Pharm - pain meds Flashcards
Common side effects of NSAIDs (6)
- Gastrointestinal ulceration
- inhibited platelet aggregation
- HTN & adverse cardiovascular events (remove block of ADH)
- decreased renal function IF low CO (inhibit prostaglandin-mediated mech)
- inhibit uterine motility (contraindicated in pregnancy)
- hypersensitivity reactions (shifts to excess leukotrienes and Phosphilipase A)
Uses for NSAIDs
3 F(x)s: anti-inflammatory, anti-pyretic, analgesic.
Treatment for: Gout, neurodegenerative diseases
Prophylaxis for: heart disease (ASA), colorectal cancer.
Effects specific to prostaglandin E2 (aka: PGE2)
- gastric cytoprotection
- vasodilation & maintain renal blood flow
- fever (increase set point)
- pain (sensitize nerve endings to bradykinin)
NSAIDs mechanism of action
Competitively inhibit COX-1 & 2 synthesis (esp. 1) –> block prostaglandin synthesis = inhibit prostaglandin signaling pathways.
* do NOT block synthesis of leukotrienes or other inflammatory molecs.
NSAIDs vs. COX-2 inhibitors
NSAIDs block COX1 & 2, but preferentially 1 (constitutive pathway).
COX-2 inhibitors = specific to COX2 (inducible) –> should reduce side effects, but COX2 also in endothelium, so still heart & renal SEs.
Aspirin
NSAID, salicylate
Use: prevents platelet aggregation, anti-inflammatory.
Mech: acetylates active site for arach. acid binding –> IRREversibly inhibits COX-1 & 2 (prostaglandin synthesis). Inhibits IkB kinase –> block NFkB activation (inflammation).
Elim: liver, short half-life
SE: Reyes in children w/ viral inf; competes w/ Ibuprofen for binding –> give ASA before Ibu; HTN (reduces ADH antagonism)
* esp. effective w/ platelets bc can’t make new COX for platelet lifetime!
acetaminophen
(tylenol), = oral analgesic & anti-pyretic (NOT anti-inflamm => not true NSAID)
*Good for chronic mild/mod. pain (less gastric damage)
Mech: COX inhibitor/exact = unknown.
SE: acute liver failure w/ overdose (or EtOH)
allopurinol
oral, Gout prophylactic;
1st choice for over-producers, OR under-excreters w/ renal failure
Mech: xanthine oxidase inhibitor (non-competitive), long half-life.
SE: hepatotoxicity, skin rash, GI upset, fever.
*Add low-dose colchicine for 1st months bc frees urate from tissues.
celecoxib
NSAID - anti-inflammatory;
Mech: COX-2 selective inhibitor –> block induced protaglandin synthesis.
SE: (more gastroprotective, but) ~high risk adverse cardiac events!
*may block constitutively active vascular endothelium.
colchicine
oral, for treatment of acute gouty attacks; (use w/in 24 hrs)
may take small dose daily for gout prophylaxis
Mech: bind & depolymerize leuk microtubules –> decreased migration to inflamed area.
SE: diarrhea, nausea, vomiting, abdom. pain
* fatal toxicity if overdose (renal/hepatic/heart cell death & bone marrow suppression)
Febuxostat
oral, for treatment of gout;
Mech: xanthine oxidase inhibitor,
SE: unknown (bc new)
*as effective as allopurinol, but #2 until more known about SEs.
Ibuprofen
oral NSAID, anti-inflammatory and fever reducer;
Mech: COX 1 & 2 inhibitor
SE:
indomethacin
oral NSAID, anti-inflammatory & fever reducer;
Mech:
SE:
infliximab
IV biological DMARD (for rheumatoid arthritis).
Mech: anti-TNF-a monoclonal antibody –> blocks inflamm. signals
SE: anaphylaxis/immune rxn
methotrexate
oral or IV DMARD (for rheumatoid arthritis);
Mech: stimulates release of adenosine from cells –> reduce inflammation.
SE: inhibit dihydrofolate reductase (high doses) –> add folate to Tx.
* effectiveness: 30-40% patients don’t respond at all.
probenecid
oral uricosuric agent, Gout prophylaxis (#1 for UNDER-excreters).
Mech: increases URAT1 transporter activity –> increase uric acid secretion (bc = structural mimic).
SE: Drug-drug interactions (decrease renal secretion of acids, alter hepatic metab.), contraind: renal insufficiency
** Advise increased fluid intake & alkalinize urine while taking this**
Sumatriptan
oral/nasal spray/subcutaneous, terminates acute migraine;
Mech: 5-HT 1B/1D agonist –> direct vasodilation;
- peripheral effect: reduce excitation & peptide release
- Central effect: decrease transmission to second order neuron
SE: “triptan sensations” (flushing, chest tightness, paresthesia) - esp. w/ subQ, overuse headaches.
contraindicated if coronary artery disease
Dihydroergotamine
subcut/intramusc/nasal spray, terminates acute migraine.
Mech: non-selective vasoconstrictor (alpha-adrenergic, 5-HT, and dopamine agonist)
SE: nausea, ischemic pain.
* contraindicated in pregnancy & angina*
Drug classes used as migraine prophylaxis (6)
- B-adrenergic antagonists
- anti-epileptics
- anti-depressants
- serotonergic antagonists
- Ca2+ channel blockers
- Botulinum toxin (botox)
stepwise order of treatment for migraines
- (mild) Mild analgesics alone (ie: NSAIDs - ASA, naproxen, etc.)
- (moderate) Combination of mild analgesic + vasoconstrictor or sedative
- (severe) Combination Tx (like #2) + anti-emetic and prophylaxis
misoprostal
oral gastric cytoprotectant,
Mech: synthetic PGE1 analog (inhibit acid secretion, promote mucus secretion, increase gastric mucosa blood flow)
Use: give w/ NSAID to protect stomach
Aspirin dosing
Analgesic/Anti-pyretic: 325-650 mg every 4 hrs (adult)
Anti-platelet: 4-6 g/day (= 400+ mg)
(Lethal dose: 10-30 g)
*half-life increases w/ dose size
Aspirin Toxicity
(reverses 2-3 days after discontinue)
- tinnitus/high freq. hearing loss
- headache, nausea, dim vision
- hyperventilation (= ox. phosphorylation uncoupling, need more O2 & glucose to maintain ATP gradient, stimulate medulla/resp. center)
- decreased ventilation (depressed medulla) w/ prolonged exposure!
Drugs/substances contraindicated in Gout
- Aspirin (all salicylates)
- Diuretics
- Alcohol & purines
* obesity also increases Gout problems*
Clinical indications for pharmacological Gout prophylaxis
- Treat w/ prophylaxis if > 2 gouty attacks per year.
* do NOT treat w/ prophylactics DURING acute attacks (for use only in “intercrititcal”/asymptomatic period.
Drug treatment for acute gouty attacks
Effective for inflammation, not uric acid:
#1: NSAIDs (Not aspirin)
- Glucocorticoids - use instead of NSAIDs if heart disease.
- Colchicine - last choice, notable SEs.
For Uric acid: ACTH (= corticotropin)
Types of Gout (& how to distinguish w/ testing)
- Overproducer: >600 mg urateexcreted/day after 1 wk of purine-restricted diet.
- Under-secreter: patients often non-compliant w/ diet **
“DMARDs” (Disease-Modifying Ant-Rheumatic Drugs)
1 Tx of Rheumatoid Arthritis… Not curative, but:
- suppress lymphocyte proliferation
- -> counteract joint inflammation & destruction
- slow joint erosion
Rituximab
biological DMARD, for rheumatoid arthritis;
Mech: partially humanized anti-CD20 antibody…exact mech unknown, but likely; Ab-stimulated cytotoxicity
Use: may be better than methotrexate, VERY effective as combo.
Types of drug treatment for Rheumatoid Arthritis
- acute relief (NSAIDS, glucocorticoids)
- chronic:
a) DMARDs - start EARLY w/ methotrexate
b) add biological after 3-4 months of DMARD
Anti-RA “Biologicals”
Class of drugs for rheumatoid arthritis;
Use: #1 @ preventing degeneration of joints, (start after DMARD).
Mech: sequester cytokines/block Rs to prevent inflamm.
- Ab analogues only: may cause Complement-dependent cell toxicity (good or SE)
Morphine
IV or IM opioid analgesic
Mech: m-opioid R agonist
SE: addiction, resp. depression, constipation
Codeine
Oral opioid analgesic & antitussive
Mech: m-opioid R agonist (prodrug: converted to morphine in liver, then moprhine-6-glucoronide)
m6g w/ longer 1/2 life, but rapidly excreted in urine (need functional kidneys)
SE: addictive, resp. depression, constipation, antidiuresis
Oxycodone
oral opioid analgesic,
Mech: m-opioid R agonist (prodrug)
SE: addictive, resp. depression, constipation
Hydromorphone
oral opioid analgesic,
Mech: m-opioid R agonist (prodrug)
SE: addictive, resp. depression, constipation
Meperidine
IV or IM opioid analgesic,
Mech: m-opioid R agonist, safer for pregnant women (bc baby DOES have the fetus to convert THIS to active, but not morphine)
SE: highly addictive, resp. depression, constipation
*drug interaction w/ MAOIs
Fentanyl
IV or transdermal patch analgesic
Mech: m-opioid R agonist (synthetic agonist w/ high affinity)
*100x more effective than morphine!
SE: addictive, resp. depression, constipation
Sufentanyl
IV or transdermal patch opioid analgesic,
Mech: m-opioid R agonist
(*high potency bc complete synthetic agonist)
SE: addictive, resp. depression, constipation
Methadone
oral treatment for heroin withdrawal,
Mech: m-opioid R agonist (*long 1/2 life)
SE: IS addictive, resp. depression, constipation
Butorphanol
IV or IM opioid, precipitates heroin withdrawal.
Mech: mixed agonist/antagonist for m & k-opioid Rs
Pentazocine
Oral, IM, IV, or SC opioid analgesic, *can precipitate withdrawal;
Mech: m-opioid R partial agonist & k-opioid R agonist
useful in patients w/ high abuse potential
SE: delusional psychosis/delirium
Buprenorphine
IM/IV opioid analgesic, for opioid addiction Tx
Mech: m-opioid R partial agonist w/ minimal activity & slow dissociation from R; reduces effect of other opioids on R!
SE: resp. depression, constipation
Tramadol
IV, IM, oral opioid analgesic,
Mech: m-opioid R partial agonist, releases 5-HT, blocks 5-HT reuptake
SE: addictive, resp. depression, constipation
Tapenadol
oral opioid analgesic,
Mech: m-opioid R agonist, inhibits NE reuptake
SE: addictive, resp. depression, constipation
Naloxone
IV, for opioid overdose.
Mech: m-opioid R competitive antagonist (central activity)
ONLY binds to opioid Rs, not effect if not using opioids
Naltrexone
IV, for opioid overdose or addiction Tx;
Mech: m-opioid R competitive antagonist
longer duration than Naloxone
ONLY binds to opioid Rs, not effect if not using opioids
N-Methytrexone
oral opioid, for relief of constipation in advanced illness.
Mech: peripherally acting m-opioid R competitive antagonist (minimal CNS activity)
SE: constipation
Alvimopan
oral opioid for accelerating time to upper/lower GI recovery, or opioid overdose/addictive Bxs.
Mech: peripheral acting m-opioid R competitive antagonist (minimal CNS activity)
SE: constipation
list of partial opioid agonists
- butorphenol
- pentazocine
- buprenorphine
Effects of mu opioid R activity
- supraspinal AND spinal analgesia,
- antidiuresis,
- euphoria & sedation
(also: Respiratory depression, miosis, decreased GI motility, smooth muscle spasm, & very significant physical dependance)
effects of delta opioid R activity
- supraspinal AND spinal analgesia,
- antidiuresis
(also: Respiratory depression, miosis, decreased GI motility, smooth muscle spasm, & very significant physical dependance)
effects of kappa opioid R activity
- spinal analgesia
- diuresis
- dysphoria & sedation
(also: some respiratory depression, miosis, decreased GI motility, and physical dependance)
Major side effects of opioid analgesics
1. addiction
- respiratory depression (threshold is constant, even though tolerance may make needed dose increase – can reach fatal “needed” dose if used for long enough) esp. w/ asthma
- constipation (w/ chronic use)
- hyperalgesia/allodynia IF used for a very long time
