27-Anti Viral Agents PDF

Made with Xodo PDF Reader and Editor 27-Anti Viral Agents Pharmacology 2 (1601314) December 10, 11 First Semester 2024-2025 Asst. Prof. Dr. Najlaa Saadi Ninth week: Tuesday, Wednesday PhD Clinical Pharmacology  Made...

Made with Xodo PDF Reader and Editor 27-Anti Viral Agents Pharmacology 2 (1601314) December 10, 11 First Semester 2024-2025 Asst. Prof. Dr. Najlaa Saadi Ninth week: Tuesday, Wednesday PhD Clinical Pharmacology  Made with Xodo PDF Reader and Editor Antiviral Drugs  Drugs directly impair viral replication (involves several stages): Adsorption Penetration Uncoating Biosynthesis Maturation Release  Drugs modulate the host –immune system  Made with Xodo PDF Reader and Editor Agents to treat herpes simplex viruses (HSV)and Varicella- Zoster Virus (VZV) infections: Acyclovir Valacyclovir Famciclovir  Made with Xodo PDF Reader and Editor Pharmacokinetic of Acyclovir  Oral, i.v, topical.  Bioavailability is 15-20%.  Cleared primarily by glomerular filtration and tubular secretion.  Cerebrospinal fluid concentrations are 50% of serum values.  Made with Xodo PDF Reader and Editor Adverse Reactions  Stinging sensation and a diffuse superficial punctate keratopathy.  Gastrointestinal symptoms, headache and neuropsychiatric reactions, severe local inflammation with i.v.  Made with Xodo PDF Reader and Editor Agents to treat Cytomegalovirus (CMV) Infections : Ganciclovir, Valganciclovir, Cidofovir Ganciclovir  Orall or i.v.  Poor bioavailability.  Eliminated in the urine, mainly unchanged.  Made with Xodo PDF Reader and Editor Adverse Reactions of Ganciclovir  Neutropenia and thrombocytopenia fever, rash, gastrointestinal symptoms, confusion and seizure  Concomitant use of potential marrow - depressant drugs, e.g. cotrimoxazole, zidovudine, should be avoided.  Made with Xodo PDF Reader and Editor Antiretroviral Agents  Nucleoside reverse transcriptase inhibitors (NRTIs).  Non nucleoside reverse transcriptase inhibitors (NNRTIs).  Protease inhibitors (PIs).  Made with Xodo PDF Reader and Editor Zidovudine (NRTIs)  Well absorbed  Distributed to most body tissues and fluids.  Eliminated primarily by renal excretion following glucuronidation in the liver.  Made with Xodo PDF Reader and Editor Drug Interaction of Zidovudine  Myelosuppressive drugs such as ganciclovir, ribavirin and cytotoxic agents toxicity.  Probenecid, Serum levels of zidovudine acid through decreased its clearance.  Made with Xodo PDF Reader and Editor (NNRTIs) Nevirapine  It used in combination with at least two other antiretroviral  It penetrates the CSF  Hepatic metabolism.  Rash and hepatitis are the commonest side effects. Administration, metabolism, and toxicity of nevirapine  Made with Xodo PDF Reader and Editor Protease Inhibitors (Ritronavir, Indinavir, Saquinavir) HIV produces protein and also a protease which cleaves the protein into component parts that are subsequently reassembled into virus particles; protease inhibitors disrupt this essential process.  Made with Xodo PDF Reader and Editor Some Adverse effect of HIV protease inhibitors  Made with Xodo PDF Reader and Editor Drug Interactions with Protease Inhibitors 1. Enzyme inducer P450 (e.g) rifampicin. 2. Enzyme inhibitors (e.g) ketoconazole, cimetidine.  Made with Xodo PDF Reader and Editor Anti-influenza Agents Amantadine  Active against influenza A virus  Mechanism of action: interfering with the uncoating and release of viral genome into the host cell. PK:  Well absorbed from the GIT.  It Is eliminated in the urine.  Made with Xodo PDF Reader and Editor Amantadine Adverse Reactions  Dizziness, insomnia, nervousness, Drowsiness, hallucinations, coma, convulsion may occur in patients with impaired renal function.  It should be avoided in epileptic patients.  ‫‪Made with Xodo PDF Reader and Editor‬‬ ‫)‪Interferons (Hepatic Viral Infection‬‬ ‫‪1. Directly on uninfected cells to induce‬‬ ‫‪enzymes that degrade viral RNA.‬‬ ‫‪2. Indirectly by stimulating the immune‬‬ ‫آﻟﻴﺔ ﻋﻤﻞ اﻹﻧﺘﺮﻓﻴﺮوﻧﺎت ﻓﻲ ﻋﻼج اﻻﻟﺘﻬﺎﺑﺎت اﻟﻔﻴﺮوﺳﻴﺔ اﻟﻜﺒﺪﻳﺔ‪:‬‬ ‫‪system.‬‬ ‫‪.1‬اﻟﺘﺄﺛﻴﺮ اﻟﻤﺒﺎﺷﺮ ﻋﻠﻰ اﻟﺨﻼﻳﺎ ﻏﻴﺮ اﻟﻤﺼﺎﺑﺔ‪:‬‬ ‫اﻹﻧﺘﺮﻓﻴﺮوﻧﺎت ﺗﻌﻤﻞ ﻣﺒﺎﺷﺮة ﻋﻠﻰ اﻟﺨﻼﻳﺎ ﻏﻴﺮ اﻟﻤﺼﺎﺑﺔ ﻟﺘﺤﻔﻴﺰ إﻧﺘﺎج إﻧﺰﻳﻤﺎت ﺗﺆدي إﻟﻰ ﺗﺤﻄﻴﻢ اﻟﺤﻤﺾ اﻟﻨﻮوي اﻟﺮﻳﺒﻲ )‪ (RNA‬اﻟﻔﻴﺮوﺳﻲ‪ ،‬ﻣﻤﺎ ﻳﻌﻴﻖ ﺗﻜﺎﺛﺮ اﻟﻔﻴﺮوس داﺧﻞ‬ ‫اﻟﺨﻼﻳﺎ‪.‬‬ ‫‪.2‬اﻟﺘﺄﺛﻴﺮ ﻏﻴﺮ اﻟﻤﺒﺎﺷﺮ ﻋﺒﺮ ﺗﺤﻔﻴﺰ اﻟﺠﻬﺎز اﻟﻤﻨﺎﻋﻲ‪:‬‬ ‫اﻹﻧﺘﺮﻓﻴﺮوﻧﺎت ﺗﻌﻤﻞ ً‬ ‫أﻳﻀﺎ ﻋﻠﻰ ﺗﺤﻔﻴﺰ اﻟﺠﻬﺎز اﻟﻤﻨﺎﻋﻲ ﻋﻦ ﻃﺮﻳﻖ ﺗﻌﺰﻳﺰ اﺳﺘﺠﺎﺑﺔ اﻟﻤﻨﺎﻋﻴﺔ ﺿﺪ اﻟﻔﻴﺮوﺳﺎت‪ ،‬ﻣﻤﺎ ﻳﺰﻳﺪ ﻣﻦ ﻗﺪرة اﻟﺠﺴﻢ ﻋﻠﻰ ﻣﻬﺎﺟﻤﺔ اﻟﻔﻴﺮوﺳﺎت واﻟﻘﻀﺎء ﻋﻠﻴﻬﺎ‪.‬‬ ‫ﺧﻼﺻﺔ‪:‬‬ ‫ﺗﻌﻤﻞ اﻹﻧﺘﺮﻓﻴﺮوﻧﺎت ﻋﻠﻰ ﻣﻜﺎﻓﺤﺔ اﻟﻔﻴﺮوﺳﺎت ﻓﻲ اﻟﺘﻬﺎب اﻟﻜﺒﺪ ﻋﻦ ﻃﺮﻳﻖ ﺗﺤﻔﻴﺰ اﻟﺨﻼﻳﺎ ﻏﻴﺮ اﻟﻤﺼﺎﺑﺔ ﻹﻧﺘﺎج إﻧﺰﻳﻤﺎت ﺗﺪﻣّ ﺮ اﻟﻔﻴﺮوﺳﺎت‪ ،‬ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ﺗﺤﻔﻴﺰ اﻟﺠﻬﺎز اﻟﻤﻨﺎﻋﻲ‬ ‫ﻟﺘﻌﺰﻳﺰ اﺳﺘﺠﺎﺑﺘﻪ ﺿﺪ اﻟﻔﻴﺮوس‪.‬‬  Made with Xodo PDF Reader and Editor Uses of Interferon  Alfa Interferon used for hairy cell leukemia, recurrent or metastatic renal cell carcinoma, Kaposi's sarcoma in AIDS patients  Alfa-2α and -2b improve the manifestations of viral hepatitis, B and C. hepatitis C may need prolonged therapy. :(Alfa-2b) ‫ب‬2-‫( و أﻟﻔﺎ‬Alfa-2α) ‫أ‬2-‫ اﻹﻧﺘﺮﻓﻴﺮون أﻟﻔﺎ‬..(Hepatitis B and C) ‫ﺗﺤﺴﻴﻦ اﻷﻋﺮاض اﻟﻤﺮﺗﺒﻄﺔ ﺑـ اﻟﺘﻬﺎب اﻟﻜﺒﺪ اﻟﻔﻴﺮوﺳﻲ‬.‫ﻋﻼﺟﺎ ﻃﻮﻳﻞ اﻷﻣﺪ ﻟﺘﺤﺴﻴﻦ اﻟﻨﺘﺎﺋﺞ‬ ً ‫ ﻗﺪ ﻳﺘﻄﻠﺐ‬C ‫اﻟﺘﻬﺎب اﻟﻜﺒﺪ‬  ‫‪Made with Xodo PDF Reader and Editor‬‬ ‫اﻵﺛﺎر اﻟﺠﺎﻧﺒﻴﺔ ﻟﻺﻧﺘﺮﻓﻴﺮون‪:‬‬ ‫‪.1‬ﻣﺘﻼزﻣﺔ ﺗﺸﺒﻪ اﻹﻧﻔﻠﻮﻧﺰا )‪:(Influenza-like syndrome‬‬ ‫‪Adverse Reactions of Interferon‬‬ ‫ﻗﺪ ﻳﻌﺎﻧﻲ اﻟﻤﺮﺿﻰ ﻣﻦ أﻋﺮاض ﻣﺸﺎﺑﻬﺔ ﻟﻺﻧﻔﻠﻮﻧﺰا ﻣﺜﻞ اﻟﺤﻤﻰ‪ ،‬اﻟﻘﺸﻌﺮﻳﺮة‪ ،‬وآﻻم اﻟﻌﻀﻼت‪.‬‬ ‫‪‬‬ ‫‪An influenza-like syndrome‬‬ ‫‪.2‬اﻟﺘﻌﺐ وﻓﻘﺪان اﻟﺸﻬﻴﺔ )‪:(Fatigue & Anorexia‬‬ ‫‪‬‬ ‫‪Fatigue &anorexia‬‬ ‫ﻣﻦ اﻵﺛﺎر اﻟﺠﺎﻧﺒﻴﺔ اﻟﺸﺎﺋﻌﺔ ﻟﻺﻧﺘﺮﻓﻴﺮون ﻫﻮ اﻟﺸﻌﻮر ﺑﺎﻟﺘﻌﺐ اﻟﺸﺪﻳﺪ وﻓﻘﺪان اﻟﺸﻬﻴﺔ‪.‬‬ ‫‪‬‬ ‫‪Convulsions, depression‬‬ ‫‪.3‬اﻟﻨﻮﺑﺎت واﻻﻛﺘﺌﺎب )‪:(Convulsions, Depression‬‬ ‫‪‬‬ ‫‪Hypotension, hypertension and cardiac‬‬ ‫ً‬ ‫وأﻳﻀﺎ ﻓﻲ زﻳﺎدة اﻻﻛﺘﺌﺎب ﻟﺪى ﺑﻌﺾ اﻟﻤﺮﺿﻰ‪.‬‬ ‫ﻳﻤﻜﻦ أن ﻳﺘﺴﺒﺐ اﻹﻧﺘﺮﻓﻴﺮون ﻓﻲ اﻟﻨﻮﺑﺎت‬ ‫‪arrhythmias‬‬ ‫‪.4‬اﻧﺨﻔﺎض ﺿﻐﻂ اﻟﺪم وارﺗﻔﺎع ﺿﻐﻂ اﻟﺪم واﺿﻄﺮاﺑﺎت اﻟﻘﻠﺐ )‪:(Hypotension, Hypertension, and Cardiac Arrhythmias‬‬ ‫‪ Bone marrow depression.‬‬ ‫اﻧﺨﻔﺎﺿﺎ أو ارﺗﻔﺎﻋً ﺎ‪ ،‬وﻗﺪ ﻳﺘﺴﺒﺐ ً‬ ‫أﻳﻀﺎ ﻓﻲ اﺿﻄﺮاﺑﺎت ﻓﻲ ﻧﻈﻢ اﻟﻘﻠﺐ‪.‬‬ ‫ً‬ ‫ﻗﺪ ﻳﺆدي إﻟﻰ ﺗﻐﻴﺮات ﻓﻲ ﺿﻐﻂ اﻟﺪم ﺳﻮاء‬ ‫‪.5‬ﺗﺜﺒﻴﻂ ﻧﺨﺎع اﻟﻌﻈﺎم )‪:(Bone marrow depression‬‬ ‫ﻳﻤﻜﻦ أن ﻳﺤﺪث ﺗﺜﺒﻴﻂ ﻓﻲ وﻇﻴﻔﺔ ﻧﺨﺎع اﻟﻌﻈﺎم‪ ،‬ﻣﻤﺎ ﻳﺆدي إﻟﻰ ﺗﻘﻠﻴﻞ ﻋﺪد ﺧﻼﻳﺎ اﻟﺪم اﻟﺤﻤﺮاء واﻟﺒﻴﻀﺎء واﻟﺼﻔﺎﺋﺢ اﻟﺪﻣﻮﻳﺔ‪.‬‬ ‫ﺧﻼﺻﺔ‪:‬‬ ‫اﻹﻧﺘﺮﻓﻴﺮون ﻗﺪ ﻳﺴﺒﺐ آﺛﺎ ًرا ﺟﺎﻧﺒﻴﺔ ﻣﺜﻞ ﻣﺘﻼزﻣﺔ ﺗﺸﺒﻪ اﻹﻧﻔﻠﻮﻧﺰا‪ ،‬اﻟﺘﻌﺐ‪ ،‬ﻓﻘﺪان اﻟﺸﻬﻴﺔ‪ ،‬اﻟﻨﻮﺑﺎت‪ ،‬اﻻﻛﺘﺌﺎب‪ ،‬اﺿﻄﺮاﺑﺎت ﺿﻐﻂ اﻟﺪم واﻟﻘﻠﺐ‪ ،‬وﺗﺜﺒﻴﻂ ﻧﺨﺎع اﻟﻌﻈﺎم‪.‬‬