Transcript Cholinergics/anticholinergics and drugs affecting the

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) 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 requires more medication, cholinergic
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crisis requires less
Distinguished 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 poisoning
 Tabin, Sarin—nerve gases
 Insecticides—malathion, parathion
 Decontaminate—clothing, flushing with water,
activated charcoal and lavage
 Atropine for muscarinic effects—hypersalivation,
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 (galantamine)-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
 Indications—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
Anticholinergics
 Atropine
 Atrovent
 Scopolamine—antiemetic, motion sickness
 Spiriva (tiotropium)
 Bentyl (antiscretory/antispasmotic)
 Cogentin
 Trihexy (Parkinson’s)
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 epitopes (distinctive molecules on nonself antigens)
 Underactive=immunodeficiency
 Overactive=autoimmune diseases
Immunity
 Natural
 Acquired immunity—active or passive (antibodies are
transferred)
 Cellular—involving activated T cells
 Humoral—involves B cells and antibodies
 All antigens elicit both types
Immunizations
 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 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
Contraindications 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
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
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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 vaccines
Pneumococcal at 65; may repeat in five years if with
chronic conditions
After Varicella, avoid close contact with newborns,
pregnant women and immunocompromised 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
 Cytokines—substances produced by bone marrow
cells, regulate cellular activities; are the key
components in producing hematopoietic and
immunostimulant drugs
 Interferons—glycoproteins w/antiviral activity
 Interleukins—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 powerful
 Difficult to maintain therapeutic dosing for prolonged
time
 Can have untoward and unanticipated side effects
 Can act as antiproliferative and immunoregulatory
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 cell
production by marrow in patients with bone marrow
transplantation or chemotherapy induced neutropenia
 Leukine—angiogenetic, used in ischemic heart
disease
Interleukins
 Proleukin (aldesleukin)—recombinant version if IL-
2
 Activates cellular immunity, produces TNF and
inhibits tumor growth
 For metastatic 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 Kaposi’s
sarcoma
 alfa n1 approved for chronic hepatitis C
 Beta for multiple sclerosis
Corticosteroids
 Decrease inappropriate or undesirable immune
response. Examples include: RA, SLE, asthma or
suppression of transplant rejection
 Glucocorticoids
 Effects—catabolism, decrease immune response,
decrease utilization and increase production of
glucose, stabilize mast cells, affect gastric mucosa,
muscle atrophy and adrenal 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 immune
response, fewer SE
 Imuran-bone marrow depression is SE
 Sandimmune (cyclosporine)—monitor renal and
hepatic toxicity, CNS toxicity
 Methotrexate—bone marrow suppression
 Remicade—infusion reactions, GI upset, others
Cytotoxic, Antiproliferative Agents
 Used primarily in cancer
 Imuran (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 Agents
 Sandimmune (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 Antibodies
 Remicade (infliximab). Inhibits TNF from binding
to receptors. Used in RA and Crohn’s.
 Enbrel (etanercept) TNF receptor binder. RA.
 Arava (Leflunomide) antiproliferative and antiinflammatory activities. Inhibits pyrimidines needed
for RNA and DNA synthesis. RA.
Drugs affecting the Endocrine
System
Review of Endocrine system
 Hypothalamus—releasing hormones that affect both
anterior and posterior pituitary
 Ant. Pituitary---GH, ACTH, TSH, FSH, LH, Prolactin,
melanocyte stimulating hormone
 Post. Pituitary—ADH, oxytocin
 Adrenals
 Thyroid
 pancreas
Hypothalamic hormones
 Generally parenteral or intranasally, broken down in
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GI system
Equivalent to gonadotropin releasing hormones
Factrel (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
Hypothalamic 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 secretions 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 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 Hormones
 Thytropar (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 Hormones
 DDAVP (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 resorption
 Take on empty stomach, with water, 30 minutes before
other intake
 Calcimar, 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 disorders
 Nolvadex (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 Agents
 Adrenal cortex produces glucocorticoids,
mineralocorticoids and adrenal sex hormones
 Hydrocortisone is prototype
 Florinef (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 calcium 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
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 atoms 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 including cholesterol
 Inhibition of pituitary secretion of TSH
Thyroid Disorders
 Goiter—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
Hypothyroidism
 Occurs secondary to disease or destruction of the
thyroid
 Causes: Hashimoto’s thyroiditis, previous exposure to
radiation, treatment with amiodarone, lithium or
iodine
Hypothyroidism
 Congenital=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 thyroxine
 Replacement indicated if TSH is >10 microunits/L
Hypothyroidism
 Myxedema coma
 Characterized 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.
Hyperthyroidism
 Characterized by excessive secretion of thyroid
hormone
 May 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
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
Drugs used in hypothyroidism
 Synthroid, 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 hyperthyroidism
 PTU is prototype of thioamide antithyroid drugs
 Can be used alone or in combination with
thyroidectomy and in Tx of thyrotoxic crises
 Acts by inhibiting conversion of T4 to more active T3.
Does not affect thyroid stores. Short acting requiring
TID dosing.
Drugs used in hyperthyroidism
 Tapazole (methimazole)---similar to PTU
 Lugol’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 131
 Radioactive 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.