Pharmacology Final

Type 1 diabetes IDDM

) Characterized by an absolute deficiency of insulin caused by massive beta-cell destruction. 2) Type I diabetics require exogenous insulin to avoid hyperglycemia and life-threatening ketoacidosis. 3) Cause of Type I diabetes: a burst of insulin secretion normally occurs after ingestion of a meal in response to circulating glucose. a. Type I diabetic, having no beta-cells, can neither respond to variations in blood glucose, nor maintain even basal secretion of insulin. ) Treatment of Type I diabetes: a Type I diabetic must rely on exogenous insulin in order to control hyperglycemia. 5) The goal is to maintain blood glucose concentrations as close to normal as possible and to avoid wide swings in blood glucose levels that may contribute to long-term complications.

4treatment approaches for peptic ulcers include:

) Eradicating H. pylori infection 2) Reducing secretion of gastric acid 3) Providing agents that protect the gastric mucosa from damage

4. Regulation of gastric acid secretion

) Gastric acid secretion by parietal cells of the gastric mucosa is controlled by Ach, histamine, prostaglandins and gastrin. 2) receptor-binding of Ach, histamine or gastrin results in the activation of a H+/K+-ATPase proton pump that secretes HCL into the lumen of the stomach. 3) Receptor binding of prostaglandins diminishes gastric acid production. This produces a mucous layer that protects gastric mucosa from acid and acid secretion.

5 Hormones of the posterior pituitary

) In contrast to the hormones of the anterior lobe of the pituitary, those of the posterior lobe, ADH and oxytocin are not regulated by releasing hormones. 2) Instead they are made in the hypothalamus, transported to the posterior pituitary and released in response to stimulation.

3theophylline

) Is a bronchodilator that relieves airflow obstruction in chronic asthma. Was once a main-stay of asthma therapy but has been replaced by beta-agonists and steroids. 2) Theophylline has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. The FDA no longer recommends this drug for acute bronchospasm or status asthmaticus.

Adverse effects for morning after pill

) Most adverse effects are believed to be due to the estrogen component. 2) Cardiovascular: the most serious side effect of oral contraceptives is cardio-vascular disease, including increased incidence of myocardial infarction. 3) Oral contraceptives have been shown to decrease the incidence of endometrial and ovarian cancer.

6 type 2 diabetes NIDDM

) Most diabetics are in this category. genetics factors rather than viruses or autoimmune antibodies are apparently causal. 2) Cause of Type II diabetes: the pancreas retains some beta-cell function, but insulin levels insufficient to maintain glucose homeostasis. . Patients with Type II diabetes are often obese. (70%). Frequently accompanied by target organ insulin resistance that limits responsiveness to insulin. b. In some cases, insulin resistance is due to a decreased number or mutations of insulin receptors. c. An as yet undefined defect in the events that occur after insulin binds to its receptor is believed to account for resistance in most patients. ) Treatment of Type II diabetes: Weight reduction, exercise and dietary modification decrease insulin resistance and correct the hyperglycemia in some patients. 4) Most Type II diabetics are dependent on pharmacologic intervention with oral hypoglycemic agents. Two issues going on in Type II: 1) A pancreatic beta-cell defect and 2) a decrease in tissue sensitivity to insulin

4Agents that modify fluid and electrolyte transport

) NSAIDS, like aspirin are effective in controlling diarrhea. 2) Bismuth subsalicylate (PEPTO-BISMOL) decreases fluid secretion in the bowel. Used for traveler's diarrhea. Also serves as a mucosal protective agent.

3 Cromolyn (Intal®)

) Not a direct bronchodilator. Mechanism is not clear, but may block the release of mediators from mast cells. 2) Pretreatment with cromolyn blocks allergen-induced and exercise-induced bronchoconstriction. 3) Cromolyn is used exclusively for propylactic (prevents) treatment of mild to moderate asthma.

6 insulin secretion

) Secretion is most commonly triggered by high bloodglucose which is taken up and phosphorylated in the beta-cells of the pancreas. 2) ATP levels rise and block K+ channels, leading to membrane depolarization and an influx of calcium which causes pulsatile insulin exocytosis. High intracellular concentrations of ATP Closure of K+ channel

5 Growth hormone (somatotropin)

) Somatotropin is produced synthetically be recombinant DNA technology. GH from animal sources is ineffective in humans. 2) GH stimulates a wide-range of processes including protein synthesis, fat metabolism, cell proliferation, and bone growth. 3) Therefore, GH is used in the treatment of growth-hormone deficiency in children. Somatrem is the drug used, and it induces the release from the liver of somatomedin, the insulin-like growth factor that is reposible for subsequent GH-like actions. In adults, it regulates metabolism. In children, it helps with linear growth. GH release is episodic, so it goes up and down. To determine deficiency, give after giving agent that stim release GH can also help wounds, but may risk diabetes

5thyroid hormones

) The thyroid gland facilitates normal growth and maturation by maintaining the level of metabolism in the tissues that is optimal for their normal function. 2) The two major thyroid hormones are T3 and T4 (thyroxine). 3) Inadequate secretion of thyroid hormone (hypothyroidism) results in bradycardia, poor resistance to cold, and mental and physical slowing. 4) Excess of thyroid hormones is secreted (hyperthyroidism), tachycardia and cardiac arrhythmias, body wasting, nervousness, tremor, and excess heat production, and exophthalmis (protruding eyeballs).

lowest, shortest

. One needs to look at the benefits versus the risks for ETR and each person must make their own decision. Current recommendations are to prescribe the _________ effective dose for the _______________ possible time to relieve symptoms.

5 treat hypothyroidism

1) Hypothyroidism is treated with levothyroxine (T4).

3Drugs used to treat allergic rhinitis

1) Rhinitis is an inflammation of the mucous membranes of the nose, and is characterized by sneezing, nasal itching, and congestion. 2) An attack may be precipitated by inhalation of allergen (such as dust, pollen, or animal dander), which interacts with mast cells coated with IgE. 3) The mast cells release mediators such as histamine_, which promote bronchiolar spasm and mucosal thickening from edema. majority of symptoms related to allergic rhinitis are mediated through histamine binding to H1 receptors. H2 RECEPTORS ARE FOR GASTRIC ACID SECRETION-ULCERS

MOA for steroids (steps)

1. Steroid hormone(s) are lipid soluble and thus readily pass through the plasma membrane of cells. 2. Inside the target cell, the steroid hormone binds to a specific receptor protein. 3. The receptor-steroid hormone complex enters the nucleus and binds to DNA causing the transcription of genes. Protein synthesis is induced.

Menstrual Cycle

1. day 0: 1st day of menstruation/endometrium sloughed off-bleeding. Estrogen and progesterone levels are very low at this point. 2. LH and FSH released and slowly stimulate follicle development. Follicle produces estrogen. 3. As estrogen increases, it changes from negative to positive feedback regulator. At the highest point, it stimulates LH and FSH from pituitary gland and that creates LH surge. 4. LH that is involved in ovulation, which is releases a mature egg that can be fertilized. 5. Follicle ruptures, egg is mature if fertilization occurs. Part of follicle becomes corpus luteum, which makes progesterone. 6. No fertilization=corpus luteum degenerates and levels of progesterone falls along with estrogen levels. 7. Menstruation again. 8. But if fertilization, the embryo and placenta will release human chorionic gonadotropic hormone to maintain corpus luteum. 9. corpus luteum and placenta will make progesterone throughout the rest of pregnancy.

4 three major factors are recognized regarding peptic ulcer disease

1. infection with gram negative H. pylori 2. increased HCL secretion 3. inadequate mucosal defense against gastric acid

5 Biosynthesis of thyroid hormones

1. iodide accumulates in thyroid gland 2. oxidation of iodide to iodine by thyroperoxidase 3. iodine incorporates into tyrosine residues of thyroglobulin (iodination) 4. condensation reaction. 2 tyrosine residues with iodine molecules come together. 5. cleavage of molecules and release in bloodstream. T3 or T4 iodines.

8during past few years, FDA has been criticized because length of time and cost to have a adrug approved. It can take 12-14 years from synthesis to regulatory clearance to bring a subscription drug to market at an out of pocket expense of 1.4 billion for a new molecular entity.

10000 chemical entities, 10 will go to clinical trials, and one will gain regulatory approval

7 National Center for Complimentary and Alternative Medicine (National Center for Complementary and Integrative Health NCCIH)

1998 established by congress. run clinical trials on herbs and establish efficacy tested echinacea (colds) and st john's wort (depression) in double-blinded placebo trials Doesn't work After 17 years of government testing at a cost of 2.5 billion, almost no clearly proven efficacy alt. therapies found. Now focus on dietary supplements and pain relief Criticized by JAMA

3. Antileukotriene drugs

5-lipoxygenase inhibitors: Zileuton (Zyflo) Decrease the synthesis of LTB4, which is a potent chemoattractant for neutrophils and eosinophils Leukotriene receptor antagonist: Montelukast (Singulair) 4) Used for the prophylaxis treatment of mild to moderate asthma. 5) Both drugs are not effective in situations where immediate bronchodilation is required. Montelukast is the market leader that claims 2 primary advantages: Dosing recommendations for children 6 months of age and older Availability in chewable tablets

Post Coital Contraception

: High-dose estrogen administered 72 hours of coitus and continued twice daily for 5 days (morning-after pill). Also RU-486 is used

Oral contraceptives/progestin pills

: also called the "mini-pill". Has had limited patient acceptance because of anxiety over the increased possibility of pregnancy. May cause irregular menstrual cycle, spotting, and increases bad cholesterol.

Estrogen

A progestin is usually included with ____________ since the combination reduces the risk of endometrial cancer associated with estrogen treatment alone. EPT is not universally beneficial: the risk of breast and endometrial cancer is slightly increased in women receiving estrogen.

6 insulin prep

A. Insulin preparations vary in their time to onset and duration of action The onset and duration of action of the insulin preparations is controlled by the size and composition of the crystals in the insulin preparation. 2) Rapid and Intermediate onset and duration; Prolonged duration. 3) The various ways to slow absorption is the inclusion of protamine (NPH insulin), changing the isoelectric point of insulin so it precipitates at site of injection (Insulin glargine) or adding a fatty acid chain, which enhances the association to albumin (Insulin detemir).

3CHECK THAT ONE WORKSHEET ON BB

ABOUT THE DIFF RESP DRUGS

5 ACTH or corticotropin

ACTH is released from the anterior pituitary. Its target organ is the adrenal cortex where corticotropin binds to specific receptors that are coupled to increases in cAMP (Gs) 2) ACTH stimulates the rate-limiting step in the adrenocroticosteroid synthetic pathway (cholesterol ----> pregnenolone). 3) Therapeutic corticotropin preparations are extracts from the anterior pituitaries of domestic animals or synthetic human ACTH. 4) Its only pharmacological use is as a diagnostic tool for certain disorders associated with ACTH. If someone is deficient in cortisol, give them ACTH In Addison's Diseases, cortisol or ACTH is deficient. so give ACTH peptide, however a cheaper alternative would be corticosteroids.

2 new drugs approved by FDA in 2015: PCSK9 inhibitors

Alirocumab (Praluent) and Evolocumab (Repatha) A works by inhib PCSK9 protein. PCSK9 binds to the LDL receptor, which takes cholesterol out of circulation, and that binding leads to receptor being degraded and less LDL cholesterol being removed from circulation. Inhibiting PCSK9 prevents receptor from being degraded and promotes removal of LDL cholesterol from circulation. Annual price for A is 10000/year statins can reduce LDL by 30-50%. PCSK9 might be slightly more potent reducing by 40-60% cant prove PCSK9 inhib prevent heart attacks or strokes.

Therapeutic uses for androgens

Androgenic effects: used in males with inadequate androgen secretion. 2) Anabolic effects: can be used for severe burns, and to speed recovery from surgery. 3) Growth: can promote skeletal growth in prepubertal boys with pituitary dwarfism. 4) Endometriosis: Danazol, a mild androgen, is used in the treatment of endo-metriosis. 5) Unapproved use: adrogenic steroids are used to increase lean body mass, muscle strength and aggressiveness in athletes and body builders.

MOA for androgens

Androgens bind to a specific nuclear receptor in a target cell. In some tissues, testosterone must be metabolized to DHT 2) The hormone/receptor complex binds to DNA and stimulates synthesis of specific RNAs and proteins. In the prostate gland, DHT is the ligand. In the muscle and liver, testosterone is the ligand.

4antidiarrheals

Antidiarrheals Increased motility of GI tract and decreased absorption of fluid are major factors in diarrhea. Antidiarrheal drugs include antimotility agents, adsorbents, and drugs that modify fluid transport.

4antacids

Are weak bases that react with gastric acid to form water and a salt, thereby diminishing gastric acidity. Because pepsin is inactive at pH greater than 4, antacids also reduce pepsin activity. 1) Commonly used antacids are salts of aluminum and magnesium (milk of magnesia). or weak bases 2) Since calcium salts stimulate gastrin release, use of calcium-containing antacids (Tums) may be counterproductive.

6 insulin administration

Because insulin is a protein, it is degraded in the G.I. Tract if taken orally. It is generally administered by subcutaneously. 2) Human insulin is produced by a special strain of E. coli that has been genetically altered to contain the gene for human insulin. 1) The symptoms of hypoglycemia are the most serious and common adverse reactions to an overdose of insulin. Can lead to insulin coma and death, if too much insulin is injected.

6VI. Oral agents: Insulin sensitizers

Biguanides: Metformin (Glucophage®) Metformin improves hyperglycemia primarily by suppressing glucose production by liver gluconeogenesis. The "average" person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one third. It is the1st drug of choice for the treatment of Type II diabetes, in particular, in overweight and obese people and those with normal kidney function. Metformin is the only antidiabetic drug that has been conclusively shown to prevent the cardiovascular complications of diabetes. It helps reduce LDL cholesterol and triglyceride levels, and is not associated with weight gain. Thiazolidinediones (TZDs): Rosiglitazone (Avandia®), Pioglitazone (Actos®) Although insulin is required for their action, these drugs do not promote its release from the pancreas. They act as insulin sensitizers, enhancing insulin's actions. They target the PPAR receptor expressed in adipose tissue whereby the end result is stimulation of gene transcription of insulin-sensitive genes. May take 1-3 months to be effective. The FDA has ruled that due to increased risk of myocardial infarction and death, that Avandia be restricted to patients who can't control diabetes with other meds. The drug can counteract insulin resistance As illustrated, one mechanism contributing to the hypoglycemic effect of thiazolidinediones is an increased expression of the glucose transporter GLUT4. The increased expression of GLUT4 (in addition to mediators of insulin signal transduction) increases the ability of cells (e.g. adipocytes) to take up glucose when stimulated by insulin.

Progesterones

Build up uterine wall for pregnancy and inhibit LH and FSH so no more ovulation. It inhibits uterine contractions and increases mucus secretions.

4C. H2-receptor antagonists

By competitively blocking the binding of histamine to H2 receptors, these agents reduce cAMP levels and secretion of HCL. 2) Cimetidine (Tagamet®) potently inhibits (>90%) stimulated secretion of gastric acid after a single dose. a. actions: these drugs are competitive antagonists of h2 receptors (reversible) Therapeutic uses: Peptic ulcers: all H2 receptor antagonists are equally effective in promoting healing of duodenal and gastric ulcers. However, recurrence is common after treatment is stopped. b. Zollinger-Ellison syndrome: caused by gastrin-producing tumor. PPIs are preferred. c. Acute stress ulcers: associated with major physical trauma. d. Gastroesophageal reflux disease (GERD)(heartburn): sometimes you can use low doses (OTC) drugs to treat this.

6diabetes

Diabetes is not a single disease but a group of syndromes all characterized by an elevation of blood glucose by a deficiency of insulin. Diabetes afflicts about 23.6 million people (10% popn) in USA, and is the eighth leading cause of death in this country. Diabetics can be divided into two groups based on their requirements for insulin: Insulin-dependent diabetes mellitus (IDDM or Type I) and non-insulin-dependent diabetes mellitus (NIDDM or Type II). 2) About 1-2 million patients have IDDM; the remaining 80% have NIDDM

5 treat hyperthyroidism

Excessive amounts of thyroid hormones are associated with a number of disease states, including Graves' disease and goiter. The goal of therapy is to decrease synthesis and/or release of additional hormone 1) Removal of thyroid: this can be accomplished by surgery or by destruction of the gland by beta particles emitted by radioactive iodine 2) Inhibition of thyroid hormone synthesis: Propylthiouracil and methimazole are concentrated in the thyroid where they inhibit both the oxidative processes and coupling of iodotyrosines to form T3 and T4. 3) Propranolol: beta-blockers are effective in blunting the widespread sympathetic stimulation that occurs in hyperthyroidism. 4) Blockade of hormone release: Pharmacological doses of iodide inhibits thyroid hormone release by mechanisms not yet understood. Rarely used as sole therapy. Thyroid hormone sensitizes cells to EP and NE so thats why beta blockers are effective.

2. Cholesterol absorption inhibitors 1. Ezetimibe (Zetia)

Ezetimibe localizes at the brush border of the small intestine, where it inhibits the absorption of cholesterol from the diet. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes. New recent data has cast serious doubt on the efficacy of Zetia. Guidelines are to use only as a "last" resort.

What is necessary for the initiation of spematogenesis?

FSH

Antiandrogens

Finasteride (Proscar) is a 5 alpha reductase inhibitor that is used to treat benign prostatic hypertrophy (BPH). This enzyme converts testosterone to DHT. DHT causes prostate to enlarge. Dutasteride works similarly Flutamide: acts as a competitive inhibitor of androgens at the target cell. Used in prostatic carcinoma. Adverse effects: less libido and ED

alpha-1 adrenergic antagonists

For treatment of benign prostate hypertrophy. Ex. Tamsulosin, Terazosin, Doxazosin Relieves outlet obstruction of bladder by reducing tension of prostatic smooth muscle in prostate. Can cause dizziness and orthostatic hypotension.

hypothalamous releases

GnRH (LHRH) to the pituitary gland. The pituitary gland releases LH to the testis, which create testosterone. The pituitary gland releases LH and FSH to the ovaries and this creates estradiol and progesterone. The end products act as inhibitors in a negative feedback loop to inhibit both the pituitary gland and the hypothalamus.

5E. Gonadotropin-releasing hormone (GnRH)

GnRH is from the hypothalamus and controls the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary. 2) GnRH is employed to stimulate gonadal hormone production in hypogonadism. 3) There are a number of drugs such as leuprolide that act as inhibitors of GnRH. These are effective in suppressing production of the gonadal hormones and are used in the treatment of prostatic cancer, endometriosis, and precocious puberty.

2Combination drug therapy

HMG-coA reductase inhibitor with bile acid agent=lowers LDL cholesterol

8 first significant empowerment of fda was to enact the food and drug act of 1906.

If drug has unknown composition, drug can be removed. dealt mostly with truth in labelling/ This act did nothing for safety and efficacy.

6 diabetes

In Type 2 diabetes there is a progressive decline in β-cell function and insulin secretion. As a result, most patients with type 2 DM will eventually need insulin.

testosterone effects

In females: androgens can cause masculinization with acne, growth of facial hair, deepening of the voice, male pattern baldness and excessive muscle development. 2) In males: excess androgens can cause impotence, and decreased spermatogenesis 3) In children: androgens can cause growth disturbances resulting from premature closing of the epiphyseal plates. Can also cause abnormal sexual maturation 4) In athletes: can cause premature closing of the epiphysis of the long bones, which interrupts development. Reduction of testicular size . The high doses taken by young athletes may result in liver damage, increased aggression, as well as other adverse effects already described above.

3 D. Corticosteroids, Inhaled corticosteroids (ICS)

Inhaled glucocorticoids (Beclomethasone) are the drugs of first choice for all forms of asthma except intermittent (less than 2 days per week). 2) Actions on lung: steroids have no direct effect on the airway smooth muscle. Instead, inhaled glucocorticoids decrease number/activity of cells involved in airway inflammation. 3) Inhaled drugs: have reduced the need for systemic treatment. 4) therefore, only a small amount of these drugs reaches the systemic circulation. 5) Spacers: is a large volume chamber that is attached to the inhaler and decreases the deposition of drug in the mouth. 6) Spacers improve delivery of inhaled glucocorticoids and are advised in virtually all patients. Deposition on the tongue and throat may promote oral candidiasis which appears as a white coating, possibly with irritation. This may usually be prevented by rinsing the mouth with water after using the inhaler

Hypothalamous

Inhibited by combination of estrogen and progesterone Stimulated by high levels of estrogen

6insulin (51 aa)

Insulin is a small protein consisting of two polypeptide chains that are connected by disulfide bonds-tert struc. It is synthesized as a precursor protein (pro-insulin) that undergoes proteolytic cleavage to form insulin and peptide C.

3Cholinergic antagonists (Ipratropium, Atrovent®)

Ipratropium is a quaternary amine that is positively charged. It is poorly absorbed and has few side effects. It is an anticholinergic agent that blocks the vagally mediated constriction of airway smooth muscle and mucus secretion.

What stimulates the synthesis of testosterone in Leydig cells?

LH

6VII. Oral agents: alpha-glucosidase inhibitor

MOA Acarbose inhibits alpha-glucosidase in the intestinal brush border and thus decreases the absorption of starch and disaccharides. 2) Consequently, the post-eating rise of blood glucose is blunted. 3) Acarbose does not stimulate insulin release nor does it increase insulin action. Thus, it does not cause hypoglycemia.

6New Diabetes categories

Maturity onset diabetes of the young (MODY): inherited, not obese, no insulin resistance, less than 25 years old and makes up 1-5% of all known diabetes cases Gestational diabetes: glucose intolerance assoc with preg. Hyperglycemia can lead to cogenital abnormalities in fetus.

2 . The fibrates-Fenofibrate (Tricor®)and gemfibrozil (Lopid)

Mechanism of action: both drugs cause a decrease in plasma triacylgycerol levels by stimulating gene expression of lipoprotein lipase (takes up free floating fatty acids from blood) following interaction with the peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear receptor supergene family that regulate lipid metabolism. PPARs act as ligand-activated transcription factors. 2) The fibrates cause a significant drop in plasma triacylglycerol levels. decreases tryglyceride and ldl levels. decrease triglyceride levels by supplementation with omega3s PPAR: ligand gated transcription factors triglyceride levels need to be lower than 500 mg/dL

2 Bile acid binding resins: cholestyramine and colestipol

Mechanism of action: cholestyramine are anion exchange resins that bind negatively charged bile acids and bile salts in the small intestine. 2) The resin/bile acid complex is excreted in the feces, thus preventing the bile acids from returning to the liver by the enterhepatic circulation. 3) Lowering the bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids. Minimal effect on triglycerides MOA: these drugs are anion exchange resins. They are positively charged compounds that stay in the intestines and they bind to neg charged bile acids/salts. Decreases cholesterol and LDL levels. Cholesterol makes bile.

2 HMG-CoA reductase inhibitors: lovastatin (Mevacor®) and Atorvastatin (Lipitor®)

Mechanism of action: the statins contain structural analogues of 3-hydroxy-3-methylglutarate (HMG), which is a precursor of cholesterol. 2) They inhibit HMG CoA reductase the enzyme that controls the rate-limiting step in cholesterol synthesis. This will deplete intracellular cholesterol. The cell looks to the extracellular space for the cholesterol needs. This results in a lowering of the plasma cholesterol levels. 3) Due to extensive first-pass effect, the primary action of these drugs is on the liver (very convenient). Might cause dementia, body aches, skeletal muscle damage

3. Alpha-adrenergic agonists: (ephedrine, pseudoephedrine), brands include Neo-synephrine and Sudafed). for congestion alpha 1 agonists

Nasal decongestants constrict dilated arterioles in the nasal mucosa and reduce airway resistance. 2) They should be used no longer than several days because rebound nasal congestion often occurs upon discontinuance of these drugs. This is called rhinits medicamentosa. These agents have no place in the long-term treatment of allergic rhinitis.

5GH-inhibiting hormone (somatostatin) from hypothalamus

Octreotide is a synthetic octapeptide analog of somatostatin. It has much longer half-life than the natural compound and has found use in the treatment of acromegaly (tumor forming in pituitary that occurs in adults and causes the excess release of GH). The analog has 2 D aa substitution, which gives it a longer half life.

4Inhibitors of the H+/K+-ATPase proton pump

Omeprazole (Prilosec) is the first of a class of drugs thatinhibit the H+/K+-ATPase proton pump of the parietal cell, suppressing secretion of hydrogen ions into the gastric lumen. The membrane-bound pump is the final step in the secretion of gastric acid. 1) Actions: acid suppression begins within 1-2 hours after first dose. 2) Therapeutic uses: used extensively for GERD and erosive esophagitis and long term treatmentn of Zollinger Ellison Syndrome 3) Adverse effects: well tolerated, but concerns about long-term safety have been raised. In animal studies, these drugs increase the incidence of gastric carcinoid tumors, kidney damage

4antimicrobial agents

Peptic ulcer disease caused by H. pylori requires antimicrobial treatment 2) To detect H. pylori, endoscopic biopsy of gastric mucosa or noninvasive tests (blood, urea breath) are used. 3) Eradication of H. pylori results in rapid healing of active peptic ulcers and low recurrence rates (less than 15%) 4) Most common regimen includes a two-week course of triple therapy with two antibiotics (amox or tetracycline) and an antisecretory drug. (this lyses the cell wall and prevents further adhesion of H pylori to gastric mucosa) A neg blood test for H. Pylori does not mean that the person is not infected. This would only happen if there was a bleeding ulcer, so only useful to use blood test if it comes back pos. Test for h pylori with urea with radioactive carbon 12. H pylori produces urease , which hydrolyses the labelled urea to carbon dioxide and ammonia.

Clinical trials

Phase I: before 1962, uncontrolled but now strict small number of healthy volunteers, need to include women there are 3 specific pharmacokinetic issues in women that should be considered when feasible: 1)effect if stages of menstrual cycle 2) effect of exogenous hormonal therapy including oral contraceptives 3)effect of drug on pharmacokinetics of oral contraceptives also need to include children Phase II: continues to evaluate the safety profile of drug identifying the most common side effects also assess efficacy for particular disease it was developed for. few dozen to a few hundred people 80% of all drugs tested are abandoned by sponsors after phase I or II because of excessive toxicity or lack of efficacy Phase III: designed to establish safety and efficacy of drug. large controlled phase III studies can involve thousands of people with target condition scattered among numerous research sites. may examine additional uses. Must have enough patients to have at least an 80% chance of finding an effect if it really exists-power of the study. use clinical trials to abandon post-hoc assumptions After completing, sponsor submits test results to FDA in form of NDA. FDA reviews and validates data. Manufacturing facility is also evaluated in order to ensure that a consistent and high quality product can be produced. Drug company submits proposed labelling. Phase IV if sponsor wants to change anything, phase IV study is initiated. Also called postmarketing/safety surveillance trial to see long term use. 1 of 7 prescriptions are written in USA for off label use.

Progestins

Progesterone is produced in response to LH by both females (secreted by the corpus luteum/placenta if pregnant) and by males (secreted by the testes). (No further ovulation if have fertilized egg implanted on uterine wall) The high levels of pregesterone released during the second half of the menstrual cycle inhibits the production of gonadotropin, and therefore, further ovulation. If conception takes place, progesterone continues to be secreted maintaining the endometrium and reducing uterine contractions. If conception does not take place, the release of progesterone from the corpus luteum ceases abruptly. This decline stimulates the onset of menstrual cycle.

4prostaglandins

Prostaglandins produced by the gastric mucosa, inhibit secretion of HCL and stimulate secretion of mucus and bicarbonate (protective). 2) A deficiency of prostaglandins is thought to be involved in the developed of peptic ulcers. by taking NSAIDS 3) Misoprostol (Cytotec) is currently the only agent approved for prevention of gastric ulcers induced by NSAIDS. It is a stable analog of prostaglandin E1. 4) Like other prostaglandins, misoprostol produces uterine contractions and is not given to pregnant women.

4 antimotility agents

Prototype drug used is loperamide (Imodium). 2) They activate presynaptic opioid receptors in the enteric nervous system to inhibit Ach release and decrease peristalsis.

5. regulation of thyroid hormones

Regulation of secretion: Feedback inhibition of both TRH and TSH secretion occurs with high levels of circulating thyroid hormone or iodide. 5) If the blood levels of iodine are too low, the pituitary responds with too much TSH causing the thyroid gland to enlarge abnormally in what we call a goiter. This is because normally the levels of TSH are controlled by negative feedback from thyroid hormone. not enough T4 and T3 produced, no inhibition of hypothalamus, so it secretes TRH to anterior pit, which releases TSH to thyroid. The thyroid grows to form goiter.

6VIII. Dipeptidyl peptidase-4 inhibitors and mimetics

Sitaglipin are orally active inhibitors used for the treatment of Type II diabetes Mechanism of action: These drugs inhibit the enzyme DPP-4, which is responsible for the inactivation of incretin hormones such as GLP-1 Prolonging the activity of incretin hormones increases insulin release in response to meals. 2) incretin memetics (liraglutide), that mimic the action of glucagon-like peptide-1 (GLP-1) that are used in the treatment of Type 2 diabetes. Incretin hormones are responsible for 60-70% of postprandial insulin secretion. Oral glucose results in a higher secretion of insulin than occurs when an equal load of glucose is given I.V. This effect is referred to as the "incretin effect" and is markedly reduced in Type II diabetes DPP-4 is a serine protease that is expressed on the surface of endothelial cells, T-lymphocytes & in a circulating form. An important role is to inactivate incretins (GLP-1 & GIP). Inhibition of incretins by DPP-4 inhibitors prolongs the half-life of incretins (GLP-1 & GIP) and is associated with increased insulin release & reduced glucagon release. Potent GLP-1 agonists exert effects by multiple mechanisms including increased glucose-dependent insulin secretion, delayed gastric emptying, reduced glucagon levels, and reduced food intake by CNS effects to cause appetite suppression. Short acting agents exert their effect mostly by slowing gastric emptying, which reduces post-prandial glucose levels.

Androgens

Steroids that have anabolic and masculinizing effects in both males and females. 2) Testosterone is synthesized by Leydig cells in the testes, and, in smaller amounts, by cells in the ovary and adrenal gland of the female. 3) In males, testosterone secretion is controlled by LH/FSH: Testosterone feedbacks to both the hypothalamus and anterior pituitary to inhibit the release of FSH/LH

4 Mucosal protective agents

Sucralfate (Carafate®): effective for treatment of duodenal ulcers. Helps form a protective coating on mucosa, which decreases inflammation as well.

MOA for Morning after pill

The combination of estrogen and progestin inhibits ovulation. 2) The estrogen provides a negative feedback on the release of LH and FSH by the pituitary gland, thus preventing ovulation. 3) The progestin may thicken the cervical mucus preventing access by the sperm.

6 pancreas

The pancreas is both an endocrine gland that produces the hormones insulin, glucagon and somatostatin, and an exocrine gland that produces digestive enzymes. The peptide hormones are secreted from cells located in the islets of Langerhans (beta-cells produce insulin, alpha-cells produce glucagon, and delta-cells produce somatostatin. 3) These hormones play an important role in regulating the homeostasis of blood glucose. Insulin decreases blood glucose, while glucagon increases it.

6 Oral agents: Insulin secretagogues

The patient most likely to respond well to oral hypoglycemic agents is one who develops diabetes after age 40 and has had diabetes less than 5 years. Oral hypoglycemic agents should not be given to patients with Type I diabetes. A. Sulfonylureas (Glimepiride (Amaryl®) is protype) MOAStimulation of insulin release from the beta-cells of the pancreas. This occurs because they mimic ATP inhibition of the potassium channel. b. Reduction in hepatic glucose production c. Increase in peripheral insulin sensitivity The sulfonyureas traverse the placenta and can deplete insulin from the fetal pancreas; therefore the NIDDM pregnant women should be treated with insulin. B. Glinides (Repaglinide, Prandin®) Action is dependent on functioning beta cells. They bind to a distinct site on the sulfonylurea receptor of ATP-sensitive K+ channels causing same actions. In contrast to sulfonylureas, the glinides have a rapid onset and a short duration of action. Also cause less risk for hypoglycemia

5 Thyroid hormone synthesis and secretion

The thyroid gland is made up of multiple follicles that consist of a single layer of epithelial cells surrounding a lumen filled with colloid (thyroglobulin), the storage form of thyroid hormone. 1) Regulation of synthesis: thyroid function is controlled by thyroid-stimulating hormone (TSH) synthesized and stored in the anterior pituitary. 2) TSH generation is governed by the hypothalamic thyrotropin-releasing hormone (TRH). TSH action is mediated by cAMP and leads to stimulation of iodide uptake. 3) The hormones are released following proteolytic cleavage of the thyroglobulin. thyroid follicle is surrounded by blood vessel. The cavity of the thyroid follicle is filled with colloid/thyroglobulin Parafollicular cells forming interfollicular clumps.

6IX. Sodium-glucose cotransporter 2 inhibitors (Canagliflozin Invokana®)

There are two types of SGLTs, SGLT1 and SGLT2. In the kidney nephron, glucose is filtered and is normally 90% of this is reabsorbed by SGLT2 in the proximal tubule. 2. Individuals with diabetes, elevated glucose levels causes a greater amount of glucose to be filtered by the kidney. The amount exceeds the reabsorption capacity of the kidney. 3. Inhibition of SGLT2 in individuals with Type 2 diabetes would lead to a decrease reabsorption and increased excretion of glucose in the urine. 4. In addition these drugs may also decrease reabsorption of sodium and cause diuresis. Therefore, SGLT2 inhibitors may reduce systolic BP. Glucose is filtered by the renal glomeruli and is reabsorbed in the proximal tubule. Approximately 90% of glucose reabsorption is produced by a sodium-glucose transporter (SGLT-2). Its inhibition results in increased glucose in the urine (glycosuria) and a lowering of plasma glucose level in patients with type 2 diabetes.

4. Adsorbents

These agents act by adsorbing intestinal toxins or microorganisms or by coating or protecting the intestinal mucosa. 2) They are much less effective than antimotility agents. Prototype: Kaopectate

Estrogen inhibits parathyroid hormone

This hormone increases bone calcium mobilization., therefore helps with osteoporosis.

Antiprogestins

To date there is only one progestin antagonist-Mifepristone (Mifeprex®). Administration to females early in pregnancy results in 85% success in abortion of the fetus due to the interference with progesterone. Immediate contractions. Administration of prostaglandin E after a single dose of Mifepristone effectively terminates gestation.

7 stringent rules for dietary supplements by fda

accurate labeling report all adverse events manufacture consistently free of contamination

3bronchoconstriction is treated with

adrenergic agonists (stim NE or EP release), cholinergic antagonists (prevents the effects of Ach)

5 hormones secreted by hypothalamus and pit

all peptides and act by binding to specific receptor sites on their target tissues Neuropeptides are released from hypothalamus and travel to the pituitary by the hypophysial portal system. Each hypothalamic regulatory hormone controls the relelase of a specific hormone from the anterior pituitary.

3antihistamines

are h1 receptor blockers ) Are the most frequently used agents in the treatment of sneezing and watery rhinorrhea associated with allergic rhinitis. 2) Combinations of antihistamines with decongestants are effective when congestion is a feature of rhinitis 3) Fexofenadine (Allegra) is an agent that doesnt cross_ the BBB, and therefore does not produce the pronounced sedation of older agents. Newer agents include, Loratadine (Claritin) and Cetirizine (Zyrtec). Benadryl-diphenhydramine-tired and sleepy

7 colonists were using ginseng root

asthma, infertility, wounds

4 dicyclomine

blocks the cholinergic receptor to prevent gastric acid secretion

4 cimetidine

blocks the h2 histamine receptor to prevent gastric acid secretion

3which are the most common processes that result in respiratory compromise?

bronchoconstriction, inflammation, and loss of lung elasticity

3Airflow obstruction in asthma is due to

bronchoconstriction. asthma attacks may be related to exposure to allergens, inhaled irritants, inflammation of airway mucosa. cold air can trigger

8 off label use is legal

but drug companies are not permitted to reference, market, or publicize off label uses, so go to phase IV study.

6Diabetes compare

check phone

3 Asthma

chronic, characterized by acute bronchoconstriction, causing SOB, cough, chest tightness. Not progressive, unlike chronic bronchitis. Asthma cannot lead to COPD.

Oral Contraceptives/Combination pills

contain both estrogen and progestin. The estrogen component suppresses ovulation while progestin prevents implantation and makes the cervical mucus impenetrable to sperm. Progestin stimulates normal bleeding at the end of the cycle.

Uses for estrogens

contraception, for postmenopausal hormone therapy and for osteoporosis.

3 inflammation of lung can be treated with

corticosteroids

2 drugs used to target hyperlipidemias

decreases production of lipoproteins or cholesterol, increase degradation of lipoprotein, and increase removal of cholesterol from the body. lipoproteins are proteins that bind to and transport fats. They transport from systemic system to the liver (good guys). They transport from liver to system/blood vessels (bad guys).

MOA for steroids

diffusion across the cell membrane and bind with high affinity to specific nuclear receptor proteins. The activated steroid-receptor complex interacts with nuclear chromatin to initiate hormone specific RNA synthesis, resulting in synthesis of specific proteins.

2 hyperlipidemias

elevated serum lipids

7Dietary Supplement Health and Education Act (DSHEA) in 1994

established legal status for dietary supplements no regulations unless product contains therapeutic claims burden of proof that herbs are unsafe shifts to FDA FDA regulates dietary supplements as foods not as drugs have to make careful statements or else the fda comes after them product cannot be removed unless proved to cause harm

Diethylstilbestrol

estrogen that has been associated with cervical and vaginal carcinoma in daughters of women that took the drug during pregnancy.

Postmenopausal hormone therapy

estrogen therapy was reserved for postmenopausal women experiencing "hot flashes" and women wishing to reduce the risk of osteoporosis. Estrogen treatment reestablishes feedback on hypothalamic control of NE secretion, which leads to decrease of hot flashes. It also reverses postmenopausal atrophy of vulva, vagina, urethra, trigone of bladder

3 mdi

ex. advair (cs and beta2 agonist) symbicort

8why does drug toxicity manifest itself after exposure to the public at large?

exposure to women and offlabel uses and sample sizes

2cholesterol/fatty drugs

ezetimibe: decreases ldl lvls modestly fenofibrate and niacin: decreases triglycerides or increases hdl levels simvastatin: decrease ldl levels

3COPD (emphysema, bronchitis)

fifth most common cause of death ) It is a chronic, irreversible obstruction of air flow: smoking_ is greatest risk factor 3) Therapy does not cure the disease or even significantly slow its progress. The drugs of choice for COPD are ipratropium (cholinergic antagonist) and beta 2 agonists (dilation of bronchial passages) 4) The main neuronal control in human airways is the PNS. Stimulation of the PNS results in release of Ach and activation of muscarinic receptors eliciting bronchoconstriction and mucous secretion. Ipratropium (Atrovent) and Tiotropium (Spiriva) are anti-cholinergics that are used via inhalation in the treatment of COPD. 5) Drugs originally used to treat asthma are now being prescribed for COPD and include Symbicort and Advair

3Mast cell sensitization

first exposure to antigen causes production of specific igE antibodies, which attach to surface of tissue mast cells and blood basophils. Attachment would be inhib by Omalizumab

testosterone inactive orally

first pass effect

5 selenium

form of selenocysteine is required for 3 enzymes that remove iodide from thyroid hormones. Important for TH inactivation and TH economy.

2total cholesterol should be less than 240 ldl cholesterol less than 130 hdl cholesterol less than 50

good

3 mild copd: bronchodilator moderate copd:bronchodilator severe copd: inhaled corticosteroid very severe: oxygen therapy, surgery

good

7 80% of german physicians prescribe herbal medications

good

2HDL

good guys compared to LDL

2 Coronary artery disease

half of all deaths in US correlated with levels of plasma cholesterol and/or triacylglycerol-containing lipoproteins

8 1992 Prescription Drug User Fee act was instituted

helps pay for review process

7 alternative medicine

herbs, homeopathy, aromatherapy, chiropractic, acupuncture, yoga, music therapy

6 diabetic coma

high blood sugar, DKA, fruity breath

3Adrenergic agonists

inhaled agonists with b2 activity are the drugs of choice for mild ( less than 2 episodes per week) asthma. b2-agonists are potent bronchodilators that relax airway smooth muscle directly. Short acting drugs: (Albuterol, Ventilin) most clinically useful b-agonists have a rapid onset of action. 2) ß2 agonists have no anti-inflammatory effects and they should never be used as the sole therapeutic agents for patients with chronic asthma. 3) Long acting drugs: salmeterol is a chemical analog of albuterol but differs by having a long lipophilic chain that increases the affinity of the drug for the b2-receptor. Salmeterol (Serevent) has a long duration of action providing bronchodilation for at least for 12 hours. The FDA has recommended a ban on two long-acting beta-2 agonists in children: salmeterol and foradil when used alone-they may potentially increase the severity of future asthma attacks

Selective Estrogen Receptor Modulators (SERMs)

interact at estrogen receptors but have different effects on different tissues; that is, they display selective agonism or antagonism according to the tissue type.

.4 Laxatives (Drugs useful for treating constipation) Are commonly used to accelerate the movement of food through GI tract.

irritants and stimulants Castor oil is broken down in the small intestine to ricinoleic acid, which is very irritating to the gut and increases peristalsis. Senna also widely used. Stim and cause evac of bowels within 8-10 hrs. . Bulking agents (Metamucil and Ex-lax) ) Form gels in the large intestine, causing water retention and intestinal distension, thereby increasing peristaltic activity. Lax of choice for constipation. . Stool softeners ) The bulk-forming agents contain plant matter that absorbs water and softens the stool. Example are the glycerin suppositories often used in newborns.

Raloxifene

is related in structure to Tamoxifen. Its clinical use is based on its ability to decrease bone resorption and overall bone turnover. Bone density is increased, and vertebral fractures are decreased. This one has no effect on endometrium so it can't expose women to uterine cancer. Acts as estrogen agonist in bone.

Tamoxifen (Nolvadex)

is used in the treatment of breast cancer in postmenopausal women that has estrogen receptors. Due to its estrogenic activity in the endometrium, hyperplasia and malignancies have been reported and this has led to the limiting of the length of time they remain on the drug.

2 Probucol

it reduced HDL levels to a greater extent than those of LDLs, it fell into disfavor. New info indicates it may be beneficial. Mechanism of action: its mechanism remains uncertain. Probucol inhibits the oxidation of cholesterol. Normally, this form of cholesterol is (incorporated into LDLs) which are then taken up by special receptors on macrophages. 2) Loaded with cholesterol, these macrophages become foam cells that adhere to the vascular endothelium and are the basis for plaque formation. Macrophages consume excess modified (oxidized) lipoprotein, becoming foam cells. The foam cells accumulate, releasing growth factors that stimulate proliferation of smooth muscle and calcification of plaque.

1962

laws relating to efficacy were put into place

3intermittent asthma mild, persistent moderate persistent severe persistent

less than 2 days per week, no daily meds more than 2 days a week but noto daily, low dose inhaled corticosteroids daily, 60-80% normal, low to medium dose inhaled corticosteroids and long acting b2 agonist continuous, less than 60% normal on spirometry, high dose inhaled corticosteroid and long acting b2 agonist

7ephedrine and kava kava

liver failure product, fda had to step in fda regulates ephedra (herbal form of stimulant ephedrine)

6 insulin shock

low blood sugar

7nitrates and sildenafil

lowers bp to unsafe levels

2 NIACIN/Vit b3

lowers serum lipoprotein concentration Mechanism of action: at gram doses, niacin strongly inhibits lipolysis in adipose tissue- the primary producer of circulating free fatty acids. 2) Niacin causes a decrease in liver triacylglycerol synthesis. 3) The most common side effects of niacin therapy are an intense cutaneous flush (accompanied by an uncomfortable feeling of warmth). Plasma triglyceride levels decrease 20-35% with niacin in a few hours and cholesterol decreases in a few days

3 Omalizumab (Xolair®)

mAB that binds to igE, which leads to a decrease binding to receptor of mast cells and basophils. Limits the degree of release of mediators of the allergic response Very expensive and not a first-line therapy. For patients with severe symptoms who do not respond to ICS

Progestins

major use in contraception. High levels prevent release of LH and FSH. Other clinical uses of progestins include dysfunctional uterine bleeding, suppression of postpartum lactation, and the management of endometriosis. The most common side effects of progestin use are weight gain, edema, and depression. Progesterones can increase LDL and decrease HDL (good cholesterol)

8 dintrophenol, highly toxic, ability to uncouple oxidative phosphorylation

marketed for weight reduction. caused lots of injuries and deaths

pituitary gland

master gland

4 adverse effeects of cimetidine

minor, but it does inhibit cytochrome p450, so it can slow metabolism and thus potentiate the action of other drugs, like warfarin, diazepam, phenytoin

7 echinacea

north america started to use it as a remedy for snakebites, spider bites, toothaches

5 posterior hormones continued

oxytocin (pitocin) Its only used in obstetrics, where is is employed to stimulate uterine contraction to induce or reinforce labor or to promote breast milk ejection. 2) To induce labor, the drug is administered IV. However, when used to induce "milk let-down", it is given as a nasal spray. Oxytocin causes milk ejection by contracting the myoepithelial cells around the mammary alveoli. vasopressin (Adh) (Pitressin) ) Has both antidiuretic and vasopressor effects. In the kidney it binds to the V2 receptor to increase water permeability and resorption in the collecting tubules. 2) The major use of vasopressin is to treat diabetes insipidus. A deficiency of this ADH causes diabetes insipidus-urinate excessively desmopressin-no pressor property Because of the pressor properties of vasopressin, this compound has been modified to desmopressin. doesn't act on V1, acts on V2 on kidney. 2) This analog is now preferred for diabetes insipidus and nocturnal enuresis because it is largely free of pressor effects and is longer-acting than vasopressin. ADH has 2 receptors (both G protein coupled receptors 1. kidney, V2, increases cyclic AMP, pores for water open, collect water 2. V1, coupled to Ip3 calcium on blood vessels, constrict, increase bp

7Commission E

panel of experts charged with evaluating the safety and efficacy of herbs available reviewed over 300 herbal drugs 1978 most accurate info available in world on safety and efficacy of herbs Provide guidelines for public, physicians, and companies Monographs imported into USA in 1998 by American Botanical Council. Johnathan Treasure offers detailed evidence that the book is not good

Oral contraceptives/Progestin implants (Norplant)

progestin is slowly released from implanted capsules providing protection for 5 years. Cheaper, reliable, and totally reversible. Doesn't rely on patient compliance

5. 2 drugs that block thyroid hormone formation

propylthiouracil (use for preg women because it doesn't cross placental barrier. It is protein bound and ionized). methimazole

First pass effect

rapid uptake and metabolism of an agent into inactive compounds by the liver, immediately after enteric absorption and before systemic circulation

6 a key goal of management in diabetes

reduce hbA1c levels below 7%

8 Food Drug and Cosmetic Act of 1938

required testing of new drugs for safety prior to marketing. toxicity studies were required as well as approval of a new drug application (NDA). Spared US from the thalidomide tragedy that swept Europe in 1960s.

3mast cell degranulation

sensitized mast cells release granules with histamine, prostaglandins, leukotrienes, etc.

3 what do u use for quick acting relief of symptoms

short acting beta2 agonist

2LDL to HDL

should be below 4:1 ratio

estrogen contraindicated in:

smokers. Can increase the risk of thromboemolism.

4 misoprostol

stim prostaglandin receptor

Clomiphene (Clomid)

stimulates ovarian function and is used in the treatment of infertility. It interferes with the inhibitory feedback of estrogens on the pituitary and hypothalamus. This results in an increase in the release of GnRH and subsequent increase in LH/FSH ultimately leading to stimulation of ovarian function. It blocks the neg feedback of estrogen to increase GnRH, LH, FSH to promote ovulation.

7 USP Verified Dietary Supplement Mark

tested and assured product is: what's on label is what's in the bottle no harmful levels of contaminants supplement will break down and release ingredients in the body supplement has been made under good manufacturing process

3chronic bronchitis

thickened inflamed mucosa, mucus plugging, destruction of alveolar walls

GnRH is gonadotropin-releasing hormone

this is sometimes called LH-RH (leutenizing hormone-releasing hormone)

Side effects of estrogens

thromboembolism, MI, hypertension, headache, peripheral edema, nausea, vomitting, endometrial hyperplasia, weight gain, breast tenderness.

8 preclinical testing

toxicity studies in animals, in vitro or who animals. Pharmacokinetics, chem, quality control, all done. All of this is incorporated into an IND or investigational new drug application that is evaluated by FDA. If all goes well, then start clinical trials.

LH surge

triggers ovulation and corpus luteum formation Estrogen rises around the same time as the LH surge, but progesterone rises after the corpus luteum is formed. No fertilization causes both estrogen and progesterone levels to fall, until menstruation again.

8 Role of fda

truth in labelling toxicity determination of efficacy after figuring out that drug has an active ingredient. fda does not fund or conduct research to bring a drug to market, but it does carry out highly applied research, inspect manufacturing facilities, and review production records

6 insulin compare

type 1 vs type 2 diabetes

Symptoms of BPH

urinary retention, urinary incontinence, UTIs

Endometriosis

uterine wall muscles grow. Tissues that lines uterus grows outside of it. Causes pelvic pain.

8 antibiotic sulfanilamide 1930s

wanted to make drug in liquid form, so dissolve in diethylene glycol. No one tested for safety, toxicity was not a requirement. 100 people died from kidney failure as deg is converted to oxalic acid which is toxic