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PBL Pharm Block 3 > Pharm 42 - Eicosanoids > Flashcards

Pharm 42 - Eicosanoids Flashcards

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1
Q

Aspirin MOA

A

Irreversible inhibits COX-1 and COX-2 by acetylating the active site serine residue

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2
Q

Aspirin clinical applications

A

Mild-to-moderate pain, HA, myalgia, arthralgia, prophylaxis of stroke and MI (@ low doses -> antiplatelet effect)

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3
Q

Aspirin adverse effects

A

GI ulcer/bleeding, Reye’s syndrome, asthma exacerbation, bronchospasm, angioedema; also tinnitus

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4
Q

Aspirin contraindications

A

Hypersensitivity; aspirin-triggered asthma; chickenpox/flu in children/teens (risk of Reye’s syndrome)

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5
Q

Aspirin therapeutic considerations

A

Increases plasma concentration of acetazolamide -> CNS toxicity; Ibuprofen may inhibit antiplatelet effect; may enhance methotrexate toxicity; increased risk of bleeding in anti coagulated pts

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6
Q

NSAID MOA and classes

A

Inhibit COX-1 and COX-2, decreasing synthesis of eicosanoids and limiting inflammatory response
Includes Proprionic acids, acetic acids, Oxicams, Fenamates, Ketones

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7
Q

Priopionic Acids (4)

A

Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen

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8
Q

Acetic Acids (5)

A

Indomethacin, Sulindac, Etodolac, Diclofenac, Keterolac

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9
Q

Oxicams (1)

A

Prioxicam (duh)

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10
Q

Fenamates (2)

A

Mefenamate, Meclofenamate

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11
Q

Ketones (1)

A

Nabumetone

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12
Q

NSAID clinical applications

A

Mild-to-moderate pain, F, OA, RA, dysmenorrhea, gout, PDA closure (indomethacin)

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13
Q

NSAID adverse effects

A

GI hemorrhage/ulceration/perforation, nephrotoxicity, Stevens-Johnson syndrome, pseudoporphyria (naproxen); also tinnitus

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14
Q

NSAID contraindications

A

GI/intracranial bleeding; coagulation defects; asthma, urticaria, or allergic rxn to NSAIDs including ASA (b/c of risk of fatal anaphylaxis); renal insufficiency

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15
Q

NSAID therapeutic considerations

A

1) Naproxen has longer T1/2, more potency, and fewer GI effects than ASA
2) Keterolac is used for 3-5 days post-surgery
3) Piroxicam has long T1/2 - dose once daily
4) Nabumetone has greatest COX-2 selectivity
5) Fenamate is less useful than ASA

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16
Q

Acetominophen MOA

A

COX-3 inhibitor in CNS

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17
Q

Acetominophen clinical applications

A

F, mild-to-moderate pain

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18
Q

Acetominophen adverse effects

A

Hepatotoxicity, nephrotoxicity; also rash and hypothermia

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19
Q

Acetominophen contraindications

A

Hypersensitivity

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20
Q

Acetominophen therapeutic considerations

A

Insignificant anti-inflammatory effects b/c of weak inhibition of peripheral COX; overdose is LEADING CAUSE OF HEPATIC FAILURE (b/c of modification by CYP40 to reactive metabolite that requires detoxification by glutathione) -> antidote is N-ACETYLCYSTEINE

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21
Q

Celecoxib MOA

A

Selective inhibition of COX-2

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22
Q

Celecoxib clinical applications

A

OA, RA in adults, ankylosing spondylitis, primary dysmenorrhea, acute pain in adults, familial adenomatous polyposis (b/c of some interaction w/ PPAR-delta)

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23
Q

Celecoxib adverse effects

A

MI, ischemic stroke, heart failure, GI bleeding/ulceration/perforation, renal papillary necrosis, exacerbation of asthma; also peripheral edema

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24
Q

Celecoxib contraindications

A

Hypersensitivity to sulfonomides or celecoxib; asthma, urticaria, or allergic rxn to NSAIDs (b/c of risk of fatal anaphylaxis); pain with CABG

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25
Celecoxib therapeutic considerations
Decreased efficacy of ACE inhibitors
26
Glucocorticoid MOA and names (4)
Induces lipocortins -> inhibit COX-2 action and prostaglandin biosynthesis Prednison, Prednisolone, Methylprednisolone, Dexaethasone
27
Glucocorticoid clinical applications
Inflammatory conditions; autoimmune diseases
28
Glucocorticoid adverse effects
Immunosuppression, cataracts, hyperglycemia, hypercortisolism, depression, euphoria, osteoporosis, growth retardation in children, muscle atrophy; topical may cause skin atrophy
29
Glucocorticoid contraindications
Systemic fungal infection
30
Zileuton MOA
Inhibits 5-lipoxygenase -> decreases leukotriene synthesis
31
Montelukast MOA (and another drug in the class)
Cysteinyl leukotriene type-1 receptor antagonistsAlso includes Zafirlukast
32
Zileuton clinical applications
Asthma, also ASA-exacerbated respiratory distress (aspirin-sensitive asthma)
33
Zileuton adverse effects
Increased liver enzymes; also, urticaria, abdominal discomfort, dizziness, insomnia; occasionally associated with Churg-Strauss
34
Zileuton contraindications
Active liver disease, elevated liver enzymes
35
Zileuton therapeutic considerations
Avoid concurrent use of dihydroergotamine, ergoloid mesylates, ergonovine, and methylergonovine b/c of increased risk of ergotism (N, V, vasospastic ischemia); pill-form reduces problems with inhaler use in kids (and can also treat other systemic allergies); requires periodic LFTs
36
Montelukast clinical applications
Chronic asthma, allergic rhinitis, also ASA-exacerbated respiratory distress (aspirin-sensitive asthma)
37
Montelukast adverse effects
Allergic granulomatosis angiitis, hepatitis; also, GI distress, hallucinations, agitation; occasionally associated with Churg-Strauss
38
Montelukast contraindications
Hypersensitivity
39
Montelukast therapeutic considerations
Excreted in breast milk; not indicated for acute asthma attacks, not appropriate as monotherapy for asthma; pill-form reduces problems with inhaler use in kids (and can also treat other systemic allergies)
40
Glucocorticoid therapeutic considerations
Does not correct underlying disease, only limits effects of inflammation; requires tapering dosage after chronic use to avoid adrenal insufficiency
41
TNF-Alpha Inhibitors MOA and names (5)
1) Enteracept: TNF receptor dimer | 2) Infliximab, Adalimumab, Certolizumab, Golimumab: anti-TNF antibodies
42
TNF-Alpha Inhibitors clinical applications
1) RA & Ankylosing Spondylitis (E, I, A, G) 2) Juvenile Idiopathic Arthritis (E, A) 3) Crohn's (I, A, C) 4) Ulcerative Colitis (I) 5) Plaque Psoriasis (E, I, A) 6) Psoriatic Arthritis (E, A, G) [Key: E=Enteracept, I=Infliximab, A=Adalimumab, C=Certolizumab, G=Golimumab]
43
TNF-Alpha Inhibitors adverse effects
Myelosuppression, heart failure, optic neuritis, REACTIVATION OF TB, increased risk of infection/leukemia/lymphoma, demyelination of CNS; also upper respiratory infection, V, abdominal pain
44
TNF-Alpha Inhibitors contraindications
Enteracept: sepsis, heart failure Infliximab: Hypersensitivity
45
TNF-Alpha Inhibitors therapeutic considerations
Give pts PPD before starting treatment (and regularly when they're on the drug); in case of infection, give aggressive antibiotics; Enteracept binds to TNF-Alpha and Beta, the rest bind only to TNF-Alpha
46
Alprostadil MOA
PGE1 analogue w/ vasodilator properties
47
Alprostadil clinical applications
Maintenance of PDA (in Tetralogy of Fallot, Eisenmenger pulmonary HTN, and aortic valve atresia), erectile dysfunction
48
Alprostadil adverse effects
Heart failure, arrhythmias/conduction defects, DIC, disorders of bone development, seizure, priapism, apnea in newborns; also hypotension, penile fibrosis/discomfort
49
Alprostadil contraindications
Sickle cell; leukemia/myeloma; neonatal RDS; Anatomical deformation of the penis (and implant/Peyronie's disease)
50
Misoprostol MOA
PGE1 analogue w/ vasodilator properties
51
Misoprostol clinical applications
Cytoprotective (increases mucus and bicarb production) and antisecretory (inhibits parietal cells) protection against gastric ulcers in long-term NSAID therapy; PUD; abortifacient (with mifepristone)
52
Misoprostol adverse effects
Anemia, cardiac arrhythmia; also GI disturbance
53
Misoprostol contraindications
Pregnancy
54
Carboprost MOA
PGF2Alpha analogue that stimulates uterine contraction; leuteolytic activity controls fertility
55
Carboprost clinical applications
Abortion in 2nd trimester, postpartum hemorrhage
56
Carboprost adverse effects
Dystonia, pulmonary edema; also D, HA, F, paresthesia, breast tenderness
57
Carboprost contraindications
Acute PID; cardiac, pulmonary, renal, or hepatic disease
58
PGF2Alpha Analogues with Vasodilator Properties (3)
Latanoprost, Bimatoprost, Travoprost
59
PGF2Alpha Analogues with Vasodilator Properties clinical applications
Ocular HTN; open-angle glaucoma
60
PGF2Alpha Analogues with Vasodilator Properties adverse effects
Macular retinal edema; also blurred vision, hyper pigmentation of eyelids/iris
61
PGF2Alpha Analogues with Vasodilator Properties contraindications
Hypersensitivity
62
Epoprostenol MOA
Prostacyclin analogue that stimulates vasodilation of pulmonary & systemic arterial vasculature; also inhibits platelet aggregation
63
Epoprostenol clinical application
Pulmonary HTN
64
Epoprostenol contraindications
Supraventricular tachycardia, hemorrhage, thrombocytopenia; also hypotension, rash, GI disturbance, MSK pain, paresthesia, anxiety, flu-like illness
65
Epoprostenol contraindications
Heart failure w/ severe L. ventricle dysfunction; chronic use in pts w/ pulmonary edema
66
Anakinra MOA
Recombinant IL-1 receptor antagonist
67
Anakinra clinical application
RA - reduces bony erosions, by decreasing metalloproteinase release from synovial cells
68
Anakinra adverse effects
Neutropenia, increased risk of infection
69
Anakinra contraindications
Hypersensitivity to drug OR to E. Coli-derived proteins

PBL Pharm Block 3 (14 decks)

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