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HIV Pharmacology

For Pharmacology NURS 422

TermDefinition
Virus Smallest infective agent Most common cause of disease in humans Consists of DNA & RNA Surrounded by protein shell Parasitic - Cannot survive without a host Drugs interrupt replication cycle in viruses Short 1/2 lives
Virus (Cont.) Can stick to cell membrane, causing phagocytosis. Can stick to sell surface and inject genetic material into host cell Makes envelope to surround viral capsid
Acyclovir ANTIVIRAL AGENT Active only against HSV (Herpes Simplex Virus), VZV (Varicella Zoster Virus aka Chickenpox), CMV (Cytomegalovirus), but is resistant to CMV
Acyclovir MOA Suppresses synthesis of viral DNA - Inhibits DNA polymerase - Incorporates itself into growing viral DNA strand
Acyclovir Administration PO (low bioavailability), IV (most often), Topical Execrated through kidneys; dosage is lowered for patients with CKD
Acyclovir Side Effects PO: GI IV: Infusion site reactions, reversible nephrotoxicity due to deposition in renal tubules. INFUSE SLOWLY (over 1-2 hours)
Antiretroviral Therapy DELAY disease progression, AVOID drug resistance, MINIMIZE clinical manifestations, PROLONG survival. Pre & Post-Exposure Prophylaxis (PrEP) 6 drug classes w/many agents; only a fraction are used
Classification of Antiretroviral Drugs Fusion Inhibitors Entry Inhibitors - CCR5 Co-receptor antagonists Nucleoside/-tide Reverse Transcriptase Inhibitors (NRTIs) Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Integrase Inhibitors Protease Inhibitors
Abacavir NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NRTI) Usually given in pairs. I.e: ABC/3TC (Abacavir + lamivudine) Can be taken with or without food
Abacavir MOA Suppresses synthesis of viral DNA by stopping reverse transcriptase. Prodrug - competitively binds to viral reverse transcriptase Once incorporated into DNA strand, stops RT from adding more bases, thus not allowing DNA to grow
Abacavir Adverse Effects BLACK BOX WARNING FOR HYPERVENTILATION May impair mitochondrial function (Lactic acidosis, fatty/enlarged liver, pancreatitis, myopathies)
Abacavir Adverse Effects (Cont.) Hypersensitivity (in the 1st 6 weeks) 5-8% Fatigue & Headache - 10% Lipodystrophy (cushing-like syndrome)
Abacavir Contraindications Genetic testing required. People who test positive for HLA-B*5701 should NEVER take this drug Avoid in patients w/ CAD Interacts with alcohol = increases ABC levels
Efavirenz (Sustiva) NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) Rarely used now Taken orally once a day ONLY ACTIVE IN HIV-1 Paired w/NRTI to decease viral load CAN CROSS BBB
Efavirenz MOA DIRECTLY binds to active center of reverse transcriptase and causes direct inhibition of RT activity
Efavirenz Drug Interactions Ritonavir = Creates toxic levels of Efavirenz
Efavirenz Adverse Effects Teratogenicity - Avoid in pregnancy Transient CNS effects (feeling drunk) Maculopapular Rash
Darunavir PROTEASE INHIBITOR Very effective HIGH side effect profile
Darunavir MOA Prevents maturation of HIV by blocking protease. Binds to active site in HIV protease. HIGH HIV resistance, which is why this drug is NEVER used alone
Protease Inhibitors Adverse Effects Hyperglycemia/Diabetes Lipodystrophy Hyperlipidemia Elevated Liver Enzymes Prolongation PR Interval
Protease Inhibitors Drug Interactions Drugs that reduce/inhibit cytochrome P-450 (MANY DRUG INTERACTIONS) Statins = Inhibits metabolism; increases risk of rhabdomylosis
Darunavir Adverse Effects Elevated blood lipid levels - 25% Rash - 10% CYP-system interactions; can increase levels of cardiac drugs
Ritonavir PROTEASE INHIBITOR - BOOSTER Powerful inhibitor, substrate & reducer of hepatic CYP 450
Ritonavir MOA "Boosts" the serum concentration of other PIs Allows for lower dosing of boosted drug and decreases pill burden (REDUCES side effects)
Ritonavir Side Effects GI Intolerance Hyperlipidemia
Raltegravir INTERGRASE STRAND TRANSFER INHIBITOR (INSTI) 1st in its class Better viral suppression than NNRTI or PI HIGH risk of HIV resistance - need to be taken with other antiretroviral drugs
Raltegravir MOA Inhibits integrase - DOES NOT allow HIV to enter into host cell. Prevents integration of viral DNA
INSTI Adverse Effects Tolerated very well Insomnia, dizziness Diarrhea, nausea, headache, fatigue, itching Women MUST use birth control - FDA pregnancy risk
Raltegravir Adverse Effects Elevated liver enzymes Rare severe hypersensitivity reaction - SJS (Steven Johnson Syndrome)
Dolutegravir Adverse Effects ALSO INSTI Lowers risk of HIV resistance MANY drug interactions
Enfuvirtide (Fuzeon/T20) FUSION INHIBITOR 1st and only in its class Never used alone Approved in children older than 6 "Drug of Last Resort" BID subQ Dosing
Enfuvirtide MOA Blocks fusion between viral and target cell membranes - NO entry of HIV into cells
Enfuvirtide Adverse Effects Significant injection site reactions Pneumonia Hypersensitivity Reactions
Enfuvirtide Considerations Pt. must show signs that their viral load is increasing DESPITE treatment Pt. must be treatment intelligent Only used when patients are resistant to other ARTs
Maraviroc (Selzentry) ENTRY INHIBITOR - CCR5 ANTAGONIST Approved in 2009 as first line treatment combined with 2 other NRTIs Effective only in HIV-1 Tropism testing required BEFORE treatment and should be done if pt. is unresponsive to drug BID Dosing
Maraviroc MOA Blocks infection by blocking CCR5 and preventing HIV binding to cell membrane, thus HIV is unable to enter host cell Best for earlier infection when CCR5 tropic virus predominates
Maraviroc Side Effects Strong hepatotoxicity Hypersensitivity reactions
Atripla COMBINATION ANTIRETROVIRAL FIXED DOSE DRUG 2 NRTI (Tenofovir/FTV) + 1 NNRTI (Efavirenz) PO once daily Do not used in pregnancy Effective in pts whose HIV is sensitive to all 3 components of drug
Created by: mkeita2
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