Analgesic Combinations Flashcards
(25 cards)
Recent Analgesia Changes
Acetaminophen - Prescribed analgesic combos to 325mg/dosage form
Hydrocodone and Acetaminophen combo - Schedule II
Extended release Hydrocodone (Zohydro ER)
Opiate VS NSAID
Opiate: Receptors in brain, spinal cord and peripheral nerves (Morphine - No “ceiling dose”, Severe pain; Codeine - “Ceiling = 60mg/dose (360mg/24hr)”)
NSAID: Analgesia by blocking prostaglandin synthesis - Inflammatory mediators, Peripheral and Central inhibition, “Ceiling analgesia”, Doses in combo products the non steroidal agent provides significant analgesia
Acetaminophen
Block prostaglandin synthesis in brain but not periphery; Diff side effect profile from other NSAIDs: No ulcers, No block of platelet aggregation (but potentiates anticoagulant warfarin), Not contraindicated in pregnancy, Used in patients with aspirin intolerance, Used in children (no Reyes syndrome), Does not interfere w/ortho adjustment and implant integration, Renal effects differ from NSAID but additive, Overdose results in fatal hepatotoxicity
Ceiling dose - 4000mg/24hr
Severe liver injury - Took more than prescribed dose in 24hr, Took more than one product, Drank alcohol
Single dose = 325mg/dose
Increased analgesia up to 1000mg/dose
Black Box warning for hepatotoxicity
Now recommend of 3000mg/day max
APAP + NSAID INCREASE ANALGESIA BUT ALSO HEPATOTOXICITY AND RENAL TOXICITY - CAFFEINE INCREASES APAP RENAL DAMAGE
Analgesic Dosing Limit
Codeine
Dental adult single oral dose - 60mg max
24hr max - 360mg (Determined by side effects)
Analgesic Dosing Limit
Hydrocodone
Dental adult single oral dose - 10mg t1/2 = 3-5hrs
PHS recommendations will produce drowsiness
Analgesic Dosing Limit
Oxycodone HCl
Dental adult single oral dose - 10mg q4-6hrs
PHS recommendations will produce drowsiness
Analgesic Dosing Limit
Meperidine
Not recommended oral
Analgesic Dosing Limit
Aspirin
Dental adult single oral dose
1000mg q6h
24hr max - 6000mg
Max for arthritis patients; Dose limited by tinnitus, GI, Platelet effects, Renal effects
Analgesic Dosing Limit
Acetaminophen
Dental adult single oral dose
1000mg q6h - FDA recommends 625mg
24hr max - 3000mg; Moderate alcohol 2000mg
Dose limit by hepatotoxicity, McNeill reduced to 3000mg
Analgesic Dosing Limit
Ibuprofen
Dental adult single oral dose
400-600mg q6h
24hr max - 3200 mg/day
Dose limit by GI, renal and hepatic toxicity
Rationale to Combine Analgesics
Analgesic actions of NSAIDs and Opiates are additive - Act at multiple analgesic sites; Recent evidence - Acetaminophen and NSAID potentiate each other
Opiates combo w/reduced abuse liability compared to pure (Opiates + NSAID/Acetaminophen)
Not useful for chronic pain patients w/tolerance to opiate
Mild Pain
Aspirin or Acetaminophen alone
Moderate Pain
Mix w/ Acetaminophen or Aspirin and Hydrocodone or Codeine; Some NSAID taken alone - Ibuprofen
Severe Pain
Emphasis on stronger opiates, oxycodone, morphine etc; NSAID used but avoid NSAID and APAP toxicity (Ceiling doses), However Ibuprofen/APAP combo relieve dental pain
Use opiates alone at higher doses
NSAID Purpose in Combo
Block inflammatory pain, prostaglandin mediated peripherally and centrally (Newer reduce swelling)
Acetaminophen Purpose in Combo
Blocks pain w/potency equal to aspirin but inhibit prostaglandin synthesis significantly greater in the brain; Side effects - Diff from ASA or NSAIDs; After dental extractions - Acetaminophen produce somewhat less swelling and bleeding than aspirin
Opiates Purpose in Combo
Act centrally (Some peripheral block pain transmission into CNS), Activate Mu (MOP) opiate receptors to block pain, Codeine is partial agonist prodrug that requires CYP2D6 to metabolize to morphine; Morphine, Hydrocodone and Oxycodone act directly on Mu (MOP) receptors, Oxycodone and Hydrocodone are orally active (Oral morphine is 1/3 - 1/4 bioavailable)
Tramadol (Ultram)
CIV; Prodrug for M1 metabolite requires CYP2D6 to convert, M1 metabolite more Mu (MOP) potent; Weak reuptake blocking for NE and 5HT (add to analgesia) but major actions are slow in onset - Serotonin syndrome or NE toxicity (Antidepressants block reuptake of NE and 5HT are helpful in chronic pain); Better drug for chronic pain patients not acute dental patients or where NSAID ceilings reached - Use in dental patients is OFF label use; Dose rate every 6hrs is too frequent for active metabolite w/ t1/2 of 7.4hrs, Give every 8-12hrs; Comparative studies w/ other analgesics for treating postop pain indicate tramadol is equivalent in analgesic to codeine (less effective than acetaminophen), codeine and acetaminophen; hydrocodone combo for treat of dental and acute musculoskeletal pain
Tapentadol (CII) (Nucynta) for chronic pain
May result in increase use - Toxicity like arrhythmia and serotonin syndrome
NSAID and Occult toxicity
Opiate drowsiness - Overdose
NSAID - GI bleeding, Nephrotoxicity, Bleeding increase; Pushing doses on NSAID lead to delayed and serious clinic problems
Patients to use Opiates-APAP combo
Patients not candidates for NSAIDS - Pregnant, Hypertension, Peptic ulcer, Increase risk of heart attack nd stroke w/COX II agent, Adverse bone healing and ortho adjustment problem
Analgesic Dosing Limit
Antihistamine/Phenothiazines
Potentiate opiate sedation - Reduce dose of antihistamine and opiate; Antihistamine action blocks effects (H1 receptors) of opiate released histamine such as itching, Anti nausea action reduce opiate induced nausea, Antihistamines said to be mildly analgesic, No evidence that neuroleptics increase analgesia - Agents do increase drowsiness; Opiate + Neuroleptic = Neuroleptanalgesia
Analgesic Dosing Limit
Barbiturates
Available in products for migraine pain
Anti-hyperalgesia action - Block AMPA/Kinate receptors; Value in migraine or neuropathic chronic pain
Anticonvulsants (Neuropathic pain) - Carbamazepine, Phenytoin, Valproate etc; Gabapetin (Neurontin) and Pregabalin (Lyrica) used for neuropathic nerve pain based on calcium channel blocking
Analgesic Dosing Limit
Stimulants
Caffiene, Amphetamines, Cocaine and Antidepressants
Current pain theory supports use of agents that contain NE increasing stimulants or antidepressant agents
Add to analgesia by augment NE descending inhibitory transmission (alpha2) and by Reducing sedative side effects of opiates, Rational for caffeine not clear - Improves Acetaminophen efficacy but only in headaches - May reduce caffeine withdrawal induced headaches and increase renal toxicity
Analgesic Dosing Limit
Sumatriptan+APAP combo
Serotonin agonist helps migraine pain, APAP effective in reducing migraine pain (Combo not a general dental agent)
