» MCAT Review: Physiology and Audio Hematopoeisis
Episode 33: Listen to this science content review and learn its format for your own audio notes.
Episode 33: Listen to this science content review and learn its format for your own audio notes.
General Principles of Toxicology Scope of Medical Toxicology: Occupational (Chemicals), Environmental (agricultural/air), Clinical (drug toxicity, accidental, intentional) Oral > Eye > Skin > Bites/Stings > Inhalation > Aspiration 90% poisonings occur in the household (children- most common): cosmetics, cleaning products, plants, pharmaceuticals, etc) Most Deaths: Antidepressants, Analgesics, Stimulants/St. drugs, Alc/glycols, Gases/Fumes, Asthma Rx Most frequently [...]
NSAIDS Aspirin Salicylic Acid Indomethacin Diclofenac Sulindac Tolmetin Ibuprofen Naproxen Ketoprofen Pranoprofen Miroprofen Phenylbutazone Apazone Piroxicam Celecoxib Acetaminophen Chloroquine Gold salts Colchicine Probenecid Sulfinpyrazone Allopurinol Common Feature of All NSAIDS 1) anti-inflammatory 2) analgesic – effective against pain of low to moderate intensity 3) anti-pyretic 4) GI/intestinal ulceration: local irritation and inhibition of PGs 5) [...]
Azathioprine Corticosteroids Cyclosporine Tacrolimus Sirolimus Mycophenolate mofetil Polyclonal antithymocyte globulin Anti-CD3 monoclonal antibodies Azathioprine (AZA) imidazole derivative of 6-mercaptopurine blocks DNA synthesis decreases the migration of leukocytes into grafts and inhibits the proliferation of premyelocytes within the bone marrow useful for blocking the 1o response NOT USEFUL for blocking the 2o immune response or for [...]
Drug Information and Nomenclature A. Drug Classification OTC drugs: Adequate directions can be written for the layman and they’re safe for the not-so-careful customer. B. Prescription Drugs Adequate directions can not be written for the layman. Directions are intended for the physician, and the proper and successful use of these drugs is the responsibility of [...]
Eicosanoids Arachidonic Acid Prostaglandins: PGE1, PGE2, PGF2a, PGI2 Thromboxane A2 Drugs NSAIDS – Aspirin, Indomethacin, Ibuprofen, Celecoxib Prostin – PGE1 Alprostadil – PGE1 Misoprostol – PGE1 derivative Dinoprostone – PGE2 Epoprostenol – PGI2 (prostacyclin) Iloprost – PGI2a Latanoprost – PGF2a Carboprost tromethamine – PGF2a derivative Leukotriene Modifiers Zafirkulast Zilueton General specific cell stimulation, or shear-stress [...]
cancer affects 1 in every 3 individuals Cancer incidence and mortality Ø Males – lung #1, prostate #2 Ø Females – lung #1, breast #2 Causes of cancer Ø most are non-inherited genetic diseases of somatic cells Ø mutations can occur spontaneously or can be induced or increased by exposure to mutagenic substances in the [...]
Agents that intercalate DNA Doxorubicin (Adriamycin) Daunorubicin (Daunomycin) Dactinomycin Plicamycin (Mithramycin) Agents that fragment DNA Bleomycins Agents that inhibit Topoisomerase II Etoposide (VP-16) Teniposide Amsacrine Agents that inhibit Microtubules Vincristine Vinblastine Paclitaxel (Taxol) Hormones and related agents Prednisone Tamoxifen Leuprolide Androgens Progestins Estrogens Miscellaneous L-Asparaginase Agents that intercalate DNA – Doxorubicin, Daunorubicin, Dactinomycin, Plicamycin Doxorubicin [...]
1. Antifolates 2. Methotrexate (MTX) 3. Pyrimidine Analogs 4. Cytosine Arabinoside – (araC, cytarabine) 5. Fluorouracil (5-FU) 6. Purine Analogs 7. Mercaptopurine (MP) 8. Thioguanine (6-TG) 9. Misc 10. Hydroxyurea 11. Rescue Drug (Not for CHEMO) 12. Leucovorin ALL OF THESE DRUGS ARE S-PHASE SPECIFIC and interfere with DNA synthesis Antifolates – Methotrexate (MTX) [...]
Nitrogen Mustards Mechlorethamine Cyclophosphamide Melphalan Chlorambucil Nitrosureas Carmustine (BCNU) Lomustine (CCNU) Semustine Streptozocin Alkyl Sulfonates Busulfan MISC Cisplatin Procarbazine Dacarbazine Mitomycin Nitrogen Mustards – Mechlorethamine, Cyclophosphamide, Melphalan, Chlorambucil General Crosslinking of the DNA strands is the main source of toxicity ALL ARE CELL CYCLE PHASE NON-SPECIFIC Dose limiting toxicity: bone marrow suppression These alkylating agents [...]
B & C are H2O soluble; excreted rapidly in kidney; overdoses are rare A,D,E, & K are fat soluble; stored; hypervitaminosis syndromes result usually multiple deficiencies of Vit B exist (not single) so supplementation is in multiple combos Thiamine (Vit B-1) – precursor for TPP which is required for decarboxylation of a-keto acids and is [...]
Levothyroxine (T4) Propylthiouracil – PTU Methimazole – MMI Potassium iodide – KI Radioactive iodide 131I Thyroid Hormone Synthesis: Thionamides: Propylthiouracil (PTU) and Methimazole (Tapezol) PTU and Methimazole inhibit the peroxidase enzyme throughout the pathway. PTU has the additional effect of blocking the peripheral conversion of T4 to T3 by inhibiting the 5′-iodinase. Actions reversible when [...]
Estrogens & Progestins Introduction to the players: Estrogens: estradiol, conjugated estrogens (Premarin), ethinyl estradiol, mestranol SERMS: clomiphene, tamoxifen, raloxifene Functional Anastrozole, exemestane (inhibit production from androgens). Block estrogens: enzyme. Progestins: progesterone, medroxyprogesterone acetate, norethindrone, norgestrel progest.: mifeprostone or mifeprix (ru 486) Sex Steroids: 1. widely used 2. efficacious 3. several potenetial SE – [...]
Class BUG Infective Stage Local of Path Stage Drug MECH Protizoans Amebiasis: invasive Cyst Extraintestinal Iodoquinol Unknown Amebiasis: luminal Cyst Large intestine Flagyl + iodoquinol Flagyl –inhibits DNA replication Amebiasis: luminal Cyst Large intestine Emitine + iodoquinol Emitine –inhibits protein synthesis Amebiasis: luminal Cyst Large intestine Chloroquine + iodoquinol Chloroquine –unknown for amebae Balantidiasis Cyst [...]
Serious side effects esp older women (older than 35) who smoke/predisposed to thromboembolic disease or cv disease. Start with lowest possible doses. (ie low dose tri-phasic preparation). Combination OC: ethinyl estradiol (most common) or — estrogen component. 19-nor steroid — progestin. Higher doses of estrogen used for OC than for ERT. Monophasic, biphasic, and triphasic [...]
INSULINS DRUGS INFO Insulin (general) Pre-pro insulin is cleaved (-NH3) in the ER — pro-insulin is cleaved in the golgi (C-peptide) — insulin (A & B chains). Glucose is primary physiological stimuli for insulin secretion. ANS — islets are innervated by vagus — cholinergic stimulation will increase insulin secretion. Phase I of secretion — @ [...]
Treatment Approaches 1) limit carb intake 2) weight loss and exercise 3) insulin for type I; for type II when fasting glucose > 250 mg/dl Insulin Preparations administered subQ, IM, and IV Onset/duration Ø Regular insulin – 0.5hr/5-7hrs Ø Isophane insulin & Lente Insulin – 1-2hrs/24-30hrs Ø Protamine Zinc Insulin, Ultralente insulin – 4-8 hrs/24-36 [...]
1. Growth Hormone Somatropin Octreotide – somatostatin analogue hMG/Menotropins (LH/FSH) hCG/Chorionic Gonadotropin (LH) Oxytocin Desmopressin Bromocryptine -Dopamine agonist used paradoxically in Acromegaly treatment; Prolactinemia Growth Hormone Secretion Ø stimulated by GHRH Ø inhibited by somatostatin Effects Ø Direct: plasma membrane receptors triggers kinase cascade (the JAK-STAT system) that eventually alters gene transcription - effects carbohydrate, [...]
Remember that the11-OH is required for activity All glucocorticoids are excreted completely in the urine (no biliary or fecal) Anti-inflammatory Effects of Glucocorticoids effective against ALL FORMS of inflammation Requires HIGH DOSES Mechanisms 1) induce synthesis of lipocortin which in turn inhibits phospholipase A2 - this inhibits the release of arachidonic acid from the plasma [...]
Most Peptic Ulcer Disease Results from: 1) infection with H. pylori 2) use of aspirin, NSAIDS 3) gastrin-secreting tumors Antacids – Sodium Bicarbonate, Calcium Carbonate, Magnesium Hydroxide, Aluminum Hydroxide Sodium Bicarbonate systemic do not use long term can change pH of blood and urine (alkalosis) Contraindications – HTN Calcium Carbonate partially systemic do not use [...]
I. Cephalosporins- A. Structure- 2 rings. B. Mechanism- inactivate transpeptidases just like PNC, but less susceptible to lactamases. C. Spectrum- 1. lactamase producers: Klebsiella, N. gonorrhoeae 2. potent inducers of -lactamases in other species: Enterobacter and Pseudomonas. 3. Staph. aureus and streptococci. 4. Activity against G(-) pathogens increases from 1st to 4th generations. 5. Activity [...]
Drugs used to treat Hypocalcemia Calcium Salts – Calcium Carbonate Calcium Citrate Calcium Lactate Calcium gluconate Ø use with caution in patients on Digitalis Vitamin D preparations drugs of choice for treatment of Chronic hypocalcemia several preps DHT – dihydrotachysterol Ø duration of action – 2 weeks Ø requires liver and kidney for metabolism Ø [...]
Introduction: All Antiviral Drugs are virustatic Antiviral Drugs for – Herpes viruses remember that these are DNA viruses Includes HSV 1&2, VZV, CMV, EBV, HHV-6, HHV-7, HHV-8 Specific Drugs Acyclovir – guanosine analogue requires phosphorylation to triphosphate form for activity the viral thymidine kinase performs the initial phosphorylation Mechanism Ø irreversibly binds to viral DNA [...]
Protozoa Amebiasis – Entamoeba histolytica Treatment directed against the trophozoites Luminal – Diiodohydroxyquinoline (Iodoquinol) Invasive – 1) Metronidazole + Iodoquinol 2) Emetine + Iodoquinol 3) Chloroquine + Iodoquinol (not understood for ameba) Balandidiasis – Balantidium coli Iodoquinol + tetracycline Tetracycline acts on bacteria that the parasite is dependent upon Giardiasis – Giardia lamblia DRUG OF [...]
Mycobacterium Tuberculosis In patients < 35, with suspected exposure to TB with positive PPD and no clinical symptoms Ø Isoniazid – 6-9 months In patients with a positive X-Ray, &/or positive smear of TB give 1st line agents Ø Isoniazid – 6 months – inhibits cell wall synthesis Ø Rifampin – 6 months – inhibits [...]
General Selective Toxicity – destroy the microorganisms w/o harming the host Bactericidal -antibiotic causes cell death (Ex. Ags, penicillin, cephalosporins, vancomycin) Bacteriostatic – antibiotic inhibits bacterial growth ( Ex. Chloramphenicol, erythromycin, clinda, tetra -cidal vs. -static not hard and fast rule – Ex. Ampicillin -cidal against S. pneumonia and -static against Enterococcus Antagonism Synergy Indifference [...]
Polyenes – Amphotericin B, Nystatin Amphothericin B Mechanism Ø Binds to ergosterol in fungal membranes better than to cholesterol in mamallian cells – selective toxicity Ø Alters fungal cell permeability and transport properties Ø No activity in bacteria, some in mycoplasma Structure Ø polyene antibiotic Ø insoluble in H2O Ø restricted activity between pH 6 [...]
I. Review of the principle reactions in protein synthesis- basic mechanism is the same for bacterial and mammalian cells. The main difference is in ribosome structure. A. Initiation- requires an initiation complex made up of ribosomes, mRNA, various initiation factors, and GTP for hydrolysis. The mRNA must have an initiation codon (AUG) that corresponds to [...]
I. Sulfonamides- Inhibitors of Folic Acid Metabolism A. Structures- all single or double ring structures. B. Mechanism- Bacteriostatic. Inhibits folic acid metabolism, depleting Tetrahydrofolate which is necessary for biosynthesis of purines (A & G), thymidine, and methionine. Mammals can get the folate they need from their diet; microbes can’t. C. Pharmacology- Variable intestinal absorption among [...]
Emetics Apomorphine Ipecac Anorexogenics Amphetamine Diethylpropion Phentermine Mazindol Sibutramin Orexogenic Dronabinol Antiemetics Anticholinergics Scopolamine H1 antagonists Dimenhydrinate Dopaminergic antagonists Chlorpromazine Metaclopramide (Reglan) Anxiolytics Diazepam Corticosteroids Dexamethasone Others Dronabinol 5HT Antagonists Ondansetron General Emesis Ø both autonomic and somatic nervous reflex elements are involved Ø Vagal afferent fiber in the GI tract® nucleus and tractus solitarius [...]
Drug Information and Nomenclature A. Drug Classification OTC drugs: Adequate directions can be written for the layman and they’re safe for the not-so-careful customer. B. Prescription Drugs Adequate directions can not be written for the layman. Directions are intended for the physician, and the proper and successful use of these drugs is the responsibility of [...]