Pharmacology

Question 0

Albuterol

Answer 0

Selective short acting ß-2 adrenergic agonist.

first line agent for treatment of acute bronchial asthma episodes

induce bronchidilation, minimal effects on inflammation

ß2 agonists alone recomended for patients with mild episodic symptoms.

Question 1

Fluticasone

Answer 1

Inhaled glucocorticoid. Most effective anti-inflammatory agent for chronic preventative treatment of bronchial asthma.

Long-term asthma treatment.

High dose glucocorticoids reserved for initial managment of acute asthma exacerbations. Inhaled glucocorticoids used to prevent acute exacerbations but do not have a role in acute episodes.

Corticosteroid, has the strongest and most predictable effects on inflammatory component of asthma.

MOA: after entering an epithelial cell, steroid binds to intracellular receptors, altering gene txn.
inhibit the formation of certain cytokines implicated in bronchial asthma
induce apoptosis of inflammatory cells, like Mø, lymphocytes and eos’s. after a few weeks, patients show significantly reduced airway inflammation.

Also decrease amount of mucus produced by goblet cells.

No direct bronchodilatory effects, but reduce hyperresponsiveness of airway by decreasing inflammation. Other drugs used in treatment of bronchial astham are less potent than glucocorticoids at reducing airway inflammation.

Question 2

Theophylline

Answer 2

bronchodilator inhibits the enzyme phosphodiesterase, increasing intracellular cAMP.

has anti-inflammatory and bronchoprotective properties also. less effective than glucocorticoids

Question 3

Ipratropium

Answer 3

blocks action of AcCh on M receptors when AcCh is released on vagal stimulation (leading to bronchoconstriction)

like ß2 agonists, has minimal effects on airway inflammation thorugh it does decrease mucus production by bronchial epithelial cells

Question 4

Zileuton

Answer 4

leukotriene inhibitors (leukotrienes are potent inducers of airway bronchoconstriction and inflammation)

these are much less dramatic than glucocorticoids

Question 5

Nifedipine

Answer 5

DHP calcium channel blocker used in treatment of hypertension.

blcokage of Ca influx into bronchial smooth muscle cells causes bronchodilation.

Has no anti-inflammatory effects

Question 6

A: 4 groups of antifungals
B: their mechanisms of action
C: examples

Answer 6

Polyenes: (amphotericin B, Nystatin): bind ergosterol molecules in fungal cell membranes, creating pores and causing cell lysis.

Triazoles (ketoconazole, fluconazole, itraconazole, voriconazole): inhibit ergosterol synthesis.

Echinocandins (caspofungin and micafungin): inhibit glucan synthesis (component of fungal cell wall.)

Pyrimidines (Flucytosine): converted to 5-fluorouracil within the fungal cell and interferes with fungal RNA and protein synthesis.

only the polyenes (amphotericin B and nystatin) depend on amount of ergosterol incorporated into fungal cell membranes for efficacy. polyenes bind ergosterol molecules, form pores int he membrane and alow leakage of ions (K+) from cells –> leads to cell lysis. decreasing ergosterol in cell membrane reduces efficacy of polyenes. This is the major mechanism of polyene resistance.

Question 7

Isoniazid chemical similar to ___ mechanism and use

Answer 7

chemically similar to B6/pyridoxine (which is depleted during isoniazid therapy).
inhibits mycolic acid syntehsis in mycobacterial cells: Mycobacterium species and has no effect on other microorgnaisms.
inhibiting mycolic acid creation prevents mycobacterial cell walll synthesia dn oformation of many virulence factors.
side efffect: neuopathy, hepatotoxicity, CYP450 inhibition in liver.

mycolic acid is long branched chain saturated fatty acid used in cell wall syntehsis of mycobacteria and formation of virulence factors.

Question 8

isoniazid associated neuropathy

Answer 8

similarity to B6/pyridoxine causes isoniazid to compete with B6 for synthesis of neurotransmitters (like GABA) resulting in defective end products.

Isoniazid also increases excretion of pyridoxine.

B6 defiency most common in patients treated with Isoniazid who are elderly, alcoholics, or have other comorbidities (liver/kidney dysfunction)
usually manifests as peripheral neuropathy.

prevention: B6 supplementation with isoniazid therapy.

Question 9

Varenicline

Answer 9

Chantix - partial agonist of nicotinic acetylcholine receptors. assists patients with cessation of tobacco use by reducing withdrawal cravings and attenuating the rewarding effects of nicotine.

partial agonist activity allows reduction of symptoms of nicotine withdrawal by mildly stimuling receptor. only limited downstream release of dopamine, so less stimluation of the reward pathways than nicotine.

reduces withdrawal cravings and attenuates rewarding effects.

Question 10

Ethambutol

Answer 10

effective component of multi-agent antibiotic regimen used in treatment of M. tuberculosis and atypical mycobacterial infections. Most notabile side effect of ethambutol is optic neuritis - which manifests as decreased visual acuity, central scotoma, color-blindness and can be reversile with discontinuation of the drug.

Question 11

drugs for TB that compromise hepatic function

Answer 11

Isoniazid, rifampin, pyrazinamide

Question 12

TB drugs that affect hearing and vestibular function

Answer 12

aminoglycosides or vancomycin. ototoxicity from direct damage to 8th cranial nerve, can cause vertigo, tinnitus, deafness. can also cause renal toxicity.
Rarely, flaccid paralysis due to neuromuscular blockade.

Question 13

antibiotics that cause blood problems

Answer 13

chloramphenicol, dapsone, trimethoprim-sulfamethoxazole.
Chlor.. can cause aplastic anemia
dapsone can cause agranulocytosis
trimeth-sulf.. can lead to megaloblastic anemia in some patients because its a folate antagonist

Question 14

antibiotics with renal function side effects

Answer 14

aminoglycosides (tubular necrosis) and amphotericin B

Question 15

Omalizumab

Answer 15

inhibits IgE binding to mast cells - used in astham by lowering IgE levels and relieves allergen-induced bronchial constriction.

Question 16

Zileuton

Answer 16

glucocorticoid and selective inhibitor of lipoxygenase pathway that leads to decreased leukotrienes - which reduces hyperresponisveness and inflammation

Question 17

Zafirlukast and montelukast

Answer 17

leukotriene D4 receptor antagonists. work by blocking receptors for chemical mediators involved in asthma. used for chronic asthma prophylaxis not acute exacerbations. similar effect to zileuton.

Question 18

cromolyn and nedocromil

Answer 18

mast cell stabilizing agents - inhibitors of mast cell degranulation independent of stimuli presence. less effective than inhaled glucocorticoids and considered second-line for treatment of allergic rhinitis and bronchial asthma.

Question 19

Ipratropium

Answer 19

antimuscarinic reverses vagally mediated bronchoconstriction.

when vagus nerve is stimulated, acch is released. in airways, acch produces bronchoconstriction by actin on M receptors. Ipratropium blocks the action of acch at M receptors.

less effective than ß2 adrenergic agonists. effect starts 60-90 minutes after initiation. Ipra enhances bronchodilatory effects of ß2 agents. ipra is poorly absorbed from resp mucosa, no systemic anticholinergic side effects.

tiotropium is long acting, newer agent for COPD.

Question 20

Methylxanthines - theophylline and aminophylline

Answer 20

cause bronchial dilation by decreasing phosphodiesterase activity, decreasing cAMP.

Question 21

Streptomycin MOA

Answer 21

inhibits initiation of protein synthesis by binding to and distorting the structure of the prokaryotic 30S ribosomal subunit.

low dose stremptomycin inhibits M. Tuberculosis grwoth.

Question 22

Mycobacterium Avium/intracellulare prophylaxis

Answer 22

common opportunistic pathogen that causes disseminated disease (MAC) in HIV+ patients. weekly azithromycin is used as prophylaxis in patients at risk for MAC (HIV+ with CD4 counts less than 50cells/mL.)

infection treated with clarithromycin or azithromycin with rifabutin and/or ethambutol

Question 23

N-acetylcystein-containing aerosol for the treatment of CF. how does it work?

Answer 23

mucous plugging occurs (from hyperviscosity of mucous) and isotonic dehydration of inner surfaces of tracheobronchial tree in CF. causes obstruction. N-acetylcysteine is a mucolytic agent that loosens thick sputum b cleaving disulfide bonds within mucus glycoproteins.

Question 24

Isoniazid

Answer 24

Antimycobacterial agent specifically inhibits the syntehsis of mycolic acids. Mycolic acids are essential componente of the unique mycobacterial peptidoglycan cell wall. without mycolic acids, the mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply. WOuld cause bacteria to lose their acid fastness on taining with carbolfuchsin dye.

Question 25

Rifampin

Answer 25

halts protein synthesis by inhibiting bacterial DNAdependent RNA polymerase preventing txn of DNA to mRNA. would inhibit in vitro culture grouwoth but wouldnt cause mycobacteria to lose acid-fastness.

Question 26

Amphotericin B side effects

Answer 26

most important adverse effects: nephrotoxicity, hypokalemia, hypomagnesemia.

mainstay treatment for many systemic mycoses.
binds the ergosterol of fungal cell membranes leading to fungal cell lysis.
relatively selective, because it has a higher affinity for ergosterol in fungal memrbanes than for cholesterol (in human cell membranes)
binds cholesterol to some degree so you have some side effects:

Acute infusion related reactions: fever chills rigors hypotension. premdication iwth antipyretics and antihistamines.
dose dependent nephrotoxicity because it decreases the glomerular filtration rate. permanent loss of renal function from cumulative dose. increasing BUN and creatinine levels indicates declining renal function.
electrolyte abnormaliteis (hypomagnesemia and hypokalemia)
anemia - suppression of renal erythropoietin synthesis
thrombophlebitis

Question 27

Echinocandins

Answer 27

antifungal medications that inhibit synthesis of the polysaccharide glucan, essential component of the fungal cell wall.

ex. caspofungin, micafungin
target: 1,3-ß-D-glucan component of the fungal cell wall
no effect on fungal cel membrane
caspofungin most active agasint Candida and Aspergillus
not active against cryptococcus neoformans and litmited actvitity against Mucor and Rhizopus species

Question 28

Flucytosine

Answer 28

antifungal that inhibits syntehsis of DNA (replication) and RNA (protein synthesis)
used with amphotericin B for crytptococcal meningitis.

Question 29

Amphotericin B & Nystatin

Answer 29

antifungals that bind ergosterol - component of the fungal cell membrane - to form pores and cell lysis in the fungal cells.

Question 30

Itraconazole and other azoles

Answer 30

anti-fungal that inhibits ergosterol synthesis.

Question 31

Griseofulvin

Answer 31

antifungal that enters fungal cells, binds microtubules and inhibits mitosis. effective only against dermatophyte fungi, accumulates in keratin-containing tissues.

Question 32

side effects of inhaled corticosteroids for persistent bronchial asthma

Answer 32

used as prophylaxis to prevent symptoms, maintain near normal pulm function, maintain normal activity levels.

Must rince to avoid oropharyngeal candidiasis. use a spacer too.
side effects, dysphonia from myopathy of laryngeal muscles. systemic side effects: increased intraocular presure, cataracts, growth retardation in kids, bone loss, suppression of hypothalamic pituitary adrenal axis.

Question 33

Theophylline overdose

Answer 33

methylxanthine drug used to treat used to treat COPD and asthma

abdominal pain, vomiting, diarrhea, cardiac arrhythmias, seizures

major cause of morbidity is seizures.
treat with gastric lavage and activated charcoal and cathartics. ß blockers for cardiac tachyarrhythmias. benzos and barbiturates for seizures.