Analgesics Flashcards
Nociceptive pain txvs Chronic neuropathic pain
nociceptive: treated with anti-inflammatory or analgesic medications
Chronic neuropathic pain: is treated with medications that act to influence neurotransmitters (i.e. antidepressants or antiepileptic drugs) in addition to anti- inflammatories and analgesics.
opiopeptins
include peptides such as the endorphins and the enkephalins.
opiate drugs work by binding to specific opioid receptors in order to produce effects that mimic the actions of opiopeptins.
5 areas of densest opiate receptors
brainstem, medial thalamus, spinal cord, hypothalamus and limbic system.
Also peripheral sensory nerves
5 Opiate receptor families
μ(mu), κ(kappa), σ(sigma), δ(delta) and ε(epsilon)
The analgesic properties of the opiates are
primarily mediated by the ??? receptors
mu
The enkephalins interact more selectively with the ???receptors in the periphery
delta
The ??? receptor appears to be less selective, interacting with drugs such as the hallucinogen, phencyclidine.
sigma
responsible for the hallucination sof opiates
which receptor only reacts to morphine?
mu3 opiate receptor.
Opiate analgesics MOA
nerve hyperpolarization
release of substance P from terminal and other pain mediators
Opiate/ Narcotic analgesics examples
- Morphine sulfate - MS Contin
- Meperidine - Demerol
- Hydromorphone - Dilaudid
- Fentanyl - Duragesic
- Oxycodone - Oxycontin, Percodan, Percocet
- Hydrocodone – Vicodin
- Codeine – T#3, T#4
- Tramadol/ Ultram
what shcedule are hydrocodone combination products (HCPs), which include opioids such as Vicodin, Lorcet, Lortab and Norco?
newly re-classified as schedule II and subject to tighter restrictions
HCPs are the most frequently-prescribed drugs in the U.S.
Morphine/ MS Contin
• Class: Opioid analgesic
• Indication: Pain relief
• MOA: Potent opioid agonist. High affinity for μreceptors. Morphine relieves pain both by raising the pain threshold at the brain stem, thalamic and spinal cord level as well as by altering the brain’s perception of pain. Patients treated with morphine may still be aware of the presence of pain but perception of the actual sensation of pain is blocked.
Morphine is also used in the setting of acute myocardial infarction. It can potentially provide pain relief, decrease anxiety and also acts as a peripheral vasodilator.
morphine char
Char: PO, PR, IM, IV. Duration of action varies by route. Significant first pass metabolism with oral route. Morphine is capable of producing a powerful sense of well being and euphoria. Highly addictive. Tolerance to dosing develops.
Morphine SE
Side effects:
• Morphine causes respiratory depression by reducing the sensitivity of respiratory center neurons to carbon dioxide.
Respiratory depression is the most common cause of death related to morphine.
• Miosis (pin point pupils) is due to enhanced parasympathetic stimulation to the occulomotor nerve.
• Itching is a common side effect due to the fact that the opiate drugs can stimulate histamine release.
• Morphine often causes nausea and vomiting due to stimulation of the chemoreceptor trigger (nausea center) in the brain.
• Constipation due to reduced G.I. smooth muscle motility. Paralytic ileus is possible.
• Morphine crosses the placenta, thus potentially creating physical dependence in infants exposed to the drug.
Fentanyl/ Duragesic
• Class: Opioid analgesic
• Indication: Pain relief, anesthesia
• MOA: Similar to morphine with 80x the
analgesic property of morphine. Used for
anesthesia and for intractable pain. • Char: I.V., transdermal patch, buccal
lozenge and film, sublingual spray and a “lollypop” form. Onset of action within minutes. Single I.M. doses have duration of action of 1-2 hours, single I.V. doses last 30 mins to 1 hour.
Patch delivers 25 – 100 mcg/ hour.
Fentanyl/ Duragesic SE
- Side effects: Respiratory depression with life threatening hypoventilation can occur.
- Patients using concomitant CYP 450 inhibitors may result in fatal blood levels of Fentanyl.
- Nausea/ vomiting.
- Constipation is a commonly occurring side effect and paralytic ileus can occur.
- Concurrent ethanol use may increase CNS depression.
- Highly addictive.
- Avoid concurrent intake of large quantities (>1 quart/day) of grapefruit juice and St Johnswort
schedule and category of Fentanyl/ Duragesic
Category CII
Pregnancy category C
other forms of Fentanyl/ Duragesic
• Transmucosal immediate-release Fentanyl products (i.e. sublingual tablets and spray, oral lozenges, buccal tablets and soluble film, nasal spray) are only available through the Transmucosal Immediate- Release Fentanyl (TIRF) ACCESS program.
Enrollment in the program is required for outpatients, prescribers for outpatient use, pharmacies (inpatient and outpatient), and distributors.
Codeine
• Class: Opioid analgesic
• Indication: Pain relief, antitussive
• MOA: Opioid agonist, is converted to
morphine in the body but mg per mg, codeine
is much weaker analgesic then morphine.
• Char: PO, IV, IM, SQ, - Lower abuse potential
than the more potent narcotic analgesics. Effective antitussive – codeine is able to suppress cough at doses which are lower then a typical analgesic dose.
Codeine schedule and category
DEA schedule CII to CV depending upon dose of codeine. Pregnancy category C.
Codeine SE
Side effects:
• Sedation,
•constipation,
• itching and increased potential for exaggerated response in certain individuals at risk due to genetic variability .
• The FDA has issued a Drug Safety Communication after reviewing reports of children who developed serious adverse effects, including death, after receiving codeine in the usual dosage range for pain relief following tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. Ultra-rapid metabolizers ~1-7 per 100 people.
Tramadol/ Ultram
- Tramadol is a centrally-acting analgesic, used for treating moderate to severe pain.
- Tramadol possesses mild agonist actions at the μ-opioid receptor and also affects reuptake at the noradrenergic and serotonergic systems.
- Respiratory depression, a common side- effect of most opioids, is not clinically significant in normal doses.
suggested that Tramadol could be effective for alleviating symptoms of depression, anxiety, and phobias because of its action on the serotonergic systems and noradrenergic
Acetaminophen-containing narcotic analgesics
- Codeine/acetaminophen - Tylenol 3 or 4
- Hydrocodone/acetaminophen -Vicodin, Lortab
- Oxycodone/acetaminophen - Percocet, Roxicet
- Propoxyphene/acetaminophen - Darvocet
- Tramadol/acetaminophen - Ultraset
NSAID-containing narcotic analgesics
- Oxycodone/aspirin - Percodan
- Oxydodone/ibuprofen - Combunox
- Hydrocodone/ibuprofen - Vicoprofen
Heroin
- Heroin does not exist naturally.
- It is produced by acetylation of morphine to diacetylmorphine which leads to a 2-3 fold increase in its potency.
- Heroin is more lipid soluble, which allows for more rapid crossing of the blood brain barrier, generally producing a much greater sense of euphoria than does morphine
At present, heroin has no accepted medical use and it therefore carries a DEA designation of category I..
Methadone
- Methadone is a synthetic, orally effective opioid that is approximately equal in potency to morphine but induces less euphoria and has a longer duration of action.
- Methadone is used in the controlled withdrawal of heroin and morphine in addicted patients.
- Dependence can develop but the withdrawal syndrome is much milder then with heroin or morphine.
Narcotic antagonists
• Naloxone – brand name, Narcan*
• Naltrexone - brand name, Revia
• Nalorphine - brand name, Nalline
* The patent for Naloxone has expired and therefore the drug is currently available in various generic forms.
Naloxone/ Narcan
- Class: Opioid antagonist
- Indication: Opioid overdose. Naloxone is used to reverse the coma and respiratory depression of opioid overdose.
- MOA: Opioid antagonists bind with high affinity to opioid receptors but do not activate the receptor mediated response.
- Char: IV, PO. IV Naloxone rapidly displaces all receptor bound opioid molecules with onset of action within 30 seconds. Half life of 60-100 minutes.
Naloxone/ Narcan char
• Char: Rapid reversal of opiate effects in addicted patients can acutely precipitate the effects of opiate withdrawal. The administration of opioid antagonists produces no notable effects in an individual that is not using or not addicted to an opiate analgesic.
Dextromethorphan

• Dextromethorphan is the dextro-isomer
of codeine.
• It is an effective antitussive and is commonly used in OTC cough medications.
• Dextromethorphan generally has little to no analgesic, sedative or G.I. effects.
NSAIDs
- The nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the synthesis of prostaglandins,
- Prostaglandins are unsaturated fatty acid derivatives containing 20 carbons that include a cyclic ring compound.
- Prostaglandins are also referred to as eicosanoids since “eicosa” refers to the 20 carbon atom structure. thromboxanes and the prostacyclins
Prostaglandin action
promote inflammation, pain, and fever, support the clotting function of platelets and protect the lining of the stomach from the damaging effects of acid.
Cox-1 function
primarily involved in the production of prostaglandins that support platelets and protect the stomach.
NSAIDs – COX 1 & 2 inhibitors
- Aspirin and other salicylates
- Ibuprofen – Motrin, Advil
- Indomethacin – Indocin
- Ketoprofen – Orudis
- Ketorolac - Toradol
- Naproxen – Alleve, Naprosyn
- Piroxicam – Feldene
- Mefenamic acid – Ponstel
- Acetaminophen - Tylenol
NSAIDs – COX 2 inhibitors
- Celecoxib - Celebrex
- Rofecoxib – Vioxx (baaaaad)
- Valdecoxib - Bextra
Aspirin/ Acetylsalicylic acid (ASA)
• Class: NSAID
• Indication: Inflammation, pain, fever
• MOA: Irreversible inhibition of COX-1 and COX-2 enzymes. Anti-inflammatory and analgesic effect largely due to blockade of prostaglandin synthesis at target tissues. Anti-pyretic effect due to blockade of prostaglandin synthesis at thermoregulatory centers in the hypothalamus.
Prostaglandin E2 (PGE2) is thought to sensitize nerve endings to the actions of bradykinins, histamines and other inflammatory mediators. Thus, aspirin serves to diminish pain by decreasing tissue sensitivity to the sensation of pain.
Char: PO, PR. Readily absorbed. Metabolized by liver, excreted in urine.
Aspirin/ Acetylsalicylic acid SE
Side effects: Many potential side effects. Primarily G.I. irritation and peptic ulcer disease, nausea, and vomiting. Increased risk of bleeding. Renal insufficiency. Increased risk of Reye’s syndrome.
• Salicylism involves dizziness, tinnitus, hyperventilation, mental status changes and potential for coma and death.
• Treatment for salicylism involves I.V. hydration,
alkalinization of urine and dialysis if renal insufficiency occurs.
Sx of Salicysm and tx
Salicylism involves dizziness, tinnitus, hyperventilation, mental status changes and potential for coma and death.
• Treatment for salicylism involves I.V. hydration,
alkalinization of urine and dialysis if renal insufficiency occurs.
Aspirin and viral URI
Don’y give aspirin to any patients with a febrile illness or suspected viral URI until after age 15 – 18–> Reyes syndrome
Ibuprofen/ Motrin, Advil
- Class: NSAID
- Indication: Inflammation, pain, fever
- MOA: Reversible inhibition of COX-1 and COX-2 enzymes. Anti-inflammatory and analgesic effect largely due to blockade of prostaglandin synthesis at target tissues.
- Char: PO, PR. No increased risk for Reye’s syndrome has been noted.
Celecoxib/ Celebrex
- Class: NSAID
- Indication: Inflammation, pain, treatment of adenomatous polyps.
- MOA: Reversible, selective COX-2 inhibition
- Char: P.O. Anti-inflammatory effects with minimal irritation of GI tract, less GI bleeding and no inhibition of platelet aggregation.
- Side effects: Presently unclear if a definite increased risk for cardiovascular disease exists with Celecoxib (but that may likely be the case).
Rofecoxib/ Vioxx
increased risk of cardiovascular events (including heart attack and stroke) in patients on Rofecoxib.–withdraen by Merck in 2004
Acetaminophen/ Tylenol
- Class: NSAID
- Indication: Pain, fever
- MOA: Not fully understood. Weak peripheral blockade of prostaglandin synthesis with stronger blockade of prostaglandin synthesis in hypothalamus.
- Char: PO, PR. Readily absorbed, metabolized in liver, excreted in urine. No increased risk of GI bleeding. No increased risk for development of Reye’s syndrome.
Acetaminophen/ Tylenol SE and category
- Side effects: overdose (>7 gm/ 24 hrs) or when acetaminophen is taken with alcohol can lead to severe hepatic necrosis leading to liver failure, coma and death.
- Never mix alcohol and Tylenol.
- In the absence of any alcohol use or any underlying liver disease, consider the maximum safe dosage in adults to be 4 grams/ 24 hrs.
- Pregnancy category B
Acetaminophen toxicity
- In acute overdose or when the maximum daily dose is exceeded over a prolonged period, the normal conjugative pathways for the metabolism of acetaminophen become saturated.
- Acetaminophen is oxidatively metabolized in the liver via the mixed function P450 system to a toxic metabolite, N-acetyl-p- benzoquinone-imine (NAPQI).
NAPQI has an extremely short half-life and normally it is rapidly conjugated with glutathione, a sulfhydryl donor, and then excreted in the urine.
• Under conditions of excessive NAPQI formation or with reduced glutathione stores, NAPQI covalently binds to vital proteins and the lipid bilayer of hepatocyte membranes. The result is hepatocellular death and liver necrosis.
Acetaminophen toxicity stages
- Stage 1 – 12 to 24 hrs – N/V
- Stage 2 – 24 to 48 hrs – may be clinically improved but liver function tests reveal rising AST, ALT, and Bilirubin levels.
- Stage 3 – 72 to 96 hrs – peak hepatotoxicity, AST may exceed 20,000.
- Stage 4 – beyond 96 hours – recovery, need for liver transplant or death.
acetaminophen/tylenol dosing in kids
Child’s dose 10 -15 mg per kg depending on age
Acetaminophen toxicity treatment
• When acetaminophen overdose is suspected, treatment involves removal of any drug remaining in the stomach by lavage or induction of emesis with syrup of ipecac
.
• The antidote, N-acetylcysteine, (NAC) should be
administered as early as possible, preferably within 8 hours of the overdose ingestion for optimal results. NAC is a precursor of glutathione and increases glutathione availability to bind to NAPQI
Acetylcysteine
- Acetylcysteine is used mainly as a mucolytic agent (Mucomyst) and in the management of acetaminophen overdose (Acetadote).
- Acetylcysteine is available in a solution form for inhalation therapy, capsule and liquid forms for oral administration and IV parenteral form.
- Acetylcysteine acts to augment the glutathione reserves in the body and together with glutathione, directly bind to toxic metabolites which serves to protect hepatocytes from NAPQI toxicity.
