1、Cholinergics/anticholinergics and drugs affecting the endocrine system,By Linda Self,Cholinergics,PNS Receptors Acetylcholine Direct and indirect acting cholinergic drugs,Direct acting cholinergics,Urecholine Actions indications,Indirect acting agents,Affect cholinesterase Neostigmine ( prostigmine)
2、 is prototype Mestinon (pyridostigmine) is drug of choice for MG Tensilon (edrophonium)diagnostic agent Antilirium (physostigmine)only agent that crosses blood brain barrier Aricept (donepazil)use in AD,Cholinergic and Myasthenic crises,Difficult to distinguish Treatments differ Myasthenic crisis re
3、quires more medication, cholinergic crisis requires less Distinguished by the timing of s/swithin one hour of anticholinesterases, likely cholinergic excess. If within three hours, myasthenic problem. Cholinergic crisis-Tx supportively, atropine, decrease anticholinesterase med Myasthenic-Supportive
4、 treatment and increase of anticholinesterase med (testing may require intubation and ventilator assist),Organophosphate poisoning,Tabin, Sarinnerve gases Insecticidesmalathion, parathion Decontaminateclothing, flushing with water, activated charcoal and lavage Atropine for muscarinic effectshypersa
5、livation, urination, defecation, laryngospasm) Protopam (pralidoxime) for nicotinic effects causes poison to release enzyme cholinesterase,AD,Use reversible indirect acting cholinergics Aricept (donepezil)does not cause liver toxicity. Can cause n/v, bradycardia, PUD, exac. of asthma Razadye (galant
6、amine)-long acting Exelon (rivastigmine) Cognex (tacrine) more hepatototoxicity,Anticholinergics,Most affect muscarinic receptors in brain, secretory glands, heart and smooth muscle Few affect nicotinic receptors, e.g., Robinul (glycopyrolate) Effects of anticholinergics are diffuse IndicationsGI (g
7、astritis, UC, irritable bowel; GU antispasmotic in overactive bladder; ophthalmology for exams, glaucoma; respiratory for bronchodilation; cardiology to increase heart rate Antilirium for overdose of anticholinergics,Anticholinergics,Atropine Atrovent Scopolamineantiemetic, motion sickness Spiriva (
8、tiotropium) Bentyl (antiscretory/antispasmotic) Cogentin Trihexy (Parkinsons),Corticosteroids; Hematopoietic, Immunizing, immunosuppressive agents and drugs used in oncology,Immunity,Defense Specificity, memory and inducibility Normal immunity ability to recognize self and non-self Recognition of ep
9、itopes (distinctive molecules on non-self antigens) Underactive=immunodeficiency Overactive=autoimmune diseases,Immunity,Natural Acquired immunityactive or passive (antibodies are transferred) Cellularinvolving activated T cells Humoralinvolves B cells and antibodies All antigens elicit both types,I
10、mmunizations,Administration of antigen to induce antibody formation (active) or serum from immune people (passive) Regulated by US FDA,Active Immunity,Vaccines and toxoids Vaccines are suspensions of microorganisms or antigenic products Toxoids are bacterial toxins that have been modified to retain
11、antigenic properties, not permanent,Indications for active immunity,Give before exposure to actual illness Diphtheria,tetanus, pertussis, hemophilus influenza (Hib) , inactivated polio vaccine, pneumococcal (PCV), hepatitis A and B, varicella, MMR, PPV, MC4, influenza Some combinations,Contraindicat
12、ions to use of agents for active immunity,Febrile illnesses Immunosuppressed Immunodeficiency states Leukemia Lymphoma In pregnancy If generalized malignancy,Passive Immunity,Immune serums are biologic products used for passive immunity Temporary Agents: cytomegalovirus immune globulin, hepatitis B
13、immune globulin, rabies immune globulin, rubella, tetanus immune globuline, varicella zoster, RSV immune globulin, tetanus immune globulin,Key Points in Immunizations,Women of childbearing age should not get pregnant for three months after receiving Rubella immunization Influenza-may start at 6 mont
14、hs; annually in those over 65 Tetanus toxoidafter initial immunization, give every ten years Children with HIVshould not receive live vaccines Pneumococcal at 65; may repeat in five years if with chronic conditions After Varicella, avoid close contact with newborns, pregnant women and immunocompromi
15、sed persons After immunizations, stay in area 30 minutes,Hematopoietic and Immunostimulant Drugs,Cytokines or biologic response modifiers given to restore normal function or increase ability of the immune system Examples: certain interferons and interleukins, colony stimulating factors,Definitions,C
16、ytokinessubstances produced by bone marrow cells, regulate cellular activities; are the key components in producing hematopoietic and immunostimulant drugs Interferonsglycoproteins w/antiviral activity Interleukinscytokines that enable communication between leukocytes and other cells involved in inf
17、lammation or cell-mediated response. Resultmaximized response to a given pathogen or foreign antigen.,Hematopoietic and immunostimulant drugs,Very powerful Difficult to maintain therapeutic dosing for prolonged time Can have untoward and unanticipated side effects Can act as antiproliferative and im
18、munoregulatory agents; can augment natural killer cells Parenteral Significant side effects decreasing compliance,Hematopoietic Agents,Epogen (epoetin alfa)=erythropoietin Use for anemia Hct 2x weekly, adjust as Hct increases to 36%,Colony stimulating factors,Neupogen (filgrastim) stimulate blood ce
19、ll production by marrow in patients with bone marrow transplantation or chemotherapy induced neutropenia Leukineangiogenetic, used in ischemic heart disease,Interleukins,Proleukin (aldesleukin)recombinant version if IL-2 Activates cellular immunity, produces TNF and inhibits tumor growth For metasta
20、tic renal cell CA Toxicity can cause GI bleed, dysrhythmias, resp. embarrassment Contraindicated in recent organ transplantation,Interferons,Alfa -2a and 2b for hairy cell leukemia and Kaposis sarcoma alfa n1 approved for chronic hepatitis C Beta for multiple sclerosis,Corticosteroids,Decrease inapp
21、ropriate or undesirable immune response. Examples include: RA, SLE, asthma or suppression of transplant rejection Glucocorticoids Effectscatabolism, decrease immune response, decrease utilization and increase production of glucose, stabilize mast cells, affect gastric mucosa, muscle atrophy and adre
22、nal cortex suppression,Corticosteroids,Prednisone is prototype Celestone (betamethasone) Decadron (dexamethasone) Solucortef (methylprednisolone) Kenalog (triamcinolone),Immunosuppressant Drugs,Use in concert with steroids Used in autoimmune disorders Newer agents modify specific components of immun
23、e response, fewer SE Imuran-bone marrow depression is SE Sandimmune (cyclosporine)monitor renal and hepatic toxicity, CNS toxicity Methotrexatebone marrow suppression Remicadeinfusion reactions, GI upset, others,Cytotoxic, Antiproliferative Agents,Used primarily in cancer Imuran (azathioprine) antim
24、etabolite that targets rapidly proliferating cells including T and B lymphocytes Rheumatrex (methotrexate) folate antagonist. Used for cancer and for autoimmune or inflammatory disorders.,Antirejection Agents,Sandimmune (cyclosporine)inhibits synthesis of IL- 2 necessary for activation of T cells an
25、d B cells. Rapamune (sirolimus) affects T cell activation and proliferation secondary to several interleukins Prograf (tacrolimus)prevents rejection of transplanted organs by inhibiting T lymphocytes,Monoclonal Antibodies,Remicade (infliximab). Inhibits TNF from binding to receptors. Used in RA and
26、Crohns. Enbrel (etanercept) TNF receptor binder. RA. Arava (Leflunomide) antiproliferative and anti-inflammatory activities. Inhibits pyrimidines needed for RNA and DNA synthesis. RA.,Drugs affecting the Endocrine System,Review of Endocrine system Hypothalamusreleasing hormones that affect both ante
27、rior and posterior pituitary Ant. Pituitary-GH, ACTH, TSH, FSH, LH, Prolactin, melanocyte stimulating hormone Post. PituitaryADH, oxytocin Adrenals Thyroid pancreas,Hypothalamic hormones,Generally parenteral or intranasally, broken down in GI system Equivalent to gonadotropin releasing hormones Fact
28、rel (gonadorelin)used for diagnostic testing of gonadotropin function Zoladex (goserelin)reduces hormonal levels so useful in metastatic breast cancer, prostate cancer and in endometriosis Lupron (leuprolide)-advanced prostate cancer, central precocious puberty, endometriosis, uterine fibroids,Hypot
29、halamic hormones,None of the GnRH equivalents can be given orally Factrel (gonaderelin) diagnostic testing Lupron( leuprolide)decreases estrogen and testosterone levels Zoladex (goserelin) decreases estrogen and testosterone levels Sandostatin (octreotide)somatostatin. Decreases GH, decreases GI sec
30、retions and motility. Given in severe diarrhea as well as with acromegaly.,Anterior Pituitary Hormones,Cosyntropin (corticotropin)-diagnostic test of adrenal function Protropin (somatrem)synthesized growth hormone. Promotes growth in those deficient in GH or in renal failure. Tissue wasting with AID
31、S. Chorex (HCG)synthetic LH. Diagnostic test of testosterone production, cryptorchidism Pergonal (menotropins)preparation containing both LH and FSH. Usually combined with HCG to induce ovulation.,Anterior Pituitary Hormones,Thytropar (thyrotropin)used as diagnostic agent to distinguish between prim
32、ary and secondary hypothyroidism Humatrope (somatropin) for children with GH deficiency. Not effective in epiphyseal closure. Tissue wasting of AIDs,Posterior Pituitary Hormones,DDAVP (desmopressin) and Pitressin (vasopressin) are synthetic equivalents of ADH. Useful in diabetes insipidus. Parentera
33、l desmopressin used as hemostatic agent in hemophilia and Von Willebrands Disease. Tx of bleeding esophageal varices. Pitocin (oxytocin) promotes uterine contractility. Used in induction of labor and to control postpartum bleeding.,Drugs used for Calcium and Bone Disorders,BisphosphanatesFosamax (al
34、endronate), Actonel (risedronate) and Zometa (zoledronic acid) Bind to bone, inhibit calcium resorption Take on empty stomach, with water, 30 minutes before other intake Calcimar, Miacalcin (calcitonin-salmon) for hypercalcemia, Pagets Disease, and osteoporosis. Slows bone resorption, may be helpful
35、 with bone pain.,Drugs used for calcium and bone disorders,Symptomatic hypocalcemia, calcium gluconate Oral calcium preparations for osteopenia or nutritional deficiency Corticosteroidsinhibit cytokine release by cytolytic effects of some bone tumors, inhibit calcium absorption from intestine and by
36、 increasing calcium excretion in urine. Used in hypercalcemia due to malignancies or Vitamin D intoxication,Drugs used for calcium and bone disorders,Estrogens most beneficial immediately after menopause. Decrease bone breakdown, increase calcium absorption from gut and increase calcitriol. Evista (
37、raloxifene) and Nolvadex (tamoxifen) act like estrogen in some tissues and prevent the action of estrogen in other body tissues Evista is classified as a selective estrogen receptor modulator and is approved for postmenopausal osteoporosis.,Calcium and bone disorders,Nolvadex (tamoxifen) is classifi
38、ed as an antiestrogen. Used to prevent and treat breast cancer. Also has estrogenic effects so can be used to prevent osteoporosis Forteo (teriparatide)recombinant DNA version of parathormone. Increases bone formatin by increasing osteoblasts. Increases serum levels of calcium and calcitriol. Not kn
39、own to cause deposition of calcium in soft tissues Vit D 400 IU for 6months to 24 years; 200IU/day 25 years and older Lasix causes increased excretion of calcium,Adrenal Agents,Adrenal cortex produces glucocorticoids, mineralocorticoids and adrenal sex hormones Hydrocortisone is prototype Florinef (
40、fludrocortisone)only mineralocorticoid described in text,Pearls,Thiazide diuretics contraindicated in hypercalcemia as decrease urinary excretion of calcium Look at albumin levels when examining calcium levels Children on growth hormone, ht. and wt. chart weekly, follow epiphyseal closure Dietary ca
41、lcium is superior to supplemental Menopausal women should have 1000 mg of calcium daily,Pearls,Vasopressin-watch for water intoxication, chest pain, MI Oxytocin can result in uterine rupture Octreotide can cause arrhythmias, bradycardia, hyperglycemia, injection site pain and symptoms of gallstones,
42、Acute hypercalcemia,Medical emergency For severe s/s or level 12mg/dL. Rehydrate IV saline Lasix Fosamax or Zometa Monitor serum calcium levels Calcium channel not so effective,Thyroid and antithyroid drugs,Thyroid produces thyroxine, triidothyronine and calcitonin Thyroxine is called T4 (has 4 atom
43、s of iodine) Triidothyronine has 3 atoms of iodine so is called T3,Thyroid,Essential for normal G&D Critical for brain development and maturation Increases rate of cellular metabolism and oxygen consumption Increases heart rate, force of contraction and cardiac output Increases fat metabolism includ
44、ing cholesterol Inhibition of pituitary secretion of TSH,Thyroid Disorders,Goiterenlargement of thyroid due to lack of iodine in diet; thyroiditis, tumors, hyper or hypo function of the thyroid Compensate for iodine deficiency, pituitary secretes more TSH; thyroid enlarges producing more hormone, po
45、ssibly effecting a normal hormone level Correction of goiter involves replacing iodine; replacement of thyroid hormone. May have regression or may need excision,Hypothyroidism,Occurs secondary to disease or destruction of the thyroid Causes: Hashimotos thyroiditis, previous exposure to radiation, tr
46、eatment with amiodarone, lithium or iodine,Hypothyroidism,Congenital=Cretinism; may occur with lack of iodine in mothers diet. S/S in infancy, can result in severe mental retardation Hypothyroidism may be subclinical but may progress. S/S initially vague but become more pronounced: cold intolerance,
47、 fatigue, aches and pains, puffy appearance, mental sluggishness, anemia, bradycardia Tx-exogenous thyroxine Replacement indicated if TSH is 10 microunits/L,Hypothyroidism,Myxedema coma Characterized by hypothermia, cardiovascular collapse, coma, hyponatremia, hypoglycemia, and lactic acidosis Predi
48、sposing factors include: cold, infection, CNS depressants Txsynthetic levothyroxine is drug of choice. In myxedema coma, Tx will be given IV.,Hyperthyroidism,Characterized by excessive secretion of thyroid hormone May be associated with overtreatment with thyroid drugs, nodular goiter, thyroiditis,
49、functioning thyroid cancer, pituitary adenoma resulting in excess TSH secretion Subclinical hyperthyroidism is defined as reduced TSH (below 0.1 microunit/L) and normal T3 and T4 levels Greatly increases the risk for atrial fibrillation,Hyperthyroidism,Thyroid storm or thyrotoxic crisis is a severe complication. Will result in: severe tachycardia, fever, dehydration, heart failure and coma Tx depends on cause. May need surgery or radioactive iodine therapy Antithyroid drugs include Propylthioruracil (PTU)and Tapazole (methimazole), and iodine preparations,
