Term
| Penicillin G: Mechanism of Action |
|
Definition
Inhibits peptidoglycan transpeptidase, the enzyme responsible for linking peptides together to form the cross-linked bacterial wall.
Penicillin is an analog of the d-ala d-ala terminal end of the dissaccharide unit of bacterial cell walls, and binds to it, inactivating the transpeptidase that would normally come to cross-link it to another disaccharide unit.
In response to the weakened cell wall, the bacteria activates another enzyme called murein hydrolase, which sets off a chain of events leading to bacterial cell lysis and death. |
|
|
Term
| Penicillin G: Mechanism of Resistance |
|
Definition
The bacteria cell has developed an enzyme called beta lactamase, which hydrolyzes the beta-lactam bond structure of penicillin.
Bacteria may also develop decreased permeability of penicillin through their porins, or alter the structure of transpeptidases so that penicillin can not bind efficiently. |
|
|
Term
| Methods of overcoming penicillin resistance |
|
Definition
1. use a drug that does not bind to beta lactamase
2. co-administer penicillin with a beta-lactamase inhibitor, such as clavulanic acid |
|
|
Term
| Penicillin G: spectrum of activity |
|
Definition
narrow spectrum
gram positive aerobes and anaerobes
high frequency of resistance to penicillin G now seen in bacteria |
|
|
Term
| Penicillin G: physiological disposition |
|
Definition
inactivated by gastric acid; only 25% absorbed orally
poor penetration into the CNS
rapidly renal excretion via secretion into the proximal tubule
probenecid inhibits secretion, prolongs plasma levels
half life 30 minutes |
|
|
Term
| Penicillin G: adverse effects |
|
Definition
low direct toxicity because mechanism is bacteria-specific (human cells do not have cell walls)
diarrhea, GI distress
thrombophlebitis at injection area
CNS tremors or convulsions at high doses (rare)
superinfection/bacterial overgrowth/pseudomembranous colitis |
|
|
Term
| Penicillin: Hypersensitivity Reaction |
|
Definition
Immediate = within 30 minutes, anaphylaxis
Accelerated = 1-72 hours, rarely get anaphylaxis
Delayed = 3-30 days, usually a self-limiting skin reaction, but can get more severe reactions including Stevens-Johnson Syndrome
Allergic to one penicillin = allergic to ALL penicillins |
|
|
Term
| Penicillin G: Mechanism of Hypersensitivity and Clinical Considerations |
|
Definition
Mechanism: drug + tissue protein = hapten formation --> antibody formation
May consider skin testing with benzylpenicilloyl polylysine to see if reaction will happen, but not an absolute predictor.
May consider in-patient desensitization procedure, which helps reduce the risk of anaphylaxis, but is risky. |
|
|
Term
| Advantages of semi-synthetic penicillins over Penicillin G |
|
Definition
improved gastric stability = can be taken orally with better effectiveness
improved activity against bacterial resistance
broadened spectrum of activity |
|
|
Term
|
Definition
IV admin only (poor oral absorption)
The only penicillin that is hepatically metabolized
Penicillinase (beta lactamase) resistant
Ineffective against gram negative bacteria |
|
|
Term
|
Definition
an older penicillin
Well absorbed due to GI acid resistance, but must be admin on an empty stomach, and has high incidence of GI distress
Inactivated by beta lactamase
Increased incidence of delayed hypersensitivity reactions.
Used against gram positive and some gram negative organisms |
|
|
Term
|
Definition
resembles ampicillin in structure and spectrum
better GI absorption, may be given with food, less GI distress
Inactivated by beta lactamase |
|
|
Term
| Augmentin (Amoxicillin + Clavulanic Acid) |
|
Definition
Clavulanic Acid inhibits beta lactamase but has no intrinsic antibacterial activity.
It can improve amoxicillin's activity against beta lactamase-producing strains of bacteria
No beta lactamase inhibitor is effective against ALL types of beta lactamase. |
|
|
Term
|
Definition
| a penicillin with a chemical structure that allows it to be effective against pseudomonas bacteria |
|
|
Term
| Cephalosporin: Structure and mechansim |
|
Definition
contains beta lactam ring like penicillin
Mechanism of action is identical to penicillin
Effective against most beta lactamase-producing bacteria |
|
|
Term
| Cephalosporins: Physiological Disposition |
|
Definition
penetrate well into most tissues, but first and second generations do not penetrate well into the CNS
Half-lives of 0.5-2 hours
Renal excretion: delayed by probenicid |
|
|
Term
| Cephalosporins: hypersensitivity and adverse reactions |
|
Definition
Cross-reactivity with other cephalosporins and penicillins: avoid in pts with history of penicillin anaphylaxis and use cautiously in pts with delayed reaction to penicillin
Adverse: thrombophlebitis, diarrhea, superinfection
Special adverse effect: mild nephrotoxicity, especially if co-admin with an aminoglycoside or in a pt with compromised renal function |
|
|
Term
|
Definition
a first generation cephalosporin
used parenterally
longer half-life than some antibiotics
primary use: prophyllaxis for surgery |
|
|
Term
|
Definition
a first generation cephalosporin
similar spectrum of activity to cephalexin, but can be used orally |
|
|
Term
|
Definition
a second generation cephalosporin
will penetrate the CNS, but less effectively than third generation cephalosporins |
|
|
Term
|
Definition
a second generation cephalosporin
particularly resistant to beta lactamases
IV admin only
used in mixed aerobic/anaerobic infections such as PID, lung abscesses |
|
|
Term
|
Definition
a third generation cephalosporin
long half life, 8 hours
good CNS penetration
drug of choice for gonorrhea and severe Lyme disease |
|
|
Term
|
Definition
a third generation cephalosporin
penetrates the CNS
good activity against p.aeruginosa (pseudomonas, a hard bacterial infection to treat) |
|
|
Term
|
Definition
an Extended Spectrum Beta Lactamase.
Present in some types of bacteria such as E.coli and Klebsiella, can hydrolyze the beta lactam ring on third generation cephalosporins = resistance to some powerful antibiotics |
|
|
Term
|
Definition
a fourth generation cephalosporin
has an extended spectrum of activity compared to third generation cephs.
Increased stability from hydrolysis by beta lactamases (maybe even ESBLs)
Penetrates the CNS well, good in treatment of bacterial meningitis
RESERVE this drug for very serious infections, to protect it from the development of bacterial resistance |
|
|
Term
| Imipenem-cilastatin: mechanism and phys disposition |
|
Definition
a carbapenem antibiotic, which is a new class of beta lactams
resistant to inactivation by beta lactamases
broadest activity of all antibiotics
not absorbed orally
rapidly hydrolyzed by dehydropeptidase I, which is present in the kidney, so must be admin with cilastatin, which inhibits dehydropeptidase I
renally excreted |
|
|
Term
| Imipenem: adverse effects |
|
Definition
cross-allergenicity with other beta lactams
up to 1.5% may get seizures, especially with higher doses, CNS lesions, renal dysfunction |
|
|
Term
|
Definition
a monobactam antibiotic
The ONLY beta lactam that has little cross-allergenicity with other beta lactam drugs: may be given to patients with penicillin allergy
Resistant to inactivation by beta lactamases
Spectrum is limited to aerobic gram negative bacteria, including enterobacteriaceae and pseudomonas |
|
|
Term
|
Definition
blocks the enzyme peptdioglycan synthetase, inhibiting bacterial cell wall synthesis
effective only against gram positive bacteria |
|
|
Term
| Vancomycin: resistance mechanism |
|
Definition
The bacteria may modify the terminal end of the peptide that the drug binds to an acts on.
Modification of the peptide does not effect structural wall integrity, but vastly reduces the affinity for vancomycin binding. |
|
|
Term
| Vancomycin: physiologic disposition |
|
Definition
only given IV except in cases of c.difficile
90% excreted via glomerular filtration
Not removed by hemodialysis |
|
|
Term
| Vancomycin adverse effects |
|
Definition
thrombophlebitis, chills, fever
Special adverse effects: ototoxicity, flushing with rapid infusion |
|
|
Term
| Erythromycin: Mechanism of Action |
|
Definition
| Binds to the L15 protein of the 50S subunit of the ribosome; inhibits translocation of the peptide; causes premature release of the (incomplete) polypeptide; a STATIC drug; effective against gram positive cocci and bacilli |
|
|
Term
| Erythromycin: Mechanism of Resistance |
|
Definition
Inducible: reduced bacterial cell membrane permeation and/or drug efflux mechanisms; production of esterases that hydrolyze the drug
-Constitutive (cross-resistance to clindamycin and other similar mechanism drugs): modification of the microsomal binding site by a methylase enzyme |
|
|
Term
| Erythromycin: Cross-resistance |
|
Definition
| Inducible resistance: to other macrolides only; Constitutive resistance: macrolides, clindamycin, and Type B streptogramins |
|
|
Term
| Erythromycin: Physiological Disposition |
|
Definition
| may be given orally and parenterally; enteric-coated in oral form to prevent destruction by gastric acid; food interferes with GI absorption |
|
|
Term
|
Definition
| the salt form of erythromycin; is better tolerated with oral admin than traditional erythromycin, but has increased risk for liver toxicity |
|
|
Term
|
Definition
| Half life 1.5 hours; Will NOT reach CNS, but WILL reach fetus |
|
|
Term
| Erythromycin: Drug interactions |
|
Definition
| Inhibits CYP P450 = potentiated effects of warfarin, carbamazepine, cyclosporin, theophylline, terfenadine, astemizole |
|
|
Term
| Erythromycin: Adverse effects |
|
Definition
| GI: anorexia, nausea, vomiting, diarrhea, acts on motilin receptors directly to stimulate gut motility = diarrhea; LIVER: acute cholestatic hepatitis (probably a hypersensitivity reaction), greatest liver risk with estolate salt; hypersensitivity; high doses given IV may cause reversible hearing loss; QT prolongation with ventricular tachycardia, especially when used in combination with other drugs |
|
|
Term
| Clarithromycin: Mechanism of Action |
|
Definition
| a macrolide similar to erythromycin; more active against mycobacterium avium than erythromycin, otherwise a similar spectrum of activity; also has cross-resistance with erythromycin |
|
|
Term
|
Definition
| a measure of lipid solubility; the ability to distribute between organic and water phases; the larger the partition coefficient, the more RAPID the absorption |
|
|
Term
| What is the effect of an acidic solution on a weak acid drug? |
|
Definition
| shifts the drug toward a more UNIONIZED state = better absorption |
|
|
Term
| What is the effect of a basic solution on a weak acid drug? |
|
Definition
| Shifts the drug toward a more ionized state = less absorption |
|
|
Term
|
Definition
| the pH at which there is 50% ionized and 50% unionized forms of the drug |
|
|
Term
|
Definition
| When the pH on either side of a membrane is the same, the total amounts of drugs on each side of the membrane are the same |
|
|
Term
| The cytochrome P450 system is an example of what type of metabolic reaction? |
|
Definition
|
|
Term
| How does cimetidine effect drug metabolism? |
|
Definition
| Forms an intermediary complex with CYP P450; inhibits Phase I reactions for other drugs |
|
|
Term
| How does probenicid effect drug excretion? |
|
Definition
| Blocks the organic anion transporter in the proximal tubule of the kidney; inhibits tubular secretion of organic anions |
|
|
Term
| What is the formula to calculate half-life? |
|
Definition
| 0.7 times Volume of Distribution, divided by Clearance |
|
|
Term
| How many half-lifes does it take to eliminate a drug from the body? |
|
Definition
|
|
Term
| What are the properties of drugs with First-Order Kinetics? |
|
Definition
-a true half life exists independent of concentration
-plasma concentration is proportional to the dose
-the steady state is reached within 4 half-lives with constant dosing
-decay of concentration is exponential |
|
|
Term
| What are the properties of drugs with Zero-Order Kinetics? |
|
Definition
-half life varies with the plasma concentration
-plasma concentration increases disproportionately with dose
-a steady state is never reached
-decay of concentration is linear |
|
|
Term
| Describe the channels responsible for action potential in an SA cardiac cell |
|
Definition
-I(f) channel permeable to Ca and Na causes initial (slow) depolarization;
-voltage gated Ca channel opens rapidly to depolarization, causing rapid depolarization;
-voltage gated K (TEA-type) channel opens slowly to depolarization, causing resting membrane potential |
|
|
Term
| Describe the channels responsible for action potential in an ventricular (myocardial) cardiac cell |
|
Definition
-voltage gated Na channel opens very rapidly and allows for initial rapid depolarization;
-voltage gated Ca channel opens to depolarization and maintains depolarization;
-voltage gated TEA-type K channel opens slowly to depolarization, causing repolarization;
-K1 channel closes to depolarization, causing relative refractory period |
|
|
Term
| Relate S1 and S2 heart sounds to the events occurring in the heart |
|
Definition
| S1 = AV valve closure, beginning of systole, includes 1) isovolumic contraction, then 2) emptying of ventricles; S2 = AV valve closure, beginning of diastole, includes first isovolumic relaxation then filling of ventricles |
|
|
Term
| What is the result of blocking the Na-K-ATPase pump in the myocardial cell? |
|
Definition
| Increased contractility: inhibits the Na-Ca exchanger leading to an accumulation of Ca in the cardiac cell, which causes calcium-induced calcium release from the SR. |
|
|
Term
| Preganglionic vs Postganglionic fibers, Sympathetic vs Parasympathetic |
|
Definition
Sympathetic: short preganglionic, long postganglionic;
Parasympathetic: long preganglionic, short postganglionic |
|
|
Term
| Graded versus Quantal Dose-Response studies |
|
Definition
Graded: in-vitro studies, continuously variable response
Quantal: whole organ or organism response, all or none response |
|
|
Term
|
Definition
-aka median effective dose
-the dose at which half the population has the desired effect of the drug
-lower number means higher potency! |
|
|
Term
|
Definition
-aka Therapeutic Index
-Ratio of lethal (or toxic) dose to effective dose
-the larger the therapeutic index, the safer the drug |
|
|
Term
|
Definition
-demonstrated best on a graded response curve
-expressed as a fraction or percentage
-the maximal amount of response of a system to a drug compared to that system's maximal possible response |
|
|
Term
|
Definition
the constant used to describe the affinity of a ligand for its binding site;
-the concentration of drug that yields half-maximal occupancy of receptors
-calculated by dividing the backwards (unbinding) rate constant (k2) by the forwards (binding) rate constant (k1)
-the lower the Kd, the higher the affinity |
|
|
Term
| Compare the mechanisms and properties of competitive vs non-competitive antagonists |
|
Definition
Competitive antagonists: compete with drug (agonist) for receptor binding; surmountable with increased concentration of the drug
-non-competitive: lowers apparent efficacy of the (agonist) drug, insurmountable with increased concentration of the drug |
|
|
Term
| Clarithromycin: physiologic disposition |
|
Definition
-can be given orally, is more stable to stomach acid than erythromycin
-longer half-life than erythromycin, twice-daily dosing
-penetrates tissues well
-metabolized by the liver, and metabolite has antibacterial activity as well
-eliminated by the kidney |
|
|
Term
| Clarithromycin: adverse effects |
|
Definition
-less GI intolerance
-high doses can lead to reversible hearing loss
-teratogenic, do not use in pregnancy |
|
|
Term
| Azithromycin: mechanism and spectrum of activity |
|
Definition
| same as erythromycin, spectrum of activity similar to clarithromycin |
|
|
Term
| Azithromycin: pharmokinetics |
|
Definition
-penetrates tissues very well (except CNS), better than clarithromycin
-allows for once daily dosing and shorter duration of treatment |
|
|
Term
| Azithromycin: physiologic disposition, adverse effects, drug interactions |
|
Definition
-well tolerated orally
-food decreases bioavailability
-antacids delay absorption
-does not inhibit CYP450, few drug interactions |
|
|
Term
| Clindamycin: structure and spectrum |
|
Definition
-derivative of lincomycin, different structure than erythromycin
-gram positive anaerobes, gram positive and gram negative anaerobes
-NOT good for enterococci or gram negative aerobes
-used in community-acquired MRSA |
|
|
Term
|
Definition
-similar to erythromycin
-does not induce methylase expression receptor modification, but is effected by constitutively expressed methylase
-gram negative species are intrinsically resistant due to drug's poor penetration of outer membrane |
|
|
Term
| Clindamycin: physiologic disposition |
|
Definition
-well absorbed in both oral and parenteral admin
-penetrates well into tissues except CNS
-metabolized by the liver, excreted in both bile and urine
-no dosage adjustment needed for renal failure, but do need to adjust for hepatic failure |
|
|
Term
| clindamycin: adverse reactions |
|
Definition
diarrhea, nausea, skin rashes
-overgrowth of c.difficile leading to pseudomembranous colitis |
|
|
Term
| metronidazole: clinical use/spectrum |
|
Definition
-anaerobic infections and pseudomembranous colitis due to c. difficile
-also used as an anti-protozoal for trichomoniasis, giardasis, and e.hystolitica tissue infections |
|
|
Term
| metronidazole: mechanism of action and resistance |
|
Definition
-chemical reaction in anaerobic bacteria causes the drug to be reduced to active form
-the reduced, active form interferes with bacterial synthesis of macromolecules, including DNA
-resistance = reduced levels of nitroreductase in the bacteria prevent reduction/activation of drug |
|
|
Term
| Metronidazole: physiologic dispostion |
|
Definition
-well absorbed orally
-permeates tissues well (except CNS)
-metabolized in liver and excreted in urine
-dosage adjustment for liver and renal failure |
|
|
Term
| metronidazole: drug interactions |
|
Definition
-inhibits CYP450 metabolism of other drugs
-disulfiram-like reaction to alcohol: nausea and vomiting |
|
|
Term
| metronidazole: adverse effects |
|
Definition
-nausea, headache, dry mouth, metallic taste
-may cause dark reddish brown urine
-caution in pts with CNS disorders, can cause vertigo, paresthesias, dizziness
-rare: seizures, pancreatitis, ataxia, peripheral neuropathy |
|
|
Term
| Vancomycin: spectrum and mechanism |
|
Definition
-active only against gram positives, esp MRSA and strep pneumoniae
-used in pseudomembranous colitis
-a beta lactam with same MOA as penicillin, etc
-parenteral admin only, not absorbed orally |
|
|
Term
| streptogramins: structure and spectrum |
|
Definition
-a combination of quinupristin and dalfopristin
-approved for vancomycin resistant infection
-not effective against e. faecalis |
|
|
Term
| streptogramins: mechanism of action |
|
Definition
quinupristin: inhibits chain termination in mech similar to macrolides
dalfopristin: binds to separate site nearby, inhibits peptide bond formation, enhances quinupristin binding |
|
|
Term
| streptogramins: mechanism of resistance |
|
Definition
-alteration of quinupristin binding site
-efflux or inactivation of dalfopristin |
|
|
Term
| streptogramins: adverse effects and interactions |
|
Definition
-arthralgia/myalgia syndrome
-inhibitor of CYP 3A4 |
|
|
Term
|
Definition
-oxazolidanone
-binds to unique section of 50S subunit, inhibits formation of ribosomal complex
-reversible hematologic adverse effects
-avoid: tyramine-rich foods, pseudoephedrine, SSRIs
-no cross-resistance with other classes, use in vancomycin-resistant infx |
|
|
Term
| daptomycin: mechanism of action and clinical use |
|
Definition
-binds to bacterial membrane and causes depolarization, leading to rapid-cell death
-vancomycin-resistant infections
-MRSA |
|
|
Term
| daptomycin: admin and phys. disposition |
|
Definition
-must be given IV
-excreted unchanged in urine
-adjust dosage for renal dysfunction |
|
|
Term
| daptomycin: adverse effects |
|
Definition
-fever, headache, insomnia, dizziness, rash
-high doses assoc with myalgia: check CK levels and consider stopping statins during treatment |
|
|
Term
| Isoniazid: mechanism of action |
|
Definition
-bactericidal for growing tubercle bacilli
-inhibits bacterial cell wall mycolic acid synthesis
-penetrates macrophages: is effective against both intra- and extracellular organisms
-activated by mycobacterial KAtG, which converts it to a reactive electrophilic compound
-inhibits the activity of InhA |
|
|
Term
| Rifampin: mechanism of action |
|
Definition
-bactericidal
-inhibits initiation of transcription by iteracting with the beta-subunit of the bacterial DNA-dependent RNA polymerase |
|
|
Term
| Rifampin: mechanism of resistance |
|
Definition
| mutation in the RNA polymerase OR decreased permeability of bacterial cell wall |
|
|
Term
| Tuberculosis: Therapeutic Approach |
|
Definition
-suspect drug resistance in any large city in the U.S.
-if suspect drug resistance, begin with ALL FOUR drugs until culture proves resistance
-duration of treatment - 6-24 months, compliance is essential
-if regimen is failing, add at least two new drugs at a time
-multi-drug resistance may require 5-7 drugs for initial therapy |
|
|
Term
| pyrazinamide: mechanisms and clinical use |
|
Definition
-unknown mechanism, may target fatty acid synthase I
-the only drug that distributes well to the CNS
-targets bugs hiding in macrophages (likes the acidic environment)
-must be hydrolyzed by an enzyme to be in its active form
-resistance = due to loss of the activating enzyme |
|
|
Term
|
Definition
-bacteriostatic
-inhibits arabinogalactan synthesis, an essential component of the cell wall
-enhances action of other lipophilic drugs such as Rifampin
-resistance mechanism unknown, but resistance occurs frequently and quickly if it is used alone |
|
|
Term
|
Definition
-aminoglycoside
-passive diffusion + oxygen dependent transport across bacterial cell membrane
-concentration-dependent killing and postantibiotic effect
-once daily dosing to lower risk of toxicity |
|
|
Term
| Rifampin: adverse effects |
|
Definition
-can produce a flu-like syndrome
-orange-red discoloration of feces, urine, saliva, and sweat
-may NOT consume alcohol: causes hepatic toxicity |
|
|
Term
| Ethambutol: adverse effects |
|
Definition
| -reversible optic neuritis and loss of red-green discrimination |
|
|
Term
|
Definition
-hepatic toxicity
-pruritis
-arthralgias
-exacerbates gout |
|
|
Term
| Streptomycin: adverse effects |
|
Definition
-poor absorption from GI tract, must be administered IM
-impaired hearing and vestibular function (sometimes irreversible) |
|
|
Term
| Approach to prophylaxis of TB |
|
Definition
-risk/benefit of INH: liver damage = 35 year old cutoff for using INH prophylactically
-exposure to known-resistant strain = use combination of other drugs (not INH)
- |
|
|
Term
| Rifampin: drug interactions |
|
Definition
| -can increase the hepatic metabolism of other drugs that are metabolized by microsomal enzymes |
|
|
Term
| Second-line agents for TB |
|
Definition
| -to be used when the patient is unable to tolerate one or more of the major drugs or in instances where resistance to a major drug has occurred |
|
|
Term
| treatment of MAC tuberculosis |
|
Definition
| -clarithromycin + ETH + rifabutin (or ciproflaxacin) |
|
|
Term
|
Definition
-used for disseminated MAC in pts with advanced HIV
-inhibits bacterial DNA-dependent RNA polymerase
-well absorbed from GI tract, widely distributed including into the lungs, metabolized in the liver
-induces P450, but less than rifampin
-decreases plasma concentration of AZT
-transient discoloration of body fluids (like rifampin) |
|
|
Term
|
Definition
-used for leprosy
-a PABA antagonist to inhibit folate biosynthesis
-adverse effects: hemolytic anemia in G6PD deficiency |
|
|
Term
|
Definition
-used in leprosy
-binds to DNA and causes oxygen radical formation
-also causes red discoloration of skin and fluids |
|
|
Term
|
Definition
-used in leprosy
-highly teratogenic
-anti-inflammatory and immuno-modulating effects
-may also cause peripheral neuropathy, sedation, constipation |
|
|
Term
|
Definition
-p. vivax = most common, responsible for relapsing malaria
-p. falciparum: causes the most severe and fatal disease, infection = medical emergency
-p. ovale: also causes relapsing marlaria but is the least common |
|
|
Term
| infective cycle of malaria |
|
Definition
-sporozoites: transmitted to humans by anopheles mosquito, invade and reside within hepatocytes
-merozoites: responsible for the ring-cell stage, progeny of sporozoites and infection of erythrocytes
-erythrocyte stage: endocytosis of merozoites by red blood cells; asexual reproduction of the bug results in the rupture of the erythrocyte and release of parasites into the circulation |
|
|
Term
| Clinical manifestations of different types of malaria |
|
Definition
-benign tertian = p. vivax and p. ovale: fever every 3rd day
-benign quartan = p. marlariae: fever every 4th day
-malignant tertian = p. faciparum: continuous fever with less pronounced cold stage, no wet stage, more dangerous due to complications of capillary blockage |
|
|
Term
| clinical cure vs radical cure of malaria |
|
Definition
clinical cure: terminate or prevent clinical attacks, do not kill dormant sporozoites, still can get relapse later
-radical cure: targets both blood and tissue schizonts, prevents relapse |
|
|
Term
|
Definition
-basically starves the parasite to death
-drug accumulates in the food vacuole of the parasite
-inhibits heme polymerase, causing accumulation of heme, inhibition of bug proteases, lysis of bug membranes
-resistance = decreased accumulation of chloroquine in bug's food vacuole |
|
|
Term
|
Definition
-unknown mechanism, redox active (?)
-ineffective against erythrocytic schizonts
-toxicity with G6PD deficiency |
|
|
Term
| pyrimethamine-sulfadoxine |
|
Definition
| inhibits parasite dihydrofolate reductase and folate biosynthesis |
|
|
Term
|
Definition
-inhibits parasite mitochondrial electron transport
-proguanil inhibits dihydrofolate reductase |
|
|
Term
| Mechanism of resistance to "quine" anti-malarial drugs |
|
Definition
-decreased accumulation of drug
-mutation in bug's transport protein genes |
|
|
Term
| Chloroquine: disposition and adverse effects |
|
Definition
-tinnitus, visual disturbance, headache, nausea, hypotension: together called CINCHONISM
-hypoglycemia, photosensitivity, dermatoses, blood dyscrasias
-arrhythmias
-severe nightmares (Mefloquine) |
|
|
Term
| Therapeutic approach to amebiasis |
|
Definition
-direct chemotherapy of invasive systemic amebae
-treatment of luminal amoeba using drugs which are not well absorbed
-may add general antibiotics to decrease intestinal flora |
|
|
Term
|
Definition
-drug of choice for luminal parasite
-unabsorbed drug is active
-mechanism unknown
-causes flatulence, itchiness, and dry mouth |
|
|
Term
| Treatment of pneumocystic carinii |
|
Definition
-first line: trimethoprim-sulfamethoxazole
-pentamidine: can be used to interfere with macromolecular synthesis functions of the fungi; does not penetrate CNS
-atovoquone: interferes with mitochondrial electron transfer, food increases absorption |
|
|
Term
| Tetracylines: drugs and MOA |
|
Definition
-tetracycline, doxycycline, minocycline, tigecycline
-enter cells via passive diffusion, and only accumulate in bacterial cells
-bind to 30S subunit of ribosome, block A site, prevent protein synthesis |
|
|
Term
|
Definition
-a tetracycline
-increased lipid solubility, lower renal clearance, wider spectrum, longer half-life
-well absorbed (95%) and can be taken with food
-penetrates CNS (only tetracycline that does this) |
|
|
Term
| Tetracylines: mechanisms of resistance |
|
Definition
-decreased influx or increased efflux of drug via various pumps
-ribosome protection by protein expression
-enzymatic activation by the organism
-cross-resistance with other drugs
-tigecycline is the least susceptible to resistance |
|
|
Term
|
Definition
-caused by taking outdated tetracyclines
-aminoaciduria, nausea, and renal tubular acidosis |
|
|
Term
| Aminoglycosides: drugs and spectrum |
|
Definition
-streptomycin
-gentamycin
-neomycin
-amikacin
-bactericidal, irreversible inhibitors of protein synthesis
-concentration-dependent killing
-effective against aerobic gram negative bacteria, and synergistically with beta-lactams or vancomycin for many types of bacterial endocarditis |
|
|
Term
|
Definition
-polar and cationic, does not enter tissues easily
-poorly absorbed orally, only given orally for GI ulceration or as preoperative bowel sterilant
-passive diffusion across outer membrane, oxygen-dependent transport across inner membrane (ineffective in anaerobes)
-modify dosing in renal dysfunction
-once daily dosing preferred to prevent toxicity |
|
|
Term
| Aminoglycosides: mechanism of resistance |
|
Definition
-major = due to enzymatic inactivation (Amikacin = less resistance by this mechanism)
-impaired uptake of drug
-mutation of ribosomal protein (streptomycin)
-enterococci that are resistant to aminoglycosides are often cross-resistant to beta-lactams |
|
|
Term
| Aminoglycosides: adverse effects/toxicity |
|
Definition
-ototoxicity from accumulation of drug in inner ear: irreversible, includes vestibular and auditory dysfunction
-toxicity more likely with renal dysfunction
-can cause reversible nephrotoxicity
-can cause neurotoxicity at high doses, including Myesthenia Gravis |
|
|
Term
|
Definition
-a broad spectrum rarely used in the US
-alternative to beta lactams for penicillin-sensitive individuals with meningitis or pneumonia
-binds to 50S subunit of ribosome and inhibits peptidyltransferase activity
-may interfere with human mitochondrial ribosomes, leading to cell death
-penetrates CNS, large volume of distribution
-caution in hepatic and renal failure, also with other CYP450 drugs
-toxicity can include bone marrow suppression and irreversible aplastic anemia
-can cause "Gray Baby syndrome" due to infant inability to deactivate and excrete the drug |
|
|
Term
| Sulfonamides: mechanism of action |
|
Definition
-structurally similar to PABA, which susceptible organisms require for folate synthesis
-drug inhibits folate production by susceptible organisms = inability to synthesize nucleic acids and amino acids
-synergistic with dihydrofolate reductase inhibitors i.e. trimethoprim and pyrimethamine
-combination of sulfonamide and DHF reductase = bactericidal (either one alone is bacteriostatic) |
|
|
Term
| Sulfonamides: clinical use/spectrum |
|
Definition
-gram positive and negative anaerobes of urinary tract and respiratory infections
-rickettsiae growth is STIMULATED by sulfonamides
-seldom used as single-drug due to resistance |
|
|
Term
|
Definition
| -an orallly administered, well-absorbed sulfonamide used to treat UTIs |
|
|
Term
|
Definition
-another orally administered, well absorbed sulfonamide
-given in combination with trimethoprim for UTIs, otitis, toxoplasmosis, nocardiosis, and other infections |
|
|
Term
| Sulfonamides: mechanism of resistance |
|
Definition
-orgs that do not synthesize folate from PABA (rickettsiae)
-impaired uptake/increased efflux
-mutation causing production of an enzyme that allows for folic-acid synthesis and has low affinity for sulfonamides |
|
|
Term
| sulfonamides: adverse effects and toxicity |
|
Definition
-hypersensitivity (1-2 weeks of therapy), including rare Stevens-Johnson
-anemia, thrombocytopenia, granulocytopenia
-crystallization in urine, causing nephritis or nephrosis
-can displace albumin-bound bilirubin, leading to life-threatening kernicterus in fetus or infant |
|
|
Term
| Fluoroquinolones: mechanism and spectrum |
|
Definition
-inhibit bacterial DNA gyrase and topoisomerase IV
-interferes with bacterial transcription and replication
-older drugs had excellent activity against gram negatives, new drugs such as cipro have some gram-positive action as well
-not good for MRSA, some strep, anerobic bacteria |
|
|
Term
|
Definition
-oral admin
-wide distribution
-absorption impaired by antacids
-dose reduction in renal failure |
|
|
Term
| Fluoroquinolones: toxicity and adverse effects |
|
Definition
-GI, dizziness, headache, rash
-CYP450 interactions
-do not give to pregnant or nursing women or children (poss. exception in cystic fibrosis)
-possible QT elongation
-do not co-admin with NSAIDs
-can get psych or neuro effects, including Tourette syndrome, if co-administered with theophylline or NSAIDs |
|
|
Term
| Acyclovir: mechanism and clinical use |
|
Definition
-an acyclic guanosine derivative
-the most extensively studied drug of anti-herpes drugs
-most effective against HSV 1 and 2
-activated only by a viral kinase = selectivity for infected cells
-higher doses required against VZV then in HSV
-used in genital herpes to shorten duration of outbreak, decrease frequency of outbreaks, decrease viral transmission
-used in cutaneous zoster and varicella as well |
|
|
Term
|
Definition
-low bioavailability
-may be administered topically, but topical admin is less effective than oral admin for primary HSV
-diffuses into most tissues including CSF
-renal clearance |
|
|
Term
| Acyclovir: mechanisms of resistance |
|
Definition
-alteration in activating viral kinase, cross-resistance with other anti-virals with this mechanism
-resistant viruses may be treated with agents not requiring viral phosphorylation |
|
|
Term
| Acyclovir: toxicities and interactions |
|
Definition
-nausea, headache
-IV admin: can get renal or neurotoxicity if infused too fast to dehydrated patient
-genetic toxicity in rodents
-other nephrotoxic agents increase chance of renal toxicity
-cimetidine and probenicid can increase exposure to the drug |
|
|
Term
|
Definition
-high bioavailability (compared to acyclovir)
-approved for genital, orolabial herpes, and herpes zoster
-can be used against CMV after transplantation (immunosuppressed pts)
-similar toxicities as acyclovir
-can get TTP or HUS in high doses with AIDS patients |
|
|
Term
|
Definition
-effective against genital, labialis, zoster herpes
-activated by viral kinase = cross-resistance with acyclovir
-similar toxicities to acyclovir |
|
|
Term
|
Definition
-an anti-CMV agent
-inhibits viral DNA and RNA polymerase
-no activation required
-administered IV only
-synergistic with acyclovir for CMV retinitis
-infusion pump required for admin
-resistance related to mutations in DNA polymerase
-toxicities: electrolyte disturbances, renal impairment, CNS effects, elevated liver enzymes, anemia, and chromosomal aberrations |
|
|
Term
| Nucleoside/nucleotide reverse transcriptase inhibitors |
|
Definition
-act by competitively inhibiting RT and incorporating into viral DNA
-effective against HIV-1 and HIV-2
-activated by cellular phosphorylation
-resistance due to mutations in viral RT
-food increases bioavailability
-can cause mitochondrial toxicity in human cells
-may get dyslipidemia and insulin resistance
-lactic acidosis with hepatic steatosis may occur: monitor aminotransferase levels and pH |
|
|
Term
|
Definition
-an NRTI, guanosine analog
-resistance is slow
-unique toxicities include: myocardial infarction, potentially fatal hypersensitivity reactions, skin rash in more than 50% of patients |
|
|
Term
|
Definition
-an NRTI
-cytosine analog
-synergistic effect with other NRTIs against HIV-1 |
|
|
Term
|
Definition
-NRTI
-do not concurrently amin with lamivudine
-administer with tenofovir
-long half life allows for once daily dosing |
|
|
Term
|
Definition
-NRTI
-acyclic nucleotide analog of adenosine
-competitively inhibits HIV RT leading to chain termination of viral DNA
-co-administered with emtricitabine as a backbone therapy
-renally excreted |
|
|
Term
| Nonnucleoside Reverse Transcriptase Inhibitors |
|
Definition
-high number of toxicities and drug reactions = not first line
-different binding site than NRTIs
-do not require phosphorylation for activation
-rapid resistance
-bind directly to HIV-1 RT |
|
|
Term
|
Definition
-inhibit the proteolytic cleavage of Gag and Gag-Pol, preventing processing of viral proteins into functional conformations
-do not require intracellular activation
-resistance is common
-can cause redistribution of body fat, osteoporosis, dyslipidemia, and insulin resistance
-active against both HIV-1 and HIV-2 |
|
|
Term
|
Definition
-an HIV PI
-once daily dosing
-admin with ritonavir for initial treatment
-hepatic clearance
-enters CSF and seminal fluids
-can cause hyperbilirubinemia
-no impact on triglycerides, LDL, fat redistribution (unlike other PIs)
-do not admin with omeprazole
-may cause PR interval elongation on ECG |
|
|
Term
|
Definition
-an HIV PI
-used in combination with ritonavir for resistance to other PIs
-do not use in sulfa allergy
-inhibits CYP3A4 |
|
|
Term
|
Definition
-HIV PI
-only co-amin with ritonavir
-can be used during pregnancy |
|
|
Term
|
Definition
-HIV PI
-increased bioavailability with food intake
-toxicities: GI, paresthesia, elevated aminotransferase levels, altered taste, headache, dyslipidemia
-do dose escalation over 1-2 weeks to prevent toxicity
-many drug interactions, including some taken advantage of to increase serum levels of other PIs |
|
|
Term
|
Definition
-HIV PI
-increased bioavailability with food intake
-toxicities: GI, paresthesia, elevated aminotransferase levels, altered taste, headache, dyslipidemia
-do dose escalation over 1-2 weeks to prevent toxicity
-many drug interactions, including some taken advantage of to increase serum levels of other PIs |
|
|
Term
| Entry inhibitor anti-virals |
|
Definition
-bind to the gp41 subunit of the viral envelope glycoprotein, preventing conformational changes required for fusion of virus to cell membrane
-not for HIV-2
-admin by subcutaneous injection
-only for experienced HIV pts |
|
|
Term
|
Definition
-entry-inhibitor anti-HIV
-binds selectively to CCR5
-given orally
-used in resistant HIV-1 strains
-may cause hepatotoxicity |
|
|
Term
|
Definition
-an integrase inhibitor
-inhibits viral DNA strand integration into host genome
-for use in pts with resistant HIV in combination therapy
-toxicity: diarrhea, nausea, dizziness, headache, dyslipidemia |
|
|
Term
|
Definition
used in HBV and HCV treatment
-binds to membrane receptor and induces intracellular signals that inhibit viral processes
-flu-like toxicity
-contraindicated in autoimmune disease, cardiac arrhythmia risk, pregnancy (abortifacient) |
|
|
Term
|
Definition
-a guanosine analog used in HCV
-phosphorylated intracellularly by host cell enzymes
-blocks capping of viral messenger RNA
-inhibits viral RNA-dependent polymerase
-toxicity = hemolytic anemia in 10-20%
-teratogenic and embryotoxic |
|
|
Term
|
Definition
-aka Tamiflu
-requires hepatic activation
-activity against influenza A and B
-approved for use in children
-must be given within 48 hours of symptom onset |
|
|
Term
| muscarinic cholinergic receptors |
|
Definition
-G protein-coupled
-M2 and M4 types inhibit cAMP or activate voltage-gaited potassium channels
-M1, M3, and M5: activate IP3, cause increased intracellular calcium
-located on parasympathetic end organs, sweat glands, and many CNS neurons, blood vessels (no innervation here = not effected) |
|
|
Term
| nicotinic cholinergic receptors |
|
Definition
-pentameric, ligand-gated cationic channels permeable to Na, K, and Ca (Nn only)
-postsynaptic receptors produce depolarization and excitation of skeletal muscle and neurons
-presynaptic enhance release of many neurotransmitters
-skeletal muscle, autonomic ganglia, adrenal medulla |
|
|
Term
| direct-acting muscarinic agonists |
|
Definition
-acetylcholine, carbachol, bethanechol
-reduce rate and contraction strength of heart
-cause NO release in blood vessels leading to vasodilation
-relaxation of bladder sphincter
-increased GI motility
-bronchoconstriction and increased resp secretions
-increased sweat and salivation |
|
|
Term
|
Definition
-acts as an indirect cholinergic agonist by preventing breakdown of acetylcholine by enzyme
-low to moderate dose effect at muscarinic receptors
-high dose effect on nicotinic receptors (may induce convulsions)
-include: edrophonium and neostigmine (myasthenia gravis and ileus), rivastigmine, donepezil, and sarin (chemical weapon) |
|
|
Term
| treatment of sarin gas exposure |
|
Definition
-atropine to block excess muscarinic activation
-pralidoxime to reactivate acetylcholinesterase |
|
|
Term
|
Definition
| blocks release of Ach from cholinergic nerve terminals by cleaving SNAP-25 |
|
|
Term
| Azole antifungal mechanism |
|
Definition
-decrease synthesis of ergosterol by inhibiting fungal CYP 450 enzymes
-broad spectrum and relatively safe |
|
|
Term
|
Definition
-oral or IV admin
-best penetration into CNS
-drug of choice for cryptococcal meningitis
-drug of choice for prophylaxis in immunocompromised pts with recent candidiasis infection
-adverse: may cause Stevens Johnson syndrome
-potent inhibitor of CYP2C9 -phenytoin and warfarin |
|
|
Term
|
Definition
-drug of choice for dimorphic fungi histoplasma, blastomyces, and sporothrix
-reduced absorption with H2 inhibitors and PPIs
-reduced bioavailability with rifampin
-avoid in pts with ventricular dysfunction, can produce congestive heart disease
-potent inhibitor of CYP3A4- statins, midazolam |
|
|
Term
|
Definition
-drug of choice for invasive aspergillosis
-also used for candida and dimorphic fungi
-visual disturbances = primary adverse effect |
|
|
Term
|
Definition
-new antifungal for aspergillus and zygomycetes
-must be taken orally with a full meal for proper absorption |
|
|
Term
|
Definition
-used topically for chronic mucocutaneous candidiasis
-orally for dermatophytes
-risk of hepatitis, monitor liver enzymes |
|
|
Term
|
Definition
-inhibits the synthesis of beta glucan to disrupt the fungal cell wall
-used in invasive aspergillosis and candidemia
-IV admin
-monitor for liver tox
-avoid co-admin with cyclosporine |
|
|
Term
|
Definition
-amphipathic polyene that binds to ergosterol, creates artificial membrane pores
-must use IV due to poor absorption from GI tract
-can accumulate in tissues and cause toxicity
-adverse effects due to binding to host cholesterol
-conventional amphotericin B deoxycholate = chills, fever, muscle spasm, hypotension: infuse slowly and limit total dose
-amphotericin B lipid formation = less renal toxicity, more liver toxicity, more expensive
-used in life-threatening systemic mycotic infections
-preferred over azoles in pregnancy |
|
|
Term
|
Definition
-a polyene macrolide similar to amphotericin, but only used in topical form due to toxicity
-used for localized candida infections |
|
|
Term
|
Definition
-orally administered for dermatophytoses
-inhibits a fungal enzyme, increasing intracellular levels of squalene to toxic levels
-well tolerated, no drug interactions, may cause GI upset |
|
|
Term
|
Definition
-orally admin for dermatophyte infection of finger or toenails
-interferes with microtubule assembly
-treatment may need to persist for 6-12 months to prevent fungal infection in new nail growth
-adverse: may get serum sickness, hepatitis, GI disturbances |
|
|
Term
|
Definition
-narrow spectrum of action, used only in combinations
-converted to active drug by fungus and blocks DNA and RNA synthesis
-serious toxicity may occur in renal failure or AIDS patients |
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