Derm/Musc Drugs Flashcards Preview

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Flashcards in Derm/Musc Drugs Deck (67):
1

Acetaminophen

What is the active metabolite

Agonist & inhibitor at what receptor?

Class: Weak COX Inhibitor

-Strong analgesic (non-opioid)

-Antipyretic

-Very weak antiinflammatory activity

 

Rx: 

-Analgesia in children

 

AE:

-Fatal liver disease if overdose

 

Note: AM404 is active metabolite, which:

-Agonist at TRPV1 channel 

-Agonist Cannabinoid CB1 receptor

-Inhibits endogenous cellular CB uptake

-Inhibits COX-1 and COX-2.

2

Aspirin

Class: Nonselective / COX-1 Inhibitors

MOA:

-Irreversible acetylation (inactivation) of COX (non-selective)

-Analgesia

-antipyresis

-antiinflammation

-inhibits thrombosis (post-MI)

AE:

-GI irritation

-Asthma Exacerbation

-prolonged bleeding time

-prolonged gestation

-inhibits renal function

3

Diclofenac

Class: Nonselective / COX-1 Inhibitors

Phase 1: Competitive, time dependent, reversible COX inhibitor.

Phase 2: with time, conformational change with tighter binding. Class 2 NSAID.

 

 

 

 

 

4

Etodolac

Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).

5

Ibuprofen

competitive, reversible COX inhibitor, competes with arachidonic acid for COX active site. Class 1 NSAID.

6

Indomethacin

Phase 1: Competitive, time dependent, reversible COX inhibitor. Phase 2: with time, conformational change with tighter binding. Class 2 NSAID.

7

Ketorolac

Effective perenteral opioid alternative, COX-1 selective. Analgesia with minimal toxicity, for use IM (slower) or IV (faster), with prolonged IM effect allowing longer dosing interval.

8

Naproxen

competitive, reversible COX inhibitor, competes with arachidonic acid for COX active site. Class 1 NSAID.

9

Celecoxib

Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).

10

Diclofenac

Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).

11

Hydroxycholorquine

Antimalarial, unknown mechanism, accumulates in lysosome. Decreases neutrophils chemotaxis, phagocytosis and superoxide synthesis. Inhibits TLR-9 signaling.

12

Leflunomide

Mechanism?

AE

Pyrimidine synthesis inhibitor - inhibits dihydrochloorate (rUMP synthesis) - wich inhibits autoreactive T cells activation and auto-antibodies by B cells

AE - Diarrhea, Elevation of liver enzymes

***Cholestiramine increases clearence

13

Methotrexate

Very potent antiinflammatory, used with anti-TNF's to prevent anti-anti-TNF Abs. Inhibits DHF to THF converison by DHF reductase, to block purine synthesis. Strong effecton decreasing joint pain index. Increase dose if disease not well-controlled. If no responde alone, can add sulfasalazine and hydrochlorquine, leflunomide, anti-TNF agent, anakinra, abatacept. Triple therapy = MTX + SSZ + HCQ (not as good as anti-TNF).

14

Sulfasalazine

sulfapyridine and salicylate bound by axo group. Unknown mechanism.

15

Etanercept

soluble TNF receptor bound to TNF-a, mimics cel-surface receptor.

16

Anakinra

Use as a Disease Modifying Anti-Rheumatic Drug

IL-1 receptor antagonist

17

Golimumab

Neutralizes soluble and cell-bound TNF-a/b.

18

Adalimumab

Neutralizes soluble and cell-bound TNF-a/b.

19

Infliximab

Mechanism

AE?

Major complication

Neutralizes soluble and cell-bound TNF-a

AE - Upper Respiratory Infection, nausea, cough, headache

***TB reaction

20

Allopurinol

Xanthine oxidase inhibitor (hypoxanthine analogue), metabolized to oxipurinol, which is the clinically effective XO inhibitor. Has a short t1/2, but oxipurinol has t1/2 = 14-26 hours (prolonged if decreased GFR). Max effect in 4-14 days.

21

Colchicine

Mechanism?

AE?

Alkaloid derivative of meadow saffron. . Readily bioavailable (> binds soluble, non-polymerized tubulin, forms complex preventing elongation/contraction of dynamic tublin polymers >> blocks cell division, signal transduction, regulation of gene expression, migration, and secretion. Arrests growth (low concentration) and promotes depolymerization (high concentration) and arrests cell at metaphase = antiinflammatory and PMN phagocytosis disruption. Also binds leukocyte membrane proteins. Biliary and stool excretion (enterohepatic circulation), with major eleimination by ABCB1 (GI tract), minor elimination by CYP3A4 (enteric and hepatic cytochrome). Also Renal elimination.

AE - Nausea Vomiting Diarrhea, hair loss , myopathy**, bone marrow suppresion

22

Probenecid

AE?

Targets URAT-1 urate transporter in proximal tubule = uricosuric. Oral, well-absorbed, t1/2= 6-12 hours, rapid hepatic metabolism and urinary excretion. Inhibits urate-anion exchange at proximal tubule to block reabsorption. Ineffective at CrCl <60 ml/min. Take with fluids, alkalinize urine, monitor urate, CBC, LFTs, creatinine.

AE: GI irritation, rash

P works in the P(roximal tubule)

23

Febuxostat

Oral, nonpurine analogue inhibitor of xanthine oxidase. Can inhibit oxidized and reduced XO forms. T1/2 4-18 hours, metabolized hepatically. Activity is not altered in mild to moderate renal insufficiency.

24

Hydrocortisone

Synthetic cortisol, ~90% circulates bound to corticosteroid binding globulin, 5-10% circulates free. Metabolized by liver, 60-90 min t1/2. 30% excreted in urine as dihydroxy ketones. Binds cytosolic receptor, dimerizes, translocates to nucleus where binds glucocorticoid response elements to upregulate or repress transcription of many proteins (20-30%), with variable action depending on cell type. Can also activate signaling pathways before entering nucleus = rapid steroid actions (prior to transcriptional changes). Example is phosphorylation and release of annexin-1, a potent antiinflammatory agents that blocks the mobilization of lymphocytes and release of inflam mediators.

25

Prednisone

Oral available, 4x antiinflammatory with less (0.3x) mineralocorticoid activity cf. hydrocortisone/cortisol. Short/medium-acting duration.

26

Prednisolone

Oral, injectable. 5x antiinflammatory with less (0.3x) mineralocorticoid activity cf. hydrocortisone/cortisol. Short/medium-acting duration.

27

Triamcinolone

Oral, injectable, topical. Intermediate duration. 5x antiinflammatory with 5^3 topical activity and no (0) mineralocorticoid activity cf. hydrocortisone/cortisol

28

Betamethasone

Oral, injectable, topical. Long duration. 25-40x antiinflammatory with 10x topical activity and no (0) mineralocorticoid activity cf. hydrocortisone/cortisol

29

Dexamethasone

Oral, injectable, topical. Long duration. 30x antiinflammatory with 10x topical activity and no (0) mineralocorticoid activity cf. hydrocortisone/cortisol

30

Fludrocortisone

Oral. 10x antiinflammatory with 0 topical activity and 250x mineralocorticoid activity cf. hydrocortisone/cortisol

31

Clobetasol

Superpotent, Class I steroid. Binds receptor and translocates to nucleus for many functions. Vasoconstriction activite correlates with clinical efficacy. Available as lotion, spray, or shampoo.

32

Triamcinolone

Upper-middle strength, Class III steroid. Available as ointment, cream, foam.

33

Desonide

Mild strength, Class VI steroid. Available as gel.

34

Hydrocortisone

Synthetic cortisol, ~90% circulates bound to corticosteroid binding globulin, 5-10% circulates free. Metabolized by liver, 60-90 min t1/2. 30% excreted in urine as dihydroxy ketones. Binds cytosolic receptor, dimerizes, translocates to nucleus where binds glucocorticoid response elements to upregulate or repress transcription of many proteins (20-30%), with variable action depending on cell type. Can also activate signaling pathways before entering nucleus = rapid steroid actions (prior to transcriptional changes). Example is phosphorylation and release of annexin-1, a potent antiinflammatory agents that blocks the mobilization of lymphocytes and release of inflam mediators.

35

Tacrolimus

Antiinflammatory ointment/cream, binds FK506 forming complex that inhibits calcineurin and blocks cytokine production.

36

Pimecrolimus

AE?

Antiinflammatory ointment/cream, binds FK506 forming complex that inhibits calcineurin and blocks cytokine production.

Risk of Cancer (lymphoma, skin cancer) and vitiligo

37

Methotrexate

Mechanism?

Very potent antiinflammatory, used with anti-TNF's to prevent anti-anti-TNF Abs in Rheumatoid Arthritis. Inhibits DHF to THF converison by DHF reductase, to block purine synthesis. Strong effecton decreasing joint pain index. Increase dose if disease not well-controlled. If no responde alone, can add sulfasalazine and hydrochlorquine, leflunomide, anti-TNF agent, anakinra, abatacept. Triple therapy = MTX + SSZ + HCQ (not as good as anti-TNF).

38

Methoxsalen

Photosensitizer, preferentially taken up by epidermal cells and binds DNA, making more susceptible to UV radiation damage.

39

Etanercept

soluble TNF receptor bound to TNF-a, mimics cel-surface receptor.

40

Infliximab

Neutralizes soluble and cell-bound TNF-a/b.

41

Benzoyl Peroxide

bacteriostatic, combined with erythromycin or clindamycin to prevent development of resistance.

42

Clindamycin

Binds 50S ribosome to suppress protein synthesis, antibiotic

43

Doxycycline

Binds 30S subunit and inhibits protein synthesis in susceptible bacteria.

44

Metronidazole

Mechanism?

for Rosea

Inhibits nucleic acid synthesis by disrupting DNA, anti-inflammatory

45

Acitretin

Retinoid, unstable in sunlight. Functional vitamin A analogue acts at retinoic acid receptor, retinoid X receptor. Alters gene expression by binding nuclear receptor. Differentiates epidermis, modulates proliferation, prevents keratinization, prevents follicle plugging (=anti-acne), antiinflammatory, apoptotic

46

Adapalene

Retinoid, unstable in sunlight. Functional vitamin A analogue acts at retinoic acid receptor, retinoid X receptor. Alters gene expression by binding nuclear receptor. Differentiates epidermis, modulates proliferation, prevents keratinization, prevents follicle plugging (=anti-acne), antiinflammatory, apoptotic

47

Isotretinoin

Oral tretinoin

48

Tretinoin

First generation retinoid, unstable in sunlight (unlike 3rd generation retinoids). Functional vitamin A analogue acts at retinoic acid receptor, retinoid X receptor. Alters gene expression by binding nuclear receptor. Differentiates epidermis, modulates proliferation, prevents keratinization, prevents follicle plugging (=anti-acne), antiinflammatory, apoptotic

49

Calcipotriene

Vitamin D analgue inhibits keratinocyte proliferation and promotes differentiation (=slows growth). Steroid-alternative.

50

Ketoconazole

Blocks 14-a-demethylase to block ergosterol synthesis and inhibit cell wall formation

51

Mycostatin

Same as Nystatin, binds ergosterol in fungal cell wall.

52

Clotrimazole

Blocks 14-a-demethylase to block ergosterol synthesis and inhibit cell wall formation

53

Econazole

Blocks 14-a-demethylase to block ergosterol synthesis and inhibit cell wall formation

54

Itraconazole

Blocks 14-a-demethylase to block ergosterol synthesis and inhibit cell wall formation

55

Terbinafine

Inhibits squalene epoxidase, reducing ergosterol synthesis and inhibiting fungal cell wall formation. Oral or topical.

56

Acyclovir

What enzyme does it need for function?

Interferes with DNA polymerase to inhibit DNA replication via chain termination - needs thymidine kinase

57

Neomycin

Aminoglycoside, binds 30S subunit of ribosome

58

Erythromycin

Binds 50S ribosome to suppress protein synthesis, antibiotic

59

Bacitracin

TMP/SMX

60

Mupirocin

Ointment, derived from Pseudomonas. Reversibly binds isoleucyl tRNA synthetase.

61

Cephalexin

First generation cephalosporin, binds penicillin binding proteins to arrest bacterial cell wall synthesis and inhibit bacterial replication.

62

Cefazolin

First generation cephalosporin, binds penicillin binding proteins to arrest bacterial cell wall synthesis and inhibit bacterial replication.

63

Polymyxin B

Peptide antibiotic

64

Imiquimod

Antiviral and anti-tumor immune modulator, binds TLR-7, to induce cytokines (INF-a and TNF-a).

65

Topical 5-fluorouracil

inhibits thymidylate synthetase >> pyrimidine antimetabolite.

66

Liquid nitrogen

Cryotherapy for removal of skin lesions

67

Permethrin

Synthetic pyrethroid, <2% absorbed percutaneously. Paralyzes mite by sodium channel disruption. Only acts on mite (not eggs), so must give multiple treatments.