MSK and Rheumatology Pharmacology

Acetaminophen

[Tylenol, APAP] PO, IV

Drug class: Analgesic-Antipyretic

MOA: CNS anti-prostaglandin, blocks peripheral pain impulse generation; inhibits hypothalamic heat regulation center

Indications: Mild to moderate pain; fever

Common SEs/ADRs: Edema, rash, increased ammonia, blood dyscrasias

Contraindications: Liver disease, hypersensitivity

Dx-Dx Interactions: Anti-convulsants may decrease APAP concentration, increase warfarin effect

Monitor: Liver function, symptom relief; 24H dose

Pregnancy category: C

Dose adjustment required in liver or renal impairment, avoid with alcohol, max 24H dose of 2g in elderly, 3g in adult

Tramadol

Ultram

Drug class: Synthetic opioid, analgesic

MOA: Opioid analgesic; mu receptor weak agonist and inhibits NE uptake and serotonin– both of which modify ascending pain pathways

Indications: moderate to moderately severe pain

Common SEs/ADRs: Flushing, dizziness, somnolence,

pruritis, constipation; seizures

Contraindications: < 14 days after MAOI (Monoamine Oxidase Inhibitors), other sedating drugs, other serotonin elevating drugs

Dx-Dx Interactions: MAOI’s, sedating drugs, SSRIs

Monitoring: symptom relief, fever, sedation

Pregnancy category: C

Dose adjustment if renal or hepatic impairment, Max 24H

dose 400mg, PO and extended release

Increases serotonin levels

NOT FOR USE IF <18 YEARS OLD

Ibuprofen

Drug class: Traditional NSAIDs: tNSAIDs

MOA: Inhibit COX1 and COX2 enzymes to reduce prostaglandin, prostacyclin, and thromboxane

Indications: pain secondary to inflammation in selected patients

Common SEs/ADRs: Nausea, dyspepsia, diarrhea, anorexia;

increases BP, fluid retention, increases bleeding (~20%)

Contraindications: Uncontrolled HTN, CKD, HF, CVD, anti-coag

use, hx GI bleeding or ulcer

Dx-Dx Interactions: Anti-coags, other NSAIDs, diruetics,

lithium, anti-HTN meds

Monitoring: CrCl, CBC, LFT

Pregnancy Category: C

Gastric protection with PPI, problems with ASA, DO NOT

GIVE TO 3RD TRIMESTER OR NURSING

SALT RETAINING

PO, liquid

Ketorolac

Toradol

Drug class: Traditional NSAIDs: tNSAIDs

MOA: Competitively inhibits COX1 and COX2 enzymes resulting in decreased formation of prostaglandin precursors

Indications: Short-term (max 5 days) analgesia for moderately

severe acute pain

Common SEs/ADRs: headache, GI pain, dyspepsia, nausea

Contraindications: Renal failure or dehydration, cerebrovascular bleeding, L&D, use with other NSAIDs, GI bleed

Dx-Dx Interactions: Aspirin, NSAIDs, ACE inhibitors, loop diuretics and thiazide diuretics

Monitoring: Analgesic response; BP, edema, renal function,

cognition, sCR, BUN, CBC, LFT, bleeding/bruising

Pregnancy Category: C

Short term use only

Reduce dose in elderly, avoid in hypertensives and acute/chronic renal disease

PO, IM, IV, nasal spray, OP drops

Celecoxib

Celebrex

Drug class: COX2 inhibitor, selective NSAID

MOA: Selectively inhibits COX2 enzymes to reduce prostaglandin and prostacyclin

Indications: Pain secondary to inflammation in selected patients

Common SEs/ADRs: headache, diarrhea, dyspepsia, rash, nausea, vomiting, increase BP, fluid retention, CV disease, increases clotting (AMI, CVA)

Contraindications: Uncontrolled HTN, CTKD, HF, CVD

Dx-Dx Interactions: Other NSAIDs, diuretics, lithium, anti-HTN

Monitoring: CrCl, EKG, CBC, LFT

Pregnancy Category: C

Helps with elderly GI bleed but increases CVD problems

Capsaicin

Drug Class: topical OTC analgesic

MOA: Agonist of TRVP1 with resulting desensitization of sensory axons and inhibition of pain transmission; also in arthritis by inducing the release of substance P depleting it, prevents reaccumulation of substance P producing inhibition of sensory axons

Indications: Topical treatment of mild myalgia, arthralgia, neuropathy

Common SEs/ADRs: Localized erythema and pain, skin burns, CNS depression, elevation of BP

Contraindications: Sensitivity to capsaicin or menthol; damaged skin

Dx-Dx Interactions: none significant

Monitoring: pain, skin integrity

Pregnancy Category: B

Multiple OTC preparation for mild pain; don’t apply to broken or damaged skin

SAMe

Drug Class: OTC Oral Anti-Osteoarthritis Agent

MOA: SAMe is a molecule naturally formed in the body from homocysteine and 5-methylene tetrahydrofolate

Indications: Oral: depression, anxiety, heart disease, fibromyalgia, functional abdominal pain, OA, bursitis, tendonitis, chronic lower back pain (CLBP), dementia, alzheimer’s, chronic fatigue syndrome, liver disease, parkinson’s

Common SEs/ADRs: GI symptoms

Contraindications:

Dx-Dx Interactions: serotonin elevating anti-depressants

Monitoring:

Pregnancy Category: unknown

Comparable to NSAIDs, celecoxib, decreases symptoms of OA, Fewer ADRs than NSAIDs, comparable to reducing pain

Glucosamine

Drug Class: OTC Oral Anti-Osteoarthritis Agent

MOA: Required for the synthesis of glycoproteins, glycolipids, and glycosaminoglycans (mucopolysaccharides) -–compounds that are found in tendons, ligaments, cartilage, synovial fluid

Indications: OA, rheumatoid arthritis, glaucoma, temporoTMD, joint pain, back pain, and weight loss

Common SEs/ADRs: unknown

Contraindications: unknown

Dx-Dx Interactions: Warfarin

Monitoring: produced naturally in humans

Pregnancy Category: unknown

Conflicting evidence of effectiveness for OA

TAKEN 3X DAILY X8 WEEKS

Methotrexate

Rheumatrix

Drug Class: nonbiologic DMARD

MOA: Inhibits dihydrofolate reductase and DNA production; inhibits production of cytokines

Indications: Recent RA <6 months, low disease activity, no poor prognostic features

Common SEs/ADRs: Arachnoiditis, subacute toxicity reaction (motor paralysis, CN palsy, seizure, coma); pulmonary fibrosis, hepatotoxicity, bone marrow suppression, acute renal failure (ARF), SJS

Contraindications: Severe renal or hepatic disease, bone marrow suppression, AIDS, alcoholic liver disease, peptic ulcer disease (PUD), ulcerative colitis

Dx-Dx Interactions: live vaccines, (increase or decrease) Warfarin, ethanol

Monitoring: CBC, LFT, CrCl, PG, CXR

Pregnancy Category: X

Initial response in 3-4 weeks, full response in 3-6 months

Folinic acid (Leucovorin) rescue for toxicity

Folic acid 5mg weekly day after administration, or 1mg daily

Hydroxychloroquine

Plaquinil

Drug Class: nonbiologic DMARD

MOA: unknown in RA but possibly suppression of T-cell response to mitogens and several others

Indications: RA, systemic lupus erythematous, malaria

Common SEs/ADRs: N/V, abdominal pain, rashes, nightmares; ocular toxicity (ophthalmology), myopathy

Sulfasalazine

Azulfidine

Drug Class: 5-aminosalicylic acid derivative synthetic, non-biologic DMARD

MOA: Systemically: sulfapyridine inhibits prostaglandin synthesis, decreases level of IgA, IgM, RF production

Locally: 5-aminosalicylic acid in colon reduces inflammation locally

Indications: management RA and ulcerative colitis, off-label: Crohn’s disease, psoriasis, psoriatic arthritis

Common SEs/ADRs: photosensitivity, headache, reversible oligospermia, cholestatic jaundice

Mycophenolate Mofetil

Cellcept

Drug Class: semi-synthetic nonbiologic DMARD

MOA: immunosuppressant of T and B lymphocytes

Indications: post-renal, hepatic, cardiac transplant; off-label RA

Common SEs/ADRs: HTN, hypotension, peripheral edema, chest pain, tachycardia, pain, headache, insomnia, elevated glucose, elevated cholesterol, decr WBC, decr RBC, decr platelets

Tofacitinib

Xeljanz

Drug Class: Antirheumatic drug, nonbiologic DMARD, Janus Associated Kinase Inhibitor (JAK inhibitor)

MOA: Inhibits JAK enzymes & prevents gene expression & intracellular activity of immune cells and IgG, IgM, IgA

Indications: Treatment of moderate to severe RA in adults not responding to, or intolerant of, Methotrexate

Common SEs/ADRs: Infection (20%); HTN (2%), Headache (4%), serious infection (2%), Diarrhea (4%); bone marrow suppression, GI perforation, hepatotoxicity, lipid abnormalities, malignancy; TB

Etanercept

Enbrel

Drug Class: biologic DMARD, TNF-alpha antagonist

MOA: Binds TNF-alpha preventing its binding to the TNF-alpha receptors

Indications: Aggressive RA, nonresponse to NB-DMARDs

Common SEs/ADRs: Headache, abdominal pain, edema; Reactivation of hepatitis; TB; lymphoma; infection; varicella

Abatacept

Orencia

Drug Class: biologic DMARDs: T-cell activation inhibitor

MOA: inhibits T-cell activity by binding to CD80 & CD86 on surface of APC and blocks C28 interaction of APCs with T-cells

Indications: RA not-responding to other DMARDs

Common SEs/ADRs: Headache, nausea; Infection, hypertension

Rituximab

Rituxan

Drug Class: biologic DMARDs: monoclonal antibody

MOA: •chimeric monoclonal antibody that reduces inflammatory response by inhibiting CD 20 B-lymphocytes and thereby decreasing the presentation of antigens to T-lymphocytes

Indications: •severe RA in combo with methotrexate when inadequate response to one or more TNFα agents; chronic lymphocytic leukemia, non-Hodgkins lymphoma, Wegener’s Granulomatosis

Common SEs/ADRs: •~30% experience rash with first infusion but fewer subsequent infusions (pre-treat with steroid); dependent edema, HTN, fever, fatigue, cytopenia

Anakinra

Kineret

Drug Class: Antirheumatic; BDMARD; Interleukin-1 Receptor Antagonist

MOA: Naturally occurring antagonist of IL-1 receptor which reduces degradation of cartilage and inhibits bone resorption

Indications: Mod to severely active Rheumatoid Arthritis unresponsive to one or more DMARDs

Common SEs/ADRs: Headache (12%), fever (12%), injection site reaction (3-73%), infection (39%), neutropinia (5%);  Anaphylaxis; infections, malignancy, neutropenia

Cyclophosphamide

Procytox

Drug Class: Alkylating Antineoplastic agent, Immunosuppressant agent; antirheumatic

MOA: Alkalating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis, cell-phase nonspecific

Indications: Malignancy, Acute Lymphoblastic Leukemia; Acute Myelocytic Leukemia; RA;  Breast Cancer, Chronic Lymphocytic Leukemia; Chronic Myelocytic Leukemia; Hodgkin and Non-Hodgkin Lymphoma; Multiple Myeloma; Corticoid refractory nephrotic syndrome

Common SEs/ADRs: Bone marrow suppression, cardiotoxicity, fertility impairment; GI distress, vomiting; hepatic toxicity; anaphylaxis; pulmonary toxicities; immunosuppression, hyponatremia, secondary malignancies; urinary/renal toxicity

Prednisone

Drug Class: Glucocorticoids

MOA: inhibits cytokines and inflammatory mediators

Indications: short-term use in RA

Common SEs/ADRs: Weight gain, fluid retention, straie, impaired wound healing, Osteoporosis, HTN, mood changes, cataracts, hyperglycemia, dyslipidemia, PUD, HPA suppression, HF

Contraindications: infection, TB

Dx-Dx Interactions: live vaccines, multiple

Monitoring: CrCl, hepatic function panel (HFP), CBC

Pregnancy Category: C/D

Lactation: not recommended

down titrate dosing if more than 2 weeks

Allopurinol

Zyloprim

Drug Class: Purine Xanthine oxidase inhibitor

MOA: Inhibits xanthine oxidase and blocks the formation of uric acid

Indications: gout prophylaxis

Common SEs/ADRs: N/D, rash; Stevens-Johnson syndrome, allopurinol hypersensitivity syndrome; bone marrow suppression

Contraindications: prior allopurinol hypersensitivity reaction

Dx-Dx Interactions: Theophylline, warfarin, ACE inhibitors, Thiazide diuretics

Monitoring: CrCl for dosing; serum uric acid level

Pregnancy Category: C

Lactation: caution

Primary metabolite is oxypurinol - is also active, long half-life, accumulates in CKD; not for acute episode but can continue during flare; possible rash with ampicillin/amoxicillin; don’t treat asymptomatic hyperuricemia; avoid with ACE inhibitors and thiazide diuretics (may enhance risk of hypersensitivity reaction); Renal dosing necessary

Colchicine

Drug Class: leukocyte migration inhibitor

MOA: Inhibits leukocyte migration, phagocytic activity

Indications: Acute gout, initial Px; pseudogout

Common SEs/ADRs: Diarrhea, N/V/D abd pain (80%), myopathy, bone marrow suppression

Contraindications: CKD, hepatic disease

Dx-Dx Interactions: May increase levels of HMG-CoA drugs (statins)

Monitoring: CrCl

Pregnancy Category: C

Reserved for people who cannot use NSAIDs or NSAID tx failure; colcrys, low therapeutic index

Probenecid

Benemid

Drug Class: uricosuric agent

MOA: Blocks proximal convoluted tubule (PCT) re-absorption of uric acid

Indications: gout

Common SEs/ADRs: N, fever, rash, hepatic toxicity; Nephrolithiasis

Contraindications: Hx of uric acid stones or nephropathy; avoid when CrCl is < 50 mL/min

Dx-Dx Interactions: Increases level of multiple antibiotics, NSAIDs

Monitoring: CrCl, uric acid, CBC

Pregnancy Category: no data

Lactation: no data

Counteracted by low dose ASA; 6-12 months to decrease gout attacks

Febuxostat

Uloric

Drug Class: Non-purine Xanthine oxidase inhibitor

MOA: Selectively inhibits xanthine oxidase to reduce uric acid production

Indications: Management of hyperuricemia in gout

Common SEs/ADRs: rash, nausea, liver function abnormalities, arthralgia

Contraindications: Use with azathioprine, mercaptopurine; severe hepatic or renal impairment

Dx-Dx Interactions: Incr conc of azathioprine, mercaptapurine, theophylline

Monitoring: liver function, uric acid

Pregnancy Category: C

Lactation: caution

40mg, 80mg tabs; with or with out meals; can continue if acute flare; use NSAID or colchicine  as bridge first 6 months; currently 2^nd line Tx (after Allopurinol) due to concerns about increased risk for CVD

Baclofen

Lioresal

Drug Class: skeletal muscle relaxant, central

MOA: Inhibits transmission of synaptic reflexes at spinal cord level

Indications: Muscle spasticity in multiple sclerosis, spinal cord lesions

Common SEs/ADRs: Drowsiness, vertigo, psych disturbances, slurred speech, ataxia

Contraindications: Hypersensitivity; seizure disorder, impaired renal function

Dx-Dx Interactions: Incr effect opiates, benzodiazepines, hypertensive agents; Incr toxicity of ethanol, CNS depressants, TCAs, clindamycin, MAOIs

Monitoring: Symptoms, blood pressure, mental status, renal function

Pregnancy Category: C

Lactation: no

Caution with renal dysfunction; don’t stop abruptly; used PO and intrathecal; PO dose 5mg BID – TID, 80mg day max; reduce dose renal impairment; avoid with St John’s wort, valerian, kava kava; caution in elderly

Cyclobenzaprine

Flexeril

Drug Class: skeletal muscle relaxant, central

MOA: Centrally-acting muscle relaxant related to tricyclic antidepressants, reduces tonic somatic motor activity decreasing muscle spasm

Indications: muscle spasm

Common SEs/ADRs: Anticholinergic effects, CNS depression, inhibits serotonin reuptake; drowsiness, dizziness, xerostomia, fatigue, headache

Contraindications: Hepatic impairment; <14 days MAOI, CHF, arrhythmias, post acute MI; other serotonin reuptake inhibitors

Dx-Dx Interactions: Incr anticholinergic effects, ethanol, serotonin reuptake inhibitors; tramadol, acetylcholinesterase inhibitors

Monitoring: Symptoms; signs of serotonin syndrome, LFTs, mental status

Pregnancy Category: B

Lactation: no

Avoid in elderly, Tablet 5mg TID, capsule (ER) 15mg Daily (not rec in elderly) forms; max 2-3 weeks use, expensive

Dantrolene

Dantrium

Drug Class: Skeletal muscle relaxant, peripheral

MoA: Acts directly on skeletal muscle to inhibit release of Ca++ from sarcoplasmic reticulum reducing spasticity

Indications: Muscle spasticity secondary to CVA, CP, SC injury, MS; malignant hyperthermia; neuroleptic malignant syndrome

Common SEs/ADRs: Alter BP, heart failure, incr heart rate, confusion, chills, hepatitis, photosensitivity

Contraindications: Hepatic impairment, cardiac disorders, COPD

Dx-Dx Interactions: Ethanol, St John’s wort, Kava Kava

Monitoring: Symptoms; LFTs; BP, pulse, temperature

Pregnancy: C

Lactation: no

CYP3A4 substrate; avoid ethanol; PO & IV forms;  PO capsule 25mg, 50mg, 100mg; max 400mg daily in divided doses Q6-8H; avoid in elderly; avoid sunlight

Amitriptyline

Elavil

Drug Class: tricyclic antidepressant

MoA: Inhibits reuptake of serotonin, norepinephrine in CNS

Indications: Chronic pain, depression, diabetic neuropathy, migraine prophylaxis, fibromyalgia

Common SEs/ADRs: anticholinergic side effects (urinary retention, tachycardia, hypotension); sedation

Contraindications: MAO inhibitor within 14 days; acute recovery phase from MI; concurrent cisapride

Dx-Dx Interactions: multiple

Monitoring: BP, heart rate; mental status; suicidal ideation; ECG if cardiac disease; sedation; urinary retention

Pregnancy: C

Lactation: not

BBW: suicide risk

Duloxetine

Cymbalta

Drug Class: SNRI (serotonin and norepinephrine reuptake inhibitor)

MoA: inhibits 5HT & NE reuptake; weak DA reuptake inhibitor

Indications: Depression, chronic pain, GAD, diabetic peripheral neuropathy (DPN), fibromyalgia (FM)

Common SEs/ADRs:

Contraindications:

Dx-Dx Interactions:

Monitoring:

Pregnancy:

Lactation:

Pregabalin

Lyrica

Drug Class: anticonvulsant, misc

MoA: Binds to calcium channels in CNS and modulates calcium entry which inhibits excitatory neurotransmitter release

Indications: Neuropathic pain, fibromyalgia, post-herpetic neuralgia, partial-onset seizures

Common SEs/ADRs: Peripheral edema, dizziness, weight gain, somnolence, ataxia

Contraindications: hypersensitivity

Dx-Dx Interactions: multiple

Monitoring: Pain, sedation, weight gain, suicidality

Pregnancy: unknown

Lactation: not recommended

Adjust dose with decreased renal clearance

Pilocarpine

Salagen

Drug Class: Cholinergic agonist

MoA: Agonist impact on muscarinic receptors that stimulates salivary gland secretion

Indications: Symptomatic treatment of xerostomia sec to salivary gland hypofunctionn from radiotherapy or Sjorgren’s syndrome

Common SEs/ADRs: Flushing, headache, dizziness, urinary frequency, weakness, sweating, lacrimation

Contraindications: Severe hepatic impairment (Child-Pugh Score >10); severe asthma; angle-closure glaucoma; cardiovascular disease, biliary tract disease, Hx nephrolithiasis,  COPD

Dx-Dx Interactions: acetylcholinesterase inhibitors, aripiprazole, Beta-blockers

Monitoring: IOP, fundi, visual fields

Pregnancy: C

Lactation: no

Systemic form (Ophthalmic drops also available); reduce dose with hepatic impairment; oral tablet

Ceftriaxone

Rocephin

Drug Class: Cephalosporin, cell wall inhibitor, ^3rd generation (IV, IM)

MoA: in actively growing bacterial cells, interferes with transpeptidation of bacterial cell wall by binding to PBP

Indications: G+, more G- coverage (citerobactor, S marcescens, providencia); AOM, sinusitis, LRTI, meningitis, empiric treatment serious infections pending C&

Common SEs/ADRs: rash, diarrhea, eosinophilia; with prolonged use bacterial or fungal superinfection; overdose-neuromuscular hypersensitivity, seizures

Contraindications: hypersensitivity to cephalosporin, anaphylaxis penicillin

Dx-Dx Interactions: warfarin (incr PT/INR); may precipitate with Ca containing solutions

Monitoring: PT/INR with Warfarin

primarily biliary tract clearance; t1/2 is 7-8H; can dose once daily (twice  daily for serious infections); enterobactor resistance emerges rapidly

Vancomycin

Vancocin

Drug Class: Glycopeptides (oral, parental)

MoA: in actively growing bacterial cells, interferes with transpeptidation of bacterial cell wall by binding to PBP

Indications: G+ organisms, esp staph that are MRSA (IV); C dificile colitis (oral)

Common SEs/ADRs: phlebitis at IV site (irritating to tissue); chills, fever, vomiting, eosinophilia; neurotoxicity (hearing loss, vertigo)(IV), nephrotoxicity (IV), neutropenia (IV)

Contraindications: hypersensitivity, severe hearing loss (IV); CKD

Dx-Dx Interactions: aminoglycosides, other ototoxic or nephrotoxic drugs

Monitoring: CrCl; peak & trough vancomycin levels

renal clearance; poorly absorbed orally; Vancomycin Flushing Syndrome with IV admin (Histamine release); renal dosing necessary