A drug that will stop bacteria from dividing but will not directly decrease the number of viable organisms.

MIC

minimal inhibitory concentration

the lowest concentration of drug (expressed in mcg/ml), which will inhibit the growth of bacteria

MBC

minimal bacteriacidal concentration

Bacteria don't always confine their wanderings to the blood. A bacteria causing meningitis may not respond to a drug that attains low CNS concentrations even though the bacteria was "susceptible" to antibiotic concentrations attained in the blood. Conversely, some antibiotics may attain urine concentrations in excess of those found in the blood and bacteria that are "resistant" to an antibiotic (based of achievable blood concentrations) may still be eradicated from the urine

This is why labs ask you where you received a culture from

(The MIC has to be high enough to kill the bug in a certrain are but low enough to not be toxic to the patient)

Drug Determinants

Drug districution:Does the drug get to the bug?

(Blood Brain Barrier- the meninges are inflamed?)

Getting to into the lungs an prostate is an issue

-Dosage and route administration need to be appropraite for a patient

BACTERIAL DETERMINANTS

antibiotics

Mechanism of Action

What is the goal of thera

You want a drug that will kill the bad (or how the bad is growing, selectivly) without hurting the good cells

1. Inhibit cell wall synthesis (just bacteria have cell walls)

2. Inhibit protein synthesis (different machinary)

3. Antimetabolites

Antibacterials

What drug should be used?

SPECTRUM OF ACTIVITY

The drug chosen should have the narrowest spectrum of activity appropriate for the clinical situation. When choosing empiric therapy think about the most common organisms at the site of the infection (want to include the bug you are trying to kill, narrow spectrum are usually cheaper and prevent susceptibility of super bugs)

What drug should be used?

antibiotics

SUSCEPTIBILITY

The identified or suspected microorganism should be susceptible to the drug used. If starting broad, susceptibilities results allow you to narrow your therapy.

What drug should be used?

Antibiotics

DRUG DISTRIBUTION

The drug must have a distribution that allows it to get to the site of infection in concentrations sufficient to adversely affect the well being of the bug. To achieve this objective, special administration techniques are sometimes necessary (e.g. intrathecal).

Antibiotics

Which drug should be used?

Toxicity and Cost

Choose the drug with the least toxicity and lowest cost. (try to balance)

Antibiotics

Which drug should be used?

Patient Allergies

(Have you ever had a bad reaction from a drug?)

Antbiotics

If a patient is allergic and you really want to you this drug what would you do?

Desensitize them: start with a very low dose, tie up some of the antbibodies and gradually increase up. DO NOT MISS A DOSE. Small increase will not initiate the complement system. Eventually will be able to use the full dose.

Antibiotics

What are 4 reasons why you would use COMBINATION THERAPY?

BETALACTAMS

(They have a certain strucuture)

DRUG BUG PAIRS

Penicillinase-resistant PCN

OXACILLIN AND DICLOXACILLIN

What bug do they attack?

*******

MSSA (methacillin sensitive staph aureus)

STREPTOCOCCI

DRUG BUG PAIRS

Aminopenicillins

AMOXICILLIN

What bug do they attack?

*******

H.(Hemophilus)  Influenzae

DRUG BUG PAIRS

Ureidopenicillins

PIPERACILLIN

What bug do they attack?

*******

PSUEDOMONAS

PCN

ADMINISTRATION

Should you ask the patient if they have an allergy before administering the first dose?

If getting a procaine PCN what else should you ask if they are allergic too?

***

PCN

Toxicity

What is a non dose related toxicity?

hypersensitivity reaction

It doesn't matter the route or the amount of exposure you will have a full repsonse

-Can also cause thrombocytopenia

PCN 

DOSE RELATED TOXICITY
******

1. Betalactam if you give enough they will have a seizure.

Twitching and seizures can occur with very high blood concentrations of penicillin.

-Overdose everyone, even when give a lot you are still well below the toxicity level.

-Unless on a high dose and has bad kidneys

2.  (High doses decrease platelet function and and increase bleeding time) High doses of penicillins (usually an anti-pseudomonal penicillin) will decrease the ability of platelets to function properly and may lead to bleeding tendencies. This effect will not alter platelet count but will prolong bleeding time. Don't confuse this effect with non-dose related thrombocytopenia which can also be caused by penicillins.

3. Procaine penicillin cause acute psychotic reactions characterized by acute anxiety, hallucinations, confusion, palpitations, and seizures. The cause is not clear but it is believed to be due to inadvertent INTRAVENOUS injection. (Make sure not in the VEIN in Injection) 

CEPHALOSPORIN

First Generation

(cefadroxil, cefazolin, cephalexin)

how effective are they at treating gram positive bugs? Gram negative bugs?

Gram Postive: +++

Gram Negative: +

CEPHALOSPORIN

Second Generation

 how effective are they at treating gram positive bugs? Gram negative bugs?

Gram Positive: +++

Gram Negative: ++

Cephalosporin

DRUG BUG PAIR

SECOND GENERATION

cefoxitin

bacteroidies fragulis

(Anerobic bug, sometimes used preventaviley in bowel and or pelvic surgery)

Cephalosporin

THIRD GENENERATION

 how effective are they at treating gram positive bugs? Gram negative bugs?

GRAM POSITIVE: ++

GRAM NEGATIVE: +++

Cephalosporin

FOURTH GENERATION

 how effective are they at treating gram positive bugs? Gram negative bugs?

GRAM POSITIVE: +++

GRAM NEGATIVE: +++

medications that cover: Legionella. chlamydia pneumonia, mycoplasma

CARBAPENEMS

(meropenem, imipenem-cilastin)

What is the toxicity that you want to watch for with these drugs?

*****

1. Seizures (decreased seizure threshold) want to watch in renal patients

2. Increased AST/ALT: need a baseline liver function tests

MACROLIDES

(Erythromyocin, Clarithromyocin, Azithromycin)

Are these drugs good against the atypicals?

YES

medications that cover: Legionella. chlamydia pneumonia, mycoplasma

MACROLIDES

(Erythromyocin, Clarithromyocin, Azithromycin)

Azithromycin VS. Doxycycline

Which one would you use?

MACROLIDES

(Erythromyocin, Clarithromyocin, Azithromycin)

DRUG INTERACTIONS ERYTHROMYOCIN

MACROLIDES

(Erythromyocin, Clarithromyocin, Azithromycin)

TOXICITIES

FLUOROQUINOLONES

Do these drugs treat atypicals?

FLUOROQUINOLONES

MOXIFLOXACIN

DRUG BUG PAIRS

What is this used to treat?

FLUOROQUINOLONES

Cipro

What is this the drug of choice for?

FLUOROQUINOLONES

TOXICITY

***
Who do you want to avoid the use of these in?

And what side effect do you want the patient to tell you if they have it?

FLUOROQUINOLONES

DRUG INTERACTIONS

*****

SULFONAMIDES

DRUG BUG PAIR

****

BACTRIM

SULFONAMIDES

When dosing Bactrim what do you dose it on?

****

sulfonamides

BACTRIM

toxicity

What can this cause?

sulfonamides

BACTRIM

toxicity in Newborns

sulfonamides

BACTRIM

WHAT CAN CAUSE FOR A REACTION AND IS SEEN MORE IN AIDS PATIENTS?

METRONIDAZOLE

DRUG BUG PAIR

What is this drug used to kill?

TRICHOMONIASIS AND C.DIFF

Pseudomembranous colitis - C. diff (can also treat with oral vancomycin)

METRONIDAZOLE

TOXICITY

What can you not have with this durg?

****

hydro-alcoholic mixture

CAN SNEAK ON YOU

(benadryl)

CLINDAMYOCIN

DRUG BUG PAIR

What is this effective against?

STAPH ( INCLUDING MRSA)

COMMUNITY AQUIRED PNEUMONIA

CLINDAMYCIN

 What is a toxicity of this drug?

*****

What would you use to treat this toxicity?

(Kill all the good bacteria in the gut and this is able to grow more rapidly)

2. Pseudomembranous colitis - diarrhea usually starts 2 to 9 days after therapy has begun but can occur up to 14 days after therapy is stopped. Colitis is caused by a superinfection of Clostridium difficile which produces a toxin. Treatment of this condition is with oral metronidazole or oral vancomycin

AMINOGLYCOSIDES

What are they very active at treating?

AMINOGLYCOSIDES

ADMINISTRATION

****

WHAT IS IMPORTANT ABOUT ADMINISTRATION OF THIS DRUG?

AMINOGLYCOSIDES

TOXICITIES

What are the two types?

*****

 1. Nephrotoxicity (reversible) MONITOR serum creatinine

VANCOMYOCIN

DRUG BUG PAIR

****

VANCOMYOCIN

WHAT IS ITS MAIN TOXCITY?

1. Nephrotoxicity – more common at blood levels above 20 mg/dl

(AT HIGH BLOOD LEVELS, DON'T MEMORISE THE LEVEL#)

VANCOMYOCINS

ARE VANCO TROUGHS EFFECTIVE ARE PEAKS EFFECTIVE?

1. Vancomycin troughs correlate to efficacy and toxicity

PEAKS ARE USELESS

TETRACYCLINES

(minocycline, doxycycline)

ADMINISTRATION

What do you want to avoid co-administering these with?

TETRACYCLINES

(minocycline, doxycycline)

Who do you not use this drug in?

CHLORAMPHENICOL

toxicity

******

-NOT USED MUCH ANYMORE

-poisonous to the mitochondria (overdose is FATAL)

- Blood dyscrasias

Quinupristin/dalfopristine (Synercid) and LINEZOLID (Zyvox)

DRUG BUG PAIR

vancomycin resistant enterococci faecium

(VRE)

antifungals

AMPHOTERICIN B

DRUG BUG PAIR

What are the clinical uses for these?

antifungals

AMPHOTERICIN B

What to we use to premedicate a patient for administration of this and what are we trying to prevent?

LIPOSOMALAMPHOTERICIN(amphotec,abelcet,ambisome)

These are very similar to Amphotericin B drugs but have less what?

nephrotoxicity

and more expensive

AZOLE ANTIFUNGALS

VORICONAZOLE

WHAT DO YOU NEED TO MONITOR?

*****

AZOLE ANTIFUNGALS

VORICONAZOLE

DRUG BUG PAIR

what is this the drug of choice for?

drug of choice for aspergillus infections

FLUCYTOSINE (5-FC; note, 5-FC is a dangerous abbreviation)

*****

FLUCYTOSINE (5-FC; note, 5-FC is a dangerous abbreviation)

TOXICITY

****

BONE MARROW SUPPRESSION

ECHINOCANDINS

(caspofungin, micafungin, anidulafungin)

ARE THESE WELL TOLERATED?

When treating active disease TB what do we always use?

*****

combination drugs, a lot of bacteria and high likelyhood that there is resistance

If histroy BCG vaccination do we still test for PPD?

How long is the treatment and with what for positive INH?

****

YES, because want to treat with interfeuron (INH) for 9 months.

-New test Quantinferon TEst blood test

TB

What is key and preventing emergent resistance to drugs?

ISONIAZID

When do you administer it?

ISONIAZID

What are its toxicities?

1. Hepatic Toxicity with age

Age incidence: <20 0% 20-34 0.3% 35-49 1.2% 50-64 2.3%(Not contraindicated)

ISONIAZID

What are the patient related varaibles?

What is a significan drug interaction?

**

1. Alcoholics have increased risk for hepatitus (liver disease)

2.PHENYTOIN: co administered increases the blood levels of both drugs.

Rifampin, Rifabutin, Rifapentine

What do they all do?

What 3 toxicities do they have?

THEY all stimulate hepatic enzymes

Rifampin, Rifabutin, Rifapentine

DRUG INTERACTIONS

WHAT ARE THE THREE ON THE EXAM?

****

TB drug( only used for TB)

PYRAZINAMIDE

What toxicity would you see?

Hepatitus

TB

Ethambutol

What toxicities would you see with this drug?

****

Dose related - Optic neuritis (blurred vision, red-green blindness, restricted visual fields)

-Avoid in children because they can't report the toxicities from Optic neuritis

Antiviral

Acyclovir

Is it absorbed well orally?

NO (15-30%)

NOT charged. When it comes across an

- Selectively converted by thymidine kinase into a charged triphosphate molecule in herpes infected cells. This activated, charged molecule cannot easily pass through cell membranes and therefore accumulates in infected cells. Once acyclovir triphosphate is inserted into the replicating viral DNA by DNA polymerase, synthesis stops

Antiviral

Valacyclovir (Valtrex)

Is absorbed orally?

YES

PRO-DRUG

50% absorbed orally

Converted to accyclovir (active drug)

Acyclovir and Valacyclovir

What is this used to treat?

HSV and VZV

(renal dysfunction, reduce the dose)

(Make sure patient is hydrated well)

Famciclovir (Famvir)

Is inactive and converted into?

This drug can be absorbed orally unlike

PENCICLOVIR (which is active)

Treats HSV and VZV

PENCICLOVIR (Vectavir)

How is this administered?

What is used to treat labialis Herpes HSV (type II)

What can be used prophylactic?

****

What do you used to treat Shingles? (Reactivation of VZV)

What complications can a patient have with this?

Acyclovir, valacyclovir and Famiciclovir (can reduce side effect by giving within 48 hours)

Postherpetic Neuralgia – may occur up to 3 months (6 months to a year) after lesion has resolved and is more common in older patients – relatively rare in children. Early aggressive treatment may decrease intensity and duration of pain. Polypharmacy to treat PHN is appropriate. Topical (lidocaine patch, caosaicin cream), Oral therapy (gabapentin, opioids).

GANCICLOVIR (Cytovene) & VALGANCYCLOVIR & FOSCARNET (Fosavir)

What do these drugs treat?

CMV in immunocompromised patients.

Foscarnet is reserved for bugs that are resistant to acyclovir so can be used for HSV and VZV infections

GANCICLOVIR (Cytovene) & VALGANCYCLOVIR & FOSCARNET (Fosavir)

This is what kind of drug is this?

What are other administration considarations?

Hazadorous drug

GANCICLOVIR (Cytovene) & VALGANCYCLOVIR & FOSCARNET (Fosavir)

What are toxicities?

GANCICLOVIR (Cytovene) & VALGANCYCLOVIR & FOSCARNET (Fosavir)

What is the drug toxicitiy you should know?

*****

CIDOFOVIR (Vistide, HPMPC)

What is it used to treat?

What is the main toxicity?

 What can be given with it to decrease this toxicity?

*****

Reserve for when Fosavir doesn't work

CMV

RENAL TOXICITY

To minimize renal toxicity, hydrate patient and give probenicid 2 g 3hr prior to each dose of cidofovir (protects the kidney)

ANTIVIRALS

AMANTADINE (also used in parkinsons) and RIMANTADINE

What can these drugs be useful to treat and they vary form season to season?

Nwuraminidase Inhibitors (zamamivir: Relenza inhaled; oseltamivir Tamiflu-capsule)

 What is it used to treat and what is its mechanism of action?

-Originally received a lot of publicicity when there was a threat of Avian Flu

-Have activity in Influenza A and B

-Mechanism of action: The surfaces of influenza viruses are dotted with neuraminidase proteins – these proteins hold new viral particles to the outside of the infected cell. Neuraminidase, an enzyme, breaks the neuraminidase bonds and allows the new particle to be released to infect other cells. Neuraminidase inhibitors block the enzyme's activity and prevent new virus particles from being released, thereby limiting the spread of infection.

RELENZA is a PAIN for administer and TAMIFLU is a pill is easy.

RIBAVIRIN

How is this handled as an inhaled drug?

NO usually use atleast 3

Highly Active Antiretroviral Therapy (HAART) or cART (combined antiretroviral therapy) is rule of thumb Treatment is based on whether patient is treatment-naïve or treatment-experienced

-Maximal and lasting suppression of viral load (undetectable viral load – eradication is currently not feasible)

-Restoration or preservation of immune function (CD4 count >350 cells/mm3)
-Maintenance and/or improvement of quality of life (right now can live to have a long life/chronic disease)
-Reduction of HIV-related morbidity and mortality

ANTIVIRAL HIV DRUG TOXICITIES

abacavir

WHAT MAIN TOX DOES IT CAUSE ?

ANTIVIRAL HIV MEDICATION

In which situation should a mother breastfeed her infant when she is HIV positive?

When used beginning the third trimester in HIV positive pregnant women, during labor, and for the first six weeks in the newborn. Transmission was reduced from 23% to 8% (NEJM 1994;331(18):1173). C-section and use of HAART and no breastfeeding has reduced the transmission rate further. All HIV mothers in the USA should receive antepartum antiretroviral therapy (AZT or combination) and exposed infants should receive 6 weeks of AZT beginning within 12 hours of birth.

-When the baby has no other source of nutrition (3rd world country)

Nucleoside Reverse Transcriptase Inhibitors (NRTI)

MECHANISM OF ACTION

**

Zidovudine (AZT, Retrovir)
Didanosine (dideoxyinosine, ddI, Videx) Lamivudine (3TC, Epivir)
Stavudine (d4T, Zerit)
Abacavir (ABC, Ziagen)
Emtricitabine (FTC, Emtriva)
Tenofovir DF (TDF, Viread)

Reverse transcriptase is used to covert viral RNA to DNA in the newly infected cell. NRTI look like nucleotides that are used to make DNA. When the viral reverse transcriptase hooks a NRTI onto the newly forming DNA chain, the DNA propagation is interrupted because the next nucleotide will not hook onto the NRTI. 

ZIDOVUDINE (AZT, ZDV, RETROVIR)

What to toxicities does this cause?

***

DIDANOSINE (ddl VIDEX)

What must you give with these drugs?

****

ABACAVIR (ABC,ZIAGEN)

what adverse reaction does it cause?

***

Hypersensitivity Reaction... If patient gets a rash STOP

genetic test to antacipate who is susceptible to it

Anti HIV

MAny come as combination

NON-NOCLEOSIDE REVERSE TRANSCIPTASE INHIBITORS (NNRTI'S)-very similar to NRTI's

NEVERAPINE

What administration technique can prevent what?

Lead-in dosing period to minimize the incidence of rash. If a rash develops, do not increase until rash resolves.

NON-NOCLEOSIDE REVERSE TRANSCIPTASE INHIBITORS (NNRTI'S)-very similar to NRTI's

DEVALVIRDINE

Toxicities: Rash: erythematous with or without itching, usually appears on trunk, face and extremities, and lasts 1-3 weeks. Continue medication through the rash. Must discontinue if rash is accompanied by fever, blisters, mucous membrane involvement, conjunctivitis, edema and arthralgias; drug induced hepatitis- hold drug until liver enzymes return to normal. (CAN TRY AND WORK THROUGH THE RASH, KEEP AN EYE ON IT)

PROTEASE INHIBITORS (PI'S)

RITONAVIR

Is this drug well tolerated?

***

NO.

Side Effects: Diarrhea, buccal mucosa ulcerations, abdominal pain, nausea, taste perversion, dry mouth, rash, headache, parethesias-oral especially
Special consideration: Ritonavir (RTV) is poorly tolerated as a single agent and has been extensively studied in combination with other PI’s. In combination, RTV dramatically increases the levels and half- life of most other PI’s by the inhibition of the P450 metabolic pathway.

PROTEASE INHIBITORS (PI'S)

Kaletra (Lopinavir/Ritonavir)

Is lopinavir well tolerated?

YES

Ritonavir inhibits the metabolism of lopinavir resulting in higher levels of lopinavir
Side Effects: GI symptoms, elevated transaminase levels, elevated triglycerides and cholesterol levels, QTc prolongation
Take oral solution with food and must be refrigerated.

PROTEASE INHIBITORS (PI'S)

Saquinavir

****

Why should you not give it "Unboosted"?

What is a major drug interaction with PI's (protease inhibitors)?

***

GENOTYPING

(RELATIVELY COMMON AND INEXPENSIVE)

PHENOTYPING

(USED IF GENOTYPE DOESN'T WORK AND IS MORE EXPENSIVE)