Parkinson's Disease Drugs

Drugs for Parkinson's Disease

• Levodopa increases dopamine synthesis in the striatum, which restores the balance between dopamine and acetylcholine, improving motor function.
• Levodopa enters the brain via active transport and converts to dopamine in dopaminergic nerve terminals.
• Levodopa can activate malignant melanoma; careful skin assessment is important.
• Additional adverse effects of levodopa include nausea, vomiting, postural hypotension, psychosis, CNS effects (anxiety, agitation, memory impairment), dyskinesias, darkened sweat and urine.
• Carbidopa inhibits levodopa decarboxylation in the intestine and peripheral tissues, increasing levodopa available to the CNS; this allows reduction of levodopa dosage by 75%.
• Carbidopa does not cross the blood-brain barrier.
• Carbidopa has no adverse effects of its own; adverse effects from levodopa/carbidopa combinations are due to potentiation of levodopa, including abnormal movements and psychiatric disturbances.
• Benztropine is a muscarinic antagonist (anticholinergic drug).
• Benztropine antagonizes acetylcholine and histamine receptors in the CNS and smooth muscle.
• Benztropine alleviates symptoms of Parkinson's disease and is a second-line therapy for tremor.
• Common adverse effects of benztropine include fever, rash, lethargy, nausea, vomiting, diarrhea, heat intolerance, delirium, confusion, worsening of pre-existing psychotic symptoms, toxic megacolon, paralytic ileus, withdrawal symptoms, and constipation.

Drugs for Thyroid Disorders

• Serum Thyroid-Stimulating Hormone (TSH) is used for screening and diagnosing hypothyroidism.
• Elevated TSH indicates hypothyroidism.
• Serum TSH is the most sensitive test for diagnosing hypothyroidism.
• Serum T4 measures total T4 or free T4.
• Serum T3 measures total T3 or free T3.
• Hypothyroidism is a severe deficiency of thyroid hormone associated with myxedema (adults), myxedema coma, and congenital hypothyroidism (infancy).
• Causes of hypothyroidism include malfunction of the thyroid gland, Hashimoto’s thyroiditis, insufficient dietary iodine, surgical removal of the thyroid, and insufficient secretion of TRH and TSH.
• Hyperthyroidism is excessive thyroid hormone secretion associated with Graves’ disease and toxic nodular goiter.
• Symptoms of hyperthyroidism include CNS stimulation, rapid heartbeat, increased metabolic rate, and weight loss.
• Thyroid hormone stimulates energy use by increasing basal metabolic rate.
• Thyroid hormone stimulates the heart by increasing heart rate and force of contraction.
• Thyroid hormone promotes growth and development and is essential for normal brain development.
• Levothyroxine (Synthroid) treats all forms of hypothyroidism, including congenital hypothyroidism, myxedema coma, simple goiter, and primary hypothyroidism.
• Drugs that reduce levothyroxine absorption include H2 blockers, proton pump inhibitors, sucralfate, cholestyramine, colestipol, aluminum-containing antacids, calcium supplements, iron supplements, magnesium salts, and orlistat.
• Drugs that accelerate levothyroxine metabolism include phenytoin, carbamazepine, rifampin, sertraline, and phenobarbital.
• Levothyroxine enhances the effects of warfarin.
• Taking levothyroxine with catecholamines (e.g., epinephrine, dopamine, dobutamine) increases risk for dysrhythmias.
• Levothyroxine should be taken in the morning at least 30 to 60 minutes before breakfast to maintain stable blood levels.
• Methimazole (Tapazole) is used as sole therapy for Graves’ disease, as adjunct to radiation therapy until effects manifest, to suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy), and in thyrotoxic crisis.

Insulin

• NPH is an intermediate-duration insulin.
• NPH is injected two or three times daily for glycemic control between meals and during the night.
• NPH is the only insulin suitable for mixing with short-acting insulins.
• NPH is a cloudy suspension that must be agitated before administration.
• NPH is only administered via subcutaneous injection.
• Insulin glargine is a long-duration insulin with a prolonged action of up to 24 hours.
• Insulin glargine is administered once daily by subcutaneous injection to treat adults and children with type 1 diabetes and adults with type 2 diabetes.
• Insulin glargine is a clear solution available in U-100 (100 units/ml) and U-300 (300 units/ml) concentrations.
• Short-Duration, Rapid-Acting Insulin (e.g., Insulin Lispro [Humalog]) has an onset of 15 to 20 minutes and duration of 3 to 5 hours.
• Short-Duration, Slower-Acting Insulin (e.g., Regular Insulin [Humulin R, Novolin R]) has an onset of 30 to 60 minutes and duration up to 10 hours.
• Intermediate-Duration Insulin (e.g., NPH Insulin [Humulin N, Novolin N]) when injected two or three times daily.
• Long-Duration Insulin (e.g., Insulin Glargine [Lantus]) has a duration up to 24 hours.
• Ultra-Long Duration Insulin (e.g., Insulin Degludec [Tresiba]) has a duration greater than 24 hours and no peak.
• Complications of insulin therapy include hypoglycemia (blood glucose below 70 mg/dL), hypokalemia, lipohypertrophy, allergic reactions.
• Drug interactions with insulin include Hypoglycemic agents (e.g., sulfonylureas, glinides, alcohol), Hyperglycemic agents (e.g., glucocorticoids) and Beta-adrenergic blocking agents (e.g., propranolol) which can mask symptoms of hypoglycemia and impair glycogenolysis.
• NPH insulin can be mixed with short-acting insulins.
• Short-acting insulin should be drawn first when mixing.
• Premixed combinations are available in pens (e.g., Humulin 70/30, Humalog Mix 75/25, Humalog Mix 50/50).

Other Antidiabetic Agents

• Sulfonylureas (e.g., Glyburide [Glynase]) promote insulin release by stimulating pancreatic islet cells.
• SGLT-2 Inhibitors (e.g., Empagliflozin [Jardiance]) decrease blood glucose by promoting glucose excretion.
• SGLT-2 Inhibitors block reabsorption of filtered glucose in the kidneys, increasing glucose excretion in urine.
• GLP-1 Agonists (e.g., Semaglutide [Ozempic]) activate GLP-1 receptors in the GI tract, pancreas, and brain.
• GLP-1 Agonists enhance insulin release, slow gastric emptying, reduce glucagon release, and increase satiety.
• Most common side effects of Metformin are gastrointestinal disturbances (e.g., nausea, vomiting, diarrhea).
• Rare but serious side effect of Metformin is lactic acidosis.
• Additional Metformin interactions include alcohol (intensifies lactic acidosis), cimetidine (increases risk of lactic acidosis), and contrast dye (risk for acute renal failure).
• GLP-1 Agonists (e.g., Semaglutide [Ozempic]) are contraindicated in individuals with personal or family history of medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2, suicidal ideation or have become pregnant.
• GLP-1/GIP Agonists (e.g., Tirzepatide [Mounjaro]) are contraindicated in individuals with personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, history of suicidal ideation or attempt
• GLP-1/GIP Agonists (e.g., Tirzepatide [Mounjaro]) are contraindicated in individuals with hypersensitivity to the drug.

Central Nervous System Pharmacology

• Peripheral Nervous System Transmitters include Acetylcholine, Norepinephrine and Epinephrine.
• Central Nervous System Transmitters include Dopamine, Epinephrine, Norepinephrine, Serotonin, GABA (Gamma-Aminobutyric Acid) and Glutamate.
• CNS drugs are used for relief of pain, suppression of seizures, production of anesthesia and treatment of psychiatric disorders (e.g., depression, anxiety, schizophrenia).
• Chronic use of CNS drugs can lead to increased therapeutic effects (e.g., antipsychotics or antidepressants), decreased side effects and physical dependence.
• Physical dependence from chronic use of CNS drugs results in abrupt discontinuation of drug use which will precipitate a withdrawal syndrome.

Diabetes

• Beta blockers, such as propranolol, can mask the symptoms of hypoglycemia (e.g., tachycardia) and may also impair glycogenolysis.
• Type 1 Diabetes (T1DM) typically develops during childhood or adolescence and accounts for 5% of all diabetes cases.
• The primary defect of T1DM is destruction of pancreatic beta cells due to an autoimmune process.
• Genetic, environmental, and infectious factors likely play a role in triggering the immune response for T1DM.
• Type 2 Diabetes (T2DM) is the most prevalent form of diabetes, accounting for 90-95% of all cases.
• T2DM is characterized by insulin resistance and impaired insulin secretion.
• T2DM is often associated with hyperinsulinemia
• T2DM has a strong family association.
• IV Glucose is the preferred treatment of hypoglycemia because it immediately raises blood glucose levels.
• Glucagon is an alternative treatment for hypoglycemia if IV glucose is not available.
• Glucagon promotes glycogen breakdown to glucose, but it is less effective in malnourished individuals who have little glycogen stored.