Pharm Quiz 4 Medium

Drugs for Parkinson's

• Levodopa stands out as the most effective medication for managing Parkinson's Disease (PD) symptoms.
• The full therapeutic effects may take several months to manifest.
• This drug functions by boosting dopamine synthesis in the striatum.
• Administered orally, it is rapidly absorbed in the small intestine, although only a small fraction reaches the brain.
• Common adverse effects include nausea/vomiting, dyskinesias, postural hypotension, dysrhythmias, and psychosis.
• Levodopa interacts negatively with Haldol and MAOIs.
• Consuming high-protein meals can diminish the therapeutic response.

Levodopa/Carbidopa

• This combination is the most effective therapy.
• Carbidopa enhances the effects of levodopa.
• Carbidopa does not have adverse effects.

Dopamine Agonists

• Dopamine agonists serve as first-line drugs for PD.
• They have severe side effects, including hallucinations, daytime sleepiness, and postural hypotension.
• Nonergot derivatives include Pramipexole and Ropinirole.

MAO-B Inhibitors

• Selegiline selectively and irreversibly inhibits MAO-B.
• Adverse effects include insomnia and orthostatic hypotension.
• Drug interactions include Levodopa, Meperidine, and SSRIs.

Amantadine

• This medication inhibits dopamine uptake.
• Adverse effects include confusion, lightheadedness, anxiety, blurred vision, urinary retention, and constipation.

Alzheimer's Disease

• This disease is characterized by neuronal degeneration in the hippocampus and a decline in cerebral volume.
• Symptoms include short-term memory loss, difficulty with language, and loss of speech.
• Symptoms progress from mild to moderate to severe.
• Treatment may slow the loss of memory and cognition and prolong independent function.

Cholinesterase Inhibitors

• Cholinesterase inhibitors work to prevent the breakdown of acetylcholine.
• These are approved for treating mild to moderate symptoms.
• Improvements are modest and short-lasting
• Adverse effects include nausea/vomiting/diarrhea, dizziness, headache, and bradycardia.
• Drug interactions include first-generation antihistamines, TCAs, and antipsychotics.
• Preparations include Donepezil, Rivastigmine, and Galantamine.

Memantine

• This is indicated for moderate to severe symptoms.
• It modulates the effects of glutamate.
• Adverse effects include dizziness, headache, and confusion.

Drugs for Epilepsy

• Partial seizures include: simple partial, complex partial, and secondarily generalized.
• Generalized seizures include: tonic-clonic, absence, atonic, myoclonic, status epilepticus, and febrile.
• Mixed seizures also exist.

How Anti-Seizure Meds Work

• Suppression of sodium influx
• Suppression of calcium influx
• Promotion of potassium efflux
• Antagonism of glutamate
• Potentiation of GABA

Diagnosis and Drug Selection

• Accurate diagnosis of the seizure type is crucial for matching the appropriate medication.
• Effective regimens may require trying several combinations.
• Management plans require monitoring plasma drug levels.

Traditional Antiepileptic Drugs

• Phenytoin is the most widely used antiepileptic drug with selective inhibition of sodium channels.
• Absorption varies among oral forms.
• It has a limited capacity to be metabolized by the liver.
• Adverse effects include nystagmus, gingival hyperplasia, measles-like rash, cardiac dysrhythmias, and hypotension (IV form).
• Drug interactions include oral contraceptives, warfarin, glucocorticoids, diazepam, and alcohol.

Carbamazepine

• Carbamazepine suppresses high-frequency neuronal discharge in and around seizure foci.
• Absorption is delayed and variable.
• It is metabolized by the liver.
• Adverse effects include blurred vision, diplopia, leukopenia, anemia, and aplastic anemia.
• Drug interactions exist.

Valproic Acid

• Effective for treating all seizure types.
• It suppresses high-frequency neuronal discharge.
• Readily absorbed from the gastrointestinal (GI) tract.
• Adverse effects include hepatotoxicity, pancreatitis, and nausea/vomiting.
• Drug interactions exist.

Phenobarbital

• It potentiates the effects of GABA.
• It allows for complete absorption.
• It is metabolized by the liver.
• Adverse effects include drowsiness and physical dependence.
• Drug interactions exist with CNS depressants and valproic acid.

Newer Antiepileptics

• Oxcarbazepine blocks voltage-sensitive sodium channels.
• Adverse effects include dizziness, drowsiness, double vision, headache, and nausea/vomiting.
• Drug interactions include oral contraceptives, alcohol, and diuretics.

Lamotrigine

• Lamotrigine blocks sodium channels.
• Adverse effects include dizziness, diplopia, blurred vision, and nausea/vomiting.
• Drug interactions exist with carbamazepine, phenytoin, phenobarbital, and valproate.

Gabapentin

• The mechanism of action is unknown.
• Rapidly absorbed after oral administration.
• Adverse reactions include somnolence and dizziness.
• It has no known drug interactions.

Levetiracetam

• The mechanism of action is yet unknown.
• Administered with rapid and complete absorption after oral administration.
• Side effects include drowsiness and weakness.
• It has no known drug interactions.

Topiramate

• Rapid absorption after oral administration.
• Adverse effects include somnolence, dizziness, ataxia, and nervousness.
• Drug interactions include phenytoin and carbamazepine.

Diabetes: Sulfonylureas

• This class features first-generation drugs like acetohexamide (Dymelor) and chlorpropamide (Diabinese).
• The drugs in this class feature second-generation drugs like glyburide (Diabeta, Glynase Prestabs, Micronase).
• Indications include stimulating the pancreas to release insulin and are insulin secretagogues.
• The ability to lower blood sugar depends on the presence of functioning pancreatic beta cells.
• Second-generation drugs have greater potency, but there are no therapeutic differences between first- and second-generation sulfonylurea drugs.
• Second-generation drugs generally have fewer adverse effects (except for hypoglycemia) and fewer drug interactions.
• First-generation sulfonylurea drugs are seldom used today but are still available.
• Sulfonylurea drugs are appropriate for normal weight adults who don't have lipid abnormalities.
• Mechanism of Action: Sulfonylureas inhibit the potassium channel in pancreatic beta cells, leading to depolarization, activation of calcium channels, and enhanced insulin secretion.
• Side Effects: Hypoglycemia, nausea, epigastric fullness, heartburn, and weight gain are common.
• Symptoms can be minimized if the drug is taken with food.
• Skin reactions can occur in 1.5% of patients.
• Elevated liver function (LFTs) and hepatotoxicity with jaundice have been reported; another class of drugs should be used if this happens.
• Weight gain can occur because these agents increase insulin secretion.
• Traditionally, sulfonylureas were first-line oral agents for type 2 DM.
• They are effective in lowering blood glucose, inexpensive, and have a long history of use.
• Metformin has advantages for overweight patients with type 2 DM and many clinicians use metformin as the drug of choice.

Meglitinides

• The drugs in this class structurally consist of the non-sulfonylurea part of glyburide and have a very similar mechanism of action.
• These drugs have a faster onset and shorter duration of action than sulfonylureas and decrease fasting and postprandial blood glucose when given alone or with metformin or a thiazolidinedione.
• These drugs allow flexibility for patients who do not maintain regular meal schedules.
• Drugs in this class include nateglinide (Starlix) and repaglinide (Prandin); Gluconorm.
• Mechanism of Action: These rapid-acting secretagogues lower blood glucose levels by stimulating insulin release from the pancreas by interacting with binding sites on the potassium channel in pancreatic beta cell membranes.
• This action depends on functioning beta cells in the pancreatic islets.
• Clinical Efficacy: As effective as glyburide or glipizide in lowering blood glucose levels; also provides synergistic activity when used with metformin.
• Administer 15-30 minutes before a a meal (short duration of action and will decrease food related hyperglycemia).
• Clinical Use: These drugs need to be given with each meal, so often three or more times per day (just before meals) so they are inconvenient for most patients; helpful for patients that have hyperglycemia related to food who haven't responded to other agents.

Biguanides

• Drug in this class: Metformin (Glucophage, Glucophage XR, Riomet); Fortamet, Glycon, Glucophage.
• Metformin is the only drug at this time in the biguanide class.
• Mechanism of Action: Metformin primarily reverses the defects of diabetes by reducing hepatic glucose production (hepatic gluconeogenesis).
• It increases peripheral utilization of glucose by increasing tissue sensitivity to insulin and reduces intestinal glucose production. Metformin DOES NOT increase insulin secretion from the pancreas and is not associated with hypoglycemia.
• Side Effects:
  • Gastrointestinal side effects include diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia (30% of patients).
  • May interfere with the absorption of B12 in the gut, so monitor this level q2-3 years.
  • Lactic Acidosis: Metformin may increase blood lactate levels as a result of enhanced lactate production and carries a BLACK BOX warning regarding lactic acidosis. Patients at risk for the development of lactic acidosis include those with hepatic failure, cardiac failure, and renal failure.
  • Metformin should not be used in patients at risk of developing acute renal failure, shock, acute CHF, MI, septicemia, liver disease, or use contrast agents.
  • IMPORTANT TO CHECK LFTs AND CREATININE (discontinue if creatinine > 1.5 mg/dl in men or 1.4 mg/dl in women).
  • NEED TO BE SURE THESE LEVELS ARE NORMAL PRIOR TO INITIATING METFORMIN.
• Clinical Use: Metformin is often the first-line treatment for Type 2 DM, especially in the overweight patient.

Thiazolidinediones (TZDs)

• This class features drugs such as pioglitazone (Actos)Actos pioglitazone + metformin (Actoplus), rosiglitazone (Avandia), and rosiglitazone + metformin (Avandamet).
• Mechanism of Action: Effective only in the presence of insulin. Decrease insulin resistance at peripheral sites and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
• They also cause activation of insulin-responsive genes in the nucleus that regulates lipid and carbohydrate metabolism.
• Side Effects: Generally well tolerated by patients.
  • May cause hypoglycemia.
  • Peripheral edema may occur within 6 months of therapy and necessitates withdrawal of med.
  • Exacerbation of congestive heart failure can occur due to fluid retention.
  • Rare causes of severe idiosyncratic hepatocellular injury were reported with the use of troglitazone (Rezulin).
  • It is recommended to monitor LFT's q 3-6 months with rosglitazone and pioglitazone.
• Clinical Use: These drugs may also be used as monotherapy or in combination with other oral agents in the treatment of Type 2 diabetes.
  • They are convenient to use and can be used in patients with renal dysfunction.
  • However, they are not generic and are expensive.

Alpha-glucosidase Inhibitors

• Drugs in this class: Acarbose (Precose); Prandase miglitol (Glyset)
• Mechanism of Action: Alpha-glucosidase inhibitors act to delay and decrease the absorption of complex carbohydrates from the GI tract and consequently delay glucose absorption.
• These drugs lower postprandial glucose levels.
• Side Effects: The side effects are mostly gastrointestinal and are secondary to the increased amount of undigested sugars that pass into the large intestine.
• They present with abdominal pain, diarrhea, and flatulence. Doses > 100 mg TID of acarbose caused increases in serum transferase.
• Clinical Use: Acarbose and miglitol can be used as first-line drugs or adjunctive drugs in the treatment of Type 2 DM.
• Patients using these in combination with other agents should be warned that they will need to treat hypoglycemia with glucose tablets or glucagon injection because sucrose-containing candy will not be absorbed.
• These drugs are appropriate for individuals with normal FBS levels but elevated postprandial readings.
• Since these drugs need to be given three or more times a day (just prior to each meal) and cause significant GI side effects, they are generally used as a second-line agent.

Dipeptidyl peptidase-4 (DDP-4) Inhibitors

• Drug in this class: Sitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta)
• Mechanism of Action: DPP-4 inhibitors, also known as gliptins, work by enhancing the incretin system in the body. The incretin system is one of the mechanisms in the body that lowers blood glucose.
• When the body senses hyperglycemia in response to a glucose load, incretins stimulate beta cells in the pancreas to release insulin and decrease glucagon secretion from alpha cells, signaling the liver to cease glucose production.
• The DDP-4 enzyme breaks down endogenous incretins. DPP-4 inhibitors block this enzyme, thereby increasing the active level of incretin hormones in the body.
• Side Effects: nasopharyngitis, URI, headaches, hypersensitivity reaction
• Clinical Use: Used as mono or combination therapy for DM and as an adjunct to diet and exercise to improve glycemic control in adults with type 2 DM.

Thyroid Disorders

• Hypothyroidism is more common in women than in men: 1.5% to 2% in women and 0.2% in men.
• Incidence of hypothyroidism increases with age.
• Causes of Hypothyroidism:
  • Primary Hypothyroidism - inadequate production of thyroid hormones (T4 and T3) that results from damage to the thyroid gland.
    • Accounts for > 90% of the cases of hypothyroidism.
    • Autoimmune (Hashimoto's) thyroiditis is the most common cause of hypothyroidism after 8 years of age.
    • Treatment of hyperthyroidism with drugs, radiation, or surgery is another cause.
    • Subacute thyroiditis
    • Radiation therapy to neck for malignant disease
    • Iodine deficiency or excess
    • Drugs
    • Congenital (approximately 1 case per 4000 live births)
  • Secondary Hypothyroidism - hypothalamic or pituitary malfunction
    • Pituitary dysfunction
    • Postpartum necrosis
    • Neoplasm
    • Infiltrative disease causing deficiency of TSH
• Signs and Symptoms of Hypothyroidism (Everything SLOW S down with one exception*): Fatigue, weakness, constipation, weight gain, cold intolerance, mental sluggishness, dry skin, course hair, deepened voice, and heavy menses in females.

Thyroid Replacement Therapy

• Levothyroxine (Levothyroid, Synthroid (generic), Levoxyl, T4) is the most commonly used product to treat hypothyroidism.
• Because T3 is produced as needed from T4 at tissue sites, replacement of anything other than T4 is not usually indicated.
• Liothyronine (Cytomel, Triostat, T3) T3 is the active thyroid hormone, but this product has an increased risk of hyperthyroidism and is more expensive, so is seldom used as first-line treatment.
• Thyroid, dessicated (Armour): This is a very old product that is made from pig thyroids; the amount of T3 isn't standardized and the potency can vary from lot to lot.
• Usual dose of levothyroxine in adults is 75 - 100 mcg/day.
• An easy way to calculate the starting dose is 1.6 mcg/kg/day.
• Elderly patients may require LOWER doses.
• A good starting dose for the elderly is 25 mcg/day.
• Pregnant women may require HIGHER doses.
• Dosage changes should occur every 4-6 weeks, and more frequent lab tests to check TSH will give inaccurate information; levothyroxine takes a minimum of 4-6 weeks to build up sufficiently in the body.
• Goal of therapy is a TSH level within normal range (this range will vary depending on age of patient and method used to do the test, so check your lab slip for the values for "normal range").

Hyperthyroidism

• Hyperthyroidism affects 2% of women and 0.2% of men in their lifetime.
• Toxic multinodular goiter usually occurs in women >55 years old and is more common than Grave's disease in the elderly.
• Causes of Hyperthyroidism:
  • Grave's disease (diffuse toxic goiter): 80% - 90% of all cases; an autoimmune disorder in which antibodies activate TSH receptors, leading to diffuse enlargement of the thyroid gland (goiter), and excess thyroid is released.
  • Iatrogenic hyperthyroidism: excessive thyroid hormone replacement
  • Toxic multinodular goiter (Plummer's disease)
  • Toxic adenoma
  • Transient hyperthyroidism (subacute thyroiditis, Hashimoto's thyroiditis)
  • Rare: pituitary tumor
  • Drugs: amiodarone
• Signs and Symptoms of Hyperthyroidism:
  • Tachycardia, palpitations, tremor, hyperreflexia, anxiety, irritability, heat intolerance, sweating, increased appetite, weight loss, diarrhea, amenorrhea, and exophthalmos.
• Treatment includes radioactive iodine ablation and drug therapy.

Drug Therapy for Hyperthyroidism

• Antithyroid Drugs:
  • Drugs in this class: propylthiouracil (PTU), preferred in pregnancy; methimazole aka tapazole.
  • Mechanism of Action: PTU and methimazole reduce the signs and symptoms of hyperthyroidism by inhibiting the synthesis of thyroid hormone.
• PTU also reduces the peripheral conversion of T-4 to the more potent T-3, but methimazole does not have this effect. Euthyroid state is usually restored within 4-8 weeks, and remission usually occurs within 3-6 months of therapy.
• Adverse effects can include skin rash, nausea and vomiting, stuffiness, benign transient leukopenia
• Adjunctive treatment can include beta blockers, such as propranolol and Iodide.

Drugs and Treatment of PUD and GERD

• H. Pylori infection:
  • Toxins and enzymes promote inflammation and ulceration (development of PUD).
  • Antibiotics are the treatment for this.
  • All regimens for PUD include a PPI plus antibiotics to treat this.
  • Triple therapy: PPI plus Clarithromycin 500mg BID or Metronidazole 500mg BID, Amoxicillin 1g BID to treat for 10-14 days.
  • Quadruple therapy: PPI plus Metronidazole 250mg qid.
  • Has been used as a second-line treatment in patients who fail first-line treatment and is now becoming more first-line treatment.
  • After treating for H. pylori, continue PPI for 8 to 12 weeks to promote healing.

GERD

• Antacids:
  • DO not prevent the overproduction of acid and neutralize the acid once in the stomach.
  • Drug effects: Reduce pain associated with acid.
  • Raising gastric pH from 1.3 to 1.6 neutralizes 50% of gastric acid
  • Raising pH 1 point neutralizes 90% of acid (1.3 to 2.3)
  • Used in combination with other salts
  • Side effects: Aluminum and calcium: constipation. Magnesium: diarrhea. Calcium carbonate: gas and belching
  • Patients with HF and HTN should use a lower dose of sodium.
  • Most medications should be given 1-2hrs after antacids.

Histamine Type 2 Antagonist

• Reduces acid secretion
• Drugs in class: cimetidine, famotidine, rantidine
• Indications: GERD, PUD, Erosive esophagitis
• Side effects: Cimetidine may cause impotence and gynecomastia; headaches, lethargy, confusion, diarrhea, urticaria, sweating, flushing, etc.
• Assess for allergies, impaired renal function, or liver function
• Use caution in patients who are confused or elderly
• Instruct to take 1hr before or after antacids

Proton Pump Inhibitors

• Achlorhydria- All gastric acid secretion is blocked
• Drugs in class: Iansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole
• Indications: GERD maintenance, erosive esophagitis, treatment of H. pylori induced ulcers
• Side effects: NONE
• Pantoprazole is the only PPI available for parenteral admin, and can be used for patients who are unable to take oral medications

Cytotec (misoprostol)

• Synthetic prostaglandin analog; has cytoprotective activity
• Protect gastric mucosa from injury by enhancing local production of mucus or bicarbonate
• Promotes local cell regeneration; Help to maintain mucosal blood flow
• Used for PREVENTION of NSAID-induced gastric ulcers
• Doses that are therapeutic enough to treat duodenal ulcers often produce abdominal cramps/ diarrhea

Overactive Bladder

• Symptoms: urgency, frequency, nocturia, urge incontinence
• Anticholinergic therapy
• Block muscarinic receptors, can cause anticholinergic side effects
• Side effects: Dry mouth, blurry vision, constipation, drowsiness, sedation, hallucinations, memory problems, confusion, delirium, decreased sweating and saliva

Oral Contraceptives

• Mechanism of action: Inhibit ovulation
• Contraindications: Thrombophlebitis, abnormal liver function, known breast CA, known pregnancy, smokers over age 35
• Types: Combination (progesterone/estrogen) and mini pill (progesterone only)
• Benefits: Decrease the risk of: Ovarian CA, endometrial CA, PID, benign breast disease, iron deficiency anemia, acne
• Oral Dosing: 28-day cycles, extended cycles, continuous cycle

Erectile Dysfunction

• Viagra
• Causes selective inhibition of PDE5; well absorbed following oral admin
• Adverse effects: Hypotension, priapism (prolonged erection), sudden hearing loss, nonarteritic ischemic optic neuropathy
• Drug interactions: Nitrates, alpha blockers, inhibitors of CYP3A4

ΒΡΗ

• Finasteride: Inhibits 5-alpha reductase, can protect against prostate CA; can decrease ejaculate volume; decrease serum PSA
• Laxatives: Bulk forming
  • Similar to dietary fiber; for temporary relief of constipation
  • Adverse effects: Intestinal obstruction, impaction

Surfactants

• Alter stool consistency by lowering surface tension
• Docusate sodium and docusate calcium

Stimulants

• Stimulate intestinal motility and increase the amount of water and electrolytes in the intestinal lumen
• Bisacodyl, senna, castor oil

Osmotics

• Draws water into the intestinal lumen
• Adverse effects: can cause loss of water
• Milk of magnesia, sodium phosphate, miralax