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MSK Exam 4 > MSK Pharmacology > Flashcards

MSK Pharmacology Flashcards

1
Q

DMARD Therapy

A

Disease Modifying Antirheumatic Drugs (DMARD) are a group of medications
that are used to suppress the body’s overactive immune and/or inflammatory
systems. When use in diseases like Rheumatoid Arthritis and other autoimmune
disease, DMARD Therapy can help to:
● Decreases pain and inflammation
● Reduce or prevent joint damage
● Preserve the structure and function of joints

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2
Q

DMARD Therapy Types include:

A

● Synthetic / Traditional DMARDs
○ Nonspecific targeting (Systemic)
● Biologic and small molecule DMARDs
○ Genetically engineered drugs that block cytokines
○ Specific targeting

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3
Q

Methotrexate (MTX) - Folate Analogue MOA

A

○ MTX is a folate analogue that enters cells via a
reduced folate carrier (RFC). Once inside the cell
MTX:
■ Inhibits dihydrofolic acid reductase
■ Inhibits purine and thymidylic acid synthesis;
which interferes with DNA synthesis, repair,
and cellular replication
○ These processes result in antiinflammatory and
antiproliferative (immunosuppressive) effects

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4
Q

Methotrexate (MTX) indications

A

○ Rheumatoid Arthritis, Rheumatoid Arthritis - Related Conditions (Felty’s Syndrome, Large
Granular Lymphocyte Syndrome), Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Systemic
Lupus Erythematosus, Vasculitis, Inflammatory Myopathies
■ PEARL: MTX works better on peripheral joints and not axial. It can help with skin
issues, but typically is used to help with joints.
○ Other Rheumatic Diseases: Systemic Sclerosis, Corticosteroid-Resistant Multisystem
Sarcoidosis, Inflammatory Ocular Disease, Multicentric Reticulohistiocytosis

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5
Q

Methotrexate (MTX) side effects

A

○ Increased liver enzymes, Drowsiness, fatigue, malaise, alopecia (≤10%), diarrhea
(≤11%), nausea and vomiting (3-10%), skin rash (≤3%), stomatitis (2-10%),
anemia (macrocytic), URI
■ Folic acid, minimum 1 mg daily, is given with MTX to help alleviate side
effects (e.g. nausea, mouth sores)
■ Leucovorin (rescue therapy) can also be given to help with side effects

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6
Q

Methotrexate (MTX) and pregnancy

A

○ Category X (Contraindicated), reliable birth control must be in place

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7
Q

Hydroxychloroquine (Plaquenil) - Antimalarial MOA

A

○ Postulated immunomodulatory and
anti-inflammatory properties via increased pH of
cytoplasmic vesicles. Antimalarials also have
inhibitory effects on pro-inflammatory cytokines.
■ The precise MOA in rheumatic diseases is
unknown.

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8
Q

Hydroxychloroquine (Plaquenil) Indications

A

○ Rheumatoid arthritis, Systemic Lupus Erythematosus, Discoid Lupus, Sjogren’s

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9
Q

Hydroxychloroquine (Plaquenil) PEARL

A

Plaquenil can help with rashes and peripheral arthritis (mild to
moderate) - more severe arthritis may require MTX or Imuran

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10
Q

Hydroxychloroquine (Plaquenil) and Pregnancy

A

○ Category C, may be helpful preventing neonatal lupus

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11
Q

Hydroxychloroquine (Plaquenil) Side effects

A

○ Retinal toxicity (greatest concern), agranulocytosis (less common),
hepatic failure (rare), hepatic insufficiency (rare)

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12
Q

Sulfasalazine - 5-Aminosalicylic Acid Derivative MOA

A

○ Although Sulfasalazine has been
shown to possess multiple
anti-inflammatory and
immunomodulatory properties, the
exact MOA in rheumatic disease is
unknown

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13
Q

Sulfasalazine Indications

A

○ Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Reactive
Arthritis, Inflammatory Bowel-Related Arthritis, Juvenile Inflammatory Arthritis

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14
Q

Sulfasalazine PEARL

A

Sulfasalazine can help with peripheral arthritis, and also axial arthritis to a degree

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15
Q

_____ can be used in moderate to severe Rheumatoid Arthritis where
biologics cannot be given, or insufficient insurance coverage, and can be
similarly effective as the addition of MTX + Biologic in certain patients.

A

Triple therapy

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16
Q

Combination Therapy options

A

○ MTX + Hydroxychloroquine
○ MTX + Biologic
○ MTX + Small molecule
○ MTX + Hydroxychloroquine + Sulfasalazine (Triple therapy)

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17
Q

Leflunomide (Arava) - T-cell Antiproliferative MOA

A

○ Anti-inflammatory and
immunomodulatory effects (reduction
in T lymphocytes)
■ Exact mechanism unknown
■ Long half-life (avg 15.5 days)
● Can remain in the blood for
2-3 years

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18
Q

Leflunomide (Arava) Indications

A

○ Rheumatoid arthritis
○ Other rheumatic diseases: Systemic Lupus Erythematosus, Psoriatic arthritis,
Ankylosing Spondylitis (effective on peripheral arthritis, but not on axial
improvement), Granulomatosis with Polyangiitis, Juvenile Idiopathic Arthritis

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19
Q

Leflunomide (Arava) and Pregnancy

A

○ Category X (Contraindicated), preferably no risk of pregnancy when used as
Arava can remain in the blood for 2-3 years

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20
Q

Due to its long half-life, if the _____ needs to be stopped it is washed out using charcoal or cholestyramine.

A

Leflunomide

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21
Q

Minocycline MOA

A

○ Inhibits bacterial protein synthesis
by binding with the 30S and
possibly the 50S ribosomal
subunit(s) of susceptible bacteria;
cell wall synthesis is not affected.

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22
Q

Minocycline Indications

A

○ Rheumatoid Arthritis (Off Label), Acne, Cellulitis, Chlamydia, Gonorrhea,
Syphilis, Leprosy

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23
Q

Minocycline side effects

A

● Minor side effects:
○ Pruritus, Urticaria, Dizziness, Fatigue, Malaise, Drowsiness, Arthralgia,Tinnitus
● Major side effects:
○ Autoimmune syndromes: drug induced lupus, hepatitis, and vasculitis autoimmune syndromes have been reported (the medication is discontinued if these occur)

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24
Q

Azathioprine (Imuran) MOA

A

○ Decreases synthesis of purine
nucleotides

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25
Q

Azathioprine (Imuran) Indications

A

○ Rheumatoid Arthritis, Systemic lupus erythematosus, Dermatomyositis,
Polymyositis, MCTD, Sarcoidosis, Vasculitis (GPA, Takayasu, Polyarteritis nodosa - off label), Sjogren’s, Pericarditis

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26
Q

TNF Inhibitors - Adalimumab (Humira) MOA

A

○ Human anti-TNF IgG 1 κ monoclonal antibody
■ Neutralizes biologic activity by binding to soluble and transmembrane
TNF-�

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27
Q

Indicated for Uveitis

A

TNF - Inhibitors - Adalimumab (Humira)

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28
Q

TNF Inhibitors - Etanercept (Enbrel) MOA

A

○ Recombinant DNA-derived protein composed of tumor necrosis factor
receptor (TNFR-𝛂) linked to the Fc portion of human IgG1

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29
Q

Etanercept (Enbrel) - TNF Inhibitor PEARL

A

● NOT effective in treating uveitis (Humira and other TNF Inhibitors are more
effective)

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30
Q

TNF Inhibitors - Infliximab (Remicade/Renflexis) MOA

A

○ Chimeric monoclonal antibody that binds to human tumor necrosis factor alpha (TNFα)
■ Renflexis is biosimilar

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31
Q

TNF Inhibitors - Infliximab (Remicade/Renflexis) PEARL

A

Infliximab is typically more effective for Enteropathic arthritis and GI related
autoimmune disease

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32
Q

Infliximab (Remicade, Renflexis) - TNF Inhibitor PEARL

A

● Infliximab can be used to treat Kawasaki’s disease refractory to IVIG
● Pregnancy: Category B

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33
Q

Certolizumab pegol (Cimzia) - TNF Inhibitor and Pregnancy

A

○ Placental transfer is minimal due to lack of functional Fc fragment.

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34
Q

Abatacept (Orencia) - T-cell Therapy MOA

A

○ Selective costimulation
modulator; inhibits T-cell
(T-lymphocyte) activation by
binding to CD80 and CD86 on
antigen presenting cells

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35
Q

Abatacept (Orencia) - T-cell Therapy PEARL

A

● No increased risk of congestive heart failure or non-melanomatous skin
cancers (Squamous cell or Basal cell carcinoma)

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36
Q

Rituximab (Rituxan) - B-cell Therapy (anti-CD20) MOA

A

○ monoclonal antibody directed
against the CD20 antigen on
the surface of B-lymphocytes.
■ Biosimilar: Truxima

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37
Q

Rituximab (Rituxan) - B-cell Therapy (anti-CD20) Side effecs

A

○ Serious infection, Bowel obstruction, Bowel perforation, Stevens-Johnson
Syndrome, Cytopenias, Hepatitis B reactivation
○ NEW: eliminates efficacy of COVID-19 vaccines - Therefore medications like
Evusheld (monoclonal antibody) are currently being used

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38
Q

Tocilizumab (Actemra) - IL-6 receptor antagonist Indications

A

Giant cell arteritis, Rheumatoid arthritis, Cytokine release syndrome

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39
Q

Sarilumab (Kevzara) - IL-6 receptor antagonist Indications

A

○ Rheumatoid Arthritis, Polymyalgia Rheumatica, COVID-19 (Hospitalized patients)

40
Q

Black Box Warning for JAK Inhibitors: Small molecule “Jakinibs”

A

Increased risk of blood clots in susceptible patients

41
Q

Biologic DMARD Therapy side effects

A

● Minor side effects:
○ Infection, Headache, Injection site reaction, Rash
● Major side effects:
○ Reactivation of TB, Serious Infection, Reactivation of Hepatitis B, Malignancy
(e.g. increased risk for Lymphoma, Cytopenias

42
Q

Alcohol Use and DMARD Therapy

A

○ Avoided in patients using MTX as concomitant use can irritate the liver
■ Patients that cannot give up alcohol should be started on a different therapy

43
Q

Steroid MSK indications

A
  • Osteoarthritis
  • Inflammatory Arthritis (eg. RA)
  • Gout, Pseudogout
44
Q

Contraindications for steroid injections

A
  • Do not inject Septic Arthritis/Bursa etc.
  • Can present similar to non-septic inflammation
  • Do not inject fractures
  • Do not inject prosthetic joints (eg.s/p TKA)
  • Do not inject through cellulitis
  • Do not inject into a tendon
  • Caution with diabetes
45
Q

Side Effects with steroid injections

A
  • Localized pain
  • Facial flushing
  • Skin depigmentation
  • Fat atrophy
  • Tendon weakening/ rupture
  • Routine injections linked to decrease
    chondrocytes, maybe the anesthetic?
  • Possible joint infection
46
Q

Contraindications for steroids in general

A
  • Active serious infection
  • Systemic fungal infections
  • Bacteremia
  • Cerebral Malaria
  • TB infections
  • Psoriasis
  • Use shortest duration possible, and consider
    co-morbid conditions: diabetes, HF, osteoporosis, etc
47
Q

Side Effects of steroids

A
  • Many exist
    In relationship to bone and long term use
  • Osteoporosis which increase risk of fractures
  • Osteonecrosis - suppressed osteoblastic activity
  • Myopathy - muscle breakdown
48
Q

Glucocorticoid Therapy and Psoriatic arthritis

A

○ Glucocorticoid therapy is generally avoided due to an increased chance of
developing erythroderma or pustular psoriasis.
○ If glucocorticoid therapy is necessary, higher doses are generally required.

49
Q

Glucocorticoid Therapy and RA

A

○ RA is sensitive to glucocorticoids. A dose of prednisone 10 mg daily can be
beneficial to patients (15 mg daily with medium and large joint involvement,
rarely 20 mg).
○ It should also be noted that prednisone may need to be withdrawn to
identify disease

50
Q

Glucocorticoid Therapy and Polymyalgia Rheumatica

A

○ Oral prednisone starting at an initial dose of 15-20 mg daily then weaning
slowly by 1 mg every once every month.
■ Coverage with a bisphosphonate or other medications for
osteoporosis prophylaxis is generally recommended.

51
Q

Prednisone MOA

A

○ Decreases inflammation by
suppression of migration of
polymorphonuclear leukocytes and
reversal of increased capillary
permeability and suppressing the
immune system by reducing activity
and volume of the lymphatic system

52
Q

Prednisone Side effects

A

○ Cushing’s syndrome, Osteoporosis, Avascular necrosis of bones, Pathological
fracture, Tendon rupture, Steroid myopathy, Wound healing impairment

53
Q

Glucocorticoid Joint Injection Medications:

A

● Kenalog / Triamcinolone Acetonide (40 mg/mL)
○ Used in large joints, more necrotic to skin (used for deeper injection)
● Depo-Medrol / Methylprednisolone (80 mg/mL)
○ Used in small joints, less necrotic to skin (used for more superficial injections)

54
Q

An increased FRAX score is indicated by:

A

○ >20% 10 year risk for a major osteoporosis related fracture
○ >3% risk for a hip fracture

55
Q

Bisphosphonate - Alendronate MOA

A

○ Inhibits the rate of bone resorption by
acting on osteoclasts or on osteoclast
precursors

56
Q

Alendronate Side effects

A

○ Osteonecrosis of the jaw, Atypical femur fracture, Erosive esophagitis,
Esophageal ulceration, Esophageal perforation, Hypersensitivity reaction,
Symptomatic hypocalcemia

57
Q

Monoclonal Antibody (Prolia / Denosumab) indications

A

○ Osteoporosis/bone loss,
■ The duration of use is not established. If fracture risk remains high
after 5 to 10 years of therapy and alternative therapy is considered.
There are no data on use beyond 10 years
○ Bone metastases from solid tumors, Giant cell tumor of bone,
Hypercalcemia of malignancy, Multiple myeloma

58
Q

Anabolic Agents: Romosozumab (Evenity) side effects

A

○ Arthralgia, Increased risk of MI and CVA, Peripheral edema, Insomnia, Rash, Headache

59
Q

Prostaglandins (PGH2) function and NSAIDs

A
  • Formed when arachidonic acid is
    converted by COX enzyme to PGH2
  • Released from mast cells, granulocytes,
    basophils
  • NSAIDs block prostaglandin biosynthesis by
    inhibiting cyclooxygenase enzyme (COX)
60
Q

NSAIDs MOA

A

NSAIDs are a group of medications with differing chemical structures, but all
share the property of blocking prostaglandins. This occurs through inhibiting the activity
of the enzyme PG G/H synthase (PGHS), which is also called cyclooxygenase (COX).

61
Q

NSAID Indications

A
  • Anti-Inflammatory
  • Analgesics- impeding PGE2
  • Antipyretic- impeding PGE2 synthesis
  • Can be given topically
62
Q

NSAID side effects

A
  • Dyspepsia
  • Peptic ulcers- common cause of GI bleeds
  • Risk of heart attack and stroke
  • Fluid retention- loss of renal prostaglandins
  • Asthma- has been associated with acute flares
  • Nephrotoxic- loss of vasodilatory effects of renal prostaglandins
  • Hepatotoxic- with long-term use, monitor Liver enzymes
  • Delayed or nonunion- Fracture healing
63
Q

the original NSAID

A

Aspirin

64
Q

Aspirin Indications

A
  • Pain/ Fever- role has significantly diminished
    overtime
  • Acute Coronary Syndrome
  • CVD risk reduction
  • TIA/ CVA risk reduction
  • Decreased incidence of cancer with daily
    ASA use. (Colon cancer)
65
Q

Aspirin side effects

A
  • Bleeding - Ecchym
  • Anaphylaxis
  • Angioedema
  • Bronchospasm
  • Nephrotoxicity
  • Hepatotoxicity
  • Salicylism
  • Reye Syndrome
66
Q

Ibuprofen uses

A
  • Anti-inflammatory
  • Analgesic
  • Oral
  • IV
  • Topical
  • Can be used for patent ductus arteriosus
  • Antagonizes the anti-platelet effect of ASA
67
Q

Ketorolac Uses

A
  • Short term analgesic
  • Used to replace opiates as an injectable
  • Can be given
    IV
    IM
    Oral- more rare
    Renal toxicity with chronic use
68
Q

Indomethacin (Indocin) uses

A
  • Often used for gout
  • NSAIDs inhibit urate crystal phagocytosis
  • Inhibiting inflammatory response
  • Potent non-selective NSAID
  • Similar side effects to other NSAID
  • Pancreatitis
  • Can be used for patent ductus arteriosus
69
Q

Meloxicam uses

A
  • Preference for COX-2 at lower doses
  • Not as selective as Celecoxib
  • Fewer GI side effects
  • Although all NSAID warnings still apply
70
Q

Celecoxib uses

A
  • Attempt to not mess with the
    “housekeeping” of COX-1
  • Less GI side effects
  • Can still be nephrotoxic
  • Potentially higher risk of CVD compared to
    other NSAIDs
71
Q

Black Box Warning for NSAIDS

A
  • “The risk of heart attack or stroke can occur as early as the
    first weeks of using an NSAID. The risk may increase with
    longer use of the NSAID.”
  • “NSAIDs can increase the risk of heart attack or stroke in
    patients with or without heart disease or risk factors for
    heart disease”
  • Increased risk of serious or potentially fatal GI adverse
    events. Increased bleeding, peptic ulcer, perforation.
72
Q

All patients should be screened for _____ prior to administration of NSAIDs

A

cardiovascular, gastrointestinal, and
renal diseases

73
Q

NSAIDs contraindications

A

● For high risk patients with cardiovascular disease, GI ulcers, or renal disease
consider an alternative therapy like Acetaminophen.
● If NSAIDs need to be used consider the addition of a PPI, misoprostol, and
elimination of H. pylori when necessary.
● Avoid concomitant use of NSAIDs with corticosteroids (increased risk for GI
ulceration).

74
Q

Non-Opioids Analgesics indications

A
  • Analgesic effects
  • Antipyretic agent
  • Headache
  • Postpartum pain
  • No effect on uric acid
  • Not effective for RA
  • No platelet inhibiting effect
75
Q

Non-Opioids Analgesics side effects

A
  • Elevated liver enzymes with therapeutic dose (Adult max 4gm/day)
  • Caution in liver disease
  • Anemia
  • Allergic Reactions or Steven Johnsons has occurred
76
Q

Capsaicin

A

(Non-Opioids Analgesics)
- Chili pepper extract
- Used as a counter irritant
- Reduces pain by desensitizing the afferent axons
- Induces release of substance P - a chemomediator of pain
- With repeated use Capsaicin depletes the neuron of substance P
- Topically used, although oral preparation exist
- Wash your hands after use

77
Q

Non-Opioids Analgesics
Indications

A
  • Neuropathic pain
  • Postherpetic neuralgia
  • Osteoarthritis
  • Musculoskeletal pain
  • Pruritus
78
Q

Non-Opioids Analgesics side effects

A
  • Dermatologic
  • Localized skin irritation, Rash, Pruritus
  • Nausea
  • Nasopharyngeal irritation
  • Coughing, eye irritant
  • Hypertension
79
Q

Neuromuscular blocking drugs

A
  • Used in surgery or for sedation
  • eg. Succinylcholine, Pancuronium
  • Not covered during this learning unit
80
Q

Antispasmodics

A
  • Meant to improve clinical spasticity
  • Inhibits the stretch reflex arc
  • Majority cause sedation, potential for abuse
  • Benzodiazepine, Baclofen, Cyclobenzaprine, Carisoprodol,
    etc
81
Q

Muscle Relaxants

A

Cyclobenzaprine (Flexeril) - Prototype Drug
- Carisoprodol (Soma) Schedule IV
- Metaxalone (Skelaxin)
- Methocarbamol (Robaxin)

82
Q

MOA of the antispasmodics

A
  • Not completely defined
  • Inhibits stretch reflex arc, centrally acting
  • Medication used for local muscle spasm
  • Cyclobenzaprine is related to TCA
  • Meant for treatment of localized tissue trauma
    and muscle strains
  • Currently on FDA watch list for possible
    relationship to serotonin syndrome
83
Q

Muscle Relaxants indications

A
  • Skeletal muscle spasm
  • Fibromyalgia
  • Musculoskeletal pain
84
Q

Cyclobenzaprine

A
  • Related to tricyclic antidepressants
  • Presumed to be helpful with
  • muscle injury and inflammation
  • reduce muscle hyperactivity
  • Antimuscarinic side effects
  • Dry mouth, ileus, tachycardia, mydriasis,
    confusion
  • Overdoses do occur- tachycardia, seizures
  • Hepatic Metabolism- CYP1A2
85
Q

Carisoprodol (Soma)

A
  • Often referred to as a sedative
  • Schedule IV
  • Abuse potential
  • Withdrawls after discontinuation
  • Anxiety, tremors, muscle twitching
  • Also has antimuscarinic side effects
  • Hepatic Metabolism- CYP2C19
86
Q

Muscle Relaxants Side effects

A
  • Antimuscarinic effects- all have some
  • Drug interactions- there is a lot
  • Avoid use with alcohol and sedatives
  • Confusion
  • Do not drive or operate machinery
  • Abuse potential
  • Avoid long term use
  • Given these and contraindications, these
    become tricky medications to use
87
Q

Drugs for Gout flare

A

○ NSAIDs (Indomethacin - Classical
treatment)/Naproxen/Other NSAIDs, Intra-articular
steroids, Systemic Glucocorticoid (Prednisone),
Adrenocorticotropic Hormone

88
Q

Drugs for Gout - Long term

A

○ Allopurinol (Zyloprim), Colchicine (Colcrys), Uloric
(Febuxostat)

89
Q

Xanthine oxidase inhibitor: Allopurinol (Zyloprim) MOA

A

○ Inhibition of xanthine oxidase, the enzyme
responsible for the conversion of
hypoxanthine to xanthine to uric acid.
○ This medication also acts on purine
catabolism and reduces the production of
uric acid without disrupting the
biosynthesis of vital purines

90
Q

Xanthine oxidase inhibitor: Allopurinol (Zyloprim) Indications

A

○ Gout treatment (Chronic urate-lowering therapy), Nephrolithiasis
(prevention of recurrent calcium or uric acid stones), Tumor lysis
syndrome prevention

91
Q

Xanthine oxidase inhibitor: Allopurinol (Zyloprim) side effects

A

○ Gout (acute), Hypersensitivity reaction, Hepatotoxicity, Agranulocytosis
■ Starting urate-lowering therapy can precipitate acute flares. For this
reason colchicine or a NSAID is also started

92
Q

Xanthine oxidase inhibitor: Febuxostat (Uloric) contraindications

A

○ Concurrent use with azathioprine or mercaptopurine
○ Hypersensitivity
○ History of heart attack

93
Q

Xanthine oxidase inhibitor: Febuxostat (Uloric) side effects

A

○ Gout (acute), Hepatic insufficiency, Agranulocytosis

94
Q

Colchicine (Colcrys) MOA

A

○ Disrupts cytoskeletal functions by
inhibiting β-tubulin polymerization into
microtubules, preventing activation,
degranulation, and migration of
neutrophils associated with mediating
some gout symptoms

95
Q

Colchicine (Colcrys) indications

A

○ Gout (prophylaxis, acute flare), Familial Mediterranean Fever (FMF)
○ Off label: Behçet syndrome, Epidermolysis bullosa acquisita, Pericarditis,
acute or recurrent treatment, Postpericardiotomy syndrome, Sweet
syndrome (acute febrile neutrophilic dermatosis)

MSK Exam 4 (6 decks)

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