Non-Opiate Analgesics Flashcards
Examples of amine autocoids
Histamine, Serotonin
Examples of lipid derived autocoids
PGs and Leukotrienes
Peptide hormone autocoids
Bradykinin, Angiotensin
Four Classes of NSAIDs
Salicylates (Aspirin) Arylpropionic Acids (Ibuprofen, Naproxen) Arylacetic acids (Indomethacin, diclofenac, ketorolac) Enolic acids (Piroxicam, Meloxicam)
Most important p-Aminophenol class drug
Acetaminophen
Three therapeutic applications of NSAIDs
Analgesic
Antipyretic (acetaminophen)
Anti-inflammatory
In which cases would you relieve pain with tylenol rather than ibuprofen
Headache Chronic Postsurgical (Tyl + Opioid Mixes)
Effects of COX-1 inhibition
Reduction of thromboxanes, causing reduced platelet aggregation. This helps platelets act as a blood thinner. Can inhibit PGE and PGI that are protective in stomach.
Effect of PGE2 and PGI2 in the stomach
Inhibit acid secretion
Promote Mucus Secretion
Inhibition leading to stomach ulcers
Effects of PGI2 (outside of stomach)
Vasodilation, Reduced Platelet aggregation
COX2 inhibition will serve an important role in
inhibition of inflammation induced by cytokines/inflamm. mediators
How does Aspirin work?
It irreversibly inhibits cyclooxygenase 1/2 by acetylation of COX. Duration effect corresponds to time required for new protein synthesis.
Important details about Salicylate absorption
Rapidly absorbed from stomach and jejunum (asp mostly in jej)
Passive diffusion of free acid
Delayed by presence of food
Important details of Salicylate distribution
Throughout most tissues and fluids
Readily crosses placenta
Competes with many drugs for binding sites
Salicylate half life
12 hours because its extensively conjugated
How do you increase excretion of Salicylates in urine?
Increase urinary pH
Ways that non-salicylates are metabolized
Oxidation
Demethylation
Conjugation
What patient population do you need to worry about giving aspirin to?
Children – Reye’s Syndrome (Liver failure, deepening coma, seizures, etc.)
Common name for Ibuprofen? Naproxen?
Ibuprofen – Advil
Naproxen – Aleve
Difference between Ibuprofen and Naproxen?
Half Lives
Ibuprofen – 2 hrs
Naproxen – 14 hours
Important acetic acid derivative pain meds (and basic information)
Diclofenac/Voltaren (Gel for arthritic pain)
Indomethacin (Reversible inhibitor of PG synth)
Ketorolac/Toradol
Risks of diclofenac/voltaren
Increased risk of peptic ulcer and renal dysfxn
Risks of long term indomethacin
Acute gouty arthritis
Ankylosing spondylitis
Pericarditis
Use of enolic acids?
Used to treat arthritis because of great joint penetration
Few GI side effects
Long half life
Examples of enolic acids
Meloxicam (20 hrs)
Piroxicam (57 hrs)
Advantages of acetaminophen over other NSAIDs
no GI toxicity
No effect on platelet aggregation
No Reyes
In low doses, OK for liver patients
Disadvantages of acetaminophen over other NSAIDs
Little clinically useful antiinflammatory activity
acute overdose may lead to fatal hepatic necrosis
Adverse effects of salicylate overdose
Metabolic Acidosis
Vertigo/Tinnitus/hearing probs
N/V, Delirium, Psychosis –> Coma
Tretment of salicylate poisoning
Reduce salicylate load (urination, dialysis)
Charcoal
Correct Metabolic Imbalance
Risks of non-salicylate NSAIDs
GI ulceration
Inhibition of Renal Fxn
Inhibition of Platelet Aggregation
Inhibition of uterine motility
Adverse effects of Acetaminophen overuse
Renal toxicity, Papillary necrosis
Dose Dependent Hepatic Necrosis (esp. w/ OH)
Name a selective Cox2 inhibitor. Why use one?
Rofecoxib (Vioxx)
Reduce ulcers and GI Bleeds
Why was Vioxx taken off the market?
High chance of blood clots, strokes, and MI
What is the only Cox2 selective inhibitor left on the market?
Celebrex
Who shouldn’t use NSAIDs
CKD, Peptic Ulcer Disease, GI bleeders
In high doses, inhibits bone healing
What are DMARDs
Disease Modifying Anti-Rheumatic Drugs
Three main classes of DMARDs
Antiproliferative agents
IL-1 Blockers
TNF-alpha blcokers
Examples of anti-proliferative DMARDs
Methotrexate, Cyclophosphamide, Azathioprine
Leflunomide
What are anti-proliferative DMARDs stopping from proliferating
B and T cell proliferation
Name the IL-1 Blocking DMARD
Anakinra (kineret)
Absolute contraindications for anakinra?
Pre-existing malignancy
Neutropenia
Three main TNF-alpha blockers
Etanercept (Enbrel)
Infliximab (Remicade)
Adalimumab (Humira)
TNF alpha blockers. How do they work and what are they used to treat
They bock the interaction between macrophages and T cell receptors, downregulating both in the process. Used to treat RA , Crohns, and Ulcerative Colitis
Downside of using a TNF-alpha blcoker
Immunosuppressants – especially contra. for patients with previous TB
Fatal toxicities associated with all DMARDs
Hepatotoxicity Hematotoxicitiy Teratogenicity Nephrotoxocity CV tox
Main drugs to give for acute gout
Colchicine + NSAIDs (indomethacin)
How does Colchicine work?
Bind to tubulin, which interferes with mitotic spindle fxn
Depolymerized microtubules stop granulocyte migration, phagocytic activity, and inhibits lactate and cytokine release.
Adverse effects of Colchicine
Toxic to rapidly proliferating intestinal epithelial cells
Nausea, vomiting, diarrhea, cramps
Main drugs for chronic gout
Allopurinol
Febuxostat
Probenecid
How does allopurinol work?
Inhibitor of xanthine oxidase
Increased half-life of prebenecid
contra-indicated in acute gout
How does febuxostat (Adenuric) work?
Its a new non-purine inhibitor of xanthine oxidase
More effective at lowering serum uric acid than tophus area than allopurinol.
How does Probenecid work?
Competes for renal tubular anion transporter
Blocks the reabsorption of urate in prox. tubules
What type of Gout should not be treated with probenecid
Overproducers
What is psuedogout?
Calcium pyrophosphate dihydrate crystal deposition disease
Leave behing positively birefringent crystals
Chondrocalcinosis on radiographs
Which ion channels are associated pain
TRP, Nav, Cav
How does blocking sodium channels prevent pain
Prevents hypopolarization/depolarization
Blocks action potentials
Mutations of Nav 1.7 cause what
Gain of fxn – Severe Pain
Loss of Fxn – diminished patients
Topical anesthetics that influence the activity of sodium channels
Lidocaine
Benzocaine
Oxybuprocaine (in optho)
Important details about Lidocaine
Local analgesia (dentistry), itching, burning 15 minute local onset, lasts 30-120 minutes
Important details for Bupivicaine
Longer lasting than Lidocaine (3.5 hrs), used in epidural anesthesia
Important details for Benzocaine
OTC, oral ulcers, ear pain
Lower allergy risk
Name important Sodium channel blockers
Lamotrigine
Amitryptiline
Carbamezipine
Important details for Lamotrigine
Off label use for peripheral neuropathy, migraine
Risk of developing Stevens Johnsons
Important details for amitryptiline?
Post-herpetic neuralgia, Polyneuropathy, Fibro, Visceral Pain
Overdose toxicity
Important details for carbamezipine
Used for trigeminal neuralgia, Bipolar, and Seizures
Can be Teratogenic
Sodium channel blockers with SNRI’s Functionality
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
What do you use Duloxetine (Cymbalta) for?
Diabetic Pain, Fibromyalgia, Peripheral Neuropathy
Details on Venlafaxine
Used off label for diabetic neuropathic pain
SNRI – anti-depresant/anxyiolytic
List SNRIs that don’t have an effect on sodium channel effect and what you use them for
Milnacipran (Fibromyalgia, SNRI)
Tapentadol (Diabetic Neuropathic Pain, NRI)
SSRIs used for pain assocaited depression
Fluoxetine (Prozac), Paroxetine (Paxil), Setraline (Zoloft)
Escitalopram, Citalopram
Pharmacokinetics of TCA/SNRIs
Rapid Oral Absorption
90% protein bound
Hepatic Metabolism (2D6)
Renal Excretion
Calcium channel blockers that have an influence on pain
Diabetic Neuralgia, Fibromyalgia, Neuropathic Pain
Gabapentin (Neurontin)
Pregabalin (Lyrica)
Ziconotide
Levetiracetam
