Pharm Exam 3 Antimicrobial Drugs

amphotericin B MOA/use

-Binds to the fungal cell membrane

-Used in severe systemic fungal infections

**tx can be difficult bc systemic infections can be resistant which makes tx prolonged and the drugs we use tend to be toxic

adverse effects of amphotericin B

•Infusion Reactions- Fevers, chills, nausea, HA (shake and bake, rigors, chill fever)

•Nephrotoxicity- Very toxic, keep patient well hydrated **N/S alongside med infusion

•Electrolyte Changes **d/t toxicity to kidneys

-Hypokalemia

-Hypomagnesemia

•Bone marrow suppression

nephrotoxicity from amphotericin B

-avoid aminoglycosides, NSAIDS, cyclosporine

-check renal function

most likely people to get systemic fungal infections

-HIV

-oncology

-immunocompromised patients

-transplant patients

-BM suppression

amphotericin B infusion reaction

-Fever, chills, rigors, nausea, and headache

-Caused by release of proinflammatory cytokines

-Symptoms begin 1 to 3 hours after start of infusion and last for about 1 hour

-Less intense with lipid-based amphotericin B formulations **helps to minimize SE including infusion reactions

amphotericin B mild reactions: pretreatment options

•Diphenhydramine + acetaminophen

•Aspirin can help but may increase renal damage

**preferably no aspirin, NO NSAIDS bc they contribute to renal toxicity

if rigors occur w amphotericin B

IV meperidine (demerol-opioid) or dantrolene (stops skeletal muscle contractions) can be given

hydrocortisone with amphotericin B

can be given with caution for infusion reaction

Amphotericin infusion produces a high incidence of phlebitis

This can be minimized by

• Changing peripheral venous sites often

• Administering amphotericin through a large central vein

• And pretreatment with heparin

Azole Antifungals MOA/use

-Inhibits ergosterol in membrane

-Used for systemic and non-systemic fungal infections

-Alternative to AmphoB

(Ergosterol: Plays a crucial role in fungal cell structure and function)

examples of azole antifungals

-Ketoconazole (Nizoral®)- IV or PO

-Fluconazole (Difucan®)- IV or PO

-Itraconazole (Sporanox®)- IV, PO, topical

-Voriconazole (Vfend)- IV or PO

-Posaconazole- PO

**broad spectrum and better tolerated

Itraconazole [Sporanox]

•Azole group of antifungal agents

•Higher toxicity level

**at usual doses, this is fairly well tolerated, maybe a little cardio suppression

itraconazole use

Systemic mycoses (alternative to amphotericin B)

itraconazole MOA

-Inhibits the synthesis of ergosterol

-Inhibits fungal cytochrome P450 - dependent enzymes

itraconazole is NTI

-monitor and draw trough levels (0.5-1)

- >1=toxic

side effects of itraconazole

-Cardio-suppression

•Transient decrease in ventricular ejection fraction

-Liver damage

•Watch for signs of liver dysfunction

-Can inhibit drug-metabolizing enzymes **inhibitor of CYP450

-GI effects

•Nausea, vomiting, diarrhea

order of liver damage with azole antifungals from most to least

1) itraconazole and voriconazole

2) amphotericin B

3) posaconazole

4) fluconazole and ketoconazole

itraconazole must be given in acidic environment to be absorbed

No

• antacids,

• PPI's (reduce the amount of acid produced in the stomach)

• Antihistamines (H2 blockers, zantac, pepcid) since these decrease acidity

(or given 2 h after these)

fluconazole (diflucan)

•Azole group of antifungal agents (for systemic and non-systemic fungal infections)

•Fungistatic

•Same mechanism of action as itraconazole

•Good PO absorption

-IV and PO dosage the same, same therapeutic level (fluoroquinolones as well)

**good bioavailability

adverse effects of fluconazole

-Nausea

-Headache

-Vomiting

-Abdominal pain

-Diarrhea

**liver damage (bottom tier)

fluconazole tablet

for thrush or vaginal yeast infection, typically only 1 tab to knock out

Voriconazole [Vfend]

•Azole group of antifungal agents

•Broad spectrum of fungal pathogens

Voriconazole [Vfend] uses

-Candidemia

-Invasive aspergillosis - Drug of choice

-Esophageal candidiasis

-Scedosporium apiospermum-resistant infections

Voriconazole [Vfend] MOA

Suppresses synthesis of ergosterol

adverse effects of Voriconazole [Vfend]

-Hepatotoxicity

-Visual disturbances, hallucinations

-Changes in color perception (photopsia)

-Teratogenicity: NO use in pregnancy

-Hypersensitivity reactions

-Nausea, vomiting, and abdominal pain

-Headache

-Drug interactions: inhibitors of CYP450

**more pronounced effects

**NTI monitor trough

ketoconazole

Azole group of antifungal agents

ketoconazole MOA

Inhibits ergosterol

ketoconazole uses

-Alternative to amphotericin B for systemic mycoses **not as effective as amph B but it is better tolerated

-Less toxic and only somewhat less effective

-Slower effects

-More useful in suppressing chronic infections than in treating severe, acute infections **start amph B until under control then do ketoconazole for chronic

adverse effects of ketoconazole

-generally well tolerated**

-GI (can be reduced if given with food)

-Hepatotoxicity

•Rare but potentially fatal hepatic necrosis

-Effect on sex hormones **gynecomastia in men

•Can inhibit steroid synthesis in humans

other adverse effects of ketoconazole

• Rash

• itching

• dizziness

• fever

• chills

• constipation

• diarrhea

• photophobia

• headache

need acidic environment for ketoconazole

-2 hours after or 6 before these other drugs

-no H2 blockers, antacids, or PPI's

Posaconazole

•Newest member of azole family

•Binds with ergosterol in the fungal cell membrane, thereby compromising membrane integrity

•Adverse effects **NTI trough levels

•Drug interactions ** CYP450 inhibitor

**middle hepatotoxicity

nystatin use

-Oral Candidiasis

-Skin Candidiasis

**swish and swallow or a tablet form

nystatin adverse effects

-No absorption from PO or topical route

-Nausea/Vomiting/Diarrhea

**goes through GI tract and it eliminated

A nurse administers ceftazidime (Fortaz) to a patent with a severe PCN allergy. Which of the following is concerning?

B.The patient reports shortness of breath

A patient is receiving a second dose of IV Cefazolin (Ancef) post-op. The nurse notes that the patient is having hives and dyspnea, and hypotension. Which of the following would you expect to administer?

C.Parenteral Epinephrine

A patient is taking TMP/SMX (Bactrim DS). Which of the following findings should the nurse report to the provider?

D. Vesicular, crusty rash **SJS very severe

TMP/SMX = Really bad Stephen Johnson’s = REALLY bad rash

The nurse is caring for a patient with candidasis. Which of the following medications should the nurse expect to administer?

A. Fluconazole (Diflucan)

You are using your hospital antibiogram and current formulary to create an order-set recommending optimal antimicrobial regimens for patients being prescribed intra-abdominal infection treatment. You are considering the selection of antimicrobials targeted against enterococci. Your hospital has a 78% ampicillin susceptibility rate and a 20% vancomycin resistant enterococci rate. In which one of the following scenarios is the empiric therapy suggested most appropriate with regard to necessary enterococcal coverage?

A. Required use of at least one enterococcal active agent for mild and moderate community-acquired infections.

B. Linezolid containing regimens for severe community-acquired infections.

C. Piperacillin/tazobactam for hospital-acquired infections.

D. Cefepime and metronidazole containing regimens for severe community-acquired infections.

C!!

K.K. is a 12-year-old girl being examined in the emergency room for possible appendicitis. She has no significant medical history. Her father reports she had hives as 4-year-old when treated with amoxicillin/clavulanate for a recurrent ear infection. Upon examination and radiologic reports, K.K. is diagnosed with appendicitis with a suspicion of perforation and is scheduled for surgical resection. What is the most appropriate treatment?

A. Cefoxitin.

B. Piperacillin/tazobactam.

C. Ciprofloxacin plus clindamycin.

D. Meropenem.

D!!

viruses

•Viruses are parasites that only reproduce inside a living cell.

•Antivirals prevent the reproduction of the virus

•Viruses are very difficult to treat

•Antimicrobials are not effective against viruses

DNA Polymerase Inhibitors

-Acyclovir (Zovirax®)- IV, PO, topically (for cold sores)

-Ganciclovir (Cytovene®)

-Famciclovir (Famvir®)- PO only

-Valacyclovir (Valtrex®)- PO only

Acyclovir (Zovirax®) use

-Herpes simplex, Varicella zoster

-5x/day, not good for compliance

adverse effects of acyclovir

-Phlebitis: change IV sites, heparin for pre-treatment, use good veins

-Nephrotoxicity-Renal Failure (IV): hydrate alongside infusion and 2 h after ** infuse med slowly over 1 h

-Oral- N/V, diarrhea

ganciclovir uses

-CMV infections, herpes

-Severe infections in immunocompromised host

Cytomegalovirus (CMV) is a common herpesvirus that can infect people of all ages

adverse effects of ganciclovir

-Bone Marrow suppression: monitor CBC!

-Teratogenic (not while pregnant)

-CNS, Nausea, Fever, Rash

famciclovir uses and route

-herpes zoster, genital herpes

-PO q 12 h increases compliance

**can be used for what acyclovir does PO

adverse effects of famciclovir

-Well tolerated

valacyclovir uses and route

-Prodrug of acyclovir

-Herpes zoster and genital herpes

-PO q 12 h

adverse effects of valacyclovir

-TTP (thrombotic thrombocytopenic purpura; immune system attacks platelets): @ risk for bleeding, monitor CBC!

-SE similar to acyclovir (Phlebitis, oral, nephrotoxicity)

influenza management

Influenza managed by vaccination (primary strategy) and drugs

drugs to manage flu

• Adamantanes (inhibit viral uncoating/release of virus)

• Neuraminidase inhibitors

vaccines to manage flu

Influenza vaccines change yearly based on identification of strains by the Centers for Disease Control and Prevention (CDC), U.S. Food and Drug Administration (FDA), and World Health Organization (WHO)

Two types of flu vaccines

-Inactivated influenza vaccine**IM

-Live, attenuated influenza vaccine**intranasal (recommended only in children 2-8)

flu vaccine important points

• Protection begins 1 to 2 weeks after vaccination; generally lasts 6 months or longer

• Small risk for Guillain-Barré syndrome (GBS, the immune system mistakenly attacks the myelin sheath)

• Nine influenza vaccines on the market

**>6 mo get shot yearly

important point about live attenuated vaccines

NEVER give to

• Pregnant women

• Immunocompromised person (lupus)

• CA

• HIV

• Transplant

• RA

• Prednisone

Neuraminidase inhibitors

-Oseltamivir (Tamiflu®), Zanamivir (Relenza®)

-Inhibit neuraminidase; symptoms resolve 1-1.5 days sooner.

-neuraminidase is the enzyme that flu uses to replicate

Neuraminidase inhibitors uses

-Treat and prophylaxis for type A and type B

-Must start within 48 hours of symptoms or else it is ineffective

adverse effects of neuraminidase inhibitors

•Oseltamivir: Gastrointestinal (nausea and vomiting) - Give with food

•Zanamivir: Bronchospasm, cough (not recommended in patients with asthma or COPD)

oseltamivir

PO

zanamivir

inhaled

neuraminidase inhibitors for flu prevention

PO for 6 weeks during flu season

XOFLUZA (baloxavir marboxil)

-Latest FDA approved anti-viral

-Ages 12 and older

-Take a single dose orally within 48 hours of symptom onset with or without food.

-polymerase acidic endonuclease inhibitor (target the PA protein's endonuclease activity, essential for influenza virus replication)

Vaccine Administration - Facts

•Significant reduction in childhood infectious diseases

-Diptheria, measles, H.Influenzae type b

-Polio, smallpox

•20th century success

•Viruses and bacteria still exist

•Vaccine is a medication - benefits and risks

HIV and HAART

-Highly Active Antiretroviral Therapy- can reduce levels of HIV to undetectable levels

-Can't cure the virus

NRTI's

Nucleoside Reverse Transcriptase Inhibitors

NNRTI's

non-nucleoside reverse transcriptase inhibitors

other HIV anti-virals

•Protease Inhibitors

•Fusion Inhibitors

•Integrase Strand Transfer Inhibitors

•CCR5 Antagonist

important point about HIV and anti-virals

Must use combination therapy to decrease resistance, using 1 drug will ensure resistance

efavirenz

-NNRTI

-Preferred agent, CNS side effects

**do not use if pregnant

nevirapine MOA/USE

-Binds to HIV reverse transcriptase and disrupts the active center of the enzyme

-Use in combo with other drugs-never use alone

adverse effects of nevirapine

•Rash- Most cases benign but could be Stevens Johnson Syndrome

•Hepatotoxicity-can occur, monitor ALT and AST baseline, 2 weeks after treatment, risk highest during 1st 12 weeks of treatment

Zidovudine (Retrovir) MOA/USE

-NRTI's

-Suppress synthesis of viral DNA

adverse effects of Zidovudine (Retrovir)

•Anemia/Neutropenia

•Lactic Acidosis- with liver failure

•GI upset

•CNS- HA, insomnia, confusion

examples of NRTI's

-Abacavir

-Emtricitabine

-Tenofovir

-Lamivudine

protease inhibitors

•Most effective antiretroviral drugs available

•Used in combo with other drugs

general side effects seen with all protease inhibitors

-Hyperglycemia/Diabetes- typically occurs 2 mo after starting therapy

-Fat Redistribution- to abdomen

-Hyperlipidemia

-Decreased Bone Mineral Density

-Increased serum transaminases- increased ALT and AST

-Drug Interactions!!!! (CYP450 inhibitor, so are azoles)

**5 fold SE

examples of protease inhibitors

-Ritonavir

-Atazanvir

-Darunavir

integrase inhibitor: raltegravir

•Integrase is one of three viral enzymes needed for HIV replication

•Prevents insertion on HIV DNA and stops replication

SE of raltegravir

•Most common SE: HA and insomnia

•Rare: hypersensitivity reactions

•Few drug interactions

•Low barrier to resistance**always combine this drug with others

Dolutegravir

•One pill once a day option

•Well tolerated

•Few drug interactions

•High barrier to resistance

**integrase inhibitor

**best drug

Elvitegravir

•One pill once a day option

•Well tolerated

•Low barrier to resistance

•Many drug interactions due to administration with boosting agent

**integrase inhibitor

Maraviroc

•CCR5 (chemokine receptor 5) antagonist

•Binds with CCR5 and blocks viral entry of HIV into CD4 cell

SE of maraviroc

•Most common SE: cough, dizziness, rash

•Rare: liver injury, cardiovascular events

STD's

-Infections or parasitic diseases transmitted primarily through sexual contact

-1 in 5 Americans and most cases go unreported

types of STDs

-Chlamydia trachomatis infection

-Gonococcal infections

-Nongonococcal urethritis

-Pelvic inflammatory disease

-Acute epididymitis

-Syphilis

-AIDS

-Trichomoniasis

-Chancroid

-Herpes simplex

-Bacterial vaginosis

-Condyloma acuminata

-Proctitis

-Venereal warts

Chlamydia trachomatis Infection

-Most common bacterial STD in the United States

-asymptomatic in women->PID->infertility

Chlamydia trachomatis Infection can cause

-Genital tract infections

-Proctitis

-Conjunctivitis: for children with mom with this (azithromycin drops)

-Lymphogranuloma venereum

-Ophthalmia and pneumonia in infants

-Pelvic inflammatory disease (PID) if untreated in women (also ectopic pregnancy and infertility)

-Sterility (often asymptomatic infection)

Treatment for uncomplicated infections of chlamydia: Adults and adolescents

•Azithromycin [Zithromax] ok in pregnancy (macrolide) or can use amoxicillin

•Doxycycline [Vibramycin] not ok in pregnancy (tetracycline)

Infants and Preadolescent children tx for chlamydia

erythromycin

Lymphogranuloma venereum

STI by strands of Chlamydia trachomatis

Neisseria gonorrhoeae

-Gram-negative diplococcus

-700,000 new cases each year (second to chlamydia)

-Transmitted almost exclusively by sexual contact

symptoms of gonorrhea

-Men: Complaints of burning sensation with urination and pus draining from penis **worse symptoms

-Women: Often asymptomatic or mild cervicitis; serious infection may result in sterility

Neisseria gonorrhoeae causes

•Urethral, cervical, and rectal infection

•Pharyngeal infection

•Conjunctivitis

Neisseria gonorrhoeae treatment

-Ceftriaxone 1gm IM + Azithromycin 1 dose

**done in the ED, doesn't require compliance

Azithromycin [Zithromax] and Doxycycline [Vibramycin] also treat

Nongonococcal Urethritis (NGU)

PID

Syndrome that includes endometritis, pelvic peritonitis, tubo-ovarian abscess, and inflammation of the fallopian tubes

causes of PID

-N. gonorrhoeae

-C. trachomatis

treatment of PID

Caused by multiple organisms, so broad coverage and combination therapy are required

hospitalized tx of PID

•IV cefoxitin or cefotetan and doxycycline

•Follow with oral doxycycline