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Block 5 - Pulm and Skeletal > Pharm - Asthma, Tb, Ca > Flashcards

Pharm - Asthma, Tb, Ca Flashcards

0
Q

Albuterol

A

Short acting beta 2 agonist
Quick onset of action
As needed for symptomatic relief
Oral or inhaled

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1
Q

What is the deal with aerosolized drugs for asthma?

A

90% actually swallowed

Should be poorly absorbed from GI tract or inactivated by first pass hepatic metabolism

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2
Q

Salmeterol

A

Long acting beta 2 agonist - Only inhaled
Moderate persistent and severe asthma
Slow onset of action and longer duration - not for acute
Slows diffusion away from receptor
Don’t use alone - use with inhaled corticosteroid

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3
Q

Who are inhaled corticosteroids recommended for?

A

Patients with persistent asthma that require short acting beta 2 agonist more than once a day

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4
Q

How do glucocorticoids work in the treatment of asthma?

A

Receptor once bound migrates to cytoplasm and inhibits NFkappaB and nucleus and inhibits AP1 involved in pro inflammatory genes, also activates anti inflammatory genes

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5
Q

Fluticasone

A

Inhaled glucocorticoid - prophylactic
Don’t reverse acute symptoms - mainstay for chronic asthma
One week onset with several months of effect
Minor side effects at high doses - oropharyngeal candidiasis, decreases in bone density, thinning of skin, purpura, dysphonia

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6
Q

Prednisone

A

Oral and systemic glucocorticoids
Management of severe episodes lasting days or chronic asthma
Same side effects as inhaled corticosteroids plus major - adrenal insufficiency from withdrawal on discontinuation, others

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7
Q

Cromolyn sodium and nedocromil sodium

A

Inhibit degranulation of pulmonary mast cells
Also reduce response of inflammatory cells
Mainly prophylactic - less effective than steroids
Only inhaled
Infrequent and minor side effects - bronchospasm, cough, laryngeal edema, joint swelling and pain, angioedema, headache, rash and nausea

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8
Q

Zafirlukast and montelukast

A

Competitive inhibitor of leukotriene receptor type 1

Normal activation would cause smooth muscle contraction

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9
Q

Zileuton

A

Inhibits 5 lipoxygenase - blocks conversion of arachidonic acid to leukotrienes

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10
Q

Leukotriene inhibitors in general

A

All oral
Metabolized in liver
Zafirlukast - some GI disturbances, mild headache, and increased amino transferase activity
Montelukast - few adverse effects
Zileuton - elevated liver alanine amino transferase can cause symptomatic hepatitis on stopping, monitor AT activity, dyspepsia

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11
Q

Theophylline

A

Possible inhibition of cAMP phosphodiesterase and competitive antagonism of adenosine receptors
Relaxes bronchial smooth muscle, other modest effects
Absorbed from GI, metabolism in liver
Lots of side effects - GI distress, anxiety, insomnia, headache, CNS effects and cardiac rhythm disturbances
Third line therapy in US but is inexpensive

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12
Q

Omalizumab

A

Anti IgE - cant bind to receptors on mast cells and basophils
Reduces both early and late phase response to allergens
Single SC injection every 2-4 weeks, dose adjusted based on serum IgE and body weight
Generally well tolerated - maybe anaphylaxis and increased cancer

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13
Q

Who is omalizumab indicated for?

A

Adults and adolescents >12 with allergies and persistent mild or moderate asthma

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14
Q

Why is tb so difficult to treat?

A

Difficult for drugs to penetrate mycolic acid cell wall
Mycobacteria have efflux pumps
Mycobacteria often sequestered within host cells

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15
Q

What is the general treatment for tb before and after drug susceptibility testing?

A

Before - RIPE

after - at least 3 to which sensitive for first 2 months

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16
Q

What is the current protocol for active tb?

A

2 months on RPI (initial phase) followed by 4 months on RI (continuation phase)
Substitute other first lines as needed based on sensitivity
Use directly observed therapy

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17
Q

When is chemo prophylaxis with isoniazid for 6 months recommended?

A

Household contacts of tb
Upon conversion to positive skin test with no symptoms
Patients with inactive tb who have never been adequately treated

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18
Q

What is MDR tb?

A

Resistant to R and I

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19
Q

What is XDR tb?

A

Resistant to R, I, fluoroquinolones, and at least one injectable second line agent

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20
Q

Isoniazid - mechanism of action

A

Most active anti tb drug, Bacteriostatic or cidal
Use confined to m. Tb and atypical mycobacteria
Prodrug - activated by myco bacterial catalase peroxidase katG
Radical adduct with NAD+ inhibits two steps in mycolic acid synthesis by inhA and kasA
NADP+ adduct inhibits mycobacterial DHFR

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21
Q

Isoniazid - mechanism of resistance

A

Lack katG catalase activity

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22
Q

Isoniazid - adverse effects

A

Two forms of enzyme lead to fast or slow acetylation - adjust dosage
Peripheral neuropathy - avoid by coadmin of pyridoxine
Hepatic toxicity - esp if over 50

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23
Q

Rifampin - mechanism of action

A

Inhibits prokaryotic DNA directed RNA polymerase

Activity against gram+ and gram-

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24
Q

Rifampin - resistance

A

Mutations in rpoB gene in tb

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25
Q

Rifampin - adverse effects

A

Sometimes hepatotoxic
Potent inducer of p450 - other drugs can fail due to increased metabolism
Rifabutin used in patients taking many other drugs

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26
Q

Pyrazinamide - mechanism of action

A

Activated to pyrazinoic acid by nicotinamidase (from pncA gene)
Growing cells can’t synthesize proteins
Semi dormant or starving cells can’t perform trans-translation

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27
Q

What is trans-translation?

A

Cells not able to grow well can stall on mRNA and it degrades
Stalled ribosomes bind tmRNA which can free it for productive translation
TmRNA also provide degradation signal on incompleted protein

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28
Q

Pyrazinamide - resistance

A

Mutations in pncA gene

29
Q

Pyrazinamide - adverse effects

A

Hepatic damage - don’t give to patients with hepatic dysfunction
Inhibits uric acid excretions and can cause acute episodes of gout

30
Q

Ethambutol - mechanism of action

A

Targets arabinosyl transferase III - synthesizes arabinose necessary for mycobacterial cell wall

31
Q

Ethambutol - resistance

A

Mutations in embB gene

Necessary but not sufficient for resistance

32
Q

Ethambutol - adverse effects

A

Optic neuritis - affects visual acuity and color differentiation
Check to see if patient color blind before therapy

33
Q

Streptomycin

A

Injected unlike other first lines - not absorbed from GI tract

34
Q

Moxifloxacin

A

Fluoroquinolone
Inhibits topoisomerase II
Needs to be tested more but possible awesome first line drug

35
Q

What are drugs used for the mycobacterium avium complex (MAC)?

A

Clarithromycin
Azithromycin
Rifabutin (does p450 like rifampin!)

36
Q

What drugs are used for leprosy?

A

Dapsone (sulfonamide like) - usually in combo with rifampin

Dapsone resistant get rifampin with clofazimine

37
Q

What IV calcium supplements are used in severe hypocalcemia?

A

Calcium gluconate over calcium chloride because latter can cause necrosis and sloughing in perivascular tissues

38
Q

What do CaSR (cinacalcet) do?

A

Allosterically modulator of CaSR at parathyroid cells and through intracellular second messengers inhibits PTH secretion

39
Q

What does calcitonin do?

A

Inhibits bone resorption and lowers serum calcium concentration

40
Q

What oral calcium supplements are used in hypocalcemia?

A

Calcium carbonate - need food
Calcium citrate - don’t need food
Both can cause ab discomfort and constipation

41
Q

What is the mechanism of action of bisphosphonates?

A

Strong affinity for calcium hydroxyapatite and deposit in bone with long half life - better for cancellous bone (spine) than cortical
Pyro phosphate analogs with same backbone and different side chains
First gen - cause osteoclast apoptosis by accumulating inside as toxic
Second and third gen - block FPPS in HMG CoA reductase pathway in osteoclasts

42
Q

What are the pharmacokinetics of bisphosphonates?

A

Oral absorbed poorly

Excreted by kidney - don’t use if GFR < 30-35

43
Q

What are the adverse effects of bisphosphonates?

A 
Esophageal irritation (empty stomach, glass of water, remain upright)
Development of hypocalcemia in patients with vitamin d deficiency
Osteonecrosis of jaw in patients with metastatic bone disease (more with potent parenterally)
Atypical femoral fractures (prolonged oral use)
44
Q

What is the mechanism of actin of raloxifene?

A

Agonist at estrogen receptors in bone

Antagonist at estrogen receptors in breast (can prevent breast cancer)

45
Q

What are the adverse effects of raloxifene?

A

Hot flashes
DVT
Leg cramps

46
Q

What are the adverse effects of calcitonin?

A

Intra nasal - nasal congestion and/or irritation

SC - GI complications

47
Q

What are the adverse effects of denosumab?

A 
Hypocalcemia
Infections
Dermatological reactions
Osteonecrosis of the jaw
Suppression of bone turnover
48
Q

What is the mechanism of action of teriparatide?

A

Administered intermittently - stimulates osteoblastic activity

49
Q

What are the adverse effects of teriparatide?

A

Don’t give to anyone with increased risk of osteosarcoma - Paget, unexplained elevated alkaline phosphatase, open epiphyses, previous skeletal radiation
May increase risk of nephrolithiasis

50
Q

What are the adverse effects of vitamin d analogs?

A

Hypercalcemia

Hypercalciuria

51
Q

What is the mechanism of action of phosphorous binders?

A

Sevelamers bind phosphorous ingested in intestinal lumen
Lanthanum high avidity for carboxyl and phosphate groups, binds to phosphate ingested through diet to make it insoluble
Limit intestinal absorption of phosphorous and increase fecal phosphorous excretion

52
Q

What is an advantage of lanthanum carbonate?

A

Unlike aluminum - doesn’t accumulate in bone to cause aluminum induced bone disease

53
Q

What are adverse effects of phosphorous binders?

A

Hypercalcemia and extra skeletal calcification

SH has diarrhea and metabolic acidosis, SC has no metabolic acidosis

54
Q

What are the advantages of cinacalcet over vitamin d analogs?

A

Work in hours as opposed to days

Don’t cause rise in serum calcium and phosphorous

55
Q

What are the adverse effects of cinacalcet?

A

Hypocalcemia - don’t use if <8.5

GI complications

56
Q

Baclofen

A

A GABAb receptor agonist

Used to decrease muscle tone

57
Q

Dantrolene

A

Blocks calcium release in skeletal muscle

58
Q

Carisoprodol

A

Muscle relaxant

Potential or dependence and abuse?

59
Q

Celecoxib

A

Cox 2 inhibitor

60
Q

Cyclobenzaprine

A

Muscle relaxant

May stimulate NE release in locus coeruleus which inhibits alpha motor neurons in spinal cord

61
Q

Etodolac

A

NSAID

62
Q

Methocarbamol

A

Muscle relaxant

Treats spasms

63
Q

Tramadol

A

A mu opiate receptor agonist used for relief of moderately severe pain

64
Q

What are drugs to relieve musculoskeletal pain?

A

Acetaminophen - safe, try it first
NSAIDs
Tramadol - less addiction potential
Opioid analgesics

65
Q

What are drugs to decrease inflammation?

A 
NSAIDs
Corticosteroids (prednisone)
Hydroxychloroquine 
Methotrexate
Biological agents (anti TNF antibody)
66
Q

What are drugs to correct a metabolic problem?

A

Allopurinol - hyperuricemia with over production
Probenecid - hyperuricemia with under excretion
Bisphosphonates

67
Q

What are the adverse effects of NSAIDs?

A

Gastropathy - esp in elderly, previous GI bleeds, corticosteroids, or warfarin users - PPI lessens risk
Nephropathy

68
Q

COX 2 selective NSAIDs

A

Lessen gastropathy in certain cases
Increased risk of cardiovascular events and stroke
Not more efficacious
Much more expensive

69
Q

What is the treatment for RA?

A

Hydroxychloroquine in mildest cases
Low dose Steroids to bridge when starting slow acting agents
Methotrexate with supplemental folate
If no effect, can combo with sulfasalazine and hydroxychloroquine or TNF inhibitors

70
Q

What is urate lowering therapy?

A

Indicated for recurrent attacks, tophi, renal stones
Uricosurics (probenecid, sulfinpyrazone) if normal renal function and no nephrolithiasis
Allopurinol or febuxostat when reduced renal function (just titrated more slowly)
Allopurinol doses t effect - serum urate <6
Azathioprine

71
Q

What is the treatment of SLE?

A

Hydroxychloroquine!
NSAIDs for arthritis and serositis
Antimalarials
Topical corticosteroids for skin disease
High dose steroids (prednisone) if severe cytopenias, pulm disease, vasculitis, or neuropsychiatric manifestations
Cyclophosphamide, azathioprine, mycophenolate, anti CD20 for nephritis and other life threatening disease

Block 5 - Pulm and Skeletal (19 decks)

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