home



=*FYI: Another, NEW updated study guide was posted with an additional section regarding last week's lecture (that was furlough'd). I know we're swamped as is, but if you have time, take one of the new added points on! The following points were added:= ===1. Identify the patho of inflammatory diseases of the heart such as pericarditis- COLLEEN (I just pulled this information directly from the PPT slides. nothing has been added from Porth but I figured it was at least better than nothing.)===

6. Differentiate types of aneurysms (ie berry, dissecting….)-Angela
===7. Identify role of gender differences in cardiac testing-Julia (yes, you read it correctly, I am contributing here, I figured I got stuff in so late for peds that the least I could do is help out here...so you don't kick me out of the study guide group! ;0)===

8. Differentiate mechanisms of action for anticoagulants vs thrombolytic agents vs antiplatelet agents-Angela
I am going to update my Huntington's disease portion the book didnt have a lot of info and what i left is kind of vague. = Um.... I hate to seem lazy but this immune/inflammatory response question (#1) is taking forever. Does anyone want to help me out by taking #2 ?? Maybe someone who has an easier section? -Jo = = By the way... I finished #1; all the info. is on a separate page which can be found on the sidebar to the left under "Inflammation and the Immune Response". Enjoy. = = =

! __WEEK 1__ :Immune Responses and Hypersensitity

 1. Describe the major cell types involved in immune and inflammatory responses the body and their response to biochemical mediators and antigens that activate the systems (ie WBC, NK, antibodies, CD4 or T4 vs CD8 or T8 cells..) JOHANNA

 2. Discuss the clinical significance of these responses as they pertain to: a) the types of exudates to chart, b) diagnostic tests performed  3. Discuss the stages of acute inflammation: cellular and vascular **// Done in Quiz already //**

 4. Differentiate acute inflammation from chronic inflammation **// Done in Quiz already //**

 5. Be able to define the IV major types of hypersensitivity reaction, discuss the pathophysiology of these reactions and recognize clinical scenarios in which these reactions are occurring. **// Done in Quiz already //**

Prototype Drugs: a. __Inflammatory, Immune, Transplantation & Rheumatoid Drugs:__ i. Rituximab (pgs 277-278 Rituximab indication is described at the top of Karch p277. On pages 277-278, follow general description of monoclonal antibodies pharmacokinetics, contraindications & cautions, adverse effects, drug-drug interactions and the lavender “Nursing considerations” box. __ii. Celebrex__  iii. Cyclosporin  iv. Aspirin  v. Ibuprofen  vi. Acetaminophen  vii. colchicine  vii. benadryl-first generation antihistamine

__WEEK2__ : Cancer  Intro: The material for this section in presented by Marlon Saria in a guest lecture on Cancer Biology and Chemotherapy. Dr. Kohlbry put this lecture in the NURS324 shell. The lecture was originally developed for the Pathophysiology & Pharmacology lecture series so it pertains to this course as well.  Outline:  1. Differentiate between benign and malignant neoplasm characteristics. For example what makes malignant cells so deadly (Porth pgs 84-87 will help)- COLLEEN

Anaplasia- lack of cell differentiation in malignant cancerous tissues. Not only do the cells vary in size and shape, but the nuclei are varied as well. (usually exceedingly large.)The tumor resembles its original source (such as if it is resembles the tissues of the liver) the lower the grade of the tumor. The more it morphs from its original source the higher the grade of tumor. **Why are they so dangerous??** According to cancer guest speaker, the more the cells morph the harder it is for the immune system to detect them as foreign invaders. So WBC’s and phagocytes don’t even recognize them and will not actively try to destroy them. Another reason they are prolific is that they can acquire abilities to destroy bacteria. Also, most cancer cells do not have typical apoptosis. Because cancer cells grow rapidly and are larger in size, they play king-of-the-hill w/ the normal WBC’s, erythrocytes, platelets, etc, thus hindering the growth of the “good” cells and crowding them out. These cells grow into smaller and more immature WBC’s. This means that they are ineffective at destroy cancer cells and fighting infection. Much like what happens w/ the left shift. They are also not well versed on contact inhibition. Cessation normally occurs when cells come into contact w/ one another. Cancer cells lack cohesiveness and adhesiveness so they disregard contact inhibition. Instead the go hog wild and grow rampantly through out the body. Metastasis is when the cancer develops into a secondary tumor in a location distant from the primary tumor. Metastasis occurs in the lymph and blood vessels. The tumor gets wedged in a lymph duct and often die due to lack of a proper environment. However, some cells can break off the tumor and travel through the lymph and into the venous system, spreading the cancer through out the body.
 * <span style="background-color: yellow; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Cell Characteristics || <span style="background-color: yellow; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Benign || <span style="background-color: yellow; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Malignant ||
 * <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Cell characteristics || Well-differentiated cells that resemble cells in the tissue of origin || Cells that are undifferentiated, with anaplasia and atypical structure that often bears resemblance to cells in the tissue or origin. ||
 * <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Rate of growth || Usually progressive and slow. My regress or come to a standstill. || Variable and depends on level of differentiation; the more anaplastic the cells, the more rapid the rate of growth. ||
 * <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Mode of growth || Grows by expansion w/out invading the surrounding tissues; usually encapsulated. || Grows by invasion; sending out processes that infiltrate the surrounding tissues. ||
 * <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">Metastasis || Doesn’t spread to metastasis. || Gain access to blood and lymph channels to metastasize to other areas of the body. ||

2. Describe the agents & mechanisms of action for chemotherapy, immunotherapy, biological response modifies (Porth pgs 98-101. This overlaps with the prototype drugs from this section of Pharmacology)- COLLEEN

**//b.//** __**//Chemotherapy Agents://**__ **//i. methotrexate//**


 * methotrexate (//Folex, Rheumatrex//) || Dosage varies with route and disease being treated; 15–30 mg P0 or IM is common || Treatment of leukemias, psoriasis, rheumatoid arthritis, and choriocarcinomas
 * Special considerations:** Hypersensitivity reactions can be severe; liver toxicity and GI complications are common; monitor for bone marrow suppression and increased susceptibility to infections; dose pack available for the oral treatment of psoriasis and rheumatoid arthritis ||

<span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Cancer chemotherapy ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;"> is a systemic treatment that enables drugs to reach the site of the tumor as well as the distant sites. It can be the primary or part of a multimodal tx plan. It is the primary tx for hematologic and some solid tumors, including testicular cancer, acute and chronic leukemia, burkitt lymphoma, hodgkin’s dx, and multiple myeloma. Most cancer drugs are designed to destroy cells that are rapidly replicating or in the phase G0 of the cell cycle. According to the cancer lecture guy the reason that people need repeated rounds of chemo is because the cells in the body are not all simultaneously in the G0 cycle at the same time. So, it is more effective to do it multiple times to ensure that you are killing off as many cancer cells as possible. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;"> The relationship between tumor cells survival and drug dose is exponential. The number of survivors is proportional to drug dose and the number of cells surviving proportional to drug dose. This means that a percentage of cells are killed rather than a number of cells. Thus, each round of chemo kills another percentage of cells until the amount equals 0. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;"> The way that methotrexate works is by interfering with the S phase of the cell cycle. This interrupts the DNA replication part of the cell cycle. You can have cell specific and non-specific drugs. Cell-specific work on a particular phase of the cell cycle. Non-specific drugs work on the cell during the resting phase, rather than the replicating phase. Combinations can be used to attack the cells in different phases. Two well-known combinations are CHOP-cyclophosphamide, doxorubicin, oncovin, and prednisone, which is used to tx Hodgkin’s dx. CMF is cyclophosphamide, methotrexate, 5-fluorouracil, use to tx breast cancer.

<span style="-webkit-background-clip: initial; -webkit-background-origin: initial; background-color: aqua; font-family: Arial;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Immunotherapy ** <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Active ** **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">- ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">this is when something like BCG, which is an attenuated strain of bacterium that causes bovine TB is instilled into the bladder. The immune system fights it off and actually ends up kills superficial bladder cancer cells in the process.

<span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Passive or adoptive immunotherapy ** **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">- ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;"> transfer of cultured immune cells into a tumor-bearing host.

**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Biologic Response Modifiers ** <span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Arial;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Cytokines- ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;"> interferons and interleukins.

=
<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Interferons assist the immune response by inhibiting [|viral replication] within host cells, activating [|natural killer cells] and [|macrophages], increasing [|antigen presentation] to [|T lymphocytes], and increasing the resistance of host cells to viral infection. There are 3 known classes of interferons; type I, type II and type III. All classes are very important in fighting viral infections. They can also prolong the cell cycle and increase the percentage of cells in the G0 phase. ======

=
<span style="-webkit-background-clip: initial; -webkit-background-origin: initial; background-color: aqua;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Interleukins ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">- enable communication between cells by binding to receptor sites on cell surface membranes of target cells. There are 18 types. IL-2 is being used for tx of metastatic renal cell carcinoma and metastic melanoma. ======

=
<span style="-webkit-background-clip: initial; -webkit-background-origin: initial; background-color: aqua;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Monoclonal antibodies ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">-re [|monospecific antibodies] that are identical because they are produced by one type of [|immune cell] that are all [|clones] of a single parent cell. Given almost any substance, it is possible to create monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. For cancer, they are combined w/ a toxin, chemotherapy drug or radioisotope to increase effectiveness. ======

=
<span style="background-color: aqua; background-position: initial initial; background-repeat: initial initial; font-family: Helvetica; font-size: 11pt;">**<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">Hematrophic growth factors ** **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">- ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 8.8pt;">growth and maturation factors that include colony-stim factors (CSF’s) These control the production of granulocytes and macrophages, erythrocytes, and platelets. ======

<span style="font-family: ,'Times New Roman',; font-size: 12pt;">__WEEK 3:__ <span style="font-family: ,'Times New Roman',;">Transplantation: (THIS ONE MIGHT JUST BE SELF STUDY) - <span style="font-family: ,'Times New Roman',;"> ** MARCIA ** <span style="font-family: ,'Times New Roman',; font-size: 12pt;"> Intro: This section greatly overlaps with immune and inflammatory response content. Many of the drugs and patho mechanisms covered in section 1 of this table are repeated in this module <span style="font-family: ,'Times New Roman',; font-size: 12pt;"> Outline: 1. Review all questions in the module that pertain to transplantation immunosupression pharmacology and rejection mechanisms. Test questions will be taken directly from a) the module, b) content in the Porth pages listed from Ch 15, c) prototype drugs in section 1. Inflammatory, Immune & Rheumatoid Drugs. You will find many of the same drugs used to suppress autoimmune disease are also used in transplant therapy.

=Immunosuppresants:=

Almost all organ transplant patients receive a similar regimen of post transplant medications. Immunosuppressants are cornerstone to successful long term transplantation. Often used in conjunction with corticosteroids, which block the inflammatory and immune reactions and decrease initial damage to the cells. The immunosuppressants include T and B cell suppressors
 * Drug Therapy **

Prolonged immunosuppression predisposes patient to malignancies Increase susceptability to infection Organ dysfunction Steroid induced side effects such as hyperglycemia, weight gain, bone dysfunction
 * Side Effects **

-Major drug to prevent allograft rejection -Activity highly specific to helper T cells -Patient then able to maintain some degree of immunity -Associated w/ multiple serious side effects including hepatotoxicity, nephrotoxicity, neurotoxicity, hyperglycemia, hirsutism, gingival hyperplasia. Causes increase in BP -Teratogenesis (Pregnancy Risk Category C) -Increased risk of infection, osteoporosis, fluid retention, bone marrow depression -Consumption of grapefruit juice increases cyclosporine levels by 50%; increase risk of toxicity -Good oral hygiene; may cause unusual gum growth & gum bleed. -Monitor BP, glucose levels, liver & kidney function ATI, p. 111
 * Cyclosporine **
 * (Neoral, Sandimmune, Gengraf)**

-Has both anti-inflammatory and immunosuppressant capabilities -Significantly decrease the number of lymphocytes, particularly T lymphocytes by interfering w/ the production and secretion of interleukin-2. -Large doses suppress B lymphocyte production, particularly immunoglobulin G (IgG) and IgA and significantly impair monocyte-macrophage function. -Side Effects: Long term use is associated w/ severe bone disorders, DM, cataracts. Post operatively to prevent rejection, it is associated with complications of decreased wound healing, increased risk of dehiscence, or tearing of the anastomosis. Causes increase in BP. Steroid psychosis. -Drug interactions: No NSAIDS -Take in morning with food -Monitor BP, weight -Monitor glucose levels (chemically induced diabetes)
 * Corticosteroids **
 * SoluMedrol - Prednisone**
 * Used as an adjunct immunosuppresssant therapy drug following transplant**

An immunosuppressive macrolide antibiotic that was originally derived from a soil fungus Unrelated to cyclosporine but acts in a similar fashion in its attack on helper T lymphocytes Side Effects: Increased BP & glucose levels Food interactions – no grapefruit Monitor liver function, blood pressure, glucose levels
 * Macrolide Antibiotics **
 * Tacrolimus FK506 (Prograf)**
 * serolimus (Rapimune)**

Certain drugs target immunocompetent cells and thus are of use as immunosuppressants. prevention of graft rejection before cyclosporine; toxic
 * Antimetabolites – Cytotoxic agents **
 * Azathioprine or AZA (Imuran)** - Used to be the drug of choice for
 * Mycophenolate Mofetil (MMF) (Cell Cept);** GI; Take after meals


 * Antibodies – Used in acute organ rejection **
 * OKT# Monoclonal Antibody**
 * Atgam Polyclonal Antibody**

-Gram positive -Gram negative Medications -Septra DS
 * Bacterial Infection **
 * Bacterial**

Medications -Acyclovir -Ganciclovir -Cytovene
 * Viral Infection **
 * CMV**
 * EBV**
 * HCV**

<span style="font-family: ,'Times New Roman',; font-size: 12pt;">__WEEK 4:-__ Male and Female Reproduction

**//c.//** __**//Reproductive Disorders//**__ **//i. Oxybutynin (Ditropan)//** **//ii. Doxacin//** **//iii. Finasteride (Porscar) 5 alpha reducatase inhibitors//** **//iv. premarin (ATI pg 488)//** **//v. testosterone (ATI pg 486)//** **//vi. tamoxifen (ATI pg 496)//**

1. Identify risk factors, patho mechanisms and pharm interventions for testicular cancer and prostate cancer JULIA <span style="color: #800080; font-family: ,'Times New Roman',; font-size: 12pt;"> 2. Identify the mechanisms of action, indications for use, side effects and treatment decisions about when to use alpha reducatase inhibitors vs alpha adrenergic blockers JULIA 3. Explain the purpose of PSA testing JULIA <span style="color: #800080; font-family: ,'Times New Roman',; font-size: 12pt;"> 4. Identify therapeutic uses of hormone therapy in treating prostate Ca JULIA

Female Repro 1. Understand the mechanism of Herceptin as a targeted therapy **ANGELA** -Background: o HER2 Test for breast cancer detects the overproduction of HER2 protein and/or gene amplification, both of which contribute to aggressive growth of cancer and it’s spread to other parts of the body. o 25% of breast cancer patients have tumors that are HER2+ o HER2=Human Epidermal Growth Factor Receptor 2 o In normal cells: HER2 proteins help send growth signals fr. outside the cell to the inside- à these signals tell the cell to grow and divide. o In HER2+ breast cancer à cancer cells have an abnormally HIGH number of HER2 genes per cell à too much HER2 proteins appear on surface of these cancer cells à aka HER2 protein overexpression. o Too much HER2 protein is thought to CAUSE cancer cells to grow and divide more quickly à this is why HER2+ breast cancer is often more aggressive than other breast cancers that are not HER2+ à IMPORTANT to find out your HER2 status. o Your tumor’s HER2 status is not heredity. HER2 is not passed down from your parents. However, there is a relationship between genetics and breast cancer in general.

o Monoclonal antibody that reacts with human epidermal growth factor receptor 2 (HER2), a genetic defect that is seen in certain metastatic breast cancers. It is used in the treatment of metastatic breast cancer in tumors that over-express HER2. o Type of immunotherapy o Used to stop the growth of breast tumors that express the HER2/neu receptor on their cell surface. o The HER2/neu receptor binds to an epidermal growth factor that contributes to cell growth à Herceptin/trastuzumab is a recombinant DNA-derived monoclonal antibody that binds to the HER2/neu receptor à thus inhibiting proliferation of tumor cells that overexpress the receptor gene. o Herceptin blocks the downstream HER2, signaling to inhibit proliferation of cells. o Herceptin is the ONLY approved HER2 therapy designed to bind to HER2_ tumor cells and flag them for destruction by the immune system.
 * -Herceptin/Trastuxumab**

2. Describe the relationship of BRCA genetic markers to breast cancer LINDSAY 3. Identify the physiological changes occurring with menopause that increase health risks for post menopausal women **ANGELA** 4. Discuss the advantages and disadvantages of HRT for relieving menopausal symptoms <span style="color: #3333ff; font-family: ,'Times New Roman',;">LINDSAY

<span style="font-family: ,'Times New Roman',; font-size: 12pt;">__WEEK 5:-__ Neurological Disorders (TOTALLY NEW INFO!)

**//d.//** __**//Neurological Disorders://**__ **//i. levodopa-EMILY//** **//ii. amantadine-EMILY//** **//iii. dantrolene-EMILY//** **//iv. Phenobarbital-JENNIFER//** **//v. phenytoin-JENNIFER//**

1. Define & differentiate between the various types of seizure disorders - **<span style="color: #000080; font-family: Arial,Helvetica,sans-serif;">JENNIFER ** <span style="color: #000000; font-family: 'Times New Roman',Times,serif; font-size: 12pt;">2. Explain pathogenesis, s/s and pharmacological management of 3.Alzheimer’s Disease shawnda 4. Huntington’s Disease shawnda <span style="font-family: ,'Times New Roman',; font-size: 12pt;"> 5.Myasthenia Gravis Kryssa <span style="font-family: ,'Times New Roman',; font-size: 12pt;"> 6.Guillain Barre Kryssa · MG is a disorder of transmission at the neuromuscular junction that affects communication between the motor neuron and the innervated muscle cell. Can occur at any age but usually between 20 and 30. 3x more common in women. · Pathophysiology:Autoimmune disease.Caused by antibody mediated destruction of acetylcholine receptors in the neuromuscular junction.Exact mechanism trigger is unclear, but thought to be related to T-lymphocytes function.75% of people with MG also have thymic abnormalities (for example thymus tumor, etc.).Neonatal MG occurs in 10% of infants born to mothers with MG. · Clinical Manifestations:This is tricky: In persons with myasthenia gravis who have fewer acetylcholine receptors in the postsynaptic membrane, each release of acetylcholine from the presynaptic membrane results in a lower endplate potential.This results in muscle weakness and fatiguability with sustained effort.Most common areas are eye and periorbital muscles.Early symptom: ptosis due to eyelid weakness or diplopia due to weakness of the extraocular muscle weakness.Progresses to generalized weakness, including respiratory.Chewing and swallowing are difficult, weakness in limbs, hard to climb stairs and lifting objects.As the disease progresses: muscles of lower face, speech impairment.Interestingly, symptoms are decreased in morning but increases as the day and activity continues. · Myasthenia crisis: a sudden exacerbation of symptoms and weakness.Occurs when muscle weakness is so severe that it compromises ventilation to the extent that ventilary support and airways protection are needed,Usually stress, illness, cold, emotional upset, after surgery, etc.. brings this on.Or from inadequate or excessive dose of the anticholinesterase drug used in treatments of the disorder. · Diagnoses and treatment:Anticholinesterase test.Nerve stimulation studies, immunoassay test for ACT receptor antibodies.Treatment methods include pharmacologic agents (anticholinerasterase drugs: pyridostigmine and neostigmine) and immunosuppressant therapy: corticosteroids, azathioprine, cyclosporine; management of myasthenic crisis; thymectomy; and plasmapheresis or intravenous immunoglobulin.Medications that exacerbate MG should be avoided such as aminoglycoside antibodies. · Plasmatherisis remove antibodies from circulation and provide short term clinical improvement.Used primarily to stabilize the condition of those in the MG crisis. · A Thymectomy (surgical removal of the thymus) may be used as a treatment of MG but the mechanism is unknown and the surgery is controversial · // It is not written in the textbook whether or not this is a degenerative disease and if it gets worse with age but it seems to me that it comes and goes throughout the lifespan and can be handled somewhat with medications and treatments //
 * Kryssa Brainerd N316B P/PH Exam I Study Guide **
 * __Myasthenia Gravis__ **

· Disorder of Neuromuscular Function.It is an acute immune-mediated polyneuropathy.It is characterized by rapidly progressive limb weakness and loss of tendon reflexes.It has been described as the most common cause of acute, flaccid paralysis in developed countries, now that poliomyelitis has been eliminated.As a syndrome, there are several subtypes of the disorder, including pure motor axonal degeneration, axonal degeneration of both motor and sensory nerves, and a variant characterized by ophthalmmoplegia, ataxia, and areflexia. · Cause: probably an immune component.Been linked to infection: Campylobacter jejuni or cytomegalovirus, Epstein-Barr Virus, and Mycoplasma pneumonia.Two thirds of patients have had an acute, influenza like illness before the onset of symptoms.One third have antibodies against nerve gangliosides. · Characterizations of GB: progressively ascending muscle weakness of the limbs, producing a symmetric flaccid paralysis.Symptoms of parasthenia and numbness often accompany the loss of motor function.Rate of disease varies, and may be disproportionate involvement between the upper and lower extremities.Paralysis may affect respiratory muscles and 30% of patients may need ventilator assistance.ANS involvement causes postural hypostension, cardiacarrythmias, facial flushing, abnormalities of sweating, and urinary retention is common.Pain is also very common in the shoulder girdle, back, posterior thighs, and occurs with even the slightest movement. · GB is usually a medical emergency.There may be a rapid development of ventilator failure and autonomic disturbances that threaten circulatory function. · Treatment:includes support of vital functions and prevention of complications such as skin breakdown and thrombophlebitis.Plasmapheresis can decrease morbidity and shortens the course of the disease.Treatment is most effective in the beginning of the disease.High dose immunoglobulin therapy as lhs proven effective. · 80-90% of people achieve a full and spontaneous recovery within 6 – 12 months
 * __Guillaine Barre Syndrome__ **

• Typically a dz of young adults (20-45yrs) • Almost twice as common in women; Northern Europeans at highest risk • Immune-mediated destruction of myelin coating on axons à degeneration of nerve fibers • Demyelinated or sclerotic patches develop throughout white matter of CNS • Significant lymphocyte invasions of lesions: – CD8+T-lymphocytes and macrophages (CD4+ T-cells also in plaque infiltrate, but the other two are thought to induce oligodendrocyte injury) • Oligodendrocytes: myelin-producing cells of the CNS • Decreased conduction velocity results • Marked by exacerbations and remissions in neurological dysfunction • Commonly affects the following areas: – Optic nerve (visual field) – Corticobulbar tracts (speech & swallowing) – Corticospinal tracts (muscle strength) – Cerebellar tracts (gait & coordination) – Spinocerebellar tracts (balance) – Medial longitudinal fasciculus (conjugate gaze of EOMs) – Posterior cell columns of the spinal cord (position & vibratory sensation) • Clinical Features (last from weeks to days and then completely or partially resolve) – Paresthesias (numbness, tingling, burning, pressure on face or involved extremity) – //Lhermitte symptom//: an electric shock produced by flexion of the neck – Pain from spasticity • Treated w/ stretching exercises – Abnormal gait – Bladder dysfunction – Sexual dysfunction – Vertigo – Nystagmus – **Fatigue** – Speech disturbances – Psychological manifestations • Represent either an emotional reaction to the dz __or__ involvement of the white matter of the cerebral cortex (more likely) • Depression • Euphoria • Inattentiveness • Apathy • Forgetfulness • Loss of memory • Diagnosis – Cerebrospinal fluid analysis • Large percentage of pts w/ MS have elevated IgG levels • Some have oligoclonal patterns – MRI • Detects multiplicity of lesions • Treatment – Non-pharm • Encourage healthy lifestyle • PT may help maintain muscle tone • Every effort should be made to avoid: • Excessive fatigue • Physical deterioration • Emotional stress • Viral infections • Extremes of environmental temperatures – Pharmacological • Treat acute relapse of the dz • __Corticosteroids__: reduce inflammation, improve nerve conduction, have important immunologic effects • Long term use not recommended • Modify the course of the dz • __Interferon β__ (cytokine; immune enhancer) • __Glatiramer acetate__ (synthetic polypeptide; simulates parts of the myelin basic protein; blocks myelin-damaging T cells) • __Mitoxantone__ (anticancer drug) • Interrupt the progression of the dz • Immunosuppressants (methotrexate; cyclophosphaminde; mitoxantrone; cyclosporine • Treat symptoms of the disorder •**Dantrolene (Dantrium)- (P) direct-acting skeletal muscle relaxant** •Botulinum toxins A and B bind __directly__ to the receptors of motor nerve terminals and inhibit the release of Ach à local paralysis •Long term use justified when reducing pain and disabling spasticity •__Indications__:control of clinical spasticity from upper motor neuron disorders; preoperatively to prevent or attenuate the devlopement of malignant hyperthermia in susceptible pts; IV for mgmt of fulminant malignant hyperthermia •__Actions__:interferes w/ the release of Ca2+ from the sarcoplasmic reticulum w/in skeletal muscles, preventing muscle contraction; doesn’t interfere w/ neuromuscular transmission •__PK__: •__Half-life__: 9h (oral); 4-8h (IV); excreted in urine •__Adverse effects__:drowsiness, dizziness, weakness, fatigue, diarrhea, hepatitis, myalgia, tachycardia, transient blood pressure changes, rash, urinary frequency •Baclofen (Lioresal) for spasticity •Diazepam (Valium) for spasticity •Cholinergic drugs for bladder problems •Antidepressants for depression
 * Multiple Sclerosis**
 * **Route** || **Onset** || **Peak** || **Duration** ||
 * Oral || Slow || 4-6 h || 8-10h ||
 * IV || Rapid || 5h || 6-8h ||

•Degenerative disorder of the basal ganglia that results in variable combinations of TREMOR, RIGIDITY, & BRADYKINESIA •Characterized by a progressive destruction of the nigrostriatal pathway à reduced concentration of dopamine (DA) •Onset usually after 50 yrs(most pts dx’d in 60s and 70s) •Clinical syndrome known as //Parkinsonism// •Cause unknown, several theories –Auto-oxidation of catecholamines during melanin synthesis –Genetics (w/ early-onset) •Clinical Features: –TREMOR •Most evident •“Pill-rolling” action •Initially unilateral, progresses to bilateral (usually) •Disappears w/ movement and sleep •Least disabling manifestation –RIGIDITY •Jerky, ratchet-like movements that require a lot of energy •Flexion contractions may develop •Initially unilateral, progresses to bilateral (usually) –BRADYKINESIA (slowness of movement) •The most disabling symptom •Small shuffling steps w/o swinging arms •Loss of postural reflexes à falls (often backward) •Emotional and voluntary facial movements become limited à stiff, mask-like expression •Stiffening of tongue, palate, and throat à difficulty swallowing à drooling •Slow monotonous speech –Falls –Fluctuations in motor function –Neuropsychiatric disorders –Limitation of ANS function (present late in dz) •Excessive sweating, salivation, and sebaceous gland secretion •Impaired lacrimation •Dysphagia •Orthostatic hypotension •Impaired thermal regulation •Constipation •Impotence •Urinary incontinence –Sleep problems –Dementia (20% of PD pts; r/t ACh degeneration) •Treatment –Non-pharm •Group support •Education •Daily exercise •Adequate nutrition –Pharmacological •__Goal__:increase the functional abilitiy of the underactive DAergic system __or__ to reduce the excessive influence of excitatory cholinergic neurons •Increase DA levels •Levodopa (discussed in greater detail later) •Carbidopa •Augment the release of DA •Amantadine (discussed in greater detail later) •Function as DA agonists or directly stimulate DA receptors •Bromocriptine •Pergolide •Pramipexole •Ropinirole •Inhibits the metabolic breakdown of DA •Selegiline •Anticholinergics given to treat overactive cholinergic sites and restore balance between reduced DA and uninhibited cholinergic neurons •Treats extrapyramidal effects (involuntary movements, muscle rigidity, & immobility w/o paralysis) •More useful in alleviating tremor and rigidity than bradykinesia –Surgical interventions •Thalamotomy or Pallidectomy •Destruction of part of the thalamus or globus pallidum in the basal ganglia via electrical stimulation or supercooled tip of a metal probe (cryothalamotomy) •Restricted to those pts who do not respond well to drug tx •Deep brain stimulation •Implants electrodes into the areas of the brain responsible for tremors or motor dysfunction •Reversible •Limited ability to cause brain damage
 * Parkinson Disease**

•Action –Increase the levels of dopamine in the substantia nigra –Directly stimulate the dopamine receptors in that area –Help to restore the balance between the inhibitory and stimulating neurons •Indications –Relief of the signs and symptoms of idiopathic Parkinson’s disease •Contraindication –Known allergy –Angle closure glaucoma –GI obstruction •Cautions –CV disease –Bronchial asthma –H/O peptic ulcer –Urinary tract obstruction –Psychiatric disorders •Adverse reactions –Anxiety –Nervousness –Headache –Blurred vision –Arrhythmias •Drug-to-drug interactions –MAOIs –Vitamin B6
 * Dopaminergics**

•Mainstay of treatment for parkinsonism •Precursor of DA that crosses the blood–brain barrier, where it is converted to DA •Almost always given in combination form with carbidopa as a fixed-combination drug (//Sinemet)// –Carbidopa decreases the amount of levodopa needed to reach a therapeutic level in the brain –The dosage of levodopa can be decreased, reducing adverse side effects
 * Levodopa (P) dopaminergics**

•Dopaminergic •An antiviral drug that also increases the release of DA. •Effective as long as there is a possibility of more DA release
 * Amantidine (Symmetrel)**

9. Differentiate between the major types of headaches described in Porth and the ppt slides for etiologies and s/s **Kristine**
 * <span style="background-color: yellow; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: Calibri;">Types of Headaches **

<span style="color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Cluster **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">- <span style="color: #000000; font-family: 'Times New Roman',serif;">less common type · <span style="color: #000000; font-family: 'Times New Roman',serif;">Tend to be episodic · <span style="color: #000000; font-family: 'Times New Roman',serif;">1-8 headaches/day possible followed by remission · <span style="color: #000000; font-family: 'Times New Roman',serif;">Vasoreactivity in the hypothalmus implicated as cause · <span style="color: #000000; font-family: 'Times New Roman',serif;">Pain is the forehead, temporal, and around the eyes · <span style="color: #000000; font-family: 'Times New Roman',serif;">Also mayinclude nasal congestion and tearing (one sided) <span style="color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Tension **<span style="color: #000000; font-family: 'Times New Roman',serif;">-Most common type · <span style="color: #000000; font-family: 'Times New Roman',serif;">Doesn’t usually interfere with daily activity · <span style="color: #000000; font-family: 'Times New Roman',serif;">Conflicting hypotheses of mechanism · <span style="color: #000000; font-family: 'Times New Roman',serif;">Neck and shoulder muscle tension-symptoms but not cause · <span style="color: #000000; font-family: 'Times New Roman',serif;">Related possible causes: psychogenic stress, oromandibular dysfunction, depression · <span style="color: #000000; font-family: 'Times New Roman',serif;">Treatment: <span style="color: #000000; font-family: 'Times New Roman',serif;">1.ASA, NSAIDs, acetomenophen <span style="color: #000000; font-family: 'Times New Roman',serif;">2.Nonpharm: acupuncture, biofeedback, PT <span style="color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Migraine **<span style="color: #000000; font-family: 'Times New Roman',serif;">-mech possibly r/t arterial inflammatory process (Two categories) <span style="color: #000000; font-family: 'Times New Roman',serif;">1.Common-no aura—85% are this type · <span style="color: #000000; font-family: 'Times New Roman',serif;">Pulsatile, throbbing, unilateral, visual disturbances · <span style="color: #000000; font-family: 'Times New Roman',serif;">n/v, photophobia, sensitivity to sound, <span style="color: #000000; font-family: 'Times New Roman',serif;">2.Classic-pain preceded by aura · <span style="color: #000000; font-family: 'Times New Roman',serif;">Similar symptoms as those listed above and · <span style="color: #000000; font-family: 'Times New Roman',serif;">Aura- Visual & motor function disturbances that begin 5-20 minutes prior to head pain. n/v

<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Migraine headaches ** <span style="color: #000000; font-family: 'Times New Roman',serif;">–Severe, throbbing headaches on one side of the head <span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Cluster headaches ** <span style="color: #000000; font-family: 'Times New Roman',serif;">–Begin during sleep; sharp, steady eye pain, sweating, flushing, tearing, and nasal congestion <span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">• **<span style="background-color: lime; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Tension headaches ** <span style="color: #000000; font-family: 'Times New Roman',serif;">–dull band of pain around the entire head
 * <span style="background-color: yellow; background-position: initial initial; background-repeat: initial initial; color: #000000; font-family: 'Times New Roman',serif;">Key symptoms: **

<span style="color: #000000; font-family: 'Times New Roman',serif;">Ergot Derivatives: **Ergotamine**
 * <span style="color: black; font-family: 'Times New Roman','serif';">Prototype drug for migraine headaches: <span style="background-color: fuchsia; background-position: initial initial; background-repeat: initial initial;">Ergotamine **
 * <span style="color: black; font-family: 'Times New Roman','serif';">Action: **<span style="color: #000000; font-family: 'Times New Roman',serif;">The ergot derivatives block alpha-adrenergic and serotonin receptor sites in the brain to cause constriction of cranial vessels, a decrease in cranial artery pulsation, and a decrease in the hyperperfusion of the basilar artery bed.
 * <span style="color: black; font-family: 'Times New Roman','serif';">Indication: **<span style="color: #000000; font-family: 'Times New Roman',serif;">They are indicated for the prevention or abortion of migraine or vascular headache.
 * <span style="color: black; font-family: 'Times New Roman','serif';">Adverse reactions: **<span style="color: #000000; font-family: 'Times New Roman',serif;">Numbness, tingling of extremities (fingers and toes), muscle pain in the extremities, pulselessness or weakness in legs, precordial distress, tachycardia, bradycardia, arrhythmias, ergotism (chest pain, nausea, vomiting, diarrhea, severe thirst, hypoperfusion, confusion)
 * <span style="color: black; font-family: 'Times New Roman','serif';">Pharmacokinetics:Route: **<span style="color: #000000; font-family: 'Times New Roman',serif;">Sublingual**Onset:** Rapid**Peak:**0.5-3h
 * <span style="color: black; font-family: 'Times New Roman','serif';">Drug-to-drug interactions: **<span style="color: #000000; font-family: 'Times New Roman',serif;">Beta blockers, the risk of peripheral ischemia and gangrene is increased


 * <span style="color: black; font-family: 'Times New Roman','serif';">To prevent migraine headaches: **<span style="color: #000000; font-family: 'Times New Roman',serif;"> Anti-inflammatory therapy, NSAIDs, Vascular smooth muscle relaxation—exact mechanism of therapy not well understood, Beta-blockers and Calcium channel blockers

10. Differentiate between the various types of seizure disorders in terms of etiologies, s/s and pharmacologic therapies as discussed in Porth and ppt slides in class-<span style="background-color: transparent; color: #000080; font-family: ,'Times New Roman',; font-size: 12pt;">JENNIFER (Same as #1)