What gives beta lactam drugs such as penicillin their absolute toxicity (their abibilty to kill bacteria without harming the host)?

they target peptidoglycan cell wall synthesis (DD transpeptidase), which is not present in eukaryotic cells

True or False?

Sulfa drugs exhibit absolute selective toxicity but are not bacteria-cidal.

True.

Their selectivity is due to their targeting of a bacteria-specific enzyme, pteroate synthetase, used in bacterial production of folic acid.

Sulfa drugs do not kill bacteria, only slow their growth = bacteriostatic

Kernicterus, renal toxicity, eosinophilia, and Steven-Johnson syndrome can all result from what type of drug?

Sulfonamides

Which sulfonamide drug is Trimethoprim, a dihydrofolate reductase inhibitor, frequently adminstered in conjunction with?

Sulfamethoxazole

- T:S = 1:5

- drugs have synergistic effect

- used to treat UTIs, resp infections, flu, strep, parasites

- common brand names: Bactrim, Azo Gantanol, Septra

What is the leading infectious cause of death in children under 5 worldwide?

Acute respiratory infections

(includes pneumonia and influenza)

- second leading is diarrhea

Ketoconazole, Fluconazole, and Clotrimazole all

belong to which class of drugs?

What are they used to treat?

    Belong to Azole antifungal class

- Used to treat fungal infections

Name 2 Polyene antifungals.

Which one can be given systemically, and which one only topically?

Amphotericin B  - is given systemically through IV

          Nystatin – given topically (to gargle) –

more toxic than Amphotericin B and not absorbed well by GI tract

What gives Polyenes their selective toxicity?

What are possible side effects from these drugs?

Polyenes such as Amphotericin B and Nystatin bind preferentially to ergosterol (found in the fungal cell membrane). The pore created by ergosterol binding lasts longer than the pore created by cholesterol binding.

          Possible side effects: renal toxicity, fever and chills, hypokalemia, arrhythmias, anaphylaxis

          *Amphotericin B contraindicated in renal patients use liposomal form

Clotrimiazole is given as a rinse to treat candidiasis. Is it fungicidal or fungistatic?

  It is fungistatic

Which has higher levels in the brain:  Fluconazole or Ketoconazole?

Fluconazole.

Ketoconazole cannot be used to treat CNS fungal infections b/c not permitted into CNS.

Which is still active in the urine: Fluconazole or Ketoconazole?

Fluconazole.

Can be used to treat fungal infections of lower urinary tract.

Which Azole can cause decreased sex steroid synthesis and liver problems, causing it to be discontinued after a day: Fluconazole or Ketoconazole?

Ketoconazole.

All azoles are considered potential teratogens and class C drugs.

Primary indication for Ketoconazole use is Pseudallescheriasis infection.

Clotrimazole and Nystatin are both used to treat _________ infections.

Topical Candida albicans infections (yeast infections, thrush, etc)

Which antiviral is used to treat Herpes Simplex infections?

          A. Acyclovir

          B. Amantadine

          C. Oseltamavir

          D. Ribavirin

A. Acyclovir

Which antiviral is effective against the A2 influenza if administered prophylactically or early in infection?

A. Acyclovir

B. Amantadine

C. Oseltamavir

 D. Ribavirin

B. Amantadine

Which antiviral is effective against both A and B strains of influenza, is a neuraminidase inhibitor, and prevents release of virions when given prophylactically?

          A. Acyclovir

          B. Amantadine

          C. Oseltamavir

          D. Ribavirin

Oseltamavir

-         given as prodrug: oseltamavir phosphate

Ritonavir has a short half life. What is it given in combination with, and what is this combination used to treat?

Ritonavir is a protease inhibitor that is commonly given in conjunction with lopinavir (another protease inhibitor) in the treatment of HIV.

This pharmacokinetic effect makes once a day dosing possible.

Which is not a nucleoside/nucleotide analog?

          A. Zidovudine (AZT)

          B. Ribavirin

          C. Acyclovir

          D. Efavirenz

D. Efavirenz

- is a Reverse Transcriptase Inhibitor used to treat HIV but works at different site from "nucs"

AZT is a thymidine analog used in HAART to treat HIV Ribavirin is a guanosine analog used for Hepatitis C

Acyclovir is a guanine analog used to treat Herpes

Which Macrolide antibiotic would be least likely to interfere with metabolism of warfarin and other CYP 450-utilizing enzymes?

          A. Erythromicin

          B. Clarithromycin

          C. Azithromycin

  C. Azithromycin

– preferred for treatment of Chlamydia trachomatis

– single 1gram dose

Are Macrolides bacteriocidal or bacterio-static? What is their mechanism of action?

  Macrolides are bacteriostatic (Erythromicin, Clarithromycin, Azithromycin).

They interfere with protein synthesis by reversible binding to the 50s bacterial ribosomal subunit

Which antibiotic is very effective against anaerobes such as Bacteroides, Prevotella, and P. gingivalis, (and also Streptococcus species), and so is commonly used in dentistry?

          A. Clindamycin

          B. Clarithromycin

          C. Azithromycin

          D. Erythromycin

A. Clindamycin

– also used for:

endocarditis prophylaxis in penicillin-allergic patients

treatment of anaerobic female ug tract infections

refractory bone infections

Which classes of drugs bind the 30S bacterial ribosome subunit and which bind the 50S subunit? Which are bacteriostatic and which are bacteriocidal?

A. Aminoglycosides

   B. Macrolides

   C. Tetracycline

   D. Clindamycin

    E. Chloramphenicol

Bind 30S: Aminoglycosides (bacteriocidal) Tetracylines (bacteriostatic)

     Bind 50S: Clindamycin (bacteriostatic)

Macrolides (bacteriostatic)

Chloramphenicol (bacteriostatic)

Which Tetracycline-type antibiotic is used to treat meningococcal carriers because of its high concentrations in tears and saliva?

Minocycline

Which is the broadest-spectrum antibiotic?

          A. Aminoglycosides

          B. Tetracycline

    C. INH

B. Tetracycline

- Aminoglycosides limited to killing gram - aerobes (obligatory anaerobes are resistant)

- INH limited to mycobacteria

Why is it better to give Aminoglycosides 3x a day than an equivalent dose 1x a day?

What type of antibiotic kills bacteria by inhibition of bacterial topoisomerase II and IV?

Quinolones

- Relatively selective for bacterial topoisomerase (as eukaryotic version is much less sensitive

- Bacterial DNA gets twisted on itself during replication without TI (gyrase)

- TI 2 in gram - , TI 4 in gram+

Name 2 classes of antibiotics that can produce photosensitivity.

Tetracyclines

Fluoroquinolones (particularly sparfloxacin)

This class of antibiotics can cause arthropathy, and is not widely used in children except for children with cystic fibrosis.

This antibiotic is cidal against protozoans, amoeba, and other anaerobic organisms that live in no or low-oxygen environments.

Metronidazole

True or False?

Cephalosporins and Metronidazole both have disulferam-like effects if taken with alcohol.

True – don’t consume with alcohol 24 hours before or 48 hours after last dose

Periphereal neuropathy is a possible adverse effect of INH.

What is given in conjunction with INH to reduce this effect?

Vitamin B6

This drug is effective against Mycobacteria tuberculosis, and is used prohphylactically to family members of Meningococcal and H. influenza infected-people.

Rifampin

-         Colors all body fluids orange-red

-         Decreases effectiveness of MANY drugs

(oral contraceptives, methodone, anticoagulants, beta-blockers, etc)

Glucocorticoids are classified by duration of action and relative anti-inflammatory/salt retaining activity.

Which of the following has the highest glucocorticoid activity relative to mineralocorticoid activity

(anti-inflammatory:salt-retaining)?

A. Hydorcortisone

B. Prednisone

C. Betamethasone

C. Betamethasone

- (35:0) entirely anti-inflammatory activity

- used to promote fetal lung maturation

When is it ok to give a woman therapeutic estrogen alone (unopposed with progestins)?

If she has had a hysterectomy

Name 2 synthetic estrogens commonly found in oral contraceptives.

Ethinyl Estradiol

Mestranol

- mestranol is converted to ethinyl estradiol in the liver

- very good at exerting feedback inhibition in the hypothalmus - negative feedback inhibition of GnRH results in lower levels of LH and FSH

At what ages do smoking and non-smoking women start to die more from taking oral contraceptives than from childbirth?

smoking women - over 35

non-smoking women - over 40

Why should a woman taking oral contraceptives be advised to use a back-up method if she is also taking Rifampin?

Why should she also get the same advice if she is taking Penicillin, Carbapenems, or Tetracyclines?

-Rifampin decreases the effectiveness of oral contraceptives (and many other drugs) by increasing P450 metabolism. P450 is responsible for converting Ethinyl Estradiol into inactive 2hydroxyethinylestradiol.

- These last 3 antibiotics also decrease the effectiveness of oral contraceptives by killing off the small intestinal bacteria that are responsible for regenerating active ethyline estradiol from the glucuronidated version in hepatic cycling

Which of the following SERMS (selective estrogen receptor modifiers) is NOT used to treat cancer?

A. Tamoxifen

B. Raloxifene

C. Clomiphene

C. Clomiphene

- used as an estrogen receptor antagonist in the hypothalmus --> more LH and FSH produced

- used to treat infertility

- Tamoxifen good at treating breast cancer but can cause endometrial cancer after 5 years

- Raloxifene also used for breast cancer but not as effective as Tamoxifen

oral contraceptives (Plan B)

contraceptive implants

replacement therapy

endometriosis

- natural progestins have the shortest half-life (progesterone)

-  synthetic progestins the longest (Levenorgestrel)

How does the synthetic androgen Danazol work?

What are some indications for its use?

- works at the hypothalmus to decrease estrogen release

- indicated for:

Replacement therapy, Anemias, Anabolic agents, Osteoporosis, Breast cancer, Endometriosis, Fibrocystic breast disease

What are the 4 places in which you can have pharmacokinetic interactions?

Absorption

Distribution

Metabolism

Excretion

Competition between drugs for albumin binding sites would lead to what type of pharmacokinetic interaction?

A change in distribution

- the more drug free (not bound to albumin), the greater the effect of the drug

- competition for tissue binding sites would also change distribution

Which of the following drugs has a mechanism of action that does NOT involve interfereing with fungal cell membranes?

A. Polyenes

B. Amphotericin B

C. Quinolones

D. Azoles

C. Quinolones

aka Fluoroquinolones

- these bactericidal antiobiotics interfere with DNA synthesis by bungling up topoisomerases

True or False?

Most quinolones are not orally active and must be administered parenterally.

False.

All quinolones ARE orally active.

Most cannot get into CNS, EXCEPT levofloxacin.

What Fluoroquinolone would be the drug of choice for rapidly progressing periodontitis associated with Enterobactericeae?

Ciprafloxacin

Which drug would not be used to treat Tuberculosis?

A. Fluoroquinolones

B. Ritonavir

C. INH

D. Rifampin

B. Ritonavir

- an antiretroviral protease inhibitor used in the treatment of HIV, often combined with letonavir to extend half-life

- Fluoroquinolones are used especially against multi-drug-resistant TB, while INH and Rifampin are the first line of defense

Common side effects of these 2 drugs include:

Buffalo hump

Hyperlipidemia

Insulin resistance

Lopinavir

Ritonavir

- protease inhibitors used in HIV treatment

- also inhibitors of P450 metalolism, so interactions with many other drugs is common

Which is not a common indication for Fluoroquinolone use?

A. Anthrax prophylaxis

B. Respiratory infections in Cystic Fibrosis patients

C. Community acquired Pneumonia

D. Multi-drug-resistant TB

E. Chronic Periodontitis

E. Chronic periodontitis

Which would NOT be used to treat periodontitis?

A. Erythromycin

B. Clindamycin

C. Metronidazole

D.

The first drug discovered that could treat a wide range of bacterial infections inside the body.

Prontosil

- a prodrug, releases sulfonamide after metabolism

What type of drugs compete with p-aminobenzoic acid in the synthesis of folic acid?

Sulfa drugs

- exhibit absolutely seletive toxicity b/c we lack enzyme pteroate synthetase

Do sulfa crystals form in acidic or basic urine?

What is the implication for people on sulfa drugs?

Crystals form in acidic urine.

- most UTIs cause urine to become alkaline, so don't have to worry

- but in people taking sulfa drugs for other reasons, must drink a lot of water to prevent crystals from forming

- crystals damage renal tubules

Which drugs do NOT get into CNS?

A. Sulfa drugs

B. Penicillins

C. Clindamycin

D. Levofloxacin

E. Ketoconazole

F. Chloramphenicol

C. Clindamycin

&

E. Ketoconazole

- Penicillins only penetrate CNS in presence of inflammation (meningitis)

- Sulfa drugs (and chloramphenicol!) penetrate in absence of inflammation

- Levofloxacin is the only Quinolone that gets into CNS

Use of Clindamycin can cause Clostridium difficile superinfection, leading to pseudomembranous colitis.

What is the drug of choice to get rid of C. difficile and what is an alternative?

Metronidazole is drug of choice.

Vancomycin is alternative.

Gray Baby Syndrome

Chloramphenicol

Drug has affinity for neonatal mitochondrial ribosomes

Mitochondrial protein synthesis is inhibited and baby cannot utilize oxygen --> failure to thrive

A professional lifeguard who wears a ton of PABA-containing sunscreen may encounter problems if he is taking which type of antibiotic?

Sulfonamides

- these drugs compete with p-aminobenzoic acid (PABA) to alter folic acid metabolism

- too much PABA may decrease effectiveness of drug

The following side effects can result from what class of drug?

Osteoporosis

Peptic ulcers

Cataracts (irreversible)

Glaucoma

Behavioral disturbances

Increased infections

Fluid retention and hypertension

Glucocorticoids

Which short-acting (8-12 hrs) glucocorticoid is equally effective for anti-inflammatory and salt-retention?

Hydrocortisone

True or False?

Estrogens stimulate production of osteoprotegrin, which limits the production of mature osteoclasts.

True

- OPG binds RANKL on osteoblast, preventing binding by osteoclast precursor

What hormone dominates in the proliferative phase of the menstrual cycle?

Which dominates in the Secretory phase?

Proliferative - Estrogen (E2)

Secretory - Progesterone

Which type of estrogens are used for post-menopausal women to minimize the risk of gall-bladder disease?

conjugated estrogens

Why are estrogens contraindicated in pregnancy?

- can increase risk of vaginal adenocarcinoma in baby

- they are teratogenic

______ is the drug that causes altered action of the object drug.

The Precipitant drug

True or False?

Slowed GI motility leads to increased drug absorption for an orally administered drug.

True

Metabolism of which drug is dependent upon the CYP2D6 enzyme?

What are some inhibitors and inducers of this enzyme?

Metabolism: CODEINE

Inhibitors: FLUOXETINE (Prozac)

Inducers: NONE

Antacids can act as a precipitant for which 2 types of antibiotics?

Tetracyclines

Fluoroquinolones