PharmaPHILIA - Extracting Concepts Of Medical With Rph FIA

 HEART FAILURE HF=complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body. Symptoms ; Dyspnea, Fatigue, Fluid retention. Also called” Congestive Heart failure (C.H.F) Action Potential= Phase 0:Fast Upstroke: Na+ channels open (fast channel) resulting in afast inward current ……Sodium current is blocked by Quinidine Phase l: Repolarization: inactivation of Na+ channel…K+ channels rapidly open & close…outward current Phase ll: Plateau: Voltage sensitive Ca++ channels open…Slow inward current(depolarizing)…. Slow outward current (Polarizing) leak of K+ Phase lll: Repolarization Ca++ channels close…K+ channels open…outward current lead to repolarization… net gain of Na+ & Loss of K+….corrected by Na+/K+-ATPase Phase lV: Forward Current Increase depolarization from gradual increase in sodium….bring the cell to Threshold of next action potential. Angiotensin-Converting Enzyme Inhibitor Angiotensinogen (α2-globulin i...

 STEROID HORMONE & ANTAGONIST Removal of Hormone OR Treatment with Hormone to regress Tumor Orcheictomy =removal of both testes in Prosthatic cancer Prednisone Synthhetic, Anti-inflammatory Corticosteroid…Cortisol at high dose,Lymphocytolytic, ↑uric acid due to breakdown of Lymphocytes MOA inactive…reduced to Prednisolone by 11-β-hydroxysteroid dehydrogenase… Bind to receptor & trigger production of Specific proteins S.E ulcer, Pancreatitis, Hyperglycemia, Glaucoma, Osteoporosis, Tamoxifen  Estrogen antagonist…used in Estrogen-Positive Breast cancer… SERM (Selective Estrogen Receptor Modulator) weak Estrogenic activity Toremifene  used in Breast cancer in Postmenupausal women MOA Bind to Estrogen receptor.complex is nonfunctional…↓Estrogen…used with GnRH analog Leuprolide ↓Estrogen level S.E Thromboembolism,Vision blurred, Hypercalcemia, Vaginal bleeding,Hot flash Aromatase inhibitors Aromatase reaction=↑Estrogen synthesis from Androstenedione in liver,fa...

ANTIBIOTICS Cell non-specific Dactinomycin  called Actinomycin D…used with Vincristine in Wilms tumor…with MTX in Soft tissue carcinoma MOA= form stable Dactinomycin-DNA compex b/w base pair of DN …interfere with DNA-depenndent RNA polymerase… single stand break by free radical or by action on Topoisomerase ll S.E =Extravasation, Stomatitis, Doxorubicin & Daunorubicin  Anthracycline antibiotics…Idarubicin, Epirubicin are analogof Daunorubicin… MOA =Doxorubicin induced free radical…memb. Lipid peroxidation…DNA strand scission…Direct oxidation of Purine, Pyrimidine, Thiol, Amine S.E= Cardiotoxicity…Dark red color vein….Dexrazone (iron chelator) used to prevent cardiotoxicity….↑skin pigmentation Bleomycin G2 Phase specific…mix of Cu-chelating Glycopeptide…. MOA= DNA-Bleomycin Fe2+ undergo into Oxidation Bleomycin-Fe3+…Superoxide form attack on Phosphodiester bond…Scission of DNA strand S.E= Pulmonary toxicity “Bleomycin lung”. ALKYLATING AGENTS Alkylating agent covalent...

 1g Tumor mass=109 cells smallest tumor burden …clinical symptoms appear at this stage Palliative Chemotherapy = survival is extended Curative Chemotherapy(Adjuvant)= Solid tumor (i.e Testicular carcinoma)…Reduced by surgery or Radiation… 🌟Treatment of Micrometastasis continue after cancer disappear Curative chemotherapy(Non-adjuvant)= Dissaminated cancer(i.e Leukemia…Drug-chemotherapy to reduce tumor before surgery…  Each drug have different Organ toxicity& Site of action  Log kill=Destruction of cancer cell by Anticancer follow 1ST Order kinetics…5-log kill 105 cells  POMP=For Acute Lymphocytic leukemia;  Prednisone, Oncovin, Methotrexate, Purinethol. Used for 21days ANTI-METABOLITES “S” phase….Cell-Cycle Specific Methotrexate=Structure related to Folic Acid….Inhibit DHFR (Dihydrofolate reductase) MOA= enter into the cell by active-transport system same like N5-methylFH4…ϴ Folate→FH2 by DHFR…ϴFH2→FH4 by DHFR…inhibit formation ofN5,N10-Methylene-FH4 C...

  Right answers of Anti microbial MCQs  Right answer : A  Because of structural similarity with pyridoxine . Isoniazid increases the excretion or pyridoxine, which can lead to peripheral neuritis, particularly in poorly nourished patients. Pyridoxine (a form of vitamin B6) deficiency may cause convulsions as well as the neuritis, involving synovial tenderness and swelling. Treatment with the vitamin can reverse the neuritis and prevent or cure the seizures. Right answer: B Right answer : E Right answer : E Right answer : D

 Nucleoside Reverse Transcriptase Inhibitor NRTI Zidovudine approved in 1987 used to Suppress Replication of HIV & Restore no.of CD4+ cells in AIDS patients HAART=”Highly Active Antiretroviral Therapy” include NRTI, NNRTI, Protease Inhibitor, Entry Inhbitor, Integrase Inhbitor e.g 2NRTIs + 1Prot.Inhibitor OR 1NNRTI+1Integrase inhibitor MOA:  👉NRTI are RiboNucleoside analogue…lack 3-OH...Enter the cell convert into TriPhosphate…incorporate into Viral DNA by Reverse transcriptase…. b/c 3-OH not present, 3,5-Phosphodiester bond not fromed in Nucleoside Triphosphate...T erminate Elongation of DNA 1. HIV enters into cell→Maraviroc (Entery Inhibitor) block entery of HIV 2. Enfuvirtide (Entery In.) block FUSION of HIV & Host memb Viral RNA→═Viral DNA by Reverse Transcriptase, NRTI & NNRTI ϴ this enzyme ═Viral DNA integrate with ═Host DNA Integrase Inhibitor ϴ this process ≈Integrated Viral DNA convert into Viral RNA & Precursor Polyprotein, Precursor Protein→Viral...

  Treatment of Respiratory Virus Infection Influenza A & B, RSV(Respiratoy syncytial virus) involved in Respiratory infection Neuroaminidase inhibitor Orthomyxovirus cause Influenza contain Neuroaminidase …essential for life cycle… Oseltamivir & Zanamivir  Sialic acid analogue… ϴNeuroaminidase,prevent release of virion & their spread….Active against Influenza A & B Oseltamivir orally prodrug…zanamivir intranasally, cotra in COPD, Asthma Inhibitor of Viral coating Amantadine & Rimantadine= only Influenza A virus….Block Viral memb. Protein M2...which act as channel for Hydrogen ion…required for fusion of viral memb with cell memb.  👍To form ENDOSOME…acidic environment require S.E= Embryotoxic… used catiously in patient with Seizure, Athersclrosis, Psychiatric  Ribavirin Synthetic Guanosine analogue… used for RNA, DNA viruses… used in children with  RSV effective in Chronic Hepatitis… not indicated in Adults with RSV… MOA:  convert into ...

  Drugs for Nematode  Mebendazole   DOC in infections of Whipworm (Trichuris trichiura), Pinworm(Entrobius vermicularis), Hookworm (Necator americanus), Roundworm(Ascaris lumbricoides)  MOA bind to Parasite‟s microtubules…↓Glucose uptake.. Parasite expel with feces… Embryotoxic & Teratogenic Pyrantal Pamoate Depolarizing agent..Neuromuscular blocker...Paralyzed parasite  Thiabendazole 👍used in Strongloidiasis & Trichinosis…interefer with microtubules…  ❌contraindicated in pregnancy  Ivermectin DOC in Onchocerciasis (river blindness) by O.vulvulus….↑CI- influx…  Hyperpolarization, paralysis of Parasite… Contraindicated in Meningitis, Pregnancy 👉Killing of Microfilaria result in Mazotti-like reaction (fever, hypotension,headache)  Diethylcarbamazepine used in Filariasis…. S.E anthralgia, Myalgia, Leukocytosis.

  Drugs for Trypansomiasis  Trypansomiasis  Trypansomiasis is  African sleeping sickness & American sleeping sicknesss caused by Trypanosoma. African sleeping sickness  African sleeping sickness caused by T.Bruci Gambiense & T.brucie rhodiense… initially live in the blood then invade CNS….inflammation of Brain & spinal cord…continuous sleep  Amrican sleeping sickness = called Chagas disease….By T.cruzi Malarsoprol Trivalent arsenical… react with Sulfahydryl group of enzyme & various substance… cell death ….Cross CSF... DOC in T.bruci rhodiense & Meningoencephalitis by T.bruci ghambiense S.E:  Hymolytic anemia... contra in patient with Influenza.. Pentavalent arsenic excrete Pentamidine Isothionate Used for Hematologic state… not penetrate in CSF… used in Blastomycosis, Pneumocystis, pneumonia in HIV pt.  Leishmaniasis MOA enter by energy dependent high affinity uptake sys... bind to DNA,RNA, Protein & interfere with thei...

Important mcqs for screening test of AKUH, GAT and NTS. Physostigmine is parasympathomimetic drug act as cholinesterase Inhibitors, indicated for chronic management of Myasthenia gravis. Duration of action is intermediate i.e 3 to 8 hours .

  Right answers with explanation Correct answer : A  Reference : lipincott 

  Amebiasis infection of intestinal tract by Entamoeba histolytica  Lifecycle of Entamoeba histolytica  Two forms… 1. Cyst: survive out of the body…2.Labile/Invasive: cannot survive out of thebody….Cyst ingested through feces-contaiminated food…pass into the lumen…  where Trpohozites liberated,multiply,invade/ulcerate Mucosa of Large Intestine…  Amoeba‟s major food intestinal flora…slowly carried toward Rectum,converted into cyst & excreted in feces  Large no. of Trophozoites within Colon wall lead to systemic invasion. Mixed amoebicides  Metronidazole DOC in Amoebic infection, Pseudomembraneous colitis…Nitroimidazole Active for both Luminal & Systemic amoeba MOA :  Nitrogen of Metronidazole converted Nitro Radical…Act as electron Acceptor…  form reduced cytotoxic compound….bind to Ferodoxin-Like low redox potential ELECTRON-TRANSPORT PROTEIN…cell death  S.E Metallic taste, Oral moniliasis… Tinidazole= sec-generation Nitro-imidaz...

  Mycobacteria  rod shaped, lipid-rich cell wall, satin poorly with Gram stain, but once stained , walls cannot decolorized easily so called “Acid-Fast”. Most common bacteria Tuberculosis…Diagnosed by Tuberclin-Skin test with PPD (Purified protein derivative) or by IGRA (interferon Gamma Releas essay), Quntiferon-TB Gold.  Chemotherapy for Tuberculosis Mycobacteria tuberculosis caused Tuberculosis i.e infection of lungs, genitourinary tract,Skeleton, Meninges. 👉 Organism grow slowly, difficult to culture, take 6month to 2yr for treatment. Stratgies to address Drug Resistance:  combination of “First-line” initial short-course for 2month with Isoniazid,Rifampicin, Ethambutol, Pyrazinamide…… then “continuation phase” Isoniazid & Rifampicin for 4 months. DOT progaramme “Directly Observed Therapy” pt. observed when take medicine to↓resistance. Isoniazid (Bacteriostatic /Bactericidal) Hydrozyde of Isonicotinic acid...synthetic analogue of Pyridoxine… MOA: ...

Infectious diseases caused by fungi called Mycosis ….cell wall composed of chitin…Contain Ergosterol Cutaneous Mycosis/Epidermis = Superficial infection invoving skin … Drugs for Subcutaneous & Systemic inections Amphotericin B (Fungicidal/Fungistatic) From S.nodosus DOC in Systemic mycosis… MOA bind to Ergosterol...form pore… Allowing leak of Electrolytes & small molecules…cell death Antifungal spectrum   activity against Candida albican, Histoplasma capsulatum,Cryptococcus neoforamans, Coccidicoides immitis, Blastomyces dermatitidis, Apergillus P.K  insoluble in water, Deoxycholate added to form colloidal suspension ↓Nephrotoxicity. …  Liposome formulation AMBISOME, AMPHOTECT, ABELCET… S.E  fever & chills, Thrombophlebitis, Nephrotoxicity, Hypotension, normocytic anemia exacerbate in HIV pt receiving Zidovudine Flucytosine (Fungistatic) Pyrimidine metabolite. MOA 5-FC enter via Cytosine permease… 5-FC converted 5-Flourodeoxyuridine 5-monophosphate (...

  Quinolone   Learn with  fun     by clicking the fun Naldixic acid is precursor of Flouroquinolone MOA enter into bacterium by Passive Diffusion through Porin ϴ replication of bacterial DNA by interfering Topoisomerase ll & Topoisomerase IV during bacterial Growth & Reproduction… Topoisomerase ll(DNA Gyrase) change DNA topology by nicking, pass through , resealing mechanism…..ϴ of Topoisomerase ll inhibit resealing step….cell death by cleavage of DNA  Topoisomerase lV required for cell division. Antibacterial spectrum 1st Generation in treatment of UTI, have moderate Gram-Ve rod activity. 2 nd Generation Expanded Gram-Ve activity rod, some Gram+Ve cocci activity &  against atypical organisms (M.pneumoniae, Chlamydia pneumonia)   3 rd Generation improved activity against Gram-Ve rod, Gram+Ve cocci, atypical organism 4th Generation activity against Gram+Ve cocci, Gram+Ve rod, Gram-Ve rods, Anaerobes T.E 👉Ciprofloxacin is DOC in A...

Bacterial ribosome 70s (50s+30s) Mammalian ribosome 80s (60s+40s) Tetracyclines (Bacteriostatic /Bacteriocidal)  Group of fused 4 rings  MOA enter into susceptible organisms by Passive diffusion & by an energy dependent mechanism to cell memb bind reversibly to 3OS subunit of ribosome  blocking access of acyl-tRNA into mRNA ϴ protein synthesis Anti-bacterial synthesis= Gram +Ve Bacilli ( Bacillus anthracis), Gram –Ve  Rod(Brucella, Vibrio, Yersinia pestis) anaerobe,Spirochete, Mycoplasma, Chlamydia  Resistance: due to alteration in R factor, Mg dependent efflux, TetA protein,  T.E:  Doxycycline used in Cholera (Vibrio cholera), Lyme disease (Borrelia burgdoferi), Chlamydial infection (Chlamydia trachomatis, Chlamydia psittaci), Mycoplasma pneumonia, Tetracycline in Rocky Mountain spotted fever (Ricketssia rickettsii), P.K   form non-absorbable chelate with Ca in dairy products … bind to tissue undergo Calcification   (teeth, bone, Gastric...

 Anti – microbial drug selectively interfere with synthesis of bacterial cell wall  Pencillins MOA:  interfere with last step of Bacterial cell wall synthesis (Transpeptidation/Cross-linkage)….result in exposure of Alteration in Osmotically memb…Cell lysis occur … either though Osmotic pressure or by Autolysin….Pencillin effective only against rapid growing bacteria  Pencillin-binding Protein  1. PBP are bacterial enzymes involved in synthesis of cell wall   2. PBP involved in maintenance of morphological feature… Pencillin also cause changes in morphological feature  Inhibition of Transpeptidase PBP catalyze cross-linkage b/w Peptidoglycan chain….  Pencillin inhibit this Transpeptidase-Catalyzed reaction…. the cross-linkage formation essential for integrity of cell wall…. As a result” Park Nucleotide” UDP-acetylmuramyl-Ala-D-Gin-L-lys-D-Ala-D-Ala accumulation  Production of Autolysin  Gram+Ve cocci produce degradative enzyme “Auto...

  PRINCIPLE OF ANTI-MICROBIAL THERAPY Selection of Anti-microbial therapy  1)organism‟s identity  2)organism‟s susceptibility to particular agent 3)site of infection  4)patient‟s factor  5)safety of agent  6) cost of therapy

ARENERGIC BLOCKER/SYMPATHOLYTICS Bind to adrenoreceptors reversibly or irreversibly, preventing its activation by endogenous catecholamine.   CLASSIFICATION α Blockers Phenoxybenzamine , Phentolamine, Prazocin, Terazocin, Doxazocin, Yohimbine, Alfuzosin, Tamsulosin β Blockers  Propranolol, Metoprolol, Acebutolol, Atenolol, Betaxolol, Bisoprolol, Carteolol, Carvedilol, Esmolol, Labetalol, Nadolol, Nebivolol, Penbutolol, Pindolol, Timolol Inhibiting reuptake or release Guanethidine, Reserpine Phenoxybenzamine: non-selective, α1 & α2 blocker, irreversible, non-competitive, MOA:  covalently block the α1 & α2 adrenoreceptor..action last about 24hrs..body has to synthesize new receptor to overcome this block.. Actions:  vasodilation..decreased peripheral resistance provoke Reflex Tachycardia… Not used in Hypertension b/c its blockade release more nor-epinephrine which stimulate β receptor…. Epinephrine Reversal b/c by blocking α adrenoreceptor it bloc...