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163 Cards in this Set
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MOA of intrinsic pathway of apoptosis… examples…
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Changes in levels of anti and proapoptotic factors lead to incr mito permeability and release of cyto c. this leads to caspase activation. Examples: embryogenesis, hormone indxn (menstruation), atrophy (endometrial lining), and injurious stimuli
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MOA of extrinsic pathway of apoptosis… examples…
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Fas ligand binding to Fas or T-killer release of perforin or granzyme, also TNF receptor binding of TNF. Both of these result in activation of caspases that mediates cell breakdown. Examples: Tkiller cells, elimination of autoreactive T cells
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What are histo findings in apoptosis…
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Cell shrinkage, nuclear shrinkage, basophilia (pyknosis), membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karyolysis), apoptotic body formation which get phagocytosed.
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Reversible signs of cell injury…
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Cell swelling, nuclear chromatin clumping, decr ATP synthesis, decr glycogen, Fatty change, Ribosomal detachment
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Irreversible signs of cell injury…
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Nuclear pyknosis (basophilia), karyolsis (nuc fading), karyorrhesis (nuc fragments), Ca influx leading to caspase activation, plasma membrane damage via phospholipase, lysosomal rupture, mito permeability
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MOA of fibrinoid necrosis and examples…
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IC deposition in capillaries or glomeruli recruit complement, C5a recruits PMNs which cause damage leading to deposition of pink staining material in walls. Eg: HS purpura, Malignant HTN, PAN, Hyperacute transplant rejxn, Rheumatoid nodules, SLE
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Acute inflammation mediated by…
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Neutrophils, eosinophils, antibodies
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Mediators involved in termination of inflammation…
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LXA4, LXB4 LIPOXINS; omega3s RESOLVINS
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Located on vasculature or stroma that aids in rolling during leukocyte extravasation… located on the leukocyte
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Selectins on vasculature; Siayl-Lewis on leukocyte
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Located on vasculature that mediates tight binding during leukocyte extravasation… located on leukocyte…
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ICAM-1 on vasculature; LFA-1 or Integrins on leukocytes
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Located on vasculature that mediates diapedsis… on leukocyte…
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Both have PECAM-1
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Signs of leukocyte adhesion deficiency and what is missing…
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Signs: delayed umbilical cord separation, gingivitis, poor wound healing, and leukocytosis*. Deficiency in beta integrin (CD16:18) or selectins
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Type of amyoid protein associated w/ multiple myeloma… where derived from…
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AL which is derived from Ig Light chains. Primary amyloidosis
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Type of amyloid protein assoc w/ chronic inflammatory conditions… where derived from…
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AA which is derived from serum amyloid associated proteins. Secondary amyloidosis
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Type of amyloid protein that is involved in senile cardiac amyloidosis and where derived from…
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Transthyretin which is derived from AF.
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Type of amyloid protein that is involved in Diabetes mellitus II and where is it derived from…
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Amylin derived from AE (E for endocrine)
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Type of amyloid protein involved in medullary carcinoma of the thyroid and where does it derive from…
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A-CAL from CALcitonin
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Type of amyloid protein involved in Alzheimers and where does it derive from…
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Beta-amyloid derived from APP
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Type of amyloid protein involved in dialysis and wher does it derive from…
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Beta2 microglobulin which is derived from MHC I proteins
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TPR, LVEDP, and MVO2 in septic shock…
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Decr TPR, decr LVEDP, incr MVO2
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Function of metalloproteases in wound healing…
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Breakdown collagen and encourage myofibroblast (contraction) migration and tissue remodeling thru collagen 1 collagen 3 conversion
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Characteristics of in situ carcinoma…
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Neoplasic cells have not invaded basement membrane, high nuc/cyto ratio, neoplasmic cells encompass entire thickness of tissue, tumor cells are monoclonal
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Definition of anaplasia…
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Abnormal cells lacking differentiation which resemble primitive cells of same tissue; little or no resemblance to tissue of origin
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Definition of desmoplasia…
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Fibrous tissue formation in response to neoplasm
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Postsurgical gastric reminants incr risk of developing… other RFs…
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Gastric adenoCA. Also, pernicious anemia, chronic atrophic gastritis, nitrosamines, type A blood
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RFs for squamous cell CA…
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Actinic keratosis, Xero Pigmentosum, Immunocompromised (transplant), Arsenic exposure
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Plummer-Vinson syndrome and what does it incr risk of developing…
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Atrophic glossitis, esophageal webs, anemia all due to Fe deficiency. Incr risk of developing squamous cell CA of esophagous
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Oncogenes need to damage how many alleles to funxn… examples of oncogenes…
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Only need to damage one gene. Examples: abl (CML), c-myc (burkits), bcl-2 (follicular), erb-B2, ras, L-myc (lung), N-myc, ret (MEN II), c-kit (GIST)
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Tumor suppressor genes need to damage how many alleles before loss of funxn… examples…
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Both alleles since LOF. Examples: Rb, BRCAs, p53, p16, APC, WT1, NFs, DPC, DCC
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BRCA1 located on what chromo, BRCA2…
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BRCA1 (17q), BRCA2 (13q)
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P53 located on what chromosome…
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17p
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Which tumor suppressor gene is associated w/ melanoma… what chromo located on…
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P16 which is located on chromo 9p
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Tumor suppressor genes located on chromo 17…
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BRCA1, p53, and NF1
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CEA involved in what cancers…
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Colon and pancreatic. Also breast and stomach
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AFP involved in what cancers…
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HCC, also non-seminomatous germ cell tumors like yolk sac and embryonal cell tumor of testis
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Beta-hCG involved in what cancers…
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Hyatidiform moles, Choriocarcinomas, Gestational trophoblast tumors
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S100 in tumor marker for…
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Melanoma, neural tumors, astrocytomas, carcinoid
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ALP elevated in…
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Metastasis to bone, obstructive biliary dx, Pagets dx of bone
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Bombesin is tumor marker for…
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Neuroblastoma, lung, and gastric cancer
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CCl4 associated with what pathology… where found…
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Centrilobular necrosis or fatty change in liver… found in fire extinguishers, cleaning agents, refrigerators
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Vinyl chloride (aerosols and PVC) assoc w/ what pathology…
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Liver angiosarcoma (malignant blood vessel tumor)
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Cigarette smoke associate w/ what tumors…
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Squ cell CA or larynx and lung, Small cell CA of lung, RCC, TCC
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Arsenic exposure assoc w/ what pathology..
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Squamous cell carcinoma of skin and liver angiosarcoma
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Tumors that can release PTHrP… what else can these release…
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Sq cell CA of lung, RCC, breast CA. also can release TNF, TGF-b, IL-1
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Cause a decr ESR…
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Sickle cell anemia, Polycythemia, CHF
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Tumors that metastasis to brain…
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Lung, Breast, Melanoma, Kidney (RCC), GI
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Tumors that metastasis to liver in descending order of commonality…
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Colon > Stomach > Pancreas > Breast > Lung. (Cancer Sometimes Penetrates Benign Liver)
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Cancers w/ highest incidence in males…
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Prostate > Lung > Colon/rectum
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Cancers w/ highest mortality in men…
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Lung > prostate
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Cancers w/ highest incidence in women…
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Breast > Lung > Colon/rectum
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Cancers w/ highest mortality in women…
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Lung > breast
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On enzyme kinetic graph, 1/V coorelates w/…
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y-intercept, increased value = decr Vmax
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On enzyme kinetics graph, how can distinguish non-competitive inhibitor from competitive inhibitor (graph w/ 1/V and 1/S)…
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Noncompetitive inhibitor is going to have same Km to it will have same x-intercept whereas competitive inhibitor is going to have same Vmax so same y-intercept
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Slope of enzyme kinetics graph (1/V and 1/S graph)
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Km/Vmax
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Which kind of inhibitor decr potency of drug…
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Competitive
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Which kind of inhibitor decr efficacy of drug..
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Noncompetitive
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Equation for Vd… what can alter Vd…
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Vd = amt in body/plasma concentration. Can be altered by liver or kidney disease
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Characteristics of drugs w/ low Vd (4-8L)…
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Distribute in blood because have high molecular wt, bound to plasma proteins, hydrophilic
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Characteristics of drugs w/ medium Vd (8-16L)..
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Distribute in extracellular space or body water. Small molecular wt and hydrophilic
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Characteristics of drugs w/ large Vd (up to 40L)…
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Distribute in tissues. Small, hydrophobic or lipophilic
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Equation for clearance of a drug…
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CL= rate of elimination of drug/plasma concentration of drug or Vd x Ke
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Equation for t1/2 of drug…
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T1/2 = (0.7 x Vd)/CL
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Equation for loading dose of drug…
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LD = (target plasma concentration x Vd)/bioavailability
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Equation for maintenance dose of drug…
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MD = (target plasma concentration x CL)/bioavailability
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Drugs that are eliminated in zero order kinetic fashion…
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Phenytoin, Ethanol, Asprin (high doses)
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Examples of drugs that are weak acids (which you would eliminate by alkalinizing urine w/ acetazolamide or NaHCO3)…
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Phenobarbitol, methotrexate, TCAs, Asprin
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Examples of drugs that are weak bases (which you would eliminate by acidifying the urine w/ ammonium chloride)…
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Amphetamines
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Geriatric patients lose which phase of metabolism of drug first…
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Phase I (redox, hydrolysis) done by p450
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After which drug metabolism phase are drugs renally excreted…
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Phase II (acetylation, glucuronidation, sulfation)
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Examples of drugs w/ high 1st pass metabolism…
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Propranolol, NO, lidocaine
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Efficacy and potency of partial agonist…
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Decreases maximal efficacy (like noncompetitive) but may have same, lower, or higher potency. Does this because it acts on same receptor as full agonist
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NT for post-gang sympathetic innervation of sweat glands…
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Ach
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NT for post-gang sympathetic innervation of gland cells (not sweat glands)…
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NE, same for smooth muscle (except renal) and cardiac muscle
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NT for post-gang sympathetic innervation of adrenal medulla…
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Trick. There is no post-ganglionic sympathetic innervation of adrenal medulla, only pre-ganglionic which is done via Ach on nicotine recptors
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NT for post-ganglionic sympathetic innervation of renal vascular smooth muscle…
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DA (D1)
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What type of receptors are nicotinic receptors…
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Na/K channels
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Characteristics of highly lipid soluble anesthetics w/ regards to blood solubility, onset of action, tension, and blood:gas portioning coefficient, and excretion…
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High lipid soluble means low soluble in blood so has high anesthetic tension, meaning blood gets saturated w/ it quickly. Has fast onset of action because distributes quickly into brain, liver, and adipose; also rapid recovery. Haas low B:G coefficient. Is metabolized in liver and less likely to be excreted in kidney
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Functions of alpha 2 receptors…
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Decr sympathetic flow, Decr insulin release
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Functions of beta 1 receptors…
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Incr HR, Incr contractility, Incr rennin release, Incr lipolysis
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Functions of beta 2 receptors…
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Vasodilation, bronchodilation, Incr HR, Incr contractility, Incr lipolysis, Incr insulin release, decr uterine tone
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Location of M1 receptors…
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CNS, enteric nervous system
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Funxn of M2 receptors… MOA
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Decr HR and contractility of ATRIA by blocking release of NE from terminal
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Funxns of M3 receptors…
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Incr exocrine gland secretions (sweat, gastric), incr gut peristalsis, incr bladder contrxn, bronchoconstrxn, incr papillary sphincter contrxn, incr ciliary mscle contrxn
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Funxns of H1 receptors…
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Incr nasal and bronchial mucus prodxn, contraction of bronchioles, pruritis, pain (allergy stuff)
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Pathway of Gq receptor…
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Phospholipase C takes lipids to PIP2 IP3 (Ca increase) and DAG (PKC)
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MOA of metyrosine… use…
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Blocks tyrosine hydroxylase so DOPA not made and thus, less NE and Epi made. Used in pheochromocytoma
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MOA of reserpine…
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Blocks VMAT (vesicular monoamine transporter) thus less DA, NE, and Epi. Used in dykinesia in Huntingtons and in HTN
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Release of NE from sympathetic nerve terminal is modulated via… MOA…
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NE modulates it itself by acting on alpha2 receptors and modulated by Ach on M2 receptors, and ATII (increases release)
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Direct cholinomimetic agonists…
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Bethanecol, carbachol, pilocarpine, methacholine
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MOA and use of bethanecol…
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Cholinergic agonist. Used post-op and neurogenic ileus and urinary retention. Resistant to AChE
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MOA and use of carbechol…
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Cholinergic agonist used for glaucoma, papillary contrxn, and release of intraocular pressure
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MOA and use of pilocarpine…
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Cholinergic agonist that simulates sweat, tears, saliva b contracting ciliary muscle of eye (open angle) and papillary sphincter (closed angle). Resistant to AChE
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Anticholinesterases,, meaning cholinesterase inhibitors, (cholinomimietics) and which ones cross BBB…
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Neostigmine, Pyridodstigmine, Edrophonium all do NOT cross BBB. Physostigmine and echothiophate cross BBB so can be used for glaucoma
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Examples of cholinesterase inhibitors and symptoms… antidote…
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Organophosphates and parathion. Cause DUMBBELSS: Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation (skeletal muscle, CNS) Lacrimation Sweating/Salivation. Give atropine or pralidoxime (regenerator)
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Muscarinic antagonists that work in eye…
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Atropine, homatropne, tropicamide
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MOA of benztropine… use…
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Muscarinic ANTagonist used in parkinsons
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MOA of ipratropium… use…
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Muscarinic ANTagonist used in asthma and COPD
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MOA of oxybutinin, glycopyrrolate… use…
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Muscarinic ANTagonists used to reduce urgency in mild cystitis and reduce bladder spasms
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Antimuscarinics used in treatment of peptic ulcer dx…
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Methscopolamine, pirenzepine, propantheline
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Drug used for muscle symptoms of cholinomimetics/cholinesterase inhibitor…
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Pralidoxime, NOT atropine because atropine only works at M receptors, not N
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SEs of atropine…
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Incr body temp, rapid pulse, dry flushed skin, cycloplegia, constipation, disorientation, closed-angle glaucoma in elderly, urinary rtn, hyperthermia
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MOA and uses of epinephrine…
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Agonist for alphas and betas, selective at low doses for beta1. used in anaphylaxis, open glaucoma, asthma, hypotsn
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MOA and uses of NE… what do you need to be careful with
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Alpha1,2 > beta1. used for hypotension but DECREASES renal perfusion
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MOA and uses of isoproterenol…
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Agonist of Beta1 = beta2. used in AV block
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MOA and uses of DA…
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Agonist of D1=D2 > beta > alpha. Used in shock (incr renal perfusion), heart failure
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MOA and uses of dobutamine…
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Agonist of Beta1 > beta2, ionotropic (strength) but not chronotropic
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MOA of phenylephrine
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Agonist of alpha1 > alpha2. sounds like phenyl’epinephrine’ so is an agonist. Used for papillary dilation, vasoconstrxn, nasal decongestion
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Selective beta2 agonists and uses…
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MAST: Metaproterenol, Albuterol, Salmeterol, Terbutaline (reduce premature uterine contrxns). All can be used for asthma
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MOA of ritodrine… uses…
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Beta 2 agonist used to decr uterine contrxns
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MOA and uses of ephedrine…
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Releases stored catecholamines. Used for nasal decongestion, urinary incontenance, hypotnsn
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Effect of epinephrine on SBP, DBP, contractility and renal blood flow…
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Incr SBP (b1), Decr DBP (b2), Incr contractility (b1), decr renal blood flow (a1)
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Alpha2 agonists and uses…
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Clonidine and alpha-methyl dopa. Used for HTN, especially during renal dx
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Selective alpha1 blockers and uses… SEs…
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Prazosin, terazosin, doxazosin. Used in HTN, urinary retention. SEs: ortho hypo, dizziness, HA
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Selective alpha2 blocker and uses… SEs…
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Mirtazapine used for depression. SEs: sedation, wt gain, incr cholesterol
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Beta1 blockers…
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BEAM: Betaxolol, Esmolol, Atenolol, Metoprolol
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MOA of acebutol…
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Partial agonist of betas (1and2) so is a beta blocker
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Non-selective alpha and beta antagonists…
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Labetalol, carvedilol
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Beta blocker used in glaucoma and MOA…
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Timolol. Decr secretion of aqueous humor from ciliary process
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SEs of beta blockers…
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Impotence, asthma exacerbation (esp if has beta2 block), CV effects (bradycardia, AV block, CHF), CNS- sedatioin, sleep. Use w/ caution in diabetics (beta2 releases insulin)
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Antidote for atropine or other antimuscarinic overdose…
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Physostigmine (gets to CNS)
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Antidote for beta blocker overdose…
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Glucagons
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Antidote for digitalis toxicity…
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Stop dig, normalize K, lidocaine, anti-dig Fab, Mg
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Antidote to Fe overdose…
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Deferoxamine
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Antidote to lead poisoning…
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EDTA, dimeraprol, succimer, penicillamine
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Antidote to mercury, arsenic, gold poisoining…
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Dimercaprol, succimer
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Antidote to Cu, arsenic, gold poisning…
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Penicillamine
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NaHCO3 used as antidote for…
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Salicyclate poisoning and TCA overdose
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Drugs that give atropine like antimusc side effects (dry mouth, constipation, disorientation, etc)…
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TCAs, 1st gen antihistamines, antipsychotics
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Drugs that cause coronary vasospasm…
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Cocaine, sumatriptan, ergots
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Drugs that cause cutaneous flushing…
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Vancomycin, Adenosine, Niacin, Ca blockers
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Drugs causing agranulocytosis…
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Clozapine, carbamazapine, colchicines, PTU, MM, dapsone. (3 Cs, PTU, MM, Dap)
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Drugs causing hemolysis in G6PD deficiency…
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INH, Sulfonamides, Primaquine (vivax, ovale dormants), Aspirin, Ibu, Nitrofurantoin
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Drugs causing acute cholestatic hepatitis…
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Macrolides
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Focal to massive hepatic necrosis caused by which drugs…
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Halothane, valproic acid, acetpminophen, amanita (Hal Val and Tylenal ain’t yer livers pal)
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Drugs causing gynecomastia…
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Spironolactone digitalis, cimetidine, chronic alcohol, estrogens, Ketoconazole
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Drugs causing hot flashes…
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Tamoxifen, clomiphene (ovary stimulant)
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Drugs causing Stevens-Johnson syndrome…
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Ethosuxamide, lamotrigine, carbamazapine, phenobarbatol, phenytoin, sulfas, penicillin, allopurinol
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Drugs causing SLE like syndrome…
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Hydralazine, INH, Phenytoin, Procainamide
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Drugs causing seizures…
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Buproprion, imipenem, INH
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Drugs that cause a disulfram like rxn w/ alcohol…
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Metronidazole, cephalosporins, procarbazine, 1st gen sulfonylureas
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Nephrotoxic and neurotoxic drugs…
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Polymyxins
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Nephrotoxic and ototoxic drugs…
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Amnioglycosides, vancomycin, loops, cisplatin, salicylates
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SEs of sulfa drugs…
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Fever, pruritic rash, SJ syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, urticaria.
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Induction, potency, and recovery times of anesthetic drugs in relation to their blood solubility and fat solubility…
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Drugs that are lipophilic have increased potency and are usually insoluble in blood. Decr blood solubility = rapid indxn and recovery
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Features of blood and lipid solubility and induction and potency of nitrous oxide…
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Low blood solubility so fast induction time and recovery but also low lipid solubility so decreased potency
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Features of blood and lipid solubility and potency and induction of halothane…
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Halothane has increased lipid and blood solubility so it has a high potency (lipid) and slow induction and recovery (high blood solubility)
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MOA of anesthetic drugs that cause lungs to increase rate and depth of breathing…
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Increased gas tension (meaning they saturate faster- decr solubility)
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MOA of drugs that have a slow onset of action due to high blood solubility…
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Incr blood solubility means increased blood:gas partition coefficient = incr solubility = more gas required to saturate blood = slower onset of action
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Correlation between AV concentration gradient of drug and solubility/onset of action…
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Incr AV concentration gradient means there is increased solubility, thus a decreased onset of action
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Effects, organ wise, of inhaled anesthetics…
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Myocardial depression, respiratory depression, nausea/emesis, incr cerebral blood flow and incr cerebral metabolic demand
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Toxicity of inhaled anesthetics…
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Inhaled anesthetics are nitrous oxide and “urines.” SEs: hepatotox (Halothane), nephrotox (methoxyflurane), proconvulsant (enflurane), malignant hypethermia, expansion of trapped gas (Nitrous oxide)
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IV anesthetics examples by name and class…
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Thiopental (barb), Midazolam (benzo), Ketamine (PCP analog), Morphine, fentanyl (opiates), Propofol
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MOA and uses thiopental… how effect terminated…
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High lipid soluble (potent), rapid entry into brain and decreases blood flow. Used to induce anesthesia and short surgical procedures. Effect terminated by redistribution into fat.
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Use and SEs of midazolam…
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Endoscopy. Adjunct to gaseous anesthetics and narcotics. May cause severe post-op respiratory depression, decr BP, amnesia
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MOA and SEs of ketamine… which organs does it stimulate and which decrease…
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Blocks NMDA receptors. Cardiovascular stimulant and cerebral blood flow decrease. SEs: disorientation, hallucination, bad dreams
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Use and benefit of propofol… MOA…
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Rapid anesthesia induction for short procedures. Less post-op nausea then thiopental. Potentiates GABAa
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Ester local anesthetics… MOA… SEs…
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Procaine, Cocaine, Tetracaine. Preferentially block actived Na channels (most effective against rapid firing neurons) by binding receptor inside cell. SEs: CNS excitation, HTN, hypotension, arrhythmias (cocaine). Allergy
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Amide local anesthetics… MOA… SEs…
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Lidocaine, Mepivacaine, Bupivacaine. Block rapidly firing neurons by binding to Na channel receptors on inside of cell. SEs: CNS excitation, CV toxicity (bupivacaine), HTN, hypotension.
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When might more local anesthetic be needed and why…
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Infected tissue often acidic so alkaline anesthetics cannot penetrate membrane as effectively. More anesthetic needed
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What is order of nerve blockade w/ local anesthetics…
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Small diameter > large diameter and myelinated fibers > unmyelinated. Size factor predominates.
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Order of sensory modality lost when given local anesthetic…
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1st: pain > temp > touch >pressure
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Succinylcholine complications and when is appropriate use of antidote…
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Hyperkalemia and hypercalcemia. Reversal of blockade only possible w/ anticholinesterases in phase II (repolarized cells, but blocked)
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MOA of nondepolarizing NM blockers… reversal of blockade…
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Competitively block Ach receptors. Reversal w/ neostigmine, edrophonium, and atropine
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