By Linda Self
Dec 24, 2015
Indirect acting agentsAffect cholinesteraseNeostigmine ( prostigmine) is prototypeMestinon (pyridostigmine) is drug of
choice for MGTensilon (edrophonium)diagnostic agentAntilirium (physostigmine)only agent that
crosses blood brain barrierAricept (donepazil)—use in AD
Cholinergic and Myasthenic crisesDifficult to distinguishTreatments differMyasthenic crisis requires more medication,
cholinergic crisis requires lessDistinguished by the timing of s/s—within one
hour of anticholinesterases, likely cholinergic excess. If within three hours, myasthenic problem.
Cholinergic crisis-Tx supportively, atropine, decrease anticholinesterase med
Myasthenic-Supportive treatment and increase of anticholinesterase med
(testing may require intubation and ventilator assist)
Organophosphate poisoningTabin, Sarin—nerve gasesInsecticides—malathion, parathionDecontaminate—clothing, flushing with
water, activated charcoal and lavageAtropine for muscarinic effects—
hypersalivation, urination, defecation, laryngospasm)
Protopam (pralidoxime) for nicotinic effects –causes poison to release enzyme cholinesterase
ADUse reversible indirect acting cholinergicsAricept (donepezil)does not cause liver
toxicity. Can cause n/v, bradycardia, PUD, exac. of asthma
Razadye (galantamine)-long actingExelon (rivastigmine)Cognex (tacrine)– more hepatototoxicity
AnticholinergicsMost affect muscarinic receptors in brain,
secretory glands, heart and smooth muscleFew affect nicotinic receptors, e.g., Robinul
(glycopyrolate)Effects of anticholinergics are diffuseIndications—GI (gastritis, 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
AnticholinergicsAtropineAtroventScopolamine—antiemetic, motion sicknessSpiriva (tiotropium)Bentyl (antiscretory/antispasmotic)CogentinTrihexy (Parkinson’s)
ImmunityDefenseSpecificity, memory and inducibilityNormal immunity –ability to recognize self
and non-selfRecognition of epitopes (distinctive molecules
on non-self antigens)Underactive=immunodeficiencyOveractive=autoimmune diseases
ImmunityNaturalAcquired immunity—active or passive
(antibodies are transferred)Cellular—involving activated T cellsHumoral—involves B cells and antibodiesAll antigens elicit both types
ImmunizationsAdministration of antigen to induce antibody
formation (active) or serum from immune people (passive)
Regulated by US FDA
Active ImmunityVaccines and toxoidsVaccines are suspensions of microorganisms
or antigenic productsToxoids are bacterial toxins that have been
modified to retain antigenic properties, not permanent
Indications for active immunityGive before exposure to actual illnessDiphtheria,tetanus, pertussis, hemophilus
influenza (Hib) , inactivated polio vaccine, pneumococcal (PCV), hepatitis A and B, varicella, MMR, PPV, MC4, influenza
Some combinations
Contraindications to use of agents for active immunity
Febrile illnessesImmunosuppressedImmunodeficiency statesLeukemiaLymphoma In pregnancy If generalized malignancy
Passive ImmunityImmune serums are biologic products used
for passive immunityTemporaryAgents: cytomegalovirus immune globulin,
hepatitis B immune globulin, rabies immune globulin, rubella, tetanus immune globuline, varicella zoster, RSV immune globulin, tetanus immune globulin
Key Points in ImmunizationsWomen of childbearing age should not get pregnant
for three months after receiving Rubella immunization
Influenza-may start at 6 months; annually in those over 65
Tetanus toxoid—after initial immunization, give every ten years
Children with HIV—should not receive live vaccinesPneumococcal at 65; may repeat in five years if with
chronic conditionsAfter Varicella, avoid close contact with newborns,
pregnant women and immunocompromised personsAfter 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
DefinitionsCytokines—substances produced by bone
marrow cells, regulate cellular activities; are the key components in producing hematopoietic and immunostimulant drugs
Interferons—glycoproteins w/antiviral activityInterleukins—cytokines that enable
communication between leukocytes and other cells involved in inflammation or cell-mediated response. Result—maximized response to a given pathogen or foreign antigen.
Hematopoietic and immunostimulant drugs
Very powerfulDifficult to maintain therapeutic dosing for
prolonged timeCan have untoward and unanticipated side
effectsCan act as antiproliferative and
immunoregulatory agents; can augment natural killer cells
ParenteralSignificant side effects decreasing compliance
Hematopoietic AgentsEpogen (epoetin alfa)=erythropoietinUse for anemiaHct 2x weekly, adjust as Hct increases to
36%
Colony stimulating factorsNeupogen (filgrastim) stimulate blood cell
production by marrow in patients with bone marrow transplantation or chemotherapy induced neutropenia
Leukine—angiogenetic, used in ischemic heart disease
InterleukinsProleukin (aldesleukin)—recombinant
version if IL-2Activates cellular immunity, produces TNF
and inhibits tumor growthFor metastatic renal cell CAToxicity can cause GI bleed, dysrhythmias,
resp. embarrassmentContraindicated in recent organ
transplantation
InterferonsAlfa -2a and 2b for hairy cell leukemia and
Kaposi’s sarcomaalfa n1 approved for chronic hepatitis CBeta for multiple sclerosis
CorticosteroidsDecrease inappropriate or undesirable
immune response. Examples include: RA, SLE, asthma or suppression of transplant rejection
GlucocorticoidsEffects—catabolism, decrease immune
response, decrease utilization and increase production of glucose, stabilize mast cells, affect gastric mucosa, muscle atrophy and adrenal cortex suppression
CorticosteroidsPrednisone is prototypeCelestone (betamethasone)Decadron (dexamethasone)Solucortef (methylprednisolone)Kenalog (triamcinolone)
Immunosuppressant DrugsUse in concert with steroidsUsed in autoimmune disordersNewer agents modify specific components of
immune response, fewer SEImuran-bone marrow depression is SESandimmune (cyclosporine)—monitor
renal and hepatic toxicity, CNS toxicityMethotrexate—bone marrow suppressionRemicade—infusion reactions, GI upset,
others
Cytotoxic, Antiproliferative AgentsUsed primarily in cancerImuran (azathioprine) antimetabolite that
targets rapidly proliferating cells including T and B lymphocytes
Rheumatrex (methotrexate) folate antagonist. Used for cancer and for autoimmune or inflammatory disorders.
Antirejection AgentsSandimmune (cyclosporine)—inhibits
synthesis of IL- 2 necessary for activation of T cells and 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 AntibodiesRemicade (infliximab). Inhibits TNF from
binding to receptors. Used in RA and Crohn’s.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 systemHypothalamus—releasing hormones that
affect both anterior and posterior pituitaryAnt. Pituitary---GH, ACTH, TSH, FSH, LH,
Prolactin, melanocyte stimulating hormonePost. Pituitary—ADH, oxytocinAdrenalsThyroidpancreas
Hypothalamic hormonesGenerally parenteral or intranasally, broken
down in GI systemEquivalent to gonadotropin releasing hormonesFactrel (gonadorelin)—used for diagnostic
testing of gonadotropin functionZoladex (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
Hypothalamic hormonesNone of the GnRH equivalents can be given
orallyFactrel (gonaderelin) diagnostic testing Lupron( leuprolide)decreases estrogen and
testosterone levelsZoladex (goserelin) decreases estrogen and
testosterone levelsSandostatin (octreotide)—somatostatin.
Decreases GH, decreases GI secretions and motility. Given in severe diarrhea as well as with acromegaly.
Anterior Pituitary HormonesCosyntropin (corticotropin)-diagnostic test of
adrenal functionProtropin (somatrem)—synthesized growth
hormone. Promotes growth in those deficient in GH or in renal failure. Tissue wasting with AIDS.
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 HormonesThytropar (thyrotropin)—used as
diagnostic agent to distinguish between primary and secondary hypothyroidism
Humatrope (somatropin) for children with GH deficiency. Not effective in epiphyseal closure. Tissue wasting of AIDs
Posterior Pituitary HormonesDDAVP (desmopressin) and Pitressin
(vasopressin) are synthetic equivalents of ADH. Useful in diabetes insipidus.
Parenteral desmopressin used as hemostatic agent in hemophilia and Von Willebrand’s 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
Bisphosphanates—Fosamax (alendronate), Actonel (risedronate) and Zometa (zoledronic acid)
Bind to bone, inhibit calcium resorptionTake on empty stomach, with water, 30
minutes before other intakeCalcimar, Miacalcin (calcitonin-salmon) for
hypercalcemia, Paget’s Disease, and osteoporosis. Slows bone resorption, may be helpful with bone pain.
Drugs used for calcium and bone disorders
Symptomatic hypocalcemia, calcium gluconate
Oral calcium preparations for osteopenia or nutritional deficiency
Corticosteroids—inhibit cytokine release by cytolytic effects of some bone tumors, inhibit calcium absorption from intestine and by 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 (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 disordersNolvadex (tamoxifen) is classified 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 known 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 AgentsAdrenal cortex produces glucocorticoids,
mineralocorticoids and adrenal sex hormonesHydrocortisone is prototypeFlorinef (fludrocortisone)—only
mineralocorticoid described in text
PearlsThiazide 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 calcium is superior to supplementalMenopausal women should have 1000 mg of
calcium daily
PearlsVasopressin-watch for water intoxication,
chest pain, MIOxytocin can result in uterine ruptureOctreotide can cause arrhythmias,
bradycardia, hyperglycemia, injection site pain and symptoms of gallstones
Acute hypercalcemiaMedical emergencyFor severe s/s or level >12mg/dL. RehydrateIV salineLasixFosamax or ZometaMonitor serum calcium levelsCalcium channel not so effective
Thyroid and antithyroid drugsThyroid produces thyroxine, triidothyronine
and calcitoninThyroxine is called T4 (has 4 atoms of iodine)Triidothyronine has 3 atoms of iodine so is
called T3
ThyroidEssential for normal G&DCritical for brain development and
maturationIncreases rate of cellular metabolism and
oxygen consumptionIncreases heart rate, force of contraction and
cardiac outputIncreases fat metabolism including
cholesterolInhibition of pituitary secretion of TSH
Thyroid DisordersGoiter—enlargement 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, possibly effecting a normal hormone level
Correction of goiter involves replacing iodine; replacement of thyroid hormone. May have regression or may need excision
HypothyroidismOccurs secondary to disease or destruction of
the thyroidCauses: Hashimoto’s thyroiditis, previous
exposure to radiation, treatment with amiodarone, lithium or iodine
HypothyroidismCongenital=Cretinism; may occur with lack of
iodine in mother’s 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, fatigue, aches and pains, puffy appearance, mental sluggishness, anemia, bradycardia
Tx-exogenous thyroxineReplacement indicated if TSH is >10 microunits/L
HypothyroidismMyxedema comaCharacterized by hypothermia,
cardiovascular collapse, coma, hyponatremia, hypoglycemia, and lactic acidosis
Predisposing factors include: cold, infection, CNS depressants
Tx—synthetic levothyroxine is drug of choice.
In myxedema coma, Tx will be given IV.
HyperthyroidismCharacterized by excessive secretion of
thyroid hormoneMay be associated with overtreatment with
thyroid drugs, nodular goiter, thyroiditis, 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
HyperthyroidismThyroid 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
Drugs used in hypothyroidismSynthroid, Levothyroid (levothyroxine)—
synthetic T4. Offers uniform dosing and potency.
Euthroid and Thyrolar (Liotrix) contains both levothyroxine and triiodothyronine in a 4:1 ratio approximating natural thyroid hormone
Drugs used in hyperthyroidismPTU is prototype of thioamide antithyroid
drugsCan be used alone or in combination with
thyroidectomy and in Tx of thyrotoxic crisesActs by inhibiting conversion of T4 to more
active T3. Does not affect thyroid stores. Short acting requiring TID dosing.
Drugs used in hyperthyroidismTapazole (methimazole)---similar to PTULugol’s (strong iodine solution) and
saturated solution of potassium iodide (SSKI)—these drugs inhibit release of thyroid hormone, causing them to accumulate in the gland
Lugol’s decreases the size and vascularity of the thyroid before thyroidectomy
Iodine preparations should not be followed by PTU, Tapazole or radioactive iodine. The latter drugs cause release of stored thyroid and can precipitate crisis.
Sodium Iodide 131Radioactive isotope of iodine. Thyroid picks up the
isotope from circulating blood. Act by emitting beta and gamma rays. Rays destroy thyroid tissue and decrease production of thyroid hormones. Also used for diagnosis and in the treatment of cancer.
Usually given in a single dose as outpatient. No special precautions. May be months before therapeutic effect. During this time, on maintenance medications.
Iodine preparations and thioamide antithyroid drugs are contraindicated during pregnancy. Can result in goiter and hypothyroidism in fetus or newborn.