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Dermatopharmacology Flashcards

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1
Q

MOA of Antihistamines?

A

H1 and H2 antihistamines are inverse agonists (downregulate constitutively activated state of receptor ) or antagonists at histamine receptors

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2
Q

Which Histamine receptor mediates itch in the skin?

A

H1

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3
Q

What antihistamines are safe in pregnancy? What pregnancy category?

A

Chlorpheniramine or Diphenhydramine have the longest safety record. Category B. Also safe in lactation.

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4
Q

First generation H1 antihistamine SE?

A

sedation and anticholinergic (dry mouth, constipation, dysuria, blurred vision)

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5
Q

Name 4 first generation H1 blockers.

A

hydroxyzine, diphenhydramine, chlorpheniramine, cyproheptadine (interferes with hypothalmic function–> increased appetitie and growth retardation in children)

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6
Q

Fexofenadine is an active metabolite of what drug that was withdrawn?

A

metabolite of terfenadine (which was withdrawn for QT elongation and torsades de pointes)

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7
Q

Loratadine dosage needs to be adjusted for

A

People with hepatic or renal impairment

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8
Q

Cetirizine (zyrtec) dosage needs to be adjusted for

A

People with hepatic or renal impairment

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9
Q

What is the most sedating of 2nd generation antihistamines?

A

Cetirizine (zyrtec). Metabolite of hydroxyzine

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10
Q

how are desloratadine and loratadine different?

A

Desloratadine is 5x more potent than loratadine

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11
Q

Doxepin side effects include

A

orthostatic hypotension, anticholinergic

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12
Q

Do not give doxepin to patients with

A

bipolar (induce manic episodes in patients with manic depressive disorder), severe heart disease (risk of heart block), severe depression (black box warning for suicides), seizure (decreases seizure threshold)

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13
Q

Retinoids have 3 interconvertable forms

A

Retinol, retinal, retinoic acid

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14
Q

Retinoids bind to two families of nuclear receptors

A

retinoic acid receptors (RAR) and retinoid X receptors (RXR). Each class has an alpha, beta and gamma

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15
Q

What are the most abundant retinoid receptors in skin?

A

RAR-gamma > RXR-alpha RARG» RXRA

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16
Q

What are the downstream effects of retinoids?

A

Inhibits AP1, NF-IL6
Inhibits TLR2
Antikeratinization (inhibits ornithine decarboxylase)
Down regulated K6, K16
Increases Th1 cytokines, Decreases TH2 cytokines

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17
Q

SE of systemic retinoids: mucocutaneous. name 5

A

cheilitis, photosensitivity, staph aureus colonization, pyogenic granuloma, sticky sensation

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18
Q

SE of systemic retinoids: systemic. Name one rare one.

A

pseudotumor cerebri, pancreatitis 2/2 hypertriglyceridemia, diffuse idiopathic skeletal hyperostosis (DISH), calcification of tendons/ligaments, premature epiphyseal closure

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19
Q

What triglyceride level should you discontinue isotretinoin? Highest risk retinoid?

A

TG> 800 because of risk of pancreatitis. Highest risk retinoid is bexarotene

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20
Q

What LFT value should you discontinue isotretinoin? Highest risk retinoid?

A

LFT> 3x ULN. Highest risk retinoid is acitretin.

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21
Q

What teratogenicity does isotretinoin have?

A

Spontaneous abortion in 20%. No defects at birth, but will have decreased mental function (30% have gross mental retardation, 60% have mild mental deficits)

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22
Q

What patients have the highest risk of DISH? (diffuse idiopathic skeletal hyperostosis (DISH)

A

People who have been on low dose isotreitnoin for many years. And people who have had multiple courses of isotretinoin.

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23
Q

What are specific features of retinoid embyropathy?

A

Craniofacial, CNS, CV, Thymic. Microtia (small ears), cleft palate, microophthalmia, hypertelorism, microcephaly, cardiac septal defects, tetralogy of Fallot, thymic aplasia

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24
Q

Bexarotene cannot be given with which lipid/cholesterol lowering agent?

A
  1. Gemfibrozil (inhibits CYP 3A4), causing high levels of bexarotene –> causes severe hypertriglyceridemia
  2. Simvastatin (CYP 3A4)
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25
Q

How do you treat Bexarotene induced high LDL and TG?

A

any statin except or simvastatin + a fenofibrate + omega 3

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26
Q

What can inactivate tretinoin?

A

UV light, benzoyl peroxide

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27
Q

Which retinoid can be used to treat kaposi sarcoma?

A

Alitretinoin, topical

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28
Q

Which retinoid binds both RXR and RAR?

A

Alitretinoin, topical

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29
Q

Which retinoid is light stable?

A

Adapalene

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30
Q

Which retinoid is preg category x?

A

Tazarotene, bexarotene, oral tretinoin (ATRA), isotretinoin, Acitretin,

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31
Q

Which retinoid binds to RXR?

A

Alitretinoin and Bexarotene

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32
Q

Which retinoid treats APML? Acute promyelocytic leukemia.

A

All-trans retinoic acid. (ATRA) 45 mg/m2/day PO in 2 divided doses

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33
Q

Which oral retinoid has the longest half life?

A

Etretinate (120 days), Acitretin (2 days)

Etretinate is 50x more lipophilic than acitretin, persists for very long

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34
Q

Which retinoid do you need contraception for 3 years after?

A

Acitretin. Concurrent alcohol use converts it to etretinate

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35
Q

What dosage of oral bexarotene do you use for CTCL?

A

75mg/day to 300 mg/day

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36
Q

Where in the GI tract are corticosteroids absorbed?

A

Upper jejunum

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37
Q

Name 2 short acting corticosteroids. What is their biologic half-life?

A

hydrocortisone and cortisone. Biologic half life is 12 hrs.

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38
Q

Name 4 intermediate acting corticosteroids. What is their biologic half-life?

A

prednisone, prednisolone, methylprednisolone and triamcinolone. Biologic half life is 24hrs.

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39
Q

Name 2 Long-acting corticosteroids. What is their biologic half-life in hrs.

A

bethamethasone, dexamethasone

Biologic half-life is 48hrs.

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40
Q

Describe the glucocorticoid and; mineralocorticoid correlation with short/intermediate/long acting

A

Short acting has highest mineralocorticoid activity, Long acting has no mineralocorticoid activity

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41
Q

Where does the glucocorticoid receptor bind to the CS?

A

Binds in the cytoplasm and translocates to the nucleus

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42
Q

What is the main carrier protein for steroid?

A

Cortisol binding globulin

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43
Q

What states increase cortisol binding globulin?

A

high estrogen, pregnancy, hyperthyroidism. Which decreases free CS

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44
Q

What states decrease cortisol binding globulin?

A

Hypothyroidism, liver disease, renal disease, and obesity

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45
Q

Where is steroid converted to its active form? What enzyme

A

Liver, 11B-hydroxysteroid dehydrogenase

For example, cortisone is converted to cortisol, prednisone is converted to prednisolone,

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46
Q

How do you adjust prednisone for liver disease?

A

Give prednisolone (active form of prednisone)

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47
Q

What is the MOA of corticosteroids?

A

Decrease NFkB, AP1, phospholipase A2, COX2,

Increase IL10, increased antiinflammatory proteins (vasocortin, lipocortin, vasoregulin)

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48
Q

Does steroids have more effect on cellular (T cells) or humoral immunity (B cells)?

A

Cellular immunity (T cells)

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49
Q

Describe the hormones released in the HPA axis

A

Hypothalamus releases CRH to the anterior pituitary, which releases ACTH to the adrenals, which secrete cortisol.

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50
Q

Exogenous adrenal insufficiency is typically seen in pts taking CS doses for how long?

A

4 weeks

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51
Q

What side effects of corticosteroids does QOD dosing not decrease the risk of?

A

Cataracts and Osteoporosis

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52
Q

What’s the difference between steroid withdrawal syndrome and adrenal addisonian crisis?

A

In addition to steroid withdrawal, an adrenal addisonian crisis will have hypotension and decreased serum cortisol.
steroid withdrawal syndrome symptoms include: arthralgias, myalgias, mood changes, headaches, fatigue and anorexia

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53
Q

What are the mineralocorticoid side effects of short-acting corticosteroids?

A

HTN, CHF, weight gain and hypokalemia

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54
Q

What are the lipid effects of corticosteroids?

A

hypertriglyceridemia (can cause acute pancreatitis), lipodystrophy (moon face, buffalo hump, central obesity)

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55
Q

What are the pediatric effects of corticosteroids?

A

growth impairment (as a result of decr in growth hormone and IGF-1 production)

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56
Q

What are the bone effects of corticosteroids? When does it take place? Who does it affect the most?

A

Greatest reduction in bone mass occurs in the first 6 months. Greatest absolute loss of bone mass occurs in young men (they have the highest baseline bone mass)

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57
Q

What are gastrointestinal effects of corticosteroids?

A

bowel perforation, peptic ulcer disease

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58
Q

What pregnancy category are steroids?

A

Preg Cat C

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59
Q

Do corticosteroids prevent post herpetic neuralgia in zoster?

A

No, but it does decrease the acute pain

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60
Q

What are intramuscular corticosteroid side effects?

A

cold abscesses, cystal deposition, menstrual irregularities, subcutaneous fat atrophy, increase RISK of HPA axis suppression because levels are constant t/o the day

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61
Q

What lab monitoring do you need for corticosteroids?

A

Fasting glucose levels, blood pressure, triglycerides, weight, height/weight for children, DEXA scan ( T score

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62
Q

MOA of apremilast? Dose adjusted for what patients?

A

PDE 4 inhibitor. Dose halved for pts with renal impairement

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63
Q

MOA of tofacitinib? FDA approved for?

A

JAK 1/3 inhibitor. FDA approved for severe RA.

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64
Q

SE of tofacitinib?

A

Increase LDL/HDL, TGs, CK and LFTs

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65
Q

MOA of ruxolitinib? FDA approved for?

A

JAK 1/2 inhibitor. FDA approved for intermediate/high-risk myelofibrosis.

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66
Q

MOA of azathioprine?

A

Azathiprine is metabolized by HGPRT to 6-mercaptopurine and then into 6-TG (thioguanine), which gets incorporated into DNA and blocks purine metabolism

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67
Q

What enzyme converts azathioprine to inactive metabolites?

A

Xanthine Oxidase and Thiopurine methyltransferase (TPMT)

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68
Q

What medications affect TPMT or XO?

A

XO is blocked by allopurinol and febuxostat

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69
Q

What is Azathioprine FDA approved for?

A

Organ transplantation. Severe RA

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70
Q

What are serious SE of azathioprine? Whats the most common SE?

A

SCC, Lymphoma, Infections (HPV, HSV, scabies)

Most common side effect; n/v and diarrhea

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71
Q

what SE do you see with azathioprine and TNF-alpha inhibitor?

A

increased risk of hepatosplenic T cell lymphoma

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72
Q

What is the MOA of cyclosporine?

A

Complexes with cyclophilin, inhibits calcineurin (an intracellular enzyme) which reduces the activity of NFAT-1–> decreasing IL2 production (decreasing numbers of CD4 and CD8 cells)

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73
Q

What is the max cyclosporine dose?

A

5mg/kg daily

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74
Q

For obese patients starting on cyclosporine, should you use real or ideal body weight?

A

Ideal body weight

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75
Q

FDA approval for cyclosporine?

A

FDA approved for psoriasis

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76
Q

What are the most notable SE of cyclosporine?

A

nephrotoxicity and hypertension (due to renal vasocontriction)

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77
Q

What do you give to treat HTN in cyclosporine?

A

CCBs (nifedipine or isradipine)

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78
Q

Does cyclosporine increase risk of NMSC?

A

yes. particularly when treated for >2 years

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79
Q

What are less notable SE of cyclosporine?

A

Hypertrichosis, gingival hyperplasia, hyperuricemia, hypomag, hyperKalemia

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80
Q

What do you do if creatinine bumps up in cyclosporine?

A

recheck cr.

  • If >30% increase, decrease cyclosporine dose by 1mg/kg for 4 weeks.
  • if >50% increase discontinue therapy
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81
Q

How does methotrexate work?

A

Blocks the making of a cofactor neccessary for purine synthesis. Binds dihydrofolate reductase with greater affinity than folic acid–> prevents converstion of DHF to THF

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82
Q

How do you bypass DHReductase in MTX?

A

Give leucovorin (folinic acid) or thymidine

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83
Q

How is folic acid different from folinic acid?

A

Folic acid is synthetic, folinic acid is naturally occuring version of Vit B9

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84
Q

What cumulative dosage of MTX to test for liver fibrosis?

A

4g

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85
Q

What lab test can you do to test of MTX liver fibrosis?

A

amino terminus of type 3 procollagen peptide assay

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86
Q

What is MTX FDA approved for?

A

Psoriasis and Sezary Syndrome

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87
Q

What are some serious SE of MTX ? Name a lung, hemotologic and cutaneous SE x2

A

acute pneumonitis, pancytopenia (occurs early <6 weeks), UV/radiation recall, cutaneous ulceration

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88
Q

What should MTX not be coadministered with? Which increase the risk of myelosuppression

A

dapsone, sulfonamides, trimethoprim

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89
Q

MOA of mycophenolate mofetil

A

inhibits IMPD (inosine monophosphate dehydrogenase), a key enzyme for de novo synthesis of purines

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90
Q

What is mycophenolate mofetil FDA approved for?

A

FDA approved for renal, cardiac and liver allograft rejection prevention

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91
Q

How should you take cellcept?

A

Without antacids and PPIs. It needs gastric acidity

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92
Q

What are some serious SE of cellcept? Not so serious SEs?

A

Serious ones: 1% risk of lymphoma and lymphoproliferative malignancies. Pseudo-Pelger-huet anomaly (nuclear hypolobulation with left shift which predicts the development of neutropenia)

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93
Q

How does hydroxyurea work?

A

impairs DNA synthesis through inhibition of ribonucelotide diphosphate reductase (RNDPR)

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94
Q

What is hydroxyurea FDA approved for (4) ?

A

sickle cell anemia, chronic myelogenous leukemia, SCC of head and neck, and metastatic melanoma

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95
Q

Most common side effect of hydroxyurea?

A

Megaloblastic anemia

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96
Q

What are some rarer SE of hydroxyurea? cutaneous x 3

A

DM-like eruption, leg ulcers, hyperpigmentation of nails and skin

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97
Q

How does cyclophosphamide work?

A

its an alkylating agent ( directly damaging DNA via cross-linking)

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98
Q

What is cyclophosphamide FDA approved for?

A

mycosis fungoides

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99
Q

What are some serious SE of cyclophosphamide? Name 3.

A

Hemorrhagic cystitits, (cased by acrolein), Transitional cell carcinoma of bladder, premature ovarian failure/infertility

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100
Q

How does chorambucil work?

A

Alkylating agent

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101
Q

What is chorambucil FDA approved for? What do we use it in derm for?

A

CLL

NXG, PG

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102
Q

What is the MOA of antimalarials?

A
  1. Inhibits UV-induced cutaneous reactions by binding to DNA and inhibiting superoxide production
  2. Decreases MHC expression by macrophage
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103
Q

What are antimalarials FDA approved for? What do we use it in derm for?

A

SLE, malaria, and RA

Use it in derm for anything with significant lymphocytic infiltrate

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104
Q

What are some mucocutaneous SE of antimalarials?

A

Blue-gray- black hyperpigmentation on shins
Yellow pigment of skin
Mobiliform drug eruption (dermatomyositis pts)
Nail hyperpigmentation

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105
Q

Which antimalarial has the most GI side effects?

A

chloroquine&raquo_space; hydroxychloroquine

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106
Q

What can you not do while on plaquenil?

A

Smoke!

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107
Q

MOA of dapsone?

A

Inhibits MPO decreasing oxidative damage

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108
Q

How long does dapsone stay in your system?

A

> 30 days after a single dose. Because it undergoes significant enterohepatic recirculation.

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109
Q

Can you take dapsone while pregnant or nursing?

A

Preg class C. Hemolysis in nursing infants

110
Q

What is dapsone FDA approved for?

A

DH and leprosy

111
Q

What is the most serious idiosyncratic reaction of Dapsone?

A

Agranulocytosis which occurs at 8 weeks. and manifests as fever, pharyngitis and occasionally sepsis

112
Q

What is the neuropathy side effect of dapson?

A

Distal motor (wasting of hand muscles)

113
Q

What can you supplement w to decrease risk of dapsone methemoglobinemia?

A

Cimetidine and Vitamin E

114
Q

name 3 TNF alpha inhibitors. what kinda protein is it?

A

etanercept (fusion) , adalimumab (fully human), infliximab (chimeric)

115
Q

which TNF alpha inhibitor has the highest injection site reactions? When does it occur?

A

etanercept> adalimumab

Occurs during 2nd injection, b/c is a delayed type of hypersensitivity

116
Q

What are some skin, neuromuscular, and malignant risks of TNF alpha inhibitors?

A

Psorasis, palmoplantar pustulosis, cutaneous vasculitis, demyelinating disease, lymphoma (hepatosplenic t cell lymphoma when given with azathioprine)

117
Q

What do TNF alpha inhibitors do to ANAs?

A

High rates of ANA and anti-dsDNA

118
Q

Can you use TNF alpha inhibitors in Hep B, Hep C, HIV?

A

Hep C and HIV okay.

Be careful in Hep B b/c of reactivation

119
Q

Do TNF alpha inhibitor have anti-drug antibodies that reduce their efficacy?

A

Infliximab and adalimumab.

120
Q

MOA of ustekinumab?

A

human IgG against p40subunit of IL12 and IL23. Stella bought a pack of 40 beers $12 for 2 for $23

121
Q

Most common side effect of ustekinumab?

A

Upper respiratory infections

122
Q

Most scary side effect of ustekinumab?

A

Reversible posterior leukoencephalopathy syndrome

-Present with confusion and memory difficulties

123
Q

MOA of rituximab?

A

chimeric IgG against CD 20

124
Q

rituximab contraindicated in people with…?

A

bronchospasm, hypotension, angioedema

125
Q

rituximab serious SE?

A

progressive multifocal leukoencephalopathy, HBV reactivation, serious infection

126
Q

Name 3 IL 17 inhibitors? how is their MOA different?

A

izekizumab, secukinumab- neutralize IL-17A

brodalumab- blocks the IL-17 receptor

127
Q

Most common SE of IL17?

A

Nasopharyngitis, candidiasis, herpes, URI

128
Q

What is omalizumab MOA? FDA indication?

A

anti-IgE antibody. FDA approved for allergic asthma and chronic idiopathic urticaria

129
Q

How does vismodegib work?

A

targets SHH by inihibiting Smoothened receptor

130
Q

How does vemurafenib and dabrafenib work?

A

BRAF inhibitor. BRAF is a serine/threonine signal transduction kinase

131
Q

Which mutation does BRAF inhibitors target?

A

V600E mutation of BRAF where valine is replaced by glutamic acid at position 600

132
Q

SE of BRAF inhibitors?

A

KP like eruption, SCC/keratoacanthoma, toxic erythema of chemotherapy (correlated with positive outcomes)

133
Q

What is sorafenib FDA approved for ?

A

HCC, RCC, thyroid carcinoma (iodine resistant), AML

134
Q

SE of sorafenib?

A

The usual BRAF + Hand Foot syndrome, and yellowing of skin

135
Q

What is the dosing for vismodegib?

A

150mg daily. New studies show M-F and 1week on 3 weeks off dosing

136
Q

How long do patients need to wait to get pregnant after taking vismodegib? sonidegib?

A

Women- 7 months (vismo) vs 21 months (sonidegib)

Men- 3 months (vismo) vs 9 motns (sonidegib)

137
Q

MOA of trametinib?

A

Inhibit MEK1/2 of MAPK pathway

138
Q

What is trametinib fda approved for?

A

late stage melanoma with V600E mutation of BRAF. Valine is replaced by E (glutamic acid) at position 600

139
Q

What drug is trametinib combined with?

A

dabrafenib (BRAF) to reduce resistance

140
Q

SE of trametinib?

A

MEK inhibitor. cardiomyopathy, retinal vein occlusion (like the BRAF inhibitors)

141
Q

MOA of ipilimumab

A

Fully human antibody that binds/inhibits CTLA 4 (CD 152), which increases T cell activation against tumor cells

142
Q

Most common SE of ipilimumab? Most serious SE?

A

common: rash, vitiligo
serious: life-threatening coliitis with bowel performation

143
Q

MOA of pembrolizumab and nivolumab?

A

PD1 inhibitor. PD1 on T cells normally binds to PD1-L on the tumor cells and brakes on the immune system

144
Q

Imatinib MOA?

A

Tyrosine Kinase inhibitor. It binds to the kinase domain of various tryosine kinases. LIkes Bcr-ABL, c-kit receptor (CD117), and platelet derived growth factor receptor

145
Q

Imatinib is FDA approved for

A

DFSP, systemic mastocytosis, myeloproliferative hypereosinophilic, GIST, ALL, CML, syndrome,

146
Q

Cutaneous SE of imatinib?

A

Most common: Superficial periorbital edema
2nd most common: rash
Other SE: hypopigmentation/depigmentation (inhibit c-kit)

147
Q

MOA of sonidegib? SE of sonidegib?

A

Binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway.
SE: all SE of vismo + rhabdomyolysis

148
Q

MOA of bacitracin

A

disrupts bacterial cell wall peptidoglycan synthesis

C55 prenol pyrophoshatase

149
Q

MOA of polymyxin B

A

increase cell membrane permeability via detergent-like phospholipid interaction

150
Q

MOA of neomycin

A

binds 30s subunit of bacterial ribosomal RNA

151
Q

Which two topicals antibiotics co-react?

A

neomycin and bacitracin

152
Q

MOA of mupirocin

A

Decreases RNA protein synthesis because it binds to bacterial isoleucyl tRNA synthase

153
Q

What topical abx are Pregnancy category B?

A

Polymycin, mupirocin, silver sulfadiazene

154
Q

What topical abx has activity against MRSA

A

Mupirocin, Retapamulin, silver sulfadiazene

155
Q

MOA of retapamulin

A

binds to L3 protein on 50s subunit of bacterial ribosome

156
Q

MOA of silver sulfadiazene

A

binds bacterial DNA, which decreases DNA synthesis, also disrupts cell walls and membranes

157
Q

What are rare SE of silver sulfadiazene?

A

hemolysis in G6PD patients, methemoglobinemia, renal insufficiency, argyria, unmasking porphyria, leukopenia

158
Q

Why is silver sulfadiazene not used in neonates <2 months?

A

neonates < 2 months. Sulfonamides may cause kernicterus in neonates.

159
Q

MOA of benzoyl peroxide?

A

strong oxidizing properties. no bacterial resistance reported to date

160
Q

MOA of metronidazole?

A

distrupts DNA synthesis

161
Q

What is metronizdale active against?

A

protozoa and anaerobes. Not active against demodex, staph, strep or fungi or even p acnes

162
Q

MOA of azelaic acid?

A
  1. inhibits tyrosinase
  2. dicarboxylic acid that disrupts mitochondrial respiration, decreasing DNA synthesis (esp in melanocytes) and ROS production by PMNs
163
Q

MOA of sodium sulfacetamide?

A

Inhibits bacterial DHS (dihydropteroate synthetase). Prevents conversion of PABA–> folic acid.

164
Q

MOA of penicillins?

A

The pencillin’s Beta-lactam ring binds to bacterial enzyme DD-transpeptidase, inhibiting formation of peptidoglycan cross-links in the bacterial cell wall causes cell wall breakdown

165
Q

Ampicillin + what can give you a morbilliform eruption?

A

mononucleosis, allopurinol, lymphocytic leukemia.

You’ll see a generalized morbilliform itchy eruption 1 week after antibiotic initiation

166
Q

What is the antibiotic of choice for human or animal bites? What if they’re penicillin allergic? sulfa allergic?

A

amoxicillin-clauvulanate (augmentin)
bactrim + clindamycin
ciprofloxacin + clindamycin

167
Q

MOA of 5 fluorouracil?

A

binds to and inhibits thymidylate synthase (which converts deoxyuridine to thymidine)

168
Q

MOA of imiquimod?

A

activator of Toll-like receptors 7 and 8, which activates NFkB and TNFalpha and IFNgamma

169
Q

What are some SE of imiquimod?

A

flu -like or GI symptoms (especially if larger areas treated)
Psoriasis

170
Q

MOA of diclofenac?

A

decreases cyclooxygenase enzymes which increases apoptosis

171
Q

MOA of ingenol mebutate?

A
  1. Induces rapid cellular death (within hours) via mitochondrial swelling/plasma membrane disruption
  2. intense inflammatory response via protein kinase c activation
172
Q

what are 4 medications used to treat AKs?

A

5FU, imiquimod, diclofenac, ingenol mebutate

173
Q

What antibiotics do you give for diabetic foot ulcers?

A

Ticarcillin-clavulanate, ceftriaxone (covers Pseudomonas)

174
Q

What are some side effects of ticarcillin and piperacillin?

A

Hypernatremia, Increased LFTs, bleeding times, hypernatremia

175
Q

What are some side effects of amoxicillin?

A

Less GI side effects than ampicillin, but increased risk of cholestatic injury

176
Q

How long do you treat b-hemolytic strep for?

A

10 days to prevent rheumatic fever

177
Q

Abx for SSSS?

A

Nafcillin

178
Q

Penicillin that causes onychomadesis/photo-onycolysis?

A

CLoxacillin

179
Q

Penicillin that causes shore nails?

A

dicloxacillin. transverse leukonychia and onychomadesis following drug-induced erythroderma

180
Q

What medication can prolong renal excretion?

A

Probenecid

181
Q

What % of people who are cephalosporin allergic are also penicillin allergic?

A

2%

182
Q

What % of people who are penicillin allergic are also cephalosporin allergic?

A

5-10%

183
Q

What medication can cause a serum-sickness-like reaction

A

cefaclor

184
Q

What medicaion causes a Jarisch-Herxheimer reaction in Lyme Disease pts?

A

Cefuroxime

185
Q

SE of cefotetan?

A

disulfiram-like reaction, hemolytic anemia

186
Q

What two antibiotics classes should not be given together?

A

Aminoglycosides and cephalosporins, because of increased risk of nephrotoxicity

187
Q

MOA of vancomycin

A

inhibits bacterila cell wall synthesis

188
Q

SE of vancomycin

A

LABD , Red man syndrome, nephrotoxicity

189
Q

MOA of vancomycin induced Linear IgA bullous Disease?

A

IgA antibodies to LAD 285 and IgA/IgG to BP180

190
Q

name the 3 macrolides?

A

erythromycin, azithromycin, clarithromycin

191
Q

MOA of macrolides?

A

Bind the macro part of the protein aka the 50s subunit of bacterial ribosome

192
Q

Macrolides are a CYP 3A4 inhibitor and must be monitored if the patient is also on what?

A

warfarin, statins, mexiletine, theophylline

193
Q

what are the side effect so erythromycin?

A

GI symptoms is dose-limiting, QT prolongation, torsades de pointes

194
Q

Why can’t you give erythromycin estolate in pregnancy?

A

it can cause hepatotoxicity (swelling of intrahepatic biliary canaliculi cause intrahepatic cholestasis) which shows as an elevated AST.

195
Q

If mom exposed to erythromycin during pregnancy, what SE do you see in fetus?

A

Pyloric stenosis and cardiovascular malformation

196
Q

What is azithromycin better than erythromycin at?

A

Azithromycin is better for GP coverage

197
Q

MOA of fluoroquinolones ?

A

Inhibit bacterial topoisomerase 2 and 4

198
Q

Topoisomerase 2 and 4 covers GN or GP? Which one is DNA gyrase?

A 
Topo 2 (aka DNA gyrase) covers GN
Topoisomerase 4 covers GP
199
Q

First generation quinolones are what? target what?

A

Topo 2 (cipro, ofloxacin)

200
Q

Third generation quinolones are? target what?

A

Topo 4 + 2 (levofloxacin, moxifloxacin)

201
Q

What abx is the treatment of choice for cutaneous anthrax?

A

cipro

202
Q

What are the most to least photosensitive quinolones? Is it UVA or UVB sensitivity?

A

UVA sensitivity.

lomefloxacin, enoxacin and sparfloxacin&raquo_space; cirpofloxacin>norfloxacin>ofloxacin»levofloxacin

203
Q

What can you not take concomitantly with ciprofloxacin.

A

Divalent cations (calcium, magnesium, aluminum, and zinc)

204
Q

MOA of tetracyclines

A

Binds 30S subunit of bacterial ribosome

Inhibits matrix metalloproteinases

205
Q

What is the abx of choice for lymphogranuloma vanereum?

A

doxycyline

206
Q

Which tetracyclines are lipophilic?

A

Mino> doxy>tetracycline

207
Q

What are some SE of minocycline?

A

vasculitis, pseudotumor cerebri, hyperpigmentation of skin/nails/teeth, serum sickness-like reaction, DRESS, lupus-like syndrome

208
Q

What are minocycline induced lupus-like syndrome antibodies?

A

ANA +, antihistone AB-, dsDNA+

209
Q

What are minocycline induced vasculitis antibodies?

A

pANCA+

210
Q

Food decreases absorption in which tetracyline?

A

tetracycline more so than doxy or mino

211
Q

How does rifampin work?

A

binds RNA polymerase, decreasing RNA protein synthesis

212
Q

Rifampin will decrease efficacy of what drugs?

A

OCPs, warfarin, azoles, statins, cyclosporine, CCBs

CYP450 inducer

213
Q

Describe rifampin-dependent antibodies

A

Anaphylaxis, flu-like symptoms, renal failure and hemolytic anemia

214
Q

What are 2 cutaneous side effect of rifampin?

A

orange-red discoloration of body fluids, worsening of porphyria (induced d-ALA synthetase)

215
Q

MOA of trimethoprim-sulfamethoxazole?

A

DHF reductase inhibitor + DHP synthetase inhibitor to decrease THF

216
Q

What antibiotic is used to treat granuloma inguinale?

A

Bactrim

217
Q

What pregnancy category is bactrim?

A

Cat C. Causes jaundice, hemolytic anemia and kernicterus of baby if taken in 3rd trimester

218
Q

MOA of clindamycin? What is it effective against?

A

GP cocci and anaerobes. Not usually GNs. Binds 50S of bacterial ribosomal RNA

219
Q

What is the D zone test?

A

To determine whether the organisms can be induced to be resistant to clindamycin who are already erythromycin-resistant

220
Q

MOA of linezolid

A

Binds 23S portion of 50S ribosomal subunit

221
Q

What are SE of linezolid?

A

Serotonin syndrome (if given with serotonergic drugs like SSRIs, MAOIs, and tricyclics)

222
Q

How does acyclovir work? How does it get processed?

A

Gets phosphorylated by herpes thymidine kinase and then by human cellular GMP kinases to acyclovir triphosphate. Then it competes with doxyguanosinetriphosphate for incorporation into viral DNA

223
Q

Acyclovir preg category?

A

Preg category B

224
Q

Acyclovir has low rate of SEs except for what SE

A

IV infusions are rarely associated withrenal impairment (2/2 crystalline nephropathy)

225
Q

What do you use if there is viral resistance to acyclovir?

A

use foscarnet or cidofovir

226
Q

Valacyclovir has greater oral bioavailability compared to acyclovir. What rare SE can it have?

A

It can rarely cause TTP/HUS in HIV patients

227
Q

Which antiviral is the best at decreasing VZV pain?

A

Famciclovir and valacyclovir

228
Q

Which antiviral has the most bioavailability?

A

Famciclovir> valacyclovir> acyclovir

229
Q

What’s penciclovir?

A

Topical for herpes labialis only.

230
Q

MOA of cidofovir?

A

Like acyclovir, it’s a competitive inhibitor of viral DNA polymerase. But unlike cidofovir, it does not require viral thymidine kinase to be phosphorlyated

231
Q

What is cidofovir used for?

A

HPV, HSV, CMV, Orf, Molluscum

232
Q

MOA of foscarnet?

A

It binds to pyrophosphate-binding site on viral DNA polymerase

233
Q

SE of bleomycin?

A

Injection pain, raynauds, loss of nail plate/ NAIL DYSTROPHY, flagellate hyperpigmentation

234
Q

MOA of podophyllin? FDA approved for?

A

Antimitotic agent that binds tubulin causing cell cycle arrest in metaphase. FDA approved for genital warts.

235
Q

Cantharidin is released from?

A

Spanish fly/Lytta vesicatoria

236
Q

Which topical can cause ring wart formation?

A

cantharidin

237
Q

MOA of azoles?

A

inhibit 14alpha demethylase, which catalyzes conversion from lanosterol to ergosterol

238
Q

Itraconazole metabolized by which CYP?

A

CYP3A4

239
Q

Itraconazole absorption is enhanced by what?

A

By an acidic environment

240
Q

What is Itraconzole FDA approved for?

A

Blastomycosis, histopasmosis, aspergillosis refractory to Ampho B, oropharyngeal/esophageal candidiasis

241
Q

Contraindications to Itraconazole?

A

CHF, active liver disease, other medications that are CYP34A

242
Q

What is fluconazole FDA approved for? Off-label used for?

A

vaginal/oropharyngeal/esophageal candidiasis (like itraconazole), cryptococcal meningitis (unique). Off-label used for coccidioidal meningitis

243
Q

What CYP is fluconazole metabolized by?

A

CYP2C9. Do not give with erythromycin

244
Q

Why is ketoconzaole not used orally today? What drugs can you not administer with ketoconazole?

A

High rate of hepatic toxicity.

Cannot give with heart medication (cisapride, terfenadine or astemizole), which can increase QT syndrome

245
Q

What is voriconazole used for?

A

Invasive aspergillosis, fusarium infections, candida infections. Itraconazole can also be given to aspergillosis

246
Q

Unique SE of voriconazole?

A

Increased risk of SCC, Severe phototoxicity (pseudoporphyria and xeroderma pigmentosum-like changes)

247
Q

CYP3A4 inihibitors acronym

A

MAGIC RACKS in GQ
Macrolide, amiodarone, grapefruit, isoniazid, cimetidine
Ritonavir, acute alcohol abuse, cipro, ketoconazole, sulfonamides
Gemfibrozil, quinidine

248
Q

CYP3A4 inducers acronym

A

Barbie steals phen-phen, induces vomitting and refuses greasy glutonous carbs chronically
Barbituates, st. johns warts, phenytoin
Rifampin, griseo, glucocorticoids, carbamazepine, chronic alcohol abuse

249
Q

MOA of terbinafine

A

Inhibits squalene epoxidase (which catalyzes the conversion of squalene to lanosterol)

250
Q

What is terbinafine FDA approved for?

A

onychomycosis and tinea capitis

251
Q

What is the treatment for onychomycosis?

A

250mg/day. 6 weeks for fingernail and 12 weeks for toenails (clinical cure is 60%)

252
Q

Is Terbinafine better for endo or ectothrix?

A

endothrix like T tonsurans

253
Q

SE of Terbinafine? Name 5

A

taste/smell disturbance, idiosyncratic hepatobiliary dysfunction/hepatitis/liver failure, depression, exacerbation of SLE, drug-induced SCLE

254
Q

What CYP does terbinafine use? what do you not want to give with it?

A

CYP2D6. Don’t give with doexpin or amitriptyline.

255
Q

What is griseofulvin FDA approved for?

A

onychomycosis and tinea corporis/cruris/pedis/capitis

256
Q

Is Griseofulvin better for endo or ectothrix?

A

Griseo is better for ectothrix like microsporum

257
Q

MOA of griseofulvin?

A

interferes with tubulin

258
Q

MOA of nystatin?

A

Binds candida cell membrane sterols, increasing membrane permeability causing cell death

259
Q

What are the echinocandins? MOA of echinocandins?

A

Echinocandins are caspofungin, micafungin, anidulafungin. They inhibit beta-1,3 D-glucan synthase

260
Q

MOA of ivermectin

A

binds glutamate-gated chloride ion channels of parasite nerve/muscle cells causing increasing membrane permeability causing hyperpolarizaion and death

261
Q

What is ivermectin FDA approved for?

A

onchocerciasis, intestinal strongyloidiasis

262
Q

What is the mazzotti reaction? how can you treat it?

A

rash/systemic symptoms/ocular reactions that occurs in onchocerciasis pts. Can treat with doxycyline.

263
Q

Can you be resistant to ivermectin?

A

Yes, resistance occurs due to SNPs of P-glycoprotein-like protein

264
Q

MOA of albendazole?

A

stops tubulin polymerization. causing immobilization and death of parasite

265
Q

What is albendazole FDA approved for?

A

Neurocysticercosis and hydatid disease

266
Q

What are the SE of albendazole?

A

Bone marrow suppression(increased risk in liver disease patients)

267
Q

MOA of thiobendazole?

A

inhibits fumarate reductase, important in anaerobic respiration

268
Q

What is thiobendazole FDA approved for?

A

strongyloides, Cutaneous larva migrans, visceral larva migrans

269
Q

What is MOA of permethrin?

A

Disables NA transport channels on cell membranes, causing paralysis

270
Q

What permethrin cream do you use for scabies vs pediculosis capitis?

A

5% cream for scabies 1 week apart, 1% cream rinse for lice

271
Q

MOA of malathion? What is it used for? in what age kids?

A

Organophosphate that inhibits acetylcholinesterase in arthropods. used for pediculosis capitis as a 0.5% lotion in children >6yo

272
Q

SE of malathion?

A

Flammable, symptoms of organophosphate poisoning

Basic Science (5 decks)

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