Pharm II exam Flashcards
definitive therapy
Once microbiology results have helped to identify the etiologic pathogen and/or antimicrobial susceptibility data are available, every attempt should be made to narrow the antibiotic spectrum. This is a critically important component of antibiotic therapy because it can reduce cost and toxicity and prevent the emergence of antimicrobial resistance in the community.
empiric therapy
Because microbiological results do not become available for 24 to 72 hours, initial therapy for infection is often empiric and guided by the clinical presentation. A common approach is to use broad-spectrum antimicrobial agents as initial empiric therapy with the intent to cover multiple possible pathogens commonly associated with the specific clinical syndrome.
normal flora
The normal flora are bacteria which are found in or on our bodies on a semi- permanent basis without causing disease.
colonization
The presence of bacteria on a body surface (like on the skin, mouth, intestines or airway) without causing disease in the person.
infection
The invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present within the body. An infection may cause no symptoms and be subclinical, or it may cause symptoms and be clinically apparent. An infection may remain localized, or it may spread through the blood or lymphatic vessels to become systemic (bodywide). Microorganisms that live naturally in the body are not considered infections. For example, bacteria that normally live within the mouth and intestine are not infections.
superinfection
- – a new infection occurring in a patient having a preexisting infection, such as bacterial superinfection in viral respiratory disease or infection of a chronic hepatitis B carrier with hepatitis D virus.
- –an infection following a previous infection, especially when caused by microorganisms that are resistant or have become resistant to the antibiotics used earlier
bactericidal
kill bacteria at drug serum levels achievable in the patient (more aggressive antimicrobial action)
bacteriostatic
bacteriostatic drugs arrest the growth and replication of bacteria at serum or urine levels achievable in the patient, thus limiting the spread of infection until the body’s immune system attacks, immobilizes, and eliminates the pathogen. If the drug is removed before the immune system has scavenged the organisms, enough viable organisms may remain to begin a second cycle of infection.
MIC
minimum inhibitory concentration - the lowest concentration of antibiotic that inhibits bacterial growth
MBC
minimum bactericidal concentration - the lowest concentration of antibiotic that kils 99.9% of bacteria
susceptible
The “susceptible” category implies that isolates are inhibited by the usually achievable concentrations of antimicrobial agent when the recommended dosage is used for the site of infection.
resistant
The “resistant” category implies that isolates are not inhibited by the usually achieveable concentrations of the agent with normal dosage schedules, and clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies.
intermediate susceptibility
The “intermediate” category includes isolates with antimicrobial MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates. The intermediate category implies clinical efficacy in body sites where the drugs are physiologically concentrated (e.g. quinolones and beta-lactams in urine) or when a higher than normal dosage of a drug can be used (e.g. betalactams).
sites with special accessibility factors to antibiotics (or lack of accessibility)
CNS: blood-brain barrier has tile-like endothelial cells with tight junctions; impede entry of all but small, lipophilic molecules. Note that when the brain becomes inflamed (e.g. meningitis), local permeability increases and some antibiotics can then enter the CSF in therapeutic amounts.
Prostate, vitreous body of eye: very difficult to get antibiotics here in therapeutic amounts
Which antibiotics are lipid-soluble and can penetrate into the CNS?
cloramphenicol
metronidazole
What are the patient factors that influence selection of antibiotic therapy? (6)
Immune system: antibiotics reduce the bacterial load but the host’s immune system must ultimately clear the infection - immunosuppressed individuals usually require higher-than-usual doses to eliminate infective organisms
Renal dysfunction: poor kidney function increases accumulation of antibiotics that would otherwise be eliminated
Hepatic dysfunction: erythromycin and tetracycline are concentrated or eliminated by the liver; use caution
Poor perfusion: decreased circulation to an area reduces the amount of antibiotic that reaches that area (e.g. diabetics/lower limbs)
Age: newborns have poorly developed renal/hepatic systems -> toxicity
Pregnancy: many antibiotics cross the placenta
Lactation: many antibiotics are present in breast milk
Name 3 anti-infectives that inhibit the CYP450 system.
Erythromycin
Sulfamethoxazole-Trimethoprim
indinavir/saquinavir
Cross-sensitivity/allergy risks between the beta-lactam antibiotics
- –Up to 10% of people with reaction (rash, anaphylaxis) to penicillin will have reaction to cephalosporin
- –Cross-reactivity is sometimes due to the beta-lactam ring, sometimes due to side chain moieties
- –Ampicillin and amoxicillin share side chains with cephalosporins, but not penicillin
Reasons for antibiotic failure
- Drug resistance
- Hypersensitivity
- Direct toxicity
- Superinfections
- Premature stoppage of administration
- Not the right drug
- Failure to reach MIC/MBC
Name 2 synergistic drug combinations and explain why they are synergistic.
Penicillins + clavulanic acid: penicillins have a beta lactam ring, and bacteria have beta lactamases. Clavulanic acid binds and inactivates the beta lactamases, which enables the pencillin to be more effective.
Aminoglycoside + vancomycin or penicillin: Vanco & penicillin create a leaky cell wall, which makes it easier for the AGs to get in to where the protein is being synthesized and interrupt it.
How do nucleoside analogs work to treat viral infection?
Nucleoside analogs are incorporated into a growing nucleic acid strand, but since they lack a 3’ OH, no further elongation will be possible, because all nucleic acid synthesis requires a 3’ OH site for adding the NEXT nucleotide.
Name 3 nucleoside analogs and what they treat.
acyclovir - Herpes simplex, varicella zoster
valacyclovir - prodrug of acyclovir
ribavirin - children with RSV
How do protease inhibitors work to treat viral infection?
In the late stages of viral assembly, viral proteases cleave polyproteins into viral proteins. Protease inhibitors prevent this cleavage and therefore inhibit the production of new infectious virus particles.
Name 2 protease inhibitors and what they treat.
indinavir - HIV
saquinavir - HIV
amantadine:
What does it treat?
How does it work?
Mode of administration?
influenza A
prevents virus from entering host cells
well absorbed orally
interferon:
What does it treat?
How does it work?
Mode of administration?
interferons: mode of action not well understood; not active orally - interlesional, subq, IV
interferon a: hepatitis B, C
interferon b: relapsing-remitting MS
interferon g: chronic granulomatous disease
oseltamivir:
What does it treat?
How does it work?
Mode of administration?
influenza a, b
inhibits viral neuraminidase (prevents the release of new virions and their spread from cell to cell)
orally active prodrug
What % of filtered Na+ is reabsorbed at: proximal tubule loop of Henle distal tubule cortical collecting duct
60% proximal tubule
20-25% loop of henle
3-5% distal tubule
1-2% collecting duct
What classes of diuretics work at each area of the tubule?
Proximal tubule: osmotics, carbonic anhydrase inhibitors
Loop of Henle: loop diuretics
Distal tubule: thiazides
Collecting duct: potassium-sparing diuretics
What is the main CAI diuretic? What is its mechanism of action? What is its major side effect? How long is it prescribed for? What is it prescribed for?
ACETAZOLAMIDE blocks the enzyme that makes H+ ions available for exchange with sodium and water Metabolic acidosis 2-4 days Altitude sickness, glaucoma
Which loop diuretic is the most potent?
Ethacrynic acid
What is the mechanism of action of loop diuretics?
Act directly on the ascending limb of the loop of
Henle to inhibit sodium and chloride resorption (which also results in decreased potassium resorption, since it’s a Na+-K+-Cl- cotransporter - each molecule of sodium reabsorbed brings one molecule of potassium and two molecules of chloride).
What is another effect of loop diuretics?
Renal prostaglandins; vasodilation; bronchodilation
What is a major toxicity of loop diuretics?
Ototoxicity
What is the main reason furosemide is prescribed?
CHF
Which diuretics are used in normal kidney function?
CAI, thiazide, mannitol
Which diuretics are used in impaired kidney function?
loop diuretics
What are the four major side effects of loop diuretics?
hypokalemia
hyperglycemia
hyperuricemia (gout)
hypomagnesemia
What is the mechanism of action of thiazides?
Inhibit tubular resorption of sodium and chloride
ions
Main reason thiazides are prescribed
hypertension
Why are thiazides good antihypertensives?
Thiazides decrease MAP and TPR
What is the mechanism of action of potassium-sparing diuretics?
- Inhibits sodium-potassium exchange in collecting ducts (less sodium reabsorbed = less potassium excreted)
- Competitively binds to aldosterone receptors thereby preventing effects of aldosterone (which are to reabsorb sodium and water)
What is the major potassium-sparing diuretic?
Spironolactone
What are the therapeutic uses of spironolactone?
hyperaldosteronism
hypertension
ascites
What is a possible side effect of spironolactone?
HYPERKALEMIA
What is another undesirable side effect of spironolactone?
gynecomastia
Patient education about ribavirin and indinavir/saquinavir
ribavirin: absorption is increased if taken with fatty meals
indinavir/saquinavir: absorption is decreased if taken with meals; drink lots of water to reduce kidney stone risk; inhibit CYP enzymes so be careful with warfarin & phenytoin
amantadine: mechanism of action, purpose, contraindication
prevents virus from entering host cells; influenza A; pregnant
oseltamivir: mechanism of action, purpose, patient education
viral neuraminidase inhibitor (prevents the release of new virions and their spread from cell to cell); influenza A, B; GI side effects - take with food
What are treatments for scabies and lice?
lindane, permethrin, pyrethrins
What is treatment for hookworms, pinworms, roundworms, tapeworms, whipworms?
mebendazole
What is treatment for giardia, trichomonas vaginalis, anaerobes?
metronidazole
Name 5 broad-spectrum drugs/drug groups.
amoxicillin quinolones streptomycin tetracycline chloramphenicol
Name 3 macrolides
erythromycin, clarithromycin, azithromycin
Name 3 aminoglycosides
neomycin
streptomycin
gentamycin
Name 3 tetracyclines
tetracycline, doxycycline, minocycline
Name 2 quinolones
ciprofloxacin, norfloxacin
Name 2 drugs that can treat prostatitis
TMP-SMZ; quinolones
What is the mechanism of action of TMP-SMZ?
blocks folate synthesis
Drug that concentrates in bone
clindamycin
short term side effects of corticosteroids (5)
hyperglycemia elevated white count sodium retention hypokalemia jitteriness/euphoria/confusion (steroid psychosis)
long term side effects of corticosteroids
- -HPA axis suppression
- -Cushingoid features (moon facies, redistribution of fat to trunk)
- -cataracts, glaucoma
- -decreased immune response - TB activation, poor wound healing
Name 2 ACE inhibitors
lisinopril, captopril
Name 2 angiotensin receptor blockers
valsartan, losartan
Name 4 calcium channel blockers
nifedipine, amlodipine
verapamil
diltiazem
Name 2 phosphodiesterase inhibitors
sildenafil, tadalafil
What is a beta lactam class that works increasingly well against gram neg?
cephalosporins - each generation adds more gram negs
What drug works against anaerobic or + cocci?
clindamycin
What should you not take at the same time as cipro?
dairy, metals
What is a major adverse effect from quinolones?
tendon rupture
What is a major adverse effect of doxycycline?
photosensitivity
What three antibiotics work against anaerobic organisms?
clindamycin, chloramphenicol, metronidazole
What diuretic is given in crush injuries (rhabdomyolysis)?
mannitol - increases urine flow to prevent obstructive myoglobin casts
Top 3 most prescribed antibiotics
Penicillin, erythromycin, cephalosporin
A patient is allergic to penicillin; what is the chance they will have a reaction to cephalosporin?
10%
name 4 anticoagulants
warfarin, heparin, dabigatran, LMW heparin
What is used to treat glaucoma?
CAi
What is used to to treat pulmonary hypertension?
phosphodiesterase inhibitors, dipyridamole
warfarin: moa, indications, interactions, side effects
inhibits recycling/reuse of vit. K DVT, MI, artificial heart valves foods with vit K; many drugs - macrolides, indinavir, erythromycin bleeding, GI narrow therapeutic index - must monitor
heparin: moa, indications, interactions, side effects
inhibits activated clotting factors
DVT, open heart surgery; anticoag. in pregnancy
-
bleeding
dabigatran: moa, indications, interactions, side effects
thrombin inhibitor
stroke prophylaxis, afib
-
bleeding
LMW heparin
replaces heparin; more predictable effects; doesn’t require as much monitoring
name 4 antiplatelet drugs
clopidogrel
ticlopidine
dipyridamole
aspirin
what is one thing all antiplatelets do
prevent platelet aggregation
which anti platelets reduce atherosclerotic events?
clopidogrel
ticlopidine
what does dipyridamole do?
coronary vasodilator
how does aspirin work?
inhibits COX-1 = reduced platelet aggregation
With which diuretics do you need to monitor electrolytes?
thiazides, loop diuretics
which diuretic type increases calcium reabsorption?
thiazides increase calcium reabsorption
which diuretic type increases calcium secretion?
loop diuretics
For patients with atrial fibrillation - what drug and for how long?
warfarin, indefinitely - prophylactic for blood clots in the atria
What diuretic is used to treat altitude sickness?
acetazolamide (CAI)
What drugs do you give to protect against repeat strokes in people who have had strokes?
anti-platelets: clopidogrel, ticlopidine, aspirin
What agents can be used for neuropathic pain?
tricyclic antidepressants; SSRIs; anticonvulsants; neuropathic agents such as gabapentin
Which diuretics can lead to hypomagnesemia?
Loop diuretics, thiazides
What types of drugs are used for mild/moderate nociceptive pain?
NSAIDs
acetaminophen
what types of drugs are used for neurogenic pain?
anticonvulsants
tricyclic antidepressants
SSRIs
What types of drugs are used for severe, intense, or chronic malignant/nonmalignant pain?
opioids
Which diuretics can lead to hypomagnesemia?
Loop diuretics, thiazides
Most of the calcium channel blockers work on both cardiac muscle and vascular smooth muscle, but one of the CCBs has a much greater affinity for vascular calcium channels than for calcium channels in the heart and is therefore particularly useful for hypertension. What is this CCB?
dihydropyridines (nifedipine, amlodipine)
What are CCBs prescribed for?
hypertension, angina
