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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
Rifampin - resistance
Mutations in rpoB gene in tb
25
Rifampin - adverse effects
Sometimes hepatotoxic Potent inducer of p450 - other drugs can fail due to increased metabolism Rifabutin used in patients taking many other drugs
26
Pyrazinamide - mechanism of action
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
27
What is trans-translation?
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
28
Pyrazinamide - resistance
Mutations in pncA gene
29
Pyrazinamide - adverse effects
Hepatic damage - don't give to patients with hepatic dysfunction Inhibits uric acid excretions and can cause acute episodes of gout
30
Ethambutol - mechanism of action
Targets arabinosyl transferase III - synthesizes arabinose necessary for mycobacterial cell wall
31
Ethambutol - resistance
Mutations in embB gene | Necessary but not sufficient for resistance
32
Ethambutol - adverse effects
Optic neuritis - affects visual acuity and color differentiation Check to see if patient color blind before therapy
33
Streptomycin
Injected unlike other first lines - not absorbed from GI tract
34
Moxifloxacin
Fluoroquinolone Inhibits topoisomerase II Needs to be tested more but possible awesome first line drug
35
What are drugs used for the mycobacterium avium complex (MAC)?
Clarithromycin Azithromycin Rifabutin (does p450 like rifampin!)
36
What drugs are used for leprosy?
Dapsone (sulfonamide like) - usually in combo with rifampin | Dapsone resistant get rifampin with clofazimine
37
What IV calcium supplements are used in severe hypocalcemia?
Calcium gluconate over calcium chloride because latter can cause necrosis and sloughing in perivascular tissues
38
What do CaSR (cinacalcet) do?
Allosterically modulator of CaSR at parathyroid cells and through intracellular second messengers inhibits PTH secretion
39
What does calcitonin do?
Inhibits bone resorption and lowers serum calcium concentration
40
What oral calcium supplements are used in hypocalcemia?
Calcium carbonate - need food Calcium citrate - don't need food Both can cause ab discomfort and constipation
41
What is the mechanism of action of bisphosphonates?
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
What are the pharmacokinetics of bisphosphonates?
Oral absorbed poorly | Excreted by kidney - don't use if GFR < 30-35
43
What are the adverse effects of bisphosphonates?
``` 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
What is the mechanism of actin of raloxifene?
Agonist at estrogen receptors in bone | Antagonist at estrogen receptors in breast (can prevent breast cancer)
45
What are the adverse effects of raloxifene?
Hot flashes DVT Leg cramps
46
What are the adverse effects of calcitonin?
Intra nasal - nasal congestion and/or irritation | SC - GI complications
47
What are the adverse effects of denosumab?
``` Hypocalcemia Infections Dermatological reactions Osteonecrosis of the jaw Suppression of bone turnover ```
48
What is the mechanism of action of teriparatide?
Administered intermittently - stimulates osteoblastic activity
49
What are the adverse effects of teriparatide?
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
What are the adverse effects of vitamin d analogs?
Hypercalcemia | Hypercalciuria
51
What is the mechanism of action of phosphorous binders?
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
What is an advantage of lanthanum carbonate?
Unlike aluminum - doesn't accumulate in bone to cause aluminum induced bone disease
53
What are adverse effects of phosphorous binders?
Hypercalcemia and extra skeletal calcification | SH has diarrhea and metabolic acidosis, SC has no metabolic acidosis
54
What are the advantages of cinacalcet over vitamin d analogs?
Work in hours as opposed to days | Don't cause rise in serum calcium and phosphorous
55
What are the adverse effects of cinacalcet?
Hypocalcemia - don't use if <8.5 | GI complications
56
Baclofen
A GABAb receptor agonist | Used to decrease muscle tone
57
Dantrolene
Blocks calcium release in skeletal muscle
58
Carisoprodol
Muscle relaxant | Potential or dependence and abuse?
59
Celecoxib
Cox 2 inhibitor
60
Cyclobenzaprine
Muscle relaxant | May stimulate NE release in locus coeruleus which inhibits alpha motor neurons in spinal cord
61
Etodolac
NSAID
62
Methocarbamol
Muscle relaxant | Treats spasms
63
Tramadol
A mu opiate receptor agonist used for relief of moderately severe pain
64
What are drugs to relieve musculoskeletal pain?
Acetaminophen - safe, try it first NSAIDs Tramadol - less addiction potential Opioid analgesics
65
What are drugs to decrease inflammation?
``` NSAIDs Corticosteroids (prednisone) Hydroxychloroquine Methotrexate Biological agents (anti TNF antibody) ```
66
What are drugs to correct a metabolic problem?
Allopurinol - hyperuricemia with over production Probenecid - hyperuricemia with under excretion Bisphosphonates
67
What are the adverse effects of NSAIDs?
Gastropathy - esp in elderly, previous GI bleeds, corticosteroids, or warfarin users - PPI lessens risk Nephropathy
68
COX 2 selective NSAIDs
Lessen gastropathy in certain cases Increased risk of cardiovascular events and stroke Not more efficacious Much more expensive
69
What is the treatment for RA?
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
What is urate lowering therapy?
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
What is the treatment of SLE?
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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