pharm 2: non and opioids, NSAIDS, APAP rx

NSAID: 1st gen names (8)

• aspirin

• Ibuprofen 

• Naproxen

• Meloxicam

• Etodolad

• Indomethacin

• Ketorolac

NSAIDS: 2nd gen name

Celecoxib

NSAIDS 1st gen are ____ of COX ___ and COX ___ inhibition → increase ____

mixed

cox 1

cox 2

prostagladin

NSAIDS 2nd gen: COX 2 ____

inhibitors

THERAPEUTIC effects of NSAIDS?

• Analgesic (reduce pain)

• Anti-inflam (reduce inflammation)

• Antipyretic (reduce F)

ADE of NSAIDS?

• GI (COX 1) → GI distress, PUD, bleeding

• Kidney (COX 1 and 2) → nephrotoxicity, sodium and water retention

• Cardiac (COX 1 and 2) → ⬆ risk of CVD events → more often with COX 2 only and not mixed with ASA (aspirin)

contradiction of NSAIDS (2)

caution in which pt population?

• PUD

• bleeding disorders

• CAUTION in renal disease, preg, CVD RF

Aspirin (ASA) MOA:

_____ inhibits _____ synthesis by ____ COX 1 and 2 activity

IRRVERSIBLY inhibits prostaglandin synthesis by ⬇ COX 1 and 2 activity

ASA have ____ duration and ______ bleeding risk

longer

increase

when should you d/c ASA before sx?

5-7 days before

indication of ASA:

low dose: reduce risk of ____ and ____ ____

moderate - high dose: mild to moderate ____ and ____

low: ⬇ risk of CVD and acute stroke

moderate - high:  mild - moderate pain, F

ADE for ASA: (2)

tinnitus

reyes syndrome

COX 2 MOA:

_____ inhibits prostaglandin synthesis → _____ COX 2 activity

 REVERSIBLY inhibits prostagladin synthesis → ⬇ COX 2 activity

COX 2 indication:

mild to moderate ____, ____, _____, ____, _____

mild - moderate pain, GOUT, OA, F, BURSITIS 

what does COX 2 inhibitors NOT protect?

NO protection against MI and stroke → ⬆ risk

contraindications for COX 2 inhibitors?

SULFA ALLERGY (celecoxib)

Ketorolac

____ - ____ ____ NSAID

High-potency parenteral NSAID

indication for ketorolac?

long or short term use?

when do we typically use rx?

• SHORT TERM (5 days) tx of moderate - severe pain

• used post op / sx

ADE for ketorolac? (2)

 GI risk, nephrotoxicity → longer duration of action

PK for ketorolac? (3)

• IM, IV, PO

Diclofenac 1% Gel - TOPICAL NSAIDS

indication?

• MILD OA pain → ONLY for 1-2 SMALLER joint (hands, knee)

  • ≠ recommended for back, hip, shoulder

OTC diclofenac systemic absorption %?

< 10%

OTC diclofenac pt edu?

•  ≠ use > 21 days CONSECUTIVELY

• limit other topicals in AA

• ≠ combine PO and topical NSAIDS

what do you try first? PO or topical NSAIDS for pain?

TOPICAL

what NSAID do you give this pt?

LOW CV risk + HIGH GI risk

celecoxib

GI RF: 65+, hx of PUD / previous bleeding, multiple NSAIDS, high NSAIDS dosing, long duration, other meds that ⬆ risk of bleeding

what NSAID do you give this pt?

HIGH CV risk + LOW GI risk

naproxen

CV RF: HF, unstable angina, MI, HIGH NSAIDS dosing / long duration

what NSAID do you give this pt?

HIGH CV risk + HIGH GI risk

AVOID NSAIDS

CV RF: HF, unstable angina, MI, HIGH NSAIDS dosing / long duration

GI RF: 65+, hx of PUD / previous bleeding, multiple NSAIDS, high NSAIDS dosing, long duration, other meds that ⬆ risk of bleeding

Acetaminophen (APAP) MOA:

______ brain _____ synthesis → analgesic and antipyretic activity

inhibits brain prostaglandin synthesis → analgesic and antipyretic activity

highlighted in yellow on drug fact of med

indication for APAP?

MILD ___, ___, ____

MILD pain, F, arthritis

ADE for APAP? (3)

N, stomach pain, hepatotoxicity 

DRUG INTERACTION of APAP?

 alcohol (hepatotoxicity), WARFARIN

pt edu for APAP?

 take with food → avoid stomach s/s

therapeutic effect for APAP?

• Analgesic (reduce pain)

• Antipyretic (reduce F)

when does APAP toxicity occur?

APAP → metabolized → N-acetyl-p-benzoquinon-imine (NAPQI)

• Normal dose: NAPQI combine w/ glutathione → produce NON TOXIC metabolites

• Overdose: glutathione = depleted and NAPQI = accumulates

APAP overdosing is ___ lethal and initial s/s = ____

s/s shows ___ hrs - ___ hrs after

highly

minimal

24 - 72 hrs after

antidote for APAP?

other antidote?

N-acetylcystein (NAC) = main one

⬇ production of NAPQI due to increasing stores of thiols

other: activated charcoal

when should you give NAC?

tx should be administered if level is ABOVE solid line

• better to OVERTREAT than UNDER

• above doted line = HIGH RISK

Maximum Adult APAP Dose

• 3000 mg / day → self suggestion 

• 4000 mg/day → doctor suggested / advised

CENTRAL Muscle Relaxants MOA:

acts w/n _______→ ______ hyperactive reflexes 

• Structural analog of GABA

acts w/n spinal cord → suppress hyperactive reflexes 

• Structural analog of GABA

DIRECT acting muscle relaxant MOA:

 _____ spasms → suppresses release of ______ from SR → skeletal muscle ≠ _____

 RELIEVES spasms → suppresses release of CALCIUM from SR → skeletal muscle ≠ contract

indication for DIRECT acting muscle relaxant? (2)

cerebral palsy or multiple sclerosis

general muscle relaxant indication?

• Chronic: treat _____ (stiffness) due to _____ sclerosis, _____ ______injury

  • ≠ benefit _____ back pain

• Acute: _____ pain

• Chronic: treat spasticity (stiffness) due to MULTIPLE sclerosis, spinal cord injury

  • ≠ benefit CHRONIC back pain

• Acute: back pain

DRUG INTERACTION of muscle relaxants? (3)

• opioids

• benzodiazepines

• alcohol (resp depression and death)

MAX time you can take muscle relaxants?

≠ LONGER than 2-3 weeks or 7+ days

high sedation muscle relaxers?

• carisiprodol

• cyclobenzaprine

• tizanidine

key safety concern for cyclobenzaprine?

anticholinergic (≠ shit, see, spit)

fall risk

key safety concern for baclofen?

seizures if ABRUPTLY d/c

seizures cause you cant come BAC

key concern for tizanidine?

hypotension

key safety concern for methocarbamol?

urine discoloration

carisoprodol is ONLY recommended for? ____ term use

short

cariSOprodol only works SO SO (short term use only)

population you should avoid with cyclobenzaprine?

older or CVD risk pts

similar to TCA

what should you monitor when taking tizanidine?

BP (alpha 2 agonist)

what drugs are considered anticonvulsants?

• gabapentin

• pregabalin

MOA for anticonvulsant?
analog of _____ and enhance ____ release

analog of GABA and enhance GABA release

indication for anticonvulsants? (6)

•  neuropathy (DM)

• seizures

• migraine prophylaxis

• fibromyalgia

• restless less syndrome

• alcohol withdrawal

DRUG INTERACTION with anticonvulsants?

opioids, alcohol, benzodiazepines

same as muscle relaxers

ADE for anticonvulsant?

peripheral edema

weight GAIN

cognitive difficulties

pt edu with anticonvulsants?

AVOID driving / hazardous activities until aware of ADE

caution: preg

ANTI-driving/activities

what drugs are Tricyclic antidepressants (TCAs) (5)?

Amitriptyline (MC)

Nortriptyline (MC)

Desipramine

Imipramine

Doxepin

MOA for TCA?

____ neuronal ___ of ___ and ___

BLOCK neuronal reuptake of norepi and serotonin

• Block receptors for histamine, acetylcholine, norepi

indication for TCA? (4)

 insomnia, depression, fibromyalgia, neuropathic pain

ADE for TCA? (4)

• anticholinergic s/s

• weight gain

• cardiac toxicity

• lower seizure threshold 

ADE for TCA overdose? (3 Cs)

Overdose → cardio toxicity, convulsion, coma

DRUG INTERACTION for TCA? (2)

• MAOIs

• Sympathomimetics (CNS stimulants and pseudoephedrine)

CAUTION for TCA? (2)

Anticholinergic agents

CNS depressants

Serotonin norepinephrine reuptake inhibitor (SNRI) drugs?

-ine

• duloxetine, venlafaxine

MOA for SNRI?

_____ normal reuptake of serotonin and norepi in _____ ______

BLOCKS normal reuptake of serotonin AND norepi in nerve block

• similar to TCA

SNRI: therapeutic effects takes ____ _____ to see an effect

several weeks

indication for SNRI? (3)

anxiety, depression, chronic pain disorders

ADE for SNRI?

same as SSRI + ⬆ sweating, HTN, ⬆ risk of mania

CAUTION with SNRI?

⬆ risk for ____

⬆ risk for SUICIDE

BBW of SNRI?

 antidepressants ⬆ risk of suicidal thoughts and behavior (PEDS and adults)

MOA for lidocaine?

 ______ _____ ion channel required for initiation and conduction of neuronal impulses

 BLOCK Na ion channel required for initiation and conduction of neuronal impulses

indication for lido? (3)

skin relief, itching, soreness

ADE for lido? (4)

•  bradycardia

• heart block

• seizures

• resp depression

RISK with lido?

_____ INCREASES 

TOXICITY INCREASES 

pt edu with lido?

• caution against activities → unintentional harm

  • ____ patch topically in AA up to ____ hrs

  • MAX ____ patch on body at 1 time 

  • LIMIT: ___ week

• caution against activities → unintentional harm

  • 1 patch in AA up to 12 hrs

  • MAX 1 patch on body at 1 time 

  • LIMIT: 1 week

topical capsaicin MOA:

____ and _____ reaccumulation of ______ ______ in peripheral sensory neurons

depleting and preventing the reaccumulation of substance P in peripheral sensory neurons

indication for topical capsaicin? (3)

 arthritis, MSK pain, neuropathic pain

ADE with topical capsaicin?

 erythema and pain (burning) on site

pt edu with topical capsaicin?

•  avoid thick application

• ≠ apply on wounds

• ≠ touch mucous membrane after

what are pure strong agonist of opioids? (3)

• hyromorphone (IV,PO)

• morphine (IV, PO)

• fentanyl (IV, transdermal)

HATE MY FEELS

what are pure moderate - strong agonist of opioids? (3)

• codeine (PO)

• oxycodone (PO)

• hydrocodone (PO)

• meperidine (IM)

mixed effect opioids?

• pentazocine

• butorphanol

• puprenophrine

opioids MOA?

binds to ____ and ____ receptors in brain, spinal cord, GI tract

binds to mu and kappa receptors in brain, spinal cord, GI tract

what does MU receptor activation do when activated?

• analgesia

• resp depression

• euphoria

• sedation

• ⬇GI motility

what do KAPPA receptors do when activated?

• analgesia

• sedation

ADE for opioids?

• Euphoria

• Drowsiness

• Resp depression (90 mins after PO ingestion)

• Constipation

• Urinary retention

• N

• Tolerance

• V

• Orthostatic hypotension 

mnemonic: E-DR. CUNT VO

pt edu with opioids?

 monitor opioid overdose and administer narcan 

morphine is used in ____ and cause ____?

NOT recommended in ___ ____ pts

used in MONA, cause itching (histamine mediated)

• NOT RECOMMENDED IN RENAL FAILURE PTS

fentanyl increased by _____ inhibitors

 increased by CYP3A4 inhibitors

fentanyl patch: applied _____ hours

fentanyl IV: last _____hrs → used for ____

• Patch: applied Q72 hours

• IV: last 1-2 hrs → used for post op

fentanyl indication?

_____ SEVERE pain in opioid tolerant pts

PERSISTENT SEVERE pain in opioid tolerant pts

codeine is ______ and can combo with _____

 monotherapy and can combo with APAP

codeine indication?

• Effective COUGH SUPPRESSANT (10 mg)

  • Converted to MORPHINE in liver → careful with FAST metabolizers

Hydrocodeine/oxycode is _____ and can combo with _____

Hydrocodeine/oxycode: monotherapy and combo with APAP

tramadol is a ____ agonist and have ____ attributes

weak agonist  and have SRNI attributes

what drugs help with OUD? (2)

• Binds tightly to _____ -______ receptors → prevent others from binding effectively

Methadone and buprenorphine

• Binds tightly to mu - opioid receptors → prevent others from binding effectively

OUD: chronic brain disease with compulsive drug seeking

MOA for methadone and buprenorphine?

stabilize opioid receptors in brain → ⬇ _____ and _____ _____ producing a strong euphoric high 

stabilize opioid receptors in brain → ⬇craving and withdrawals WITHOUT producing a strong euphoric high 

ADE for methadone?

____ ½ life

T/F: need specific training to dispense and prescribe opioid (OTPs)

QT prolongation

long ½ life

T