NOTES-AUTONOMIC-DISORDERS.pdf

GLAUCOMA- ocular disorders that lead to an optic neuropathy characterized by changes in the optic nerve (optic disk) that is associated with loss of visual sensitivity and field Tests/Biomarkers Tonometry: Measures intraocular pressure (IOP) to check for elevated pressure, which is a risk fact...

GLAUCOMA- ocular disorders that lead to an optic neuropathy characterized by changes in the optic nerve (optic disk) that is associated with loss of visual sensitivity and field Tests/Biomarkers Tonometry: Measures intraocular pressure (IOP) to check for elevated pressure, which is a risk factor for glaucoma. Ophthalmoscopy: Examines the optic nerve for damage or changes that are indicative of glaucoma. Perimetry (Visual Field Test): Assesses the extent of peripheral vision loss, which can indicate damage to the optic nerve. Gonioscopy: Evaluates the angle where the cornea and iris meet to determine if the drainage angle is open or closed. Optical Coherence Tomography (OCT): Provides detailed images of the optic nerve and retinal layers to detect structural changes. POAG - primary open angle glaucoma PACG -primary angle close glaucoma Cause: unknown Cause: there is a physical damage of the trabecular Factors: meshwork = increased IOP Increased susceptibility of the optic nerve to ischemia, excitotoxicity, autoimmune reactions and other abnormal physiologic processes Secondary OAG Causes: exfoliation syndrome, pigmentary glaucoma pretrabecular - normal meshwork is covered and prevents outflow of aqueous humor trabecular - meshwork is altered or material accumulates in the intertrabecular space posttrabecular glauc  - episcleral venous blood is increased CLINICAL PRESENTATION CLINICAL PRESENTATION Presence of optic disc changes and visual field loss Usually visualized by gonioscopy. with or without increased IOP High IOP = 40-90mmHg Normal tension glaucoma - (+) disc changes, visual field loss < 21 mmHg Ocular hypertension (+/-) disc changes, visual field loss + > 21mmHg TREATMENT TREATMENT B-adrenergic blocking agents Miotic Betaxolol Pilocarpine Timolol Secretory inhibitor Nonspecific adrenergic agents Latanoprost Divepirin- prodrug of epinephrine  - 3rd line Prostaglandin agonist Alpha-2 adrenergic agonist Osmotic agents Apraclonidine glycerin - 1-2 mg/kg Brimonidine Mannitol 1-2mg/kg Direct acting cholinergic agonists Carbachol - last resort Pilocarpine - prodrug of epinephrine - 3rd line Cholinesterase inhibitors Echothiophate Carbonic anhydrase inhibitor - topical Brinzolamide Carbonic anhydrase inhibitor - systemic Acetazolamide Prostaglandin analogs Latanoprost Bimatoprost Dosing: OD Combination Timolol-dorzolamide Timolol-brimonidine MYASTHENIA GRAVIS most common primary disorder of neuromuscular transmission. The usual cause is an acquired immunological abnormality The normal neuromuscular junction releases acetylcholine (ACh) from the motor nerve terminal in discrete packages (quanta). The ACh quanta diffuse across the synaptic cleft and bind to receptors on the folded muscle end-plate membrane. Stimulation of the motor nerve releases many ACh quanta that depolarize the muscle end-plate region and then the muscle membrane causing muscle contraction. In acquired myasthenia gravis, the post-synaptic muscle membrane is distorted and simplified, having lost its normal folded shape. The concentration of ACh receptors on the muscle end-plate membrane is reduced, and antibodies are attached to the membrane. ACh is released normally, but its effect on the post-synaptic membrane is reduced. The post-junctional membrane is less sensitive to applied ACh, and the probability that any nerve impulse will cause a muscle action potential is reduced. LABORATORY/ ASSESSMENTS The Edrophonium Chloride (Tensilon®) Test Serum Antibodies in Myasthenia Gravis -acetylcholine receptor (AChR) Weakness - - muscle-specific receptor tyrosine kinase (MuSK) abnormal neuromuscular transmission characteristically improves after intravenous administration of edrophonium chloride Electromyography Repetitive Nerve Stimulation (RNS) The amplitude of the fourth or fifth response to a train of low frequency nerve stimuli falls at least 10% from the initial value in myasthenic patients S/Sx Muscle Weakness: Particularly in the eyes, face, throat, and limbs. Ptosis: Drooping of one or both eyelids. Diplopia: Double vision. Difficulty Swallowing: Trouble with eating or drinking. Speech Changes: Slurred or nasal speech. Facial Weakness: Reduced ability to make facial expressions. Weakness in Limbs: Difficulty with tasks requiring sustained effort, such as climbing stairs or lifting objects PHARMACOLOGIC APPROACH Cholinesterase Inhibitors Immunosuppressant Drugs MOA: retard the enzymatic hydrolysis of ACh at cholinergic synapses, so that ACh accumulates at the ○ Primary Drugs: Azathioprine neuromuscular junction and its effect is prolonged (Imuran), Mycophenolate Mofetil Pyridostigmine bromide (Mestinon) (CellCept), Methotrexate neostigmine bromide (Prostigmin) ○ Mechanism of Action: Suppress the Primary Drug: Pyridostigmine (Mestinon) overall activity of the immune Mechanism of Action: Inhibits the enzyme system to reduce the production of acetylcholinesterase, which breaks down antibodies that target acetylcholine acetylcholine at the neuromuscular junction. receptors. This increases the availability of acetylcholine, ○ Dosage: improving neuromuscular transmission and Azathioprine: Initial dose of muscle strength. 1-2 mg/kg/day, adjusted based on tolerance and response.  Dosage: Typically started at 60 mg orally Mycophenolate Mofetil: every 4-6 hours. The dose can be adjusted Typically 1-1.5 g twice daily. based on patient response. Methotrexate: Dosing Common Side Effects: Nausea, diarrhea, varies; often 7.5-25 mg abdominal cramps, increased salivation, weekly. muscle twitching. ○ Common Side Effects: Nausea, Considerations: diarrhea, liver toxicity, bone marrow ○ Monitoring: Assess for effectiveness suppression, increased risk of and adjust dose based on symptom infections. control. ○ Considerations: ○ Interactions: May interact with other Monitoring: Regular blood medications that affect cholinergic tests to monitor liver activity. function, blood counts, and signs of infection. Interactions: Be cautious with other medications that may affect liver function or bone marrow. ○ Immunosuppressant Drugs Plasma Exchange Cyclosporine inhibits predominantly Plasma exchange is used as a short-term intervention T-lymphocyte-dependent immune responses and is for patients with sudden worsening of myasthenic sometimes beneficial in treating myasthenia gravis. symptoms for any reason, to rapidly improve strength before surgery, and as a chronic intermittent improve 1 to 2 months after starting cyclosporine and treatment for patients who are refractory to all other improvement is maintained as long as therapeutic treatments doses are given. Maximum improvement is achieved 6 months or longer after starting treatment Primary Drugs: Azathioprine (Imuran), Mycophenolate Mofetil (CellCept), Methotrexate  Mechanism of Action: Suppress the overall activity of the immune system to reduce the production of antibodies that target acetylcholine receptors. Dosage: ○ Azathioprine: Initial dose of 1-2 mg/kg/day, adjusted based on tolerance and response. ○ Mycophenolate Mofetil: Typically 1-1.5 g twice daily. ○ Methotrexate: Dosing varies; often 7.5-25 mg weekly. Common Side Effects: Nausea, diarrhea, liver toxicity, bone marrow suppression, increased risk of infections. Considerations: ○ Monitoring: Regular blood tests to monitor liver function, blood counts, and signs of infection. ○ Interactions: Be cautious with other medications that may affect liver function or bone marrow. Intravenous Immune Globulin (IVIG) Several groups have reported a favorable response to corticosteroids high-dose (2 grams/kg infused over 2 to 5 days) IVIG. Possible mechanisms of action include Primary Drug: Prednisone down-regulation of antibodies directed against AChR Mechanism of Action: Anti-inflammatory and and the introduction of anti-idiotypic antibodies immunosuppressive effects. Reduces immune system activity that attacks acetylcholine receptors. Dosage: Initial high-dose therapy (e.g., 20-60 mg/day) with gradual tapering based on clinical response. Monoclonal antibodies Thymectomy Primary Drugs: Eculizumab (Soliris), Note: While not a pharmacotherapy, Rituximab (Rituxan) thymectomy (surgical removal of the thymus Mechanism of Action: gland) can be an important part of treatment ○ Eculizumab: Inhibits complement for patients with thymoma or generalized protein C5, reducing the MG, often improving long-term outcomes and complement-mediated destruction reducing the need for medications. of acetylcholine receptors. ○ Rituximab: Targets CD20 on B-cells, reducing the production of antibodies against acetylcholine receptors. Dosage: ○ Eculizumab: Initial dose of 900 mg IV every 7 days for 4 weeks, then 1200 mg every 2 weeks. ○ Rituximab: Typically 375 mg/m² IV once weekly for 4 weeks. Common Side Effects: Infusion reactions, infections, headaches, fatigue, nausea. Considerations: ○ Monitoring: Regular monitoring for infections and other infusion-related reactions. ○ Interactions: Consider interactions with other immunosuppressive therapies. General Considerations: Patient Education: Educate patients about the importance of medication adherence, potential side effects, and the need for regular follow-ups. Monitoring and Follow-Up: Regular assessment of symptom control, side effects, and overall health is essential. Adjust treatments based on response and tolerability. Drug Interactions: Be vigilant about potential drug interactions, especially with immunosuppressive and corticosteroid therapies, to avoid adverse effects and ensure effective management of MG