Pharm - Asthma, Tb, Ca Flashcards
Albuterol
Short acting beta 2 agonist
Quick onset of action
As needed for symptomatic relief
Oral or inhaled
What is the deal with aerosolized drugs for asthma?
90% actually swallowed
Should be poorly absorbed from GI tract or inactivated by first pass hepatic metabolism
Salmeterol
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
Who are inhaled corticosteroids recommended for?
Patients with persistent asthma that require short acting beta 2 agonist more than once a day
How do glucocorticoids work in the treatment of asthma?
Receptor once bound migrates to cytoplasm and inhibits NFkappaB and nucleus and inhibits AP1 involved in pro inflammatory genes, also activates anti inflammatory genes
Fluticasone
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
Prednisone
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
Cromolyn sodium and nedocromil sodium
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
Zafirlukast and montelukast
Competitive inhibitor of leukotriene receptor type 1
Normal activation would cause smooth muscle contraction
Zileuton
Inhibits 5 lipoxygenase - blocks conversion of arachidonic acid to leukotrienes
Leukotriene inhibitors in general
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
Theophylline
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
Omalizumab
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
Who is omalizumab indicated for?
Adults and adolescents >12 with allergies and persistent mild or moderate asthma
Why is tb so difficult to treat?
Difficult for drugs to penetrate mycolic acid cell wall
Mycobacteria have efflux pumps
Mycobacteria often sequestered within host cells
What is the general treatment for tb before and after drug susceptibility testing?
Before - RIPE
after - at least 3 to which sensitive for first 2 months
What is the current protocol for active tb?
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
When is chemo prophylaxis with isoniazid for 6 months recommended?
Household contacts of tb
Upon conversion to positive skin test with no symptoms
Patients with inactive tb who have never been adequately treated
What is MDR tb?
Resistant to R and I
What is XDR tb?
Resistant to R, I, fluoroquinolones, and at least one injectable second line agent
Isoniazid - mechanism of action
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
Isoniazid - mechanism of resistance
Lack katG catalase activity
Isoniazid - adverse effects
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
Rifampin - mechanism of action
Inhibits prokaryotic DNA directed RNA polymerase
Activity against gram+ and gram-
Rifampin - resistance
Mutations in rpoB gene in tb
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
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
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
Pyrazinamide - resistance
Mutations in pncA gene
Pyrazinamide - adverse effects
Hepatic damage - don’t give to patients with hepatic dysfunction
Inhibits uric acid excretions and can cause acute episodes of gout
Ethambutol - mechanism of action
Targets arabinosyl transferase III - synthesizes arabinose necessary for mycobacterial cell wall
Ethambutol - resistance
Mutations in embB gene
Necessary but not sufficient for resistance
Ethambutol - adverse effects
Optic neuritis - affects visual acuity and color differentiation
Check to see if patient color blind before therapy
Streptomycin
Injected unlike other first lines - not absorbed from GI tract
Moxifloxacin
Fluoroquinolone
Inhibits topoisomerase II
Needs to be tested more but possible awesome first line drug
What are drugs used for the mycobacterium avium complex (MAC)?
Clarithromycin
Azithromycin
Rifabutin (does p450 like rifampin!)
What drugs are used for leprosy?
Dapsone (sulfonamide like) - usually in combo with rifampin
Dapsone resistant get rifampin with clofazimine
What IV calcium supplements are used in severe hypocalcemia?
Calcium gluconate over calcium chloride because latter can cause necrosis and sloughing in perivascular tissues
What do CaSR (cinacalcet) do?
Allosterically modulator of CaSR at parathyroid cells and through intracellular second messengers inhibits PTH secretion
What does calcitonin do?
Inhibits bone resorption and lowers serum calcium concentration
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
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
What are the pharmacokinetics of bisphosphonates?
Oral absorbed poorly
Excreted by kidney - don’t use if GFR < 30-35
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)
What is the mechanism of actin of raloxifene?
Agonist at estrogen receptors in bone
Antagonist at estrogen receptors in breast (can prevent breast cancer)
What are the adverse effects of raloxifene?
Hot flashes
DVT
Leg cramps
What are the adverse effects of calcitonin?
Intra nasal - nasal congestion and/or irritation
SC - GI complications
What are the adverse effects of denosumab?
Hypocalcemia Infections Dermatological reactions Osteonecrosis of the jaw Suppression of bone turnover
What is the mechanism of action of teriparatide?
Administered intermittently - stimulates osteoblastic activity
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
What are the adverse effects of vitamin d analogs?
Hypercalcemia
Hypercalciuria
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
What is an advantage of lanthanum carbonate?
Unlike aluminum - doesn’t accumulate in bone to cause aluminum induced bone disease
What are adverse effects of phosphorous binders?
Hypercalcemia and extra skeletal calcification
SH has diarrhea and metabolic acidosis, SC has no metabolic acidosis
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
What are the adverse effects of cinacalcet?
Hypocalcemia - don’t use if <8.5
GI complications
Baclofen
A GABAb receptor agonist
Used to decrease muscle tone
Dantrolene
Blocks calcium release in skeletal muscle
Carisoprodol
Muscle relaxant
Potential or dependence and abuse?
Celecoxib
Cox 2 inhibitor
Cyclobenzaprine
Muscle relaxant
May stimulate NE release in locus coeruleus which inhibits alpha motor neurons in spinal cord
Etodolac
NSAID
Methocarbamol
Muscle relaxant
Treats spasms
Tramadol
A mu opiate receptor agonist used for relief of moderately severe pain
What are drugs to relieve musculoskeletal pain?
Acetaminophen - safe, try it first
NSAIDs
Tramadol - less addiction potential
Opioid analgesics
What are drugs to decrease inflammation?
NSAIDs Corticosteroids (prednisone) Hydroxychloroquine Methotrexate Biological agents (anti TNF antibody)
What are drugs to correct a metabolic problem?
Allopurinol - hyperuricemia with over production
Probenecid - hyperuricemia with under excretion
Bisphosphonates
What are the adverse effects of NSAIDs?
Gastropathy - esp in elderly, previous GI bleeds, corticosteroids, or warfarin users - PPI lessens risk
Nephropathy
COX 2 selective NSAIDs
Lessen gastropathy in certain cases
Increased risk of cardiovascular events and stroke
Not more efficacious
Much more expensive
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
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
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
