Pharmacology Exam IIAntimicrobials Cell Wall Synthesis Inhibitors (Bactericidal) Drug Name Mechanism Spectrum Inhibits peptidoglycan Narrow-limited

to Vancomycin
formation G+

Clinical Uses
Route: IV or IM Multi-drug resistant Staph Route: Topical

Adverse Eff.
Nephrotoxicity Hearing Loss Nephrotoxicity

Absorption
Not well absorbed in GI or CSF Not well absorbed in GI Not well absorbed in GI Poor stability in acid

Termination
Renal Excretion

Resistance
Yes

Notes
Quinopristin/Dalfopristin & Linozolid is used if microbe is vanco resistant more later

Bacitracin Penicillin -lactam Penicillin G

Inhibits peptidoglycan carrier Inhibits peptidoglycan cross-linkage (via transpepdidase)

Narrow-some G+

Broad:G- esp. spirochetes

Route: IM Group A Strep Route: Oral Gonorrhea & Syphilis

-lactamasepenicillinase sensitive

Coadministration with Procaine or Benzathine prolongs blood level

Penicillin V Penicillin H Phenoxymethyl Penicillin Amoxicillin + Clavulanic Acid (Augmentin) Pipercillin + Tazobactam Ticarcillin Cephalosporins -lactam 1st-Cephalexin Inhibits peptidoglycan (via 1st-Cephazolin cross-linkage transpepdidase) nd 2 -Cefaclor 3rd-Cefotaxim 3rd-Cefixime 4th-Cefepime Carbapenem -lactam Imipenem + Inhibits peptidoglycan (via Cilastatin cross-linkage transpepdidase Meropenem Ertapenem Monobactams -lactam Aztreonam Inhibits peptidoglycan
cross-linkage (via transpepdidase More broad than penicillin: 1st generation is narrow for G-, broad for G+ 4th generation is most broad for G- & narrow for G+ More broad than both penicillins & cephalosporins

Good Stability in Acid Broad Route: Oral

Penicillinase sensitive Clavulanic Acid:Irreversibl e inhibition of penicillinase Tazobactam: Irreversible inhibition of penicillinase Renal Excretion Augmentin XR is higher dose that is effective against amoxicillin resistant microbes

Broad-G- bacilli

Route: IM

Not well absorbed in GI Not well absorbed in GI Nephrotoxicity ( if combined w/ aminoglycoside) GI upset Nausea Anemia (reversible) Allergy (5%)

Route: IV or IM

Route: Oral Route: IM or IV Route: Oral Route: IM Route: Oral Route: IV or IM Route: IV or IM

Resistant to Penicillinases Distribute to CSF

Cilastatin inhibits hepatic peptidases

Broad vs. Pen G:Gbacilli

Route: IV or IM

Not well absorbed in GI

Broad lactamase resistance

Cell Membrane Drugs (Antifungal & Bactericidal) Drug Name Mechanism Spectrum Fungicidal Broad:GPolymyxin
Detergent effect

Clinical Uses
Route: IV or IM

Adverse Eff.
Nephrotoxic

Absorption
Not well absorbed in GI

Termination
Renal Excretion

Resistance

Notes
Doesnt require active replication Can be given w/ Bacteristatic drug

Nystatin Amphotericin B

Fungicidal polyene Disrupts sterol site in membrane Fungicidal polyene Disrupts sterol site in membrane

Route: Topical Route: IV or IM Deep fungal infect. Only in hospitals where renal fn can be monitored

Nephrotoxic Nephrotoxic (decreases fn 70-80%) Headache

Azole Group Imidazole Triazole Itraconazole Fluconazole Clotrimazole Terbinafine

Fungicidal Inhibits synthesis of sterols in membrane Route: IV or IM (can be oral) Fungal menigitis Route: Topical Fungicidal Binds to skin hair and nails Route: Topical Mild GI upset & hepatotoxicity (reversible) Mild GI upset & hepatotoxicity (reversible) Not well absorbed in GI Distributes to CSF

Slow Fast Liver metabolism Renal excretion

Cannot be combined with polyenes Inhibits metabolism of other drugs

Useful topicallycommon in antifungal creams

Nucleic Acid Synthesis Inhibitors (Bactericidal) Drug Name Mechanism Spectrum Fluroquinolones Broad:G+ & GCiprofloxacin Inhibit bacilli, some Levofloxacin topoisomerase (prokaryotic enzyme) mycobacteria Rifampin
RNA Synthesis Narrow:G+, few G(like Pen G except no spirochetes)

Clinical Uses
Route: Oral

Adverse Eff.
Dizziness, seizures Mild GI upset cartilage formation (kids) Mild GI upset Orange secretions Mild GI upset Headache Pulmonary Fibrosis (rare)

Absorption
Well absorbed in GI

Termination
Metabolized by liver Renal excretion

Resistance

Notes

Route: Oral

Nitrofurantoin

Alters DNA so that it cannot act as template for replication

UTI

Well absorbed in GI Distributed in TBW Well absorbed in GI

Metabolized & activated by bacteria Rapid renal exc.

Protein Synthesis Inhibitors (Bacteriostatic) Drug Name Mechanism Spectrum Aminoglycosides Broad:G- bacilli Gentamycin Binds to receptor on Amikacin Tobramycin Netilmycin Tetracyclines Tetracycline Oxytetracycline Minocycline Doxycycline Chloramphenicol
Binds 50S subunit & inhibits peptide bond form. Binds to receptor on 30S Subunit Blocks amino-acyltransfer RNA 30S Subunit (bacteriostatic) Causes misread (bactericidal) (main) + TB Broader Broader except w/TB Broadest (last resort)

Clinical Uses
Route: IV or IM

Adverse Eff.
Irreversible effect on vestibular fn

Absorption
Not well absorbed in GI

Termination
Renal Excretion

Resistance
Rapid and common

Notes
Old drug w/ much resistance

Extremely Broad: G+, G-, actinomycetes, Rickettsia, Chlamydia, E. Histolytica, esp. Mycoplasma (TB) Broad: G+, G-, Rickettsia

Route: Oral, IV, IM Route: Oral, IV, IM For young children Route: Oral only E. Histolytica Route: Oral only E. Histolytica Route: Oral

Allergy 5% Brown color on teeth Phototoxicity Opportunistic inf.ections: Broad spec. destroys normal flora Allergy Toxic Bone Marrow Suppression vs. Aplastic anemia Mild GI upset Newborn cardiac toxicity Mild hepatotoxicity

Mild GI upset Or @ site of injection

Renal Excretion Renal Excretion Fecal Excretion Fecal Excretion

Well absorbed in GI Distributed in CSF

Liver metabolism (binds to glucuronic acid) Renal excretion

Macrolides Erythromycin

Binds 50S subunit & inhibits peptide bond form.

Clarithromycin Azithromycin Clindamycin

Binds 50S subunit & inhibits peptide bond form.

Broad: G+, some G-, esp. Mycoplasma (TB) (like Pen G) Slightly Broader G+, GSlightly Broader for GMainly G+, few G-

Route: Oral

Well absorbed in GI

Biliary excretion Fecal Excretion Renal 3-5%

Route: Oral

Allergy (5%) Colitis-type GI upset Mild Bone Marrow suppression Pain & Inflam. @ site of administration Joint & Muscle Pain GI upset Monitor bone marrow for thrombocytopeni

Mild GI upset (520%)

Liver Metabolism

Vancomycin resistant Drugs Quinupristin/ Binds 50S subunit & peptide bond Dalfopristin inhibits form. Linezolid
Binds 50S subunit & Blocks formation of 70S unit

Broad: Limited to G+ (staph, strep, enterococcus) Slightly Broader: Limited to G+ (staph, strep, enterococcus)

Route: IV

Not well absorbed in GI

Liver Metabolism Biliary excretion Fecal excretion Liver Metabolism Renal excretion

Route: Oral

Well absorbed in GI

Anti-Metabolite Drugs (Reversible Competitive Antagonists) Drug Name Mechanism Spectrum Clinical Uses Sulfonamides (Sulfa Drugs) Narrow: G+, some Route: Oral Sulfisoxazole PABA Anologs Acetylsulfisoxazole Succinylsulfathiazole TrimethoprimSulfamethoxazole Flucocytosine
folic acid GUsed more often Route: liquid Oral for children

Adverse Eff.
Allergy Bone Marrow suppression CNS toxicity in newborns ( bilirubin)

Absorption
Well absorbed in GI Distributes in TBW & CSF

Termination
Renal excretion

Resistance

Notes
Soluble in urine GI Flora will activate by removing Acetyl group GI Flora will activate by removing Succinyl

Decrease GI Flora prior to surgery Inhibits DHFR & PABA Fungicidal Broader Route: Oral Recurrent UTIs Route: Oral

Distributes to CSF Bone Marrow suppression Mild GI upset Well absorbed in GI Distributed in TBW

Renal Excretion Metabolized by 5-fluoro-uracil of fungus Renal excretion

Anti-Viral Drugs (non-retroviral) Drug Name Mechanism Anti-Herpes Drugs (non-retroviral) Acyclovir Guanosine

Spectrum
Narrow

Clinical Uses
Route: Topically

Adverse Eff.
Mild GI upset Mild Nephrotoxicity

Absorption
Well absorbed in GI Distributes in CSF Well absorbed in GI Distributes to CSF (not as well as Acyclovir Metabolized by kinases to triphosphate level Metabolized by kinases to triphosphate level Predrug is metabolized by GI flora to activate Distributes to CSF if inflame. meninges Little distributed to CSF Not well absorbed in GI Well tolerated

Termination
Renal Excretion

Resistance

Notes

Valacyclovir Ganciclovor

nucleotide analog DNA synthesis or alters structure & fn Predrug to Acyclovir Guanosine nucleotide analog DNA synthesis or alters structure & fn Thymidine analog DNA synthesis Adenosine analog Inhibits viral DNA polymerase

Route: Oral Used for Cytomegalovirus (CMV) Route: Topical in conjunctiva

Idoxuridine

Bone Marrowanemia CNS-dizziness, headaches Teratogenic Too potent for mammalian cells

Vidarabine Adefovir/Dipivoxil

Route: Oral Lamivudine resistant Hep B

Mild GI upset & Nephrotoxicity

Anti-Influenza Drugs (non-retroviral) Amantadine Blocks viral

uncoating

Narrow

Route: Oral Route: Oral Prophylactic & therapeutic Route: Inhalation of fine powder

Mild GI upset Mild GI upset

Renal Excretion Renal excretion

Oseltamir Zanamivir

Blocks new virion release Blocks new virion release

Anti-Viral Drugs (non-retroviral) Continued Drug Name Mechanism Spectrum -Interferon Inhibits viral DNA Lamivudine
polymerase

Clinical Uses
Hep B & C DNA Viruses & Hep B virus

Adverse Eff.

Absorption

Termination

Resistance

Notes
Non-nucleoside antiviral

Anti-Viral Drugs (retroviral) Drug Name Mechanism Spectrum Nucleoside reverse transcriptase inhibitors *Zidovudine (AZT) Thymadine analog is Viral specific (not
substrate for viral reverse transcriptase Purine analog is substrate for viral reverse transcriptase

Clinical Uses
Route: Oral

Adverse Eff.
GI upset Anemia GI upset Anemia

Absorption

Termination

Resistance
High rate of mutation in reverse transcriptase

Notes
-OH group stops transcription

mammalian-specific) Route: Oral

*Didanosine

Non-Nucleoside reverse transcriptase inhibitors *Nevirapine *Efavirenz Protease Inhibitors Indinavir Inhibits viral
protease

*Use all three for Tx GI upset Nephotoxicity Hyperglycemia Diabetes Fat redistribution Hyperlipidemia

Selective for viral RT

Fusion Inhibitors Enfuvirtide

Inhibits fusion of HIV to CD4+ cells

Very expensive$20,000/yr