HIV and Immune System Pharmacology

HIV and Immune System Pharmacologyv    MOAØ     Nucleoside Reverse Transcriptinase Inhibitors (NRTI’s) §       Mimics neucleocides needed to convert RNA→DNA & Inhibits enzyme Ø     NonNucleoside Reverse Transcriptinase Inhibitors (NNRTI’s)§       Binds near active site to inactivates reverse transcriptase enzymeØ     Protease Inhibitors (PI’s)§       Inhibit protease enzyme needed from DNA at tail end of process.  §       Prevents new RNA virus from splitting Ø     Fusion Inhibitors§       Targets 1^st step w/ fusion & initial entry w/ cell§       Tie up CD4 receptor site so virus can’t latch on§       Last-ditch effort v    Therapy recommendationsØ     Single-Drug: IneffectiveØ     HAART: Highly Active Antiretrovial Therapy§       Combinations of RT’s and PI’s into nice cocktailv    IndicationsØ     Active HIVv    ContraindicationsØ     Severe allergy: weigh pros/consØ     Intolerable toxicity:  N/V, diarrhea, rash, pancreatitis, liver/kidney toxicity, bone marrow depression, hepatitis patients v    Side Effects/Adverse EffectsØ     Same and nonretroviral: nausea, vomiting, diarheaØ     Tolerate: Strict drug schedule.Ø     Myalgias/ joint painv    Drug interactionsØ     MULTIPLE!!  Look up!v    Specific AgentsØ     NRTI’s: §       Zidovudine (AZT, Retrovir): ·       Newborns with HIV mom  ·       Post-exposure prophylaxis§       Lamivudine (Epivir): ·       Rapid PO absorption. ·       Bactrim ↑ level to toxicicity.  §       Tenovir (Viread): ·       ↓ effecacy of PI’s Ø     NNRTI’s: Great PO & heavily metabolized by cytochrome P450 system §       Delavirdine (Rescriptor): ·       Nasty rash §       Efavirenz (Sustiva): ·       Psychiatric problems §       Nevirapine (Viramune):·       Stevens-Johnson Syndrome·       No women with CD4 count ↓ 200- hepatotoxicity risk Ø     Protease Inhibitors (PI’s): ∆ fat distribution, ↑ cholesterol & blood sugars§       Amprenavir (Agenerase):           Take w/ fatty meal§       Nelfinavir (Viracept):       Take w/ fatty meal§       Indinavir (Crixivan):        Kidney stones. Combo w/ 2 retrovirals. §       Lopinavir/ritonavir (Kaletra):      Ritonavir ↓ metabolism of lopinavir  Ø     Fusion Inhibitors: §       Enfuvirtide (Fuzeon):       Limited usage—last efforts v    Immunosuppressant AgentsØ     MOA:§       Varies§       Suppress certain T lymphocyte cells w/ cellular immunity Ø     Indications§       Organ rejection prevention§       SLE-lupus§       RA§       Psoriasis§       IBS§       Crones Disease Ø     Contraindications§       Allergy§       Relative·       Renal/hepatic failure·       Pregnancy & teratogens Ø     Side Effects/Adverse Effects§       Susceptibility to infection§       Hepatotoxcitity!Ø     Interactions§       Cyclosporine has many·       Cardiovascular meds:                      ↑ cyclosporine level ·       Cytochrome P-450 system ·       Nephrotoxic agents·       HIV agents ·       Anti-infectives:                    ↑ cyclosporine levelsØ     Specific Agents§       Cyclosporine (Neoral)·       Post-transplant ·       RA & psoriasis §       Azathioprine (Imuran)·       ↓ B & T cell production ·       Severe RA & kidney transplant§       Basiliximab (Simulect)·       Interleukin 2 antagonist w/ complement cascade·       Perioperative care w/ kidney transplants§       Sirolimus (Rapamune)·       ↓ T-cell function·       Combo w/ steriods/Cyclosporin for kidney transplants§       Mycophnolate mofetil (CellCept)·       ↓ B & T cells·       Renal/Heart transplants·       Combo w/ steroids/Cyclosporin§       Tacrolimus (Prograf)·       Inhibits T-cell activation·       Liver/Kidney transplants…↑ Nephrotoxicity w/ Cyclosporin Ø     Special Considerations§       Contact with others §       Pregnancy§       Leukocyte count- ↓ 3,000 dangerous§       RBC counts§       Children§       Co-morbidities v    Immunizing AgentsØ     Toxoids§       Inactivated bacterial toxins§       Usually enough to stimulate antibody response§       Immunity may not be lifelong b/c toxoid inactivatedØ     Vaccines§       Usually lifelong§       Not as strong as live vaccine, may require boosters§       Live vaccines usually attenuated (weakened) of bacteria/virus which sets off immune system.  Can have lifelong immunity. Ø     Immunoglobulin Therapy§       Passive immunity where we give you antibodies to help pt fight.  v    MOA: Ø     Immune responseØ     Active: Vaccines and toxoidsØ     Passive: Immunoglobulins: need quick antibodiesv    IndicationsØ     ImmunityØ     Temporary protectionv    ContraindicationsØ     Allergies§       Toxin§       Synthetic components: Many ppl allergic to synthetic components and not toxoid itself. Ex: egg product/horsesØ     Febrile illness§       Important for kids b/c many immunizations when children.  Immune system already busy.  Kids that are febrile PRIOR to getting med.Ø     Immunocompromised state§       Don’t give any LIVE vaccine to thesev    Side EffectsØ     Fever AFTER immunization§       Soreness at injection site§       Expect to go away after few daysv    Adverse EffectsØ     Serum Sickness: Caused by equine vaccines/toxins that causes laryngeal swelling/tongue and facial edema, and rash v    Special PopulationsØ     Preterm infants- (if child born 2 weeks premature and is 4 wks old, really only 2 weeks old.)  Immunize based on REAL birthday. Ø     Pregnancy:  Never give live vaccines. After 1^st trimester if necessary.Ø     Limited Immunodeficient: Not immunocompromized but immunodificient. ARE able to receive vaccines. Ø     Active disease: Want to give toxoids (=killed bacteria)/killed vaccines /immunoglobulins.  v    Specific Agents (active)Ø     Haemophilus influenzae (Hib)§       Only vaccinate for kids under 5§       Cause meningitis, epiglotitis Ø     Hepatitis B (Recombivax)§       What we get.  Get boosters.  Ø     Influenza (FluShield)§       Live immunizationØ     Measles, mumps, rubella (MMR II)§       Viral illnesses.  Have boosters§       Not recommended/contraindicated w/ pregnant womemØ     Diptheria, tetanus, and pertussis (DTaP)§       Both Toxoids.  Pertussis is inactivated, but back in gear.  Ø     Pneumococcal (Pneumovax)§       Fights pneumococcal pnemonia, but other pneumococcal.  Don’t call “pnemonia vaccine” b/c fights other stuff.  Given to those over age 65 and few kids. 23 strains.Ø     Polio (IPV)§       Completely inactivated b/c very dangerousØ     Varicella (Varivax)§       Live; childhood immunization.  Pts older than 13 and never been exposed to chickenpox or vaccinated, may give this.  Ø     Meningococcal (Menomune)§       Ppl in dorms.Ø     Rabies (Imovax)§       Kills quickly.  If body can’t fight, die in 3 days.§       Only get it if you’ve had risk for exposure.  Ø     HPV (Gardasil)§       Very common. STD ONLY!!  Protect with strains that lead to cervical cancer. Men always asymtomatic.  Given w/ ages 9-26.  v    Passive: (many times combo w/ active)Ø     Hepatitis B immune globulin (H-BIG2)Ø     Immune globulin (Gammagard)§       Just IgG that’s powerful with fighting infection.Ø     Rabies immune globulin (RIG)Ø     Tetanus immune globulin (Hyper-Tet)Ø     Varicella zoster immune globulin (VZIG)