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Kaplan Section 8 - Toxicities and Antidotes

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How does cyclosporine work?   Binds to cyclophilin in T-lymphocytes --> this complex….1. inhibits calcineurin (resp for activation of IL-2) --> no activation of IL-2, 2. inhibits lymphokine production, 3. inhibits interleukin release ==>reduced function of T-lymphocytes  
How does tacrolimus work?   antibiotic that also inhibits calcineurin (but doesn't bind to cyclophilin)  
When should you use cyclosporine?   DOC for organ/tissue transplantation  
When should you use tacrolimus?   Renal and liver transplantation  
What is mycophenolate and how does it work?   inhibit de novo synthesis of purines, adjunctive immunosuppressive actions --> allow dose reductions of cyclosporine  
What are the adverse effects of cyclosporine?   1. peripheral neuropathy, 2. nephrotoxicity, 3. hyperglycemia, 4. HTN, 5. hyperlipidemia, 6. hirsutism, 7. gingival overgrowth, 8. cholelithiasis  
What is Rh0 (D) Ig?   Human IgG antibodies to Rh0 antigens on RBC's  
When should you use Rh0 Ig's?   Give to an Rh- mom within 72 hours of delivery of an Rh+ child --> bind to all the Rh antigens that mom might have got from baby --> so mom doesn't develop her own anti-Rh antibodies --> prevent hemolytic disease of the newborn in subsequent pregnancies  
Should Rh- woman who miscarries a fetus be given Rh0 Ig?   Yes.  
What is abciximab and what is it used for?   Monoclonal antibody. Antagonist of 2b/3a receptors on platelets --> prevents crosslinking of fibrinogen --> antiplatelet  
What is daclixumab and what is it used for?   Monoclonal antibody. Block IL-2 receptors --> decreases inflammation --> decreases rejection --> give in kidney transplants  
What is Infliximab and what is it used for?   Monoclonal antibody. Binds to TNF-a. Give in RA and Crohn's.  
What is Muromonab and what is it used for?   Monoclonal antibody. Block allograft rejection in renal transplants.  
What is Palivizumab and what is it used for?   Monoclonal antibody. Blocks the RSV protein --> give to patients with RSV  
What is Rituximab and what is it used for?   Monoclonal antibody. Binds to surface protein --> give to Non-Hodgkin's lymphoma patients  
What is Trastuzumab and what is it used for?   Monoclonal antibody. Antagonist of HER2/neu receptors --> give to breast cancer patients  
What is Aldesleukin?   IL-2. Increases lymphocyte differentiation and increases NK's  
What do you use Aldesleukin for?   Renal cell carcinoma and metastatic melanoma  
Interleukin-11   Increases platelet formation  
When should you use IL-11?   Thrombocytopenia  
What is Filgrastim?   G-CSF -- increases granulocytes  
When should you use Filgrastim?   Bone marrow recovery to stimulate replacement of granulocytes  
What is Sargramostim?   GM-CSF. Increases granulocytes and macrophages  
When should you use Sargramostim?   Bone marrow recovery to stimulate replacement of granulocytes and macrophages  
What is erythropoietin?   Hormone that stimulates the production of RBC's  
When should you use erythropoietin (EPO)?   In anemic patients, esp those with renal failure because EPO is produced mainly by peritubular fibroblasts of the renal cortex  
What is thrombopoietin (THPO)?   hormone produced mainly by the liver & kidney that regulates production of platelets by bone marrow. It stimulates the production & differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets  
When should you use THPO?   In patients with thrombocytopenia  
What does IFN-alpha do?   1. stimulate both macrophages and NK cells to elicit an anti-viral response, 2. active against tumors, 3. bind to opioid receptors on thermosensitive neurons --> release PGE2 --> fever, 4. IFN-α interacts with μ-opioid receptor --> analgesic  
When should you use INF-a?   Hep B and C, leukemias, melanoma  
What does IFN-beta do?   1. stimulate both macrophages and NK cells to elicit an anti-viral response, 2. active against tumors  
When should you use INF-B?   Multiple sclerosis  
What does IFN-gamma do?   produced in activated T-cells & NK cells; released by Th1 cells recruits leukocytes to a site of infection --> increased inflammation; stimulates macrophages to kill bacteria that have been engulfed; regulates the Th2 response  
Patient comes in with these symptoms: miosis, salivation, sweats, GI cramps, diarrhea, muscle twitches --> seizures, coma, respiratory failure. What type of drug toxicity are they experiencing? What is the antidote?   AchE inhibitors; resp support, atropine + pralidoxime (bind to organophosphate-inactivated acetylcholinesterase; for irreversible AchEi's)  
Patient comes in with these symptoms: inc HR, inc BP, hyperthermia (hot, dry skin), delirium, hallucinations. What type of drug toxicity are they experiencing? What is the antidote?   Atropine and other M blockers. Control CV sx's and hyperthermia; give physostigmine (crosses BBB)  
Patient comes in with these symptoms: NV, dyspnea with hyperventilation, mydriasis, vertigo, CV signs prominent, dec BP, syncope, inc HR, arrhythmias. What type of drug toxicity are they experiencing? What is the antidote?   Carbon monoxide poisoning (> 10% carboxyHb); give hyperbaric O2 and decontamination (if milk OD, can give humidified 100% O2)  
Patient comes in with these symptoms: anxiety/agitation, hyperthermia (warm, sweaty skin), mydriasis, inc HR, inc BP, psychosis, seizures. What type of drug toxicity are they experiencing? What is the antidote?   CNS stimulants; Control CV sx's, hyperthermia, and seizures; Give BZ's or anti-psychotics  
Patient comes in with these symptoms: Lethargy, sedation, dec HR, dec BP, hypoventilation, miosis, coma, resp failure. What type of drug toxicity are they experiencing? What is the antidote?   Opioid analgesics. Give ventilatory support. Give naloxone at frequent intervals.  
Patient comes in with these symptoms: Confusion, lethargy, hyperventilation, hyperthermia, dehydration, hypoK+, acidosis, seizures, coma. What type of drug toxicity are they experiencing? What is the antidote?   ASA. Correct acidosis and electrolytes; make the urine more alkaline to help rid the body of the ASA. Possible hemodialysis.  
Patient comes in with these symptoms: Disinhibition (initial), lethargy, ataxa, nystagmus, stupor, coma, hypothermia, resp failure. What type of drug toxicity are they experiencing? What is the antidote?   Sedative-hypnotics and EtOH. Ventilatory support. Give flumazenil if BZ's are implicated.  
Patient comes in with these symptoms: Agitation, confusion, hallucination, muscle rigidity, hyperthermia, inc HR, inc BP, seizures. What type of drug toxicity are they experiencing? What is the antidote?   SSRI's - serotonin syndrome. Control the hyperthermia and seizures. Can use: cyproheptadine (anti-5HT2), antipsychotics, and BZ's.  
Patient comes in with these symptoms: Mydriasis, hyperthermia (hot dry skin), 3 C's - convulsions, coma, cardiotoxicity --> arrhythmias. What type of drug toxicity are they experiencing? What is the antidote?   TCA's. Control seizures and hyperthermia. Correct acidosis. Can give antiarrhythmics.  
Patient comes in with these symptoms: GI distress, garlic breath, "rice water" stools, torsades, and seizures. What type of toxicity are they experiencing? What is the antidote?   Acute arsenic poisoning (in pesticides, wood preservatives, ant poisons, etc); Antidote is dimercaprol or activated charcoal.  
Patient comes in with these symptoms: pallor, skin pigmentation, alopecia, stocking glove neuropathy, myelosuppression. What type of toxicity are they experiencing? What is the antidote?   Chronic arsenic poisoning. Antidote is penicillamine or succimer.  
Child comes in with these symptoms: severe GI distress --> necrotizing gastroenteritis with hematemesis and bloody diarrhea, dyspnea, shock, coma. What type of toxicity are they experiencing? What is the antidote?   Iron (from prenatal supplements, anemia meds); antidote is deferoxamine IV  
Patient comes in with these symptoms: NV, GI distress, malaise, tremor, tinnitus, paresthesias, encephalopathy, red or black feces. What type of toxicity are they experiencing? What is the antidote?   Acute lead poisoning. Decontaminate with gastric lavage and dimercaprol. Use succimer PO in children.  
Patient comes in with these symptoms: anemia (dec heme synth), neurop (wrist drop), nephrop (proteinuria, failure), hepatitis, mental retard (from pica), dec fertility, inc still births. What type of toxicity are they experiencing? What is the antidote?   Chronic lead poisoning. Decontaminate with gastric lavage and dimercaprol. Use succimer PO in children.  
Patient comes in with these symptoms: Chest pain, dyspnea, pneumonitis, hx of inhaling some vapor. What type of toxicity are they experiencing? What is the antidote?   Acute mercury vapor. Give succimer (PO) or dimercaprol (IM).  
Patient comes in with these symptoms: GI distress and bleeding, shock, renal failure, hx of inorganic salt ingestion from amalgams (dentistry or chemical reagent). What type of toxicity are they experiencing? What is the antidote?   Acute mercury salt ingestion. Give activated charcoal, then succimer (PO) or dimercaprol (IM).  
Patient comes in with these symptoms: CNS effects, ataxia, paresthesias, auditory and visual loss. What type of toxicity are they experiencing? What is the antidote?   Chronic mercury exposure - organic Hg. Give activated charcoal for ingestion, then succimer (PO) or dimercaprol (IM).  
Patient comes in with acetaminophen poisoning. What do you give as the antidote?   Acetylcysteine  
Patient comes in with insecticide poisoning. What do you give as the antidote?   Malathion/parathion - irreversible organophosphates, atropine + pralidoxime  
Patient comes in with physotigmine/neostigmine/pyridostigmine poisoning. What do you give as the antidote?   AchE inhibitors; Give atropine  
Patient comes in with Fe poisoning. What do you give as the antidote?   Deferoxamine  
Patient comes in with Digoxin poisoning. What do you give as the antidote?   Digoxin immune Fab; Ig from sheep that binds to digoxin, rendering them unable to bind to their action sites on target cells. The complexes accumulate in the blood and are expelled by the kidney.  
Patient comes in with heavy metals poisoning (arsenic, gold, mercury, lead). What do you give as the antidote?   Dimercaprol  
Patient comes in with rare heavy metals poisoning (Cd, Cr, Co, Mn, Zn). What do you give as the antidote?   EDTA  
Patient comes in with Theophylline poisoning. What do you give as the antidote?   It's a bronchodilator and inhibits phosphodiesterase. Antidote is esmolol.  
Patient comes in with B-agonist poisoning. What do you give as the antidote?   Esmolol (B-blocker)  
Patient comes in with methanol poisoning. What do you give as the antidote?   Fomepizole (ADH inhibitor) or EtOH -- use up all the alcohol dehydrogenase --> prevent methanol from becoming formaldehyde (toxic - can cause blindness!)  
Patient comes in with ethylene glycol poisoning. What do you give as the antidote?   Fomepizole (ADH inhibitor) or EtOH -- use up all the alcohol dehydrogenase --> prevent ethylene glycol from becoming glycoaldehyde (toxic!)  
Patient comes in with BZ poisoning. What do you give as the antidote?   Flumazenil  
Patient comes in with Zolpidem/Zaleplon poisoning. What do you give as the antidote?   These are non-BZ sedative/hypnotics (bind to BZ1 receptor)  
Patient comes in with opioid poisoning. What do you give as the antidote?   Naloxone  
Patient comes in with carbon monoxide poisoning. What do you give as the antidote?   O2  
Patient comes in with Copper poisoning (e.g. Wilson dz). What do you give as the antidote?   Penicillamine  
Patient comes in with Fe poisoning. What do you give as the antidote?   Penicillamine  
Patient comes in with Pb poisoning. What do you give as the antidote?   Penicillamine  
Patient comes in with Hg poisoning. What do you give as the antidote?   Penicillamine  
Patient comes in with atropine poisoning. What do you give as the antidote?   anti-cholinergic, so give physostigmine  
Patient comes in with antihistimine poisoning. What do you give as the antidote?   anti-cholinergic, so give physostigmine  
Patient comes in with anti-parkinson drugs poisoning. What do you give as the antidote?   anti-cholinergic, so give physostigmine  
Patient comes in with heparin poisoning. What do you give as the antidote?   Protamine  
Patient comes in with Warfarin poisoning. What do you give as the antidote?   Vitamin K  
Patient comes in with any oral poisoning. What do you give as the antidote?   Activated charcoal  
Patient takes ephedra. What are the adverse side effects of taking ephedra?   It's ephedrine --> sympathomimetic --> anorexia (causes wt loss), insomnia, tachy, urinary retention, arrhythmias, HTN, psychosis  
What is an herbal medicine that people take to decrease the frequency of migraines?   Feverfew  
Why do people take garlic to combat hyperlipidemia?   Garlic inhibits HMG-CoA Reductase (stop cholesterol synthesis) and ACE (stops production of ANGII, a potent vasoconstrictor --> lowers BP)  
Who usually takes saw palmetto?   Those with BPH. Saw Palmetto is a 5a-reductase inhibitor (converts testosterone into more potent form, dihydrotestorsterone) and androgen receptor inhibitor (androgen stimulates growth of prostate).  
Why do people take St. John's wort and what should they be warned about?   They take it for depressive disorders (may enhance 5HT functions in the brain). Induces CYP450 so could make their other meds less effective. If taken with SSRI's (creates too much 5HT!!) could lead to sorotonin syndrome.  


   





 
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