Alterations of Pulmonary Function DRUGS

Week 6

Monoclonal Antibodies: Tocilizumab

Classification: Monoclonal Antibodies

Other classifications: DMARDs (disease modifying anti-rheumatoid drugs)/tumor necrosis factor (TNF) modifier.

Indications: Severe and/or critical COVID-19, in addition to dexamethasone.

Mechanism: Inhibiting IL-6 (blocks an inflammatory signal that contributes to severe inflammation).

Desired effects: To reduce severe inflammation, improve respiratory function, prevent organ damage and decrease ICU stays and mortality in severe COVID-19 patients.

Adverse effects: Headache, dizziness, hypertension, gastrointestinal perforation (hole in the stomach or intestinal wall), abdominal pain, gastritis, mouth ulcerations, neutropenia (low neutrophils), thrombocytopenia (low platelets), rash, infusion reactions, upper respiratory infections, nasopharyngitis, bronchitis, serious infections, anaphylaxis, anti-tocilizumab antibody formation, and secondary malignancy.

Remember: Tocilizumab targets IL-6 inflammation. Unlike dexamethasone, it targets a specific inflammatory pathway.

Antivirals: Nirmatrelvir/ritonavir

• paxlovid contains nirmatrelvir tablets co-packaged with ritonavir tablets

  • recommended dosage is 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (1 100mg tablet) with all 3 tablets taken together orally twice daily for 5 days

• treatment of mild to moderate covid 19 in adults with positive results of direct sars cov 2 testing and who are at high risk for progression to severe covid 19 including hospitalization or death

• prescribing window: within 5 days of symptom onset

Antivirals: Nirmatrelvir/ritonavir (cont.)

indications for use:

• treat mild to moderate covid 19 in clients who have

  • a positive result from a viral test result and

  • a high risk of getting severe covid 19 including hospitalizationa nd death

• MOA: Co-packaged drugs have very different MOAs

  • nirmatrelvir: inhibits sars cov 2 main protease/enzyme: when this protease/enzyme is inhibited it cannot process polyprotein precursors. this blocks part of virus life cycle and prevents viral replication

  • ritonavir: acts as a pharmacokinetic enhancer. inhibits cytochrome p450-mediated metabolism of nirmatrelvir, increases plasma concentrations of nirmatrelvir

• desired effects

  • stops virus from multiplying

  • reduces severe outcomes

• adverse effects

  • common: htn, severe allergic reaction

  • rare: Stevens-Johnson syndrome. toxic epidermal necrolysis, liver problems

Explain the mechanism of action of nirmatrelvir/ritonavir (Paxlovid).

Nirmatrelvir:

• Inhibits the SARS-CoV-2 main protease.

• Prevents processing of polyprotein precursors.

• Blocks viral replication.

Ritonavir:

• Acts as a pharmacokinetic enhancer.

• Inhibits CYP450-mediated metabolism of nirmatrelvir.

• Increases plasma concentrations of nirmatrelvir.

Desired effect: Stops the virus from multiplying and reduces the risk of severe COVID-19 outcomes.

Important nursing connection: Because ritonavir inhibits drug metabolism, it can also increase levels of other medications, causing potentially serious drug interactions.

Exam trick: If asked which drug actually blocks viral replication, choose nirmatrelvir. If asked which drug boosts the concentration of nirmatrelvir, choose ritonavir.

systemic glucocorticoids

• wide therapeutic application

• short term use due to potentially serious adverse effects

• suppress histamine release and inhibit the synthesis of prostaglandins by COX-2 inhibit the immune system by suppressing certain functions of phagocytes and lymphocytes - reduce inflammation

• adverse effects

  • supression of normal functions of adrenal gland (adrena insufficency) DONT STOP ABRUPTLY, hyperglycemia, peptic ulcers, electrolyte imbalances; mask infections

systemic glucocorticoid: dexamethasone

indications for use: for clients needing supplmental o2 for severe acute covid 19

• other indications: inflammation, allergies, cerebral edema, septic shock

MOA: suppresses migration of polymorphonuclear leukocytes, fibroblasts and normal immune response

desired effects: decreases inflammation, revereses increases capillary permeability causes lysosomal stabilization

adverse effects: htn, seizures, hyperglycemia

anticoagulants: heparin

indications for use: prevention dose anticoagulation for severe acute COVID-19

MOA: binding of heparin to antithrombin III in activates several clotting factors and inhibits thrombin activity

desired effects: reduces chance clients will develop blood clots

adverse effects: severe bleeding and serious hemorrhaging, heparin induced thrombocytopenia: caused by abnormal antibodies that activate platelets causing clots to form and depleting platelet counts in blood

antidote for heparin therapy: protamine

• reverses anticoagulant activity of heparin

• indications

  • if serious hemorrhage occurs

  • onset of action - 5min

• MOA: binds to heparin. to form stable ion pair that does not have anticoagulant activity

• desired effects: neutralizes anticoagulant activity of heparin

  • makes heparin ineffective

• adverse effects

  • severe respiratory distress, anaphylaxis, pulmonary edema

Filler card: Pharmacotherapy for bacterial pneumonia

antibiotics

Macrolides: azithromycin

indications: infections of respiratory track and pneumonia

MOA: binds to ribosomal subunits of susceptible bacteria. suppresses protein synthesis. prevents production of protein needed for bacteria to grow.

desired effects: bacteriostatic (prevents growth of bacteria, RATHER than outright killing it)

adverse effects: skin reactions, hepatotoxicity

Penicillins: amoxicillin

indications: infections of respiratory tract, pneumonia

MOA: binds to bacterial cell wall

• interfers with cell wall replication in susceptible bacteria

• causes bacterial cell wall autolysis

desired effects

• bactericidal - kills bacteria

adverse effects: allergic reactions, anaphylaxis

• Special feature: Broader antibacterial coverage than natural penicillin and good absorption when taken orally.

Fluoroquinolones: Ciprfloxacin

indication: respiratory infections (including pneumonia), bone/joint, GI, ophthalmic infections, sinusitis, prosatitis; post-exposure prophylaxis for anthrax, plague, tularemia (bioterrorism relevance)

MOA: ciprofloxacin inhibits two bacterial enzymes: DNA gyrase and topoisomerase IV

these enzymes are critical for bacterial dna syntheiss and replicaion

desired effect: bactericidal action against gram negative bacteria

adverse effects: common: nausea, vomiting and diarrhea. serious: dysrhythmias, liver failuire. cns effects: dizziness, headche, sleep disturbances

Antacids, ferrous sulfate, and sucralfate decrease absorption – What is the nursing implication?

cephalosporin antibiotic: cefotaxime

Classification: Cephalosporin antibiotic

Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to penicillin binding proteins, leading to bacterial cell lysis

Indications: Treatment of gram-negative infections and clients allergic to penicillin or with penicillin-resistant infections, including serious lower respiratory tract infections, CNS infections, genitourinary infections, bone/joint infections, bacteremia and septicemia.

Desired Effect: Bactericidal action against gram-negative pathogens

Adverse Effects: Possible cross-sensitivity with penicillin, gastrointestinal upset, and reduction in prothrombin levels

Cefotaxime is not absorbed from the GI tract, which necessitates its administration via the IM or IV route.