Non opioid anagesics Flashcards
Non- opouids that can be effective for severe pain
IV tylenol and Ketoralac
Ceiling effect of APAP and ASA is between _________. What might be more effecatious?
- 650 and 1300 mg.
- NSAIDS
exceeding the ceiling dose results in________
More adverse side effects with no added efficacy
Non- opioid analgesics have an andvantages as they do not develop_________.
Tolerance
Does nothing for inflammmatory response
Tylenol
What non opoid analgesics inhibit platelet functioning, and which ones do not?
- NSAIDs and ASA inhibit platelet functioning
- Tylenol does not - can use prior to surgery
Central effect - MOA not entirely known….may:
- Cause NMDA activation in CNS
- Inhibit substance P in spinal cord
- Cause desensitization of TRIP A channel
Good choice for:
- Peptic ulcer disease
- Pediatrics
- Parturients
- Patients who need well functioning platelets
Acetomenophen
Tylenol PO dose
325-650mg q4-6 hours
Tylenol IV dose
1gm over 15 minutes - q4-6 hours and NOT to exceed 4000mg in 24 hours
APAP has similar potency to _______. Likewise, single anesthetic doses have the same _________ curve
- ASA
- Time - effect
When does IV APAP peak, when should it be given
It peaks in 15 minutes, so the infusion shoulg be given 15 minutes prior to the patient waking up
APAP is ______________ to an _____________ that is ______________. The name of this meotabolite is ______________.
- hydroxylated
- actve metambolite
- hepatotoxic
- N-acetyl- p- benzoquinone
Maximum sage dose to APAP
4gm/day
Doses of APAP should be lowered with _________ because they will produce _______ of the active metabolite.
- ETOH use
- more
What breaks down the N-acetyl-p-benzoquinone? What is significant about it?
- The active metabolite for tylenol is broken down by glutathione
- when glutothione is outnumbered by the active metabolite ie overdose- it causes hepatic injury
In acetomenophen overdose what can be substituted for glutathione?
- Acetylcystine - if given within 8 hours
- Activated charcole- only if it is given within 30 minutes of oral overdose
APAP and Renal toxicity
Renal papillary accumulation of metabolites causes reanal cell necrosis with longterm use
What has a higheer risk of renal injuty that APAP?
NSAIDs
Arachadonic acid is released from___________ by the enzyme ___________. This pathway is upregualted by __________.
- Phosphalipids
- Phosphalipase II
- Inflammation
Arachadonic acid is immediately metabolized by
- ________
- ________
- ________
The first tow are the ones we are mostly concerned with.
- Cyclooxygenase
- Lipoxygenase
- Epoxcygenase
Metabolism of Arachadonic acid via Cyclooxygenase leads to the formation of:
- ____________
- ____________
- ____________
- ____________
- Prostaglandins
- Prostacycline
- Thromboxane A2
- Inflammatory pain responses
for platelet aggreagation
Thromboxane A2
causes pain, fever and inflammtion
prostaglandins produced from COX-2
COX-2 are called “________”
Incucible
COX-1 are called “__________”
constrictive
Arachadonic acid metabolized by Liopoxygenase leads to the formation of:
- ________
- ________
- Leukotrienes
- Lipoxins
Arachadonic aced metabolized by epooxygenase lead to the formation of:
- ___________
Epoxygeicosatetraenoic Acid- which further regulates infalmmation and is being reserched
Asmatic patients can be __________ sensitive. We must ask thse patients if they have tolerated ______ or _______ in the past because of the risk of ___________.
- Leukotrienes
- ASA
- NSAIDs
- Bronchospasm
Normally provide gastric protection, hemostasis and platelet aggrigation and renal function
Prostaglandins produced by COX-1
If we block one pathway the prostaglandins will be shuttled down the other pathway. This resulted in what from VIOXX
It was a selective COX-2 inhibitor so it caused increased COX-1 action including increased platelet aggregation and caused thrombosis and MI
NSAIDs block __________ which sets up patients who are at risk for ESRD because all _________ are being inhibited including those for __________
- COX-1 and COX-2
- prostaglandins
- renal protection (COX-1)
Inflammation
COX-2 inducible pathway that can be increased 20 fold
ASA is best at inhibiting platelt aggregation
at lower doses 81mg
Irreversible inhabition of COX
ASA
Reversible inhabition of COX-1
NSAIDs
why does ASA need to se d/c’d 1 week to 10 days pre-op
it irreversibley inhibits COX-1 and inhibits platelet function for the lifetime of the platelet
Large doses of ASA can decrease
Prothrombin
ESRD and ASA
ASRD NOT induced by ASA
A single dose of ASA can precipitate __________ there is also corss sensitiveity with ________
- Asthma
- other NSAIDs
Higher doses of ASA can cause ___________. which my present as __________,
- CNS stimulation
- Ringing in the ears (tinnitus)
With really high doses of ASA a patient can become _________, with CNS symptoms. There is an increased risk for __________ because ASA is an __________ and becomes ________ in the blood and can cross the __________. This will lead to _________.
- Acidotic
- CNS toxicity
- acid
- non-ionized
- BBB
- SEIZURES
Can cause an increase in LFTs that is usually reversible
ASA
ASA analgesic/antipyretic dosing
325-650mg
ASA antiinflammatory dosing and consiterations
- 1000mg (3-5g/day)
- increase dose gradually
- follow serum salicylate levels
- rarely used (GI side effects)
What is the preferred anti-inflammatory
NSAIDs over ASA
ASA clearance
- Hepatic
- With an E1/2t 15-20 minutes for ASA
- E1/2t 2-3 hours for salicylic acid
Acidosis, tinnitus
Salicylate overdose
rye syndrome
ASA should not be used during viral syndromes in children and teenagers
- do not interfere with platelet aggregation
- rarely associated with GI bleeding
- well tolerated by asthmatics
Non-acytylated salicylates
more effective than full doses of ASA or APAP but have a ceiling effect
NSAIDs
NSAIDs Mechanism of action
- Non-selective COX inhibition
- Block the conversion of arachadonic acid to to prostaglandins
- Decreases production of prostaglandins
NSAIDs and Joints
- NSAIDs are acidic
- Joint pain with lactic acidosis will trap NSAIDs in joints
NSAIDs and protein binding
- highly protein bound at >95%
- Displaces/competes other protein bound drugs
- increases level of warfarin, phenytoin, sulfonulureas, sulfonamides, digoxin
Nsaids Vd
Small Vd
NSAIDs half life
- varies depeding on drug <6 to >12
- Ibuprofun vs naproxen
NSAIDS and asthma
can have an anaphylactoid reaction in ASA sensitive patients
NSaids and platelet inhabition
- Blocks COX-1 synthesis of thromboxane A2 which inhibits platelets
- It is reversible
- stop 48-72 hours before surgery
Hepatic injury and aseptic menningitis are rare side effects
NSAIDs
NSAIDS prefnancy class
- 1st and 2nd trimester class B- ok to use if necessary
- 3rd trimester - Class D- Causes premature closure of DA which is under the influence of prostaglandins- if we inhibit them it closes
Periop inhabition of COX-1 may result in
- renal injury
- gastric ulceration
- excessive bleeding - back to OR
- NSAIDS may cause GI effects including ___________, _________, and __________.
- The inhibiton of PGs will _______acid production and _______ mucous production.
- The local irritaion is caused by NSAIDS being lipid souable at a ________, entering gastric mucosal cells becoming _________.
- Dyspepsia , GI bleed, Pepetic ulcer disease
- increase, decrease
- low, ion trapped
Risk factors for NSAIDs and adverse GI effects
- High doses
- Prolonged use
- Previous GI ulcer/bleed
- Excessive ETOH- higher risk for GI bleed
- elderly
- corticosteroid use
___________ can block the Arachadonic acid pathway higher up than NSAIDs and ASA and thus re helpful in Asthma
Corticosteroids
Low GI risk NSAIDS
- Ibuprofun and Naproxen at low doses
- Etodolac, sulindac
- Celecoxib- selective COX-2
Moderate GI risk NSAIDS
- Ibuprofen and Naproxen at mod-high doses
- Dilofenac, oxaprozinm meloxicam, nabumetone
High GI risk NSAIDS
- Ketoralac - this is why we limit the # of doses
- Telmetin, piroxicam, indomethacin
- ASA
Isoniazid
Used for TB- will increase the risk of APAP toxicity
NSAIDS and renal adverse effects
- Decreased synthesis of renal vasodialator PGs (PGE2)
- Those dependant on them can go int renal failure
- Epinepherine release due to stress respone decreases renal profusion
- Fluid and sodium retenton - HTN/Renal failure
NSAIDS and rare renal adverse effects
interstitial nephritis
risk factors for NSAIDS and renal adverse effects
- Age
- CHF
- DM
- HTN
- Renal insuffiency
- Ascites
- volume depletion
- diuretic therapy
Drug qualities of NSAIDs that increase the renal risks
- Longer half life
- Higly potent COX inhibitors
- Higher dose
Highly potent COX inhibitors
- Ketoralac
- Indomethicin
Renal sparing- COX-2 selective
- Celecoxib
- Sulindac, nabumetone
NSAIDS and antihypertensives
- not recommended
- Bringing PGs down will offest the decrease in PGs by antihypertensive drugs (ACEIs, B-Blockers)
NSAIDS and Diuretics
Reduces the effect
NSAIDS and lithium
Increases litium levels- compeditive protein binding
NSAIDs and anticoagulats
increases risk of GI bleed
NSAIDS and probenecid
- (Gout) increases levels of most NSAIDs
- AVOID with Ketoralac
Only IV NSAID available in US
Ketorolac
- can be comparable to opioids
- Similar efficacy to morphine
- No ventilatory of cardiac depression
Ketoralac
GI risks the same as NSAIDs
Ketoralac
Can produce life threatening bronchospasm
Ketoralac
Avoid in elderly due to renal toxicity
Ketoralac
Length of Tx with Ketoralac
Max 5 days
Ketoralac IV onset
10 minutes- give when waking up
Ketoralac E1/2t and dosing schedule
- 5 hours (prolonged in elderly 30-50%)
- Dose q6-8 hours (elderly q8-12 hours)
Ketoralac and protein binding
99% protein bound and conjugated in the liver
Ketoralac dose
- 30mg IV x 1 q6 hours
- 120mg daily max
Ketoralac elderly dosing
If used at all with elderly cut the dose in half
Selective COX-2 inhibitor
Celacoxib (Celebrex)
celacoxib and renal effects
same as all NSAIDs
inhibits the production of prostacyclin
- Celecoxib (COX-2 inhibitor)
- prastacyline is a vasodialtor and platelet inhibitor
Celecoxib dosing
- Use the lowest dose
- <200mg/day
- 200mg/day = Naproxin 500mg BID
should avoid in patiets with sulfonomide allergy
Celacoxib
Blackbox warning
Celacoxib
- CV - thrombotic events, MI, Stroke
- GI - bleeding
Drug of choice for neuropatheic pain syndromes
Tricyclic antidepressants and Anticonvulsants
anticonvulsnt meds for pain
- Gabapentin
- Pregabalin
- Carbamazepine
- Phenytoin- induces CYP 450
- Clonazapam
- Lamitrogen
Used in short bursts for pain
corticosteroids
topical causing desensitization of TRIP1
Capsaicin
- alpha 2 agonist for sympathetically maintained pain
- centrally modulates analgesia and decreases sympathetic NS outflow
Transdermal clonondine
