Tuberculosis, HIV, and Influenza (Ch. 95, 98, 99)

Mycobacterium tuberculosis

-aerobic

-non-spore forming

-non-motile bacillus

-slow growth

TB Diagnosis

-blood test (gold standard, preferred if received vaccine)

-sputum

-chest x-ray

-tuberculin skin test

Who is tested for TB?

-contacts of patients with TB, residents and staff of high-risk congregate settings

-people who have immigrated from a high-risk country within the last 5 years

-staff of mycobacterium labs

-youth exposed to high-risk adults

TB Treatment

always use 2 or more active drugs, long duration

RIPE = rifampin, isoniazid, pyrazinamide, ethambutol

Directly Observed Therapy (DOT)

administration of each dose is carried out in the presence of an observer from the health department

Intermittent Dosing

consider 2-3 times/week dosing

-are larger doses but less frequently administered, as effective as daily dosing

Treatment of Latent TB

1. standard ⭐️ = isoniazid daily for 9 months, self-admin

2. isoniazid & rifapetine once weekly for 3 months & DOT; not safe for everyone

Treatment of Active TB

1. induction phase

-eliminate actively dividing extracellular tubercle bacilli

-rifampin, isoniazid, ethambutol, pyrazinamide x 2 months

2. continuation phase

-eliminate intracellular "persisters"

-rifampin + isoniazid x 4/5 months

-may last longer

Causes of Drug Resistant TB

inadequate drug therapy = principle cause

-inherent resistance

-development of resistance during tx course

-inadequate drug therapy

Isoniazid

1st line drug for active TB, can be used in latent

-superior to alternative drugs with regard to efficacy, toxicity, ease of use, patient acceptance, and affordability

-can be taken by all pts infected with sensitive strains

Isoniazid MOA

suppresses growth by inhibiting synthesis of mycolic acid (component of mycobacterial cell wall); selective for tubercle bacilli

-bactericidal against active TB

-bacteriostatic against dormant TB

note: think I for inhibits mycolic acid

Isoniazid AE

1. hepatotoxicity

-no ETOH, monitor liver fx, contraindication for liver pts and alcoholics

2. peripheral neuropathy

-supplement B6 (pyridoxine) to treat

3. GI distress, dry mouth, urinary retention

Isoniazid Nursing Considerations

-contraindicated in liver pts and alcoholics

-this drug can be administered with pyridoxine (B6), especially for peripheral neuropathy

-patients should limit or avoid alcohol

-can develop resistance

-can cause increased levels of phenytoin

Rifampin

DOC for active TB (per book is equal to isoniazid), 1st line drug

-kills active and semi-dormant TB

-resistance can develop rapidly when rifampin is used alone, so it is given in combination with other agents

Rifampin MOA

-inhibits bacterial DNA-dependent RNA polymerase

-suppresses RNA synthesis (which suppresses protein synthesis)

-bactericidal

-host remains unaffected, selective toxicity to microbes

Before the appearance of resistant tubercule bacilli, what was the most frequently prescribed regimen for patients with uncomplicated pulmonary TB?

rifampin + isoniazid

Rifampin Nursing Considerations

1. monitor liver fx

2. red-orange bodily fluids is normal

3. drug decreases efficacy of other drugs such as warfarin, PO contraceptives, and meds for HIV

Rifampin AE

-hepatotoxicity

-discoloration of body fluids (will stain contact lenses)

-GI upset

-flu-like sx

-cutaneous reactions (flushing, itching, rash)

Ethambutol

1st line drug in active TB

-active against tubercle bacilli that are resistant to isoniazid and rifampin

Ethambutol MOA

-bacteriostatic

-inhibits arabinosyl transferase, impairing cell wall synthesis

Ethambutol AE

1. optic neuritis (most significant one)

-blurred vision, constriction of visual field, disturbance of color discrimination

-withdraw immediately if this presents

2. gouty arthritis RT hyperuricemia

3. allergic reactions, GI upset, confusion

note: think E for eyes!

Ethambutol Contraindications

-children under 8 y/o

-use caution in DM patients DT interactions with PO meds

Ethambutol Nursing Considerations

-assess color discrimination and baseline visual acuity PRIOR to administering med

-monitor eye fx monthly

-educate pt to report changes in vision to HCP

-take with food if GI upset

Pyrazinamide

1st line drug for active TB

Pyrazinamide MOA

-metabolized into pyrazinoic acid, lowering pH & inc. activity

-also thought to inhibit fatty acid synthase I (mycobacterial enzyme)

Pyrazinamide AE

1. hepatotoxicity

2. polyarthralgia

-severe joint pain

-tx = NSAIDs

3. rash, photosensitivity with dermatitis, GI upset, gouty arthritis RT hyperuricemia

Pyrazinamide Nursing Considerations

-monitor liver fx

-limit alcohol

-manage polyarthralgia with NSAIDs

Bacille Calmette-Geurin (BCG) Vaccine

-freeze-dried preparation of M. bovis

-used in countries with high prevalence

-not routinely used in US

-can produce false-positives in skin test

-variable protection against pulmonary TB in adults

1st line TB treatment

RIPE drugs

-rifampin

-isoniazid

-pyrazinamide

-ethambutol

2 phases of Treatment for drug-susceptibile TB

intensive and continuation

HIV and TB combined nursing considerations

patients should avoid using rifampin

Acyclovir

1st line agent & DOC for HSV and VZV

-resistance is rare

Acyclovir Indications

-prophylaxis for recurrent cold sores

-chicken pox if started < 24 hrs

-shingles

-HSV-2

***does NOT cure but decreases s/sx; patients must avoid sexual contact when they have lesions and use a condom when they don't

Acyclovir Nursing Considerations

-resistance is rare & few AE with PO form

-renal injury may occur with IV, so give slow & pre-hydrate

-reduce dose in renal pts

***does NOT cure but decreases s/sx; patients must avoid sexual contact when they have lesions and use a condom when they don't

Inactivated Flu Vaccine - Route

IM or intradermal injection

Recombinant Flu Vaccine - Route

IM or intradermal injection; good for elderly

Live & Attenuated Flu Vaccine - Route

intranasal spray

-NO PREGNANCY/IMMUNOCOMPROMISED

Inactivated Flu Vaccine AE

-soreness at injection site

-fever, myalgia, malaise

-guillain-barre syndrome (rare)

Live Flu Vaccine AE

-runny nose

-nasal congestion

-headache

-sore throat

-cough

-muscle aches

-fever

*flu-like s/sx

Influenza Nursing Considerations

-do NOT give to pts with acute febrile illness

-can give to people with minor illnesses with or without fever

-egg allergy, hx of severe history in past, and guillain-barre syndrome are contraindications

Oseltamivir

indicated for influenza A & B

-take within < 48 hours sx onset (ideally right away)

-can be used prophylactically, blunts response to live vaccine

-AE = NV; take with food to avoid GI upset

Best time to vaccinate for flu

october and november

3 Types of Influenza Vaccines

1. inactivated

2. recombinant

3. live, attenuated

Which flu vaccine is recommended for adults 65+?

recombinant

ex. flublok (RIV)

Why should oseltamivir be started no later than 2 days after symptom onset?

the benefits decline greatly when treatment is delayed

AIDS Diagnosis

-CD4 count <200 cell/mL

-presence of AIDS defining illness

HIV Modes of Transmission

-semen and vaginal fluids

-needle sharing or sticks

-infected blood

-birth/pregnancy

-breastfeeding (contraindication)

Treatment goals for HIV

-reduce associated morbidity

-prolong duration and quality of life

-suppress viral load

-restore and maintain immune fx

-prevent transmission

What is Antiretroviral Therapy used for?

used to suppress the virus and stop progression of HIV

Highly Active ART

combination of multiple agents

How does ART work?

lowers viral load by inhibiting replication

-NOT!!!! a cure for HIV

Who should be treated with ART?

-everyone, regardless of CD4 count

-do NOT initiate in pts with opportunistic infections who are at risk for immune reconstitution inflammatory syndrome (IRIS)

Before initiating ART

-CD4 count

-viral load (plasma rna)

-genotypic resistance test

-screen for hep abc in liver pts and STIs

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

1. drugs = abacavir, emtricitabine, tenofovir

2. MOA

-terminates DNA synthesis by incorporating into viral DNA by reverse transcriptase

3. classic AE ⭐️

-hepatic steatosis

-lactic acidosis (hyperventilation, nausea, abd pain)

-lipoatrophy

4. specific considerations

-abacavir → hypersensitivity reaction

-emtricitabine → hyperpigmentation, reduce dose for renal

-tenofovir → osteomalacia, reduce dose in renal dysfunction

NRTI Drugs

abacavir, emtricitabine, tenofovir

NRTI MOA

terminates DNA synthesis by incorporating into viral DNA by reverse transcriptase

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

1. drugs = efavirenz

2. MOA

-binds directly and non-competitively to reverse transcriptase, blocking DNA polymerase activity

3. classic AE ⭐️ = rash

NNRTI prototype

efavirenz

NNRTI MOA

binds directly and non-competitively to reverse transcriptase, blocking DNA polymerase activity

Efavirenz

1. class: NNRTI

2. MOA = binds directly and non-competitively to reverse transcriptase, blocking DNA polymerase activity

3. AE

-rash (possible SJS)

-CNS effects

-may cause hepatotoxicity

4. nursing

-CYP drug, interacts with PO BC and st. john's wort

-contraindicated in pregnancy, liver & renal dysfx

-monitor liver enzymes

4. patient education

-take on EMPTY STOMACH

-use barrier method for BC

NRTIs vs. NNRTIs

1. NRTI

-came 1st

-suppresses reverse transcriptase to prevent further DNA strand growth

-RF lactic acidosis and hepatomegaly

2. NNRTIs

-not structurally RT nucleosides

-binds to reverse transcriptase to directly inhibit

-AE = rash

-avoid in pregnancy ❌

Protease Inhibitor MOA

prevents the HIV protease enzyme from cleaving polyprotein into individual proteins responsible for assembling new viron

Protease Inhibitor AE

-GI upset (take with food)

-lipodystrophy (altered fat distribution)

-hyperlipidemia

-hyperglycemia

-elevated ALT

-increased bleeding

Protease Inhibitor Nursing Considerations

-CYP, avoid combined use with statins (remember hyperlipidemia AE)

-usually give with 2 reverse transcriptase inhibitors in ART

Lopinavir/Ritonavir

lopinavir is active, ritonavir BOOSTS EFFECTS

Lopinavir/Ritonavir Drug Interactions

-PO contraceptives

-disulfiram

-metronidazole

-grapefruit juice

Lopinavir/Ritonavir AE

-diarrhea (take with food)

-PR and QT interval prolongation (contraindicated in AV block)

-PO solution can lead to toxicity in neonates

Maraviroc

1. class: CCR5 antagonist

2. MOA = blocks entry into cell

3. considerations

-must be combined

-dosing in BID

-must confirm that strain is CCR5 (50-60% cases) before initiation

Raltegravir

1. class: integrase inhibitor (INSTI)

2. indication = 1st line agent in combination

3. MOA = inhibits integrase, preventing incorporation of viral DNA into host genome

4. AE

-insomnia

-headache

-hypersensitivity (rash, SJS)

-hepatotoxicity and failure

5. drug interactions

-PPIs

-rifampin can decrease efficacy

Raltegravir MOA

inhibits integrase, preventing incorporation of viral DNA into host genome

HIV 1st Line Treatment

1. INSTI ("-gravir") + 2 NRTIs (AET)

2. PI + 2 NRTIs

HIV Alternative Regimens

NNRTI + 2 NRTIs

HIV Treatment Monitoring

-CD4 count

-viral load (plasma HIV RNA) ***goal = undetectable

-adverse effects

-adherence

HIV - Pregnant Patients

-effective treatment reduces perinatal transmission of HIV

-use the same treatment as non-pregnant patients

Post-Exposure Prophylaxis (PEP)

use of ART after a single high-risk event to prevent spread

-take ASAP after the exposure WITHIN 72 hours

-common agents are emtricitabine and tenofovir

Pre-Exposure Prophylaxis (PrEP)

-prevention of infection for people at a high risk for HIV

-common agents are emtricitabine and tenofovir