MSK second exam

what is the chemically mediators

histamine increase vascular permeability increase blood flow, prostaglandins and leukotrienes are pain response vascular permeability, and chemotaxis, and serotonin increase capillary blood flow and vascular permeability

what is arachidonic acid

fatty acid chain that it browken down by Cox 1 and Cox2 into prostaglandins leading to inflammation redness swelling and pain and it can form into lipoxygenase

what are prostaglandins

naturally occurin 20-carbon cyclopento fatty acid derviatives,

what are salicylates

made from willow tree bark made from oxyhydroxy benzoci acid added acetly group to get aspirin needs to have ortho formation

where does Aspirin covalently bound

Ser530 on Cox-1 and Ser 516 on Cox 2 it prefers cox 1 over 2

what are side effects of aspirin

disturbance of Gi tact, nausea and vomiting, peptic ulcers, gastric ulceration and bleeding due to gastric acidity inhibit Cox-1 and inhibit platelet aggregation, do not use before surgery

what are derivatives of salicylic acid

sodium salicylate, magnesium and choline salicylate all increase the solubility of Aspirin by making it an ion, phenyl salicylate is an internal antiseptic and mild analgesic and methyl is an external analgesic and counter irritant

what are key characteristic of ASA

mild analgesics, stable in dry enviorment but not humid, avoid in people who bleed easily and history or peptic ulcer, and can cause asthma related hypersensitivity

what is salsalate

as effective as aspirin in pain sense with less side effects as it doesn’t cause GI bleeding and less likely to cause asthma allergy

what is salicylamide

not acidic or a salicylate but it is analgesic and antipyretic with mininal anti inflammatory does not cause Gi upset and aspirin hypersensitivity

what is diflunisal

longer acting, slower onset and non-narcotic, more potent than aspirin with less side effect and is more effective but is more expensive

what is indomethacin

what are arylacetic acids

have and arly group attached to a carbon attached to a carboxyl acid carbon can have a methyl group making it a chiral carbon thye are acidic beside nabumetone

what is indomethacin

NSAID very potent is more antipyretic than ASA and APAP, and more analgesic than ASA can be used short term for gout spondylitis and osteoarthritis, AEs are mainly GI tract CNS(headache and dizziness) and tinnitus

what is sulindac

prodrug nsaid with a sulfur group used to treat rheumatoid arthritis,gouty arthritirs, osetoarthritis and spondylitis

what is ibuprofen and ibufenac

same structure except ibuprofen has a chiral carbon and is a racemic mixture (ibuprofen only relevant), only the S isomer has anti-inflammatory effect, is more potent than ASA but less than indomethacin, moderate GI upset used to treat rheumatoid arthritis and osteoarthritis

what is fenoprofen calcium

NSAID racemic mixture, used to treat rheumatoid arthritis and osteoarthritis , less potent than indomethacin ibuprofen naproxen, do not use with hydantoins sulfonamides and sulfonylureas as it displaces their binding site

what is naproxen

chiral drug S+ is isomer used to treat rheumatoid arthritis osteoarthritis spondylitis and acute gout, do not give to pregnant lactating or children under 16

what is tolmetin

NSAID rheumatoid arthritis and osteoarthritis less potent than indomethacin but more than pheulbutazone

what is suprofen

NSAID opthamic use to prevent miosis during cataract extraction

what is ketoprofen

NSAID inhibits cox, and leukotrienes synthesis and migration into joints is used for long term management of rheumatoid arthritis and osteoarthritis

what is nabumetone

prodrug nsaid as it does not have carboxylic acid until metabolized, so less GI AEs, prodrgu is 6-methoxynaphthalene 2 acetic acid used to treat rheumatoid arthritis and osteoarthritis

what is oxaprozin

NSAID rheumatoid arthritis and osteoarthritis treatment and does not have an alpha methyl group

what is flurbiprofen

topical nsaid indicated for ophthalmic use inhibits intraoperative miosis during cataract surgery oral form is used rheumatoid arthritis and osteoarthritis

what is ketorolac

injectable NSAID is best for severe to moderate pain after surgery than anti-inflammatory CI in patient taking NSAIDS and aspirin

what is diclofenac

NSAID used to treat rheumatoid arthritis and osteoarthritis and spondylitis, is also considered a N-arylanthranilic acid as it inhibits COX, lipoxygenase pathway and arachidonic acid release

what is etodolac

treats rheumatoid arthritis is a racemate mixutre with S+ being the anti-inflammatory selective for COX-2 best saftey profile

what is N-arylanthranilic acid

class on nsaids that has a nitrogen group attached to a ar group diclofenac is analog of this group

what is mefenamic acid

nsaid relief of mild to moderate pain treats rheumatoid arthritis and osteoarthritis and primary dysmenorrhea, AEs, are diarrhea GI ulceration bleeding headache nausea and drowsiness, can not be used for more than 7 days

what is meclofenamate sodium

NSAID relief of mild to moderate pain acute and chronic treatment of rheumatoid arthritis and osteoarthritis and primary dysmenorrhea, analog of mefenamic acid high incidence of diarrhea

what are the selective COX-2 inhibitors

celecoxib AEs are increased risk of serious cardiovascular events,thrombotic events, MI and stoke

what are the Aniline and p Aminophenol derivates

para conformation is acetaminophen and phenacetin is analgesic and antipyretic APAP forms NAPQI bad and NAC is the antidote as it restores sulur deposits

what is opiate

drug derived from opium

what is an opioid

peptides that have pharmacologic activity that include natural and synthetic compounds and peptides

what is enkephalins

natural hormones work at the delta site is met and leu enkephalin

wha tis endorphin and dynorphins

endogenous hormones endorphins act at the mu opioid receptors and dynorphins act at the kappa receptor

what does the delta receptor do

analgesia, GI motility, olfaction immune stimulation respiratory depression, cognitive function and motor integration

what does the kappa receptor do

regulation of nociception, analgesia, sedation, miosis, diuresis, dysphoria, neuroendocrine secretions

what does the mu receptor do

main receptor, analgesia, euphoria, increase GI transit time, thermoregulation, immune suppression, respiratory depression, emetic effects, tolerance and physical dependance agonist is morphine and antagonists is naloxone and naltrexone

where are the opioid receptors located

every step in pain perceptor with mu being the most common except in the brain where kappa is the most common

what is the opioid receptor structure

7 transmembrane G protein couple inhibitor that inhibits neuron excitability

what is the full agonist of the opioid receptor

Codeine Fentanyl Heroin Hydrocodone Hydromorphone Levorphanol Meperidine Methadone Morphine Oxycodone Oxymorphone

what is the partial agonist at the opioid receptor

buprenorphine butorphanol pentazocine tramadol

what is the agonist-antagonist at the opioid receptor

Nalbuphine buprenorphine butorphanol and pentazocine

what is the antagonist at the opioid receptor

Naloxone, naltrexone

how is morphine inactivated

mainly UGT but also 3A4 minor pathway

how is codeine activated

2D6 metabolized

what is the AEs of opioids

GI nausea vomiting constipation, CNS drowsiness delirium physical dependance, dermatologic is mild itching, cardiac QT prolongation (drug dependant), respiratory depression and urinary retention

what are the phenanthrenes

morphine buprenorphine butorphanol heroin, hydrocodone, hydromorphone levorphanol oxycodone oxymorphone, methylnaltrexone, naloxone, naloxegol and naltrexone have probable cross reactivity

what is a pseudo allergy to opioids

causes headache, hives redness, mild itching sweating flushing, mild hypotension tachycardia and sneezing

what is a true allergy to opioids

difficulties swallowing headache, angioedema/swelling of lips tongue face or mouth cutaneous reactions, severe hypotension shock and difficulty breathing

what are the benzomorphans

pentazocine

what is the phenylpiperidines

Fentanyl, alfentanil, meperidine, remifentanil, sufentanil, loperamide, diphenoxylate, carfentanil

what is the dipehnylhepatens

methadone and propoxyphene

what is the phenylpropanolamine

tramadol and tapentadol

what are phenylpiperidine analogs

atropine meperidine and loperamide less potent than fentanyl can be used as analgesics but have a different use

what is loperamide

antidiarrheal opioid receptor agonist and calcium calmodulin antagonist and CCB, has low systemic absorption as it is effluxed by the p-glycoprotein in intestinal wall and BBB, high first past metabolized but can still be abused in high doses

what is methadone

R is more potent than S at the opioid receptor, R and S both antagonize NMDA receptor, S prevents reuptake of serotonin and NE, and S methadone bind the the hERG to cause QT prolongation which can lead to Torsades de Point

what is tramadol

is like venlafaxine SNRI, positive enatominer block serotonin reuptake, and negative blocks NE reuptake both enantiomers are mu opioid receptors agonist but M1 and O metabolites agonist the mu receptor more

what AEs do all opioids cause

constipation nausea, vomiting, addition, tolerance, dependence, sedation inability to think clearly and slowed/stopped breathing

what is morphine fisher

MVP agonist is metabolized by UGT2B7 (moderate concerns for PG differences), is renally doses at 50 but CI at 30 metabolites are M3G and M6G(active), very good in liver disease at it does not rely on CYP enzymes

what is morphine interaction drugs and clinical pearls

interact with BZDs alcohol Gabapentinoids alcohol and SKMRs, pearls are M3G is a neurotoxin that can accumulate in renal failure, causes most histamine release of any opioids and it is the active metabolite of codeine, does not have good absorption through skin or buccal

what metabolizes codeine

CYP2D6

what is methadone fisher

interacts with MOR, some kappa NMDA antagonism and SERT and NET antagonist a little is better than fentanyl at treating neuropathic pain, metabolized 2B6 3A4 2D6 2C19 and 2C9, is good in renal until 10 and metabolite is EDDP

what is tramadol fisher

bad interact at MOR SERT and NET, metabolized by 2D6 3A4 and 2B6 has active metabolite M1 has more opioid activity and is good in renal until 30 CrCL

What is tapentadol fisher

interacts as MOR agonist and NET antagonist,metabolized by UGT2B7, and UGT1Am CI in CrCL below 30 and metbaolite is tapentadol-o-glucuronide

what is methadone interactions and clinical pearls

BZDs alcohol gabapentinoids, anti-infects, antidepressants amiodarone, pearls are lipophilic, prolongs QT max starting dose is 40mg if not naive and 2.5 if naive can be used to treat OUD

what is tramadol interaction and clinical pearls

bupropion, TCAs SSRIs, gabapentinoids, BZDs alcohol SKMRs, clinical pearls are increase seizure risk, increase serotonin syndrome risk, hypoglycemia and hyponatremia, couples with APAP,

what is tapentadol interactions and clinical pearls

BZds, alcohol, gabapentinoids, SKMRs, pearls are it is expensive and unknown if it increase seizure risk and can cause orthostatic hypotension

what is buprenorphine fisher

partial agonist at mu receptor and antagonist at the kappa and agonist of nociceptin/orphanin, metabolized by 3A$, UGT1A1 and UGT2B active metabolite norbuprenorphine is good in patches and sublingual formualtion

what is buprenorphine drug interactions and pearls

BZDs, alcohol gabapentinoids and SKMRs, pearls high affinity and slow dissociation, patch can be used in opioid naive patients, can prolong QT at higher doses, no OPAID or immunosuppression, and less respiratory depression than other agonist and can be used to treat OUD

what is fentanyl fisher

mu agonist, metabolized by 3A4, good in renal impairment and as a patch

what is fentanyl interaction and pearls

BZDs, alcohol, TCAs, gabapentinoids, SSRIs, SNRIs, and SKMRs, pearls patch and oral require patient to be opioid tolerant, fentanyl loves fat giving ti quicker onset and shorter duration, unpredictable absorption in cachexia, reduce dose for continuous infusion and TDF in severe renal impairment, good to start in renal impairment, hypotension and inability to swallow

what makes you opioid tolerant

60 mg MEDD

what is the kinetics of transdermal fentanyl

time to onset 12 hours, Tmax between 24-36 hours, steady state 3 to 6 days and t1/2 after removal is 20-27 hours

what is hydromorphone fisher

Mu and kappa agonist, Metabolised by UGT2B7 and UGT2B1, not good in renal impairment needs to be dose in 60 CrCl and CI in 20 H3G metabolite

what is hydromorphone interactions and pearls

BZDs, alcohol, gabapentinoids and SKMRs, H3G metabolite causes neurotoxicity in renal impairment, high affinity for MOR, and high street value

what is oxycodone fisher

agonist at mu opioid metabolism is 3A4, 2D6 active metabolite noroxycodone, oxymorphone and renal dosing below 60 and CI below 20

what is oxycodone interaction and clinical pearls

BZDs alcohol gabapentinoids, and SMKRs and pearls are coupled with APAP, more expensive than morphine Xtampza needs to be taking with meals but less abuse potential and prolongs QTC above 100 mg TDD

what is hydrocodone fisher

agonist at mu and kappa receptors, metabolism at 3A$ and 2D6 into norhydrocodone and hydromorphone and renal dosing at 60 and CI in 20

what is interactions of hydrocodone and pearls

BZDs alcohol gabapentinoids SKMRs, pearls IR not available by itself formulated with APAP and ibuprofen and is used in cough syrups

what is oxymorphone fisher

interactions are BZds, alcohol gabapentinoids, and SKMRs, pearls can be difficult to get cover has less drug interaction and good in renal impairment and is metabolized into 6-OH-oxymorphone which is active

what is a common issue with morphine

itching is most common with epidural intraspinal injection morphine has the most issues as it release the most histamine and bradycardia is common with morphine

what opioids can interact to increase seizure risk with bupropion and some antibiotics

tramadol, meperidine, morphine if renal failure and hydromorphone if high dose and renal failure

what opioids increase QT prolongation (interact with amitriptyline citalopram and sertraline

methadone the most than oxycodone if over 1— mg TDD and buprenoprhine the highest

what opioids can induce Serotonin syndrome (interact with SSRIs SNRIs, TCA and MAOIs

tramadol, methadone, meperidine and fentanyl

what medication do benefits never outweight the risk

codeine always a better drug and meperidine due to seizure and

what are short terms Opioid AEs

changing in BMs cant pee, feeling sick to your stomach, throwing, itchy, feeling sleepy, not able to think clearly slowed/stopped breathing low blood pressure and heart rate, acute severe confusion

what is long -term opioid AEs,

addiction tolerance, dependence, more pain, sleep apnea sleep problems, weaker bones, lower sex hormones, lower cortisol and weaker immune system

what is general strategies for opioid AEs

minimize use and minimize PD DDI, change formulation/route of administration, select or rotate to a different opioid/another therapy, prophylaxes to protect against, treat AI and education patient and their care partners

what is the most common AE of opioids

cosntipation

what is the definition of constipation

any of the following new or worsening straining, sensation of incomplete evacuation, reduce frequency and harder stool consistency

what should be used for prophylaxis for opioid constipation

PEG senna or bisacodayl

what should not be used in opioid constipation

fiber psyllium and methylcellulose are Ci and docuate doesn’t work

what if PEG and glycerin

PEG takes 1-3 days to work is nonabsorbable draws in water into the colon, less GI side effects, Glycerin works in 15 to 30 minutes draws water into the rectume and is CI in neutropenic

what is lubiprostone

draws in chloride to increase water absorption is CI if using methadone

what is senna

stimulates the mucosal nerve plexus to increase motility and increase fluid secretion senna max dose is 4 tablets Q12h and Bisacodyl had a suppository form

what are the pamora

methylnaltrexone and naloxegol can not take with bowel obstruction AEs are stomach pain nausea diarrhea hyperhidrosis an anxiety

what is methylnaltrexone

not a CYP3A4 substrate needs dose adjustment in hepatic impairment and renal below 60CrCL

what is naloxegol

CYP3A4 metabolism do not use in haptic impairment or CRCL below 60