antiflamm, antipyretic,analgesics Flashcards
what is the physiologic process of inflammation?
Cyclooxygenase allows prostaglandin formation which modulates inflammation
what is the physiologic process of pain?
Prostaglandin E2 (PGE2) is thought to sensitize nerve endings to the action of bradykinin, histamine and other mediators release by the inflammatory process
what is the physiologic process of fever?
Anterior hypothalamic thermoregulatory center becomes elevated
Infection triggers WBC leading to cytokine production and subsequent PGE2 production
what are 3 of the most common “non-selective” (by FDA standards) cox inhibitors?
Diclofenac (Voltaren)*
Ibuprofen (Motrin, Advil)*
Naproxen (Naprosyn, Aleve)*
what are the 2 nonacetylated salicylates?
Magnesium salicylate ( Doans Pills) Salicylsalicylic Acid (Salsalate)
what are the 2 Cox-2 selective inhibitors?
Celecoxib (Celebrex)*
Meloxicam (Mobic)*
where are the 3 major ADRs of NSAIDs?
GI
CV
Renal dysfunction
what are 3 less common but dangerous ADRs of NSAIDs?
Allergies
Antiplatelet effects
CNS
2 ADRs of Cox1 inhibition? which drugs do this?
GI mucosa… peptic ulcer and GI bleeding
NSAIDS + ASA
3 ADRs of Cox 1+2 inhibition? which drugs do this?
kidney…
1. Na+ and H2O retention
2. hypertension
3. hemodynamic acute kidney injury
NSAIDs
what are 2 ADRs for when there is more Cox-2 inhibition than Cox-1 . which drugs do this?
cardiovascular…
MI and stroke
NSAIDS
(ASA does the opposite, irreversibly inhibits Cox 1)
how does the inhibition of Cox1 cause peptic ulcers and GI bleeding?
inhibits PGE2 (prostoglandin) which usually serves for gastric protection (increased mucus secretion, increase HCO3, increase mucus flow)
how does the inhibition of Cox1 and Cox2 cause kidney issues?
inhibits PGE2 (prostoglandin) and PGI2 (prostacyclin) which together …
- vasodilate afferent arteriole (increase GFR)
- increase Na+ and H2O secretion
how does the inhibition of Cox2 >Cox1 cause cardiovascular issues?
inhibits PGI2 (prostacyclin) and TXA2 (thromboxane) which together…
- vascular: Cox 2 and PGI2: vasodilates and inhibits platelet aggregation
- platelets: Cox1 and TXA2: vasoconstriction and platelet aggregation
when Cox2 inhibition is increased, you get more vasoconstriction, Plts aggregating… leads to stroke and MI …
what irreversibly inhibits platelet Cox 1? what does this mean?
low dose ASA
-it inhibits vasoconstriction and plt aggregation
to avoid dyspepsia and diarrhea with NSAIDS, what do they recommend?
take them with food or milk
can taking with food/milk help NSAID-caused GI bleeding and ulcer ?
NO
can you hae a GI bleed/ulcer without symptoms?
YES (poor coorelation between ulcers/bleed and symptoms)
how can you prevent ulcers with NSAIDs?
take NSAID with PPI or misoprostol.
what is ketolorac (toradol) used for?
analgesia (cox 1) : moderate to severe pain. good for when you want to avoid narcotics (i.e. drug addict or fear of respiratory depression or poor metabolizer )
which Cox pathway is targets for analgesia, which for inflammation?
Cox 1- analgesia
cox 2- inflammation
what are the dosing limits for ketolorac (toradol)?
why are there these limits?
IM loading dose then…
- max per day: 40mg
- max days in a row: 5 days
- max day-period: 20days
- risk of ulcers-GI bleed increases!!!!
which cox pathway is “cardioprotective”? what does this have to do with ASA?
cox 2- vasodilates and prevents plt aggregation
- ASA is considered “cardioprotective”, it turns off Cox 1 and allows for Cox 2
NSAIDs elevate BP on average __ - ___ mmHg above pt’s baseline
8-10 mmHg
what is the boxed warning on all NSAIDs?
why is this?
May increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal.
(they upset the balance between Cox 1 and Cox 2)
NSAID-associated heart failure is thought to be due to increased _____ _______ _______ and reduced _____ _______ caused by prostaglandin inhibition
increased peripheral vascular resistance
reduced renal perfusion
Cox 2 inhibition by NSAIDs poses more of a risk for patients with CVD or CVD risk:
- increased risk of death or repeat attack within ___ years.
- ___% of pts who used an NSAID post-MI died within the 1st year compared to those that didnt.
5 years
20% died within the 1st year
what are the 4 agents with high cox2 selectivity? (maybe weeds)
Celecoxib
DICLOFENAC
Etodolac
MELOXICAM(“preferential” selective)
high cox 2 selectives have greater ____ risk but lesser ___ risk
greater CV risk
less GI risk
what are the 5 agents with moderate cox2 selectivity? (maybe weeds)
Diflunisal IBUPROFEN Nabumetone Piroxicam Sulindac
what agents have low Cox-2 selectivity?
Flurbiprofen Indomethacin Ketoprofen Ketorolac NAPROXEN Oxaprozin Tolmentin
what is our only non-selective Cox 2 inhibitor (aka only inhibits Cox 1)? this has increased _____ risk but decreased ______ risks
ASA (aspirin)
- increased GI
- decreased CV
which drug has sulfa in it? (look at for sulfa allergy)
celecoxib
which of the highly selective Cox 2 inhibitors inhibits Cox 2 more than Cox 1 but not enough to be deemed a “COX2selective” by the FDA?
Meloxicam
why is meloxciam maybe a good option for some?
its a highly selective Cox 2 inhibitor
SO….if they have NO CVD risk, better tolerated (Less GI effects) than ibuprofen or naproxen
how can NSAIDs cause acute kidney injury (AKI)?
Prostaglandins maintain glomerular pressure by causing vasodilation of afferent arteriole
NSAIDs inhibit prostaglandins decreasing perfusion, leading to afferent arteriole constriction and reduced glomerular blood flow
what are the risk factors for NSAID induced AKIs? (maybe weeds)
Preexisting kidney disease, systemic lupus (inflamm Dz), high renin activity (CHF, hepatic disease), diuretic therapy, CAD, and advanced age
pts with NSAID-induced AKI have LOW …. and HIGH ….
LOW: urinary volume and Na+, GFR and bloodflow
HIGH: SCr, BUN, K+
do NSAIDS normally cause increased Cr?
NO! not part of how drug works so if increased Cr occurs immediately stop the drug!
txt for NSAID-induced AKI? is the recovery fast or slow?
Stop drug, hydrate & support
Usually rapid recovery
what is our main concern with allergies to NSAIDS?
Angioedema: tongue/lips swelling, hard to control.
*if it happens with one NSAID will likely happen with another! avoid ALL NSAIDS
those with _____ and ______ can get increased asthmatic symptoms when taking ASA & NSAIDs. how does this happen?
nasal polyps and asthma
Prostaglandin inhibition (but not leukotriend inhibition) can shift toward leukotriene production increasing risk of asthma exacerbation
- AVOID NSAIDS
what is the MOA of ASA?
binds irreversibly and inhibits COX-1 mediated TXA2 formation.
( does so by blocking arachodonic acid from binding and becoming active)
how long does aspirin last? why?
Effect last for the life of the platelet (7 days) and only goes away when new platelets are made.
what group of analgesics can you use if you need to avoid platelet effect?
Nonacetylated salicylates
(MgSalicylate“doans” pills and salsalate)
have least effect on platelets, least likely to cause excess bleeding
(while aspirin bind irreversibly and other NSAIDs bind reversibly in platelets)
4 CNS effects of NSAIDs
Headache: Occurs mostly with indomethacin and tolmetin
Tinnitus
Dizziness
CONFUSION: Occurs much more often in the elderly
what is the absorption of aspirin? (maybe weeds)
Rapidly absorbed with peak plasma level in 1-2 hours
which drug has zero order kinetics? what does this mean?
aspirin
- a constant amount (in mg) of drug is eliminated per unit time (regardless of plasma concentration)
- RATHER THAN 1st order: eliminated by constant % of the drug eliminated per unit time. (dependent on plasma concentration)
what is the dose of aspirin for mild- moderate pain?
for arthritis?
for cardioprotective effects?
325-650mg four times a day (max 4g/day) - mild to moderate pain
650mg q4hours (max 5.4 g/day) - arthritis
81mg- unstable angina, MI, TIAs, etc. (antiplt effect)
3 ADRs of aspirin
- fecal blood loss (harmless)
- salicylism: at high doses- vomitting, tinnitus, decr. hearing, vertigo
- hyperpnea: at OD levels- respiratory alkalosis –> metabolic acidosis
what is salicylism?
toxic condition: vomitting, tinnitus, decr. hearing, vertigo
what is hyperpnea?
respiratory alkalosis that leads to metabolic acidosis
what is the antidote to hyperpnea from aspirin? (4)
- stomach irrigation
- IV Fluids
- sodium bicarb
- dialysis (if extreme)
what is Reye’s syndrome? (weeds maybe)
if children have viral infection and you give them aspirin = mitochondrial damage and awful effects, can lead to coma
efficacy difference between different NSAIDs?
NO, all about the same efficacy. choose based on what ADRs you want to avoid
when do you switch between NSAIDs?
try the one you chose for 2 weeks, increase dose, then you can maybe change
why wouldnt you want to combine two NSAIDs?
it increases the risk of ADRs without increasing efficacy
what do you have to do if you give NSAIDs and someone has Hx of HTN or has HTN-controlled with meds? why?
monitor: can decrease effect of BP meds b/c decrease GFR, and increase Na+ and H2O
what is the monitoring process of ASA w/ HTN pts?
- check BP before starting
- check BP in 2 wks
- if BP increases- stop NSAID or inc. HTN meds
what do you need to do if you prescribe NSAIDs and on diuretics/ACE/ARBs ?
recheck SCr 3-7 days after starting b/c of increased risk of renal failure
what does acetaminophen help with?
analgesic, antipyretic. MILD pain reliever
NOT- anti-inflammatory
what is the MOA of acetaminophen?
Inhibits PGE2 synthesis in (hypothalamic heat-regulating center)
= antipyresis (cause vasodilation and sweating)
* only CNS effects { no plt and very little peripheral }
what is the metabolism and elimination of acetaminophen?
Hepatic metabolism, renal elimination (where overdose comes in)
what is significant about the hepatic metabolism of acetaminophen?
Acetaminophen broken into inactive metabolites and NAPQI
- liver produces glutathion to bind NAPQI to form a nontoxic metabolite
- Overdose levels of acetaminophen –> NAPQI reacts with sulfhydrl group and liver can’t make enough glutathion = LIVER DAMAGE
what is the dosing of acetaminophen for healthy pts vs elderly/alcoholism/hepatic dysfunction pts ?
healthy: 4g
alcoholism/elderly/hepatic dysfunction: < 3g
what is used for any pain if the patient also has GI upset or an ulcer, child with virus or chickenpox (b/c of the risk of Reyes), or a bleeding disorder?
acetaminophen!
what common substance is added to pain meds to increase analgesia?
caffeine
in OTC pain relievers/ migraine meds
how can caffeine cause analgesia?
binds with adenosine receptor - inhibiting neuronal activity
- mimics adenosines natural activity
what does adenosine naturally do in the body?
Adenosine binds to different adenosine receptors located in the CNS and PNS
Receptor A2A activation leads to inhibition of pain transmission
what drugs can be used for neuropathic pain before moving to opiods? (weeds)
anti-epileptics: “gabas” and “carbamazepines”
anti-depressants: TCAs, SNRIs,
topicals: lidocaine, capsacian, diclofenac
what is methyl salicylate (wintergreen oil) ? (weeds)
topical pain reliever : counterirritant (a cooling or warming effect to divert attention away from pain sensation)
how does capcasian work? (weeds)
a red pepper derivative: 1st- releases substance P, continuous stimulation of nerves leads to
depletion of substance P
=decreasing pain
Visceral pain is typically severe and typically best responds to ________
narcotics
what is Used in children to decrease pain of procedures before IVs, circumcisions ? (weeds)
lidocaine/prilocaine (EMLA) - topical
