deleterious thromboxane effects Rofecoxib and valdecoxib (both discontinued) are associated with significant ischemic stroke risk In 2005, a consensus statement issued by the Food and Drug Administration (FDA) Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee concluded that COX-2 selective agents that the preponderance of data demonstrates that the cardiovascular risk associated with celecoxib is similar to that associated with commonly used, older, nonselective NSAIDs COX-2 inhibitors do not affect platelet function and should be considered when there are concerns regarding postoperative hemostasis

Answer 69

5-10X less potent than morphine, inhibits NE and acts on mu receptors ## Footnote Tramadol is metabolized by hepatic P450 to desmethyltramadol.

Answer 70

Activated by acetylation to morphine, has rapid onset and high dependency ## Footnote Heroin is hydrolyzed to monoacetylmorphine and morphine, leading to its potent effects.

Answer 71

Bind to Mu receptors to produce limited or no effects ## Footnote These agents provide analgesia with limited respiratory depression and low dependence.

Answer 72

Pure opioid receptor antagonist at μ receptors, displaces agonist ## Footnote Onset is less than 60 seconds with a duration of 30-45 minutes.

Answer 73

Associated N/V after rapid IV administration, cardiovascular stimulation ## Footnote Caution is advised due to potential neonatal withdrawal effects.

Answer 74

Irreversibly acetylates COX ## Footnote Aspirin is a prototypical NSAID with various clinical uses including analgesic and anti-inflammatory.

Answer 75

* Anti-inflammation * Analgesic * Anti-pyretic * Treatment of gout * Prophylaxis of heart disease * Prophylaxis of colorectal cancer * Treatment of Alzheimer's disease ## Footnote Aspirin has a long history of use dating back to ancient medicine.

Answer 76

* COX-1 * COX-2 ## Footnote COX-1 is essential for normal physiological functions, while COX-2 is inducible in response to injury.

Answer 77

* ↓ platelet aggregation * Gastric ulceration * Renal dysfunction * ↑ asthmatic bronchospasm ## Footnote These side effects highlight the need for careful monitoring when using NSAIDs.

Answer 78

* Ibuprofen * Naproxen * Tiaprofenic acid * Diclofenac ## Footnote These agents are used clinically for pain relief and inflammation.

Answer 79

Exhibits strong central inhibition of prostaglandin synthesis, analgesic and antipyretic effects ## Footnote It does not have anti-inflammatory mechanisms.

Answer 80

* Osteoarthritis * Rheumatoid arthritis * Acute gout * Dysmenorrhea * Post-operative pain * Prevention of Alzheimer’s disease ## Footnote COX-2 inhibitors are designed to provide analgesia without affecting platelet function.

Answer 81

FDA approved in Jan of 2025 for moderate to serve pain First FDA approved pain medication in 20 years Target: Selective inhibition of voltage-gated sodium channel NaV in the PNS. This slide introduces Suzetrigine, a non-opioid investigational analgesic developed by Vertex Pharmaceuticals. Its focus is on treating moderate-to-severe pain by selectively targeting the NaV1.7 sodium channel, which plays a key role in pain signaling.

Answer 82

Blocks NaV1.7 sodium channels crucial in nociceptive signaling NaV1.7 Role: Amplifies pain signals in sensory neurons Selectivity: High selectivity for NaV1.7 over other NaV subtypes (e.g., NaV1.5, NaV1.6) Outcome: Reduces pain perception without central nervous system depression ## Footnote This selectivity helps reduce pain perception without central nervous system depression.

Answer 83

Absorption: Oral bioavailability reported in early studies Distribution: Likely peripheral action, minimal CNS penetration Metabolism: Under investigation – presumed hepatic Half-Life: Under study; candidate for once-daily dosing Excretion: Renal and/or biliary elimination anticipated The pharmacokinetics of Suzetrigine are still being fully characterized. However, it's expected to be orally bioavailable and largely peripheral in action. Once-daily dosing may be possible based on its half-life.

Answer 84

Indications Studied: - Acute pain (e.g., abdominoplasty, bunionectomy) - Chronic neuropathic pain (e.g., diabetic peripheral neuropathy) Phase II Results: - Significant reduction in pain scores vs. placebo with 50mg to 100mg BID dosing - Well tolerated, minimal CNS or GI side effects Suzetrigine has shown promise in Phase II trials for both acute and chronic pain conditions. The current Phase III trials aim to establish its safety profile and optimal dosing regimen.

Answer 85

* Significant reduction in pain scores vs. placebo * Well tolerated with minimal CNS or GI side effects ## Footnote Dosages studied were 50mg to 100mg BID.

Pharmacology I: Lecture 6 - Opioids/NSAIDs Flashcards

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