* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download FUN2: 10:00-11:00 Scribe: Joan
Toxicodynamics wikipedia , lookup
Discovery and development of beta-blockers wikipedia , lookup
Polysubstance dependence wikipedia , lookup
Orphan drug wikipedia , lookup
Cannabinoid receptor antagonist wikipedia , lookup
Discovery and development of angiotensin receptor blockers wikipedia , lookup
Drug design wikipedia , lookup
Nicotinic agonist wikipedia , lookup
NK1 receptor antagonist wikipedia , lookup
Pharmacognosy wikipedia , lookup
Drug discovery wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Prescription costs wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Theralizumab wikipedia , lookup
Drug interaction wikipedia , lookup
Psychopharmacology wikipedia , lookup
FUN2: 10:00-11:00 Scribe: Joan-Marie Manolakis Monday, December 1, 2008 Proof: Teresa Kilborn Dr. Pillion Pharmacology Page 1 of 5 Dental-Optometry Pharmacology I. Introduction [S1]: He will use a Socratic method. We will be responsible to medicate people in the future and everything that we do can interact with the drugs they’re taking. Sometimes changing a person’s medical therapy can cause unexpected changes and that at first wouldn’t make much sense. Today, think about how the body is introduced to and handles drugs. Someone once told him that pharmacology is just one big dose-response curve. II. Concepts for you to learn: [S2] a. What are drugs? i. Response: things you take when you are sick. ii. Professor asks: Is a glass of water a drug? 1. Why not? In a way it is because if you take much or too little there will be bad affects. This is a common link with drugs. The right amount causes a favorable response. iii. What are drugs? 1. Response: a synthetic. 2. Synthetics made by drug companies to mimic hormones or normal chemicals. 3. It mimics the drugs’ structure. Water does not mimic insulin because they have two different functions. 4. There is a structure-function relationship. 5. For a drug to work, it’s a chemical with a certain structure. Two different structures do two different things in the body. 6. Structure is determined by bonding properties. 7. Splenda is a drug. It is sugar that is altered. It’s a glucose molecule with chlorides in place of hydrogens, and the body doesn’t handle it. It goes in your mouth and goes right through you. It mimics the structure of sugar and fits on the same receptors on our taste buds. 8. A receptor is a binding site made of mostly proteins because they are big and can fold into certain shapes. He relates receptors to a lock and key. The one that fits the lock will make it unlock and work. 9. Sometimes drugs are made to go into the keyhole and not work on purpose because we want to block a reaction from taking place. We use this to block bacterial or tumor cell growth. 10. Sometimes people don’t make enough thyroid hormone and have a hypothyroid problem. We would give them thyroid hormone (or at least a drug that looks like it) so it’ll fit into the receptor and does what thyroid hormone would do. Hyperthyroidism can be combated by an antagonist. Its presence prevents thyroid hormone from binding to its receptor. You block the affect. It is a competitive reaction. The more antagonist present, the more you can block the affect. If you have too much antagonist, you become hypothyroid. You want to give the right amount of dose. 11. This is difficult because the body metabolizes the drugs throughout the day. iv. Not all drugs are taken orally. Example: insulin. It is taken by injection not orally because it you want it to get into the bloodstream. It’s different because it’s made of amino acids, it’s a protein or peptide. If eaten, the body will digest it in the stomach. v. If you eat a cheeseburger, your body must handle proteins, lipids, fats, and carbohydrates. If it can’t handle it, it’ll leave the body. We eat them because we like them, and they provide nutrients. vi. Respiration takes place every second every day. It gets out poisonous CO2 and allows for the intake of oxygen. It goes to the lungs and exchanges on hemoglobin and is carried to the body. 1. The oxygen allows for energy production. a. Oxygen plus organic compounds produces energy. b. Example: campfire. You add oxygen and wood (carbohydrate) and get heat, CO2, and water. The same thing happens in the body. The body produces heat and is continuously losing oxygen and burning carbohydrates. This keeps our body at a constant temperature (37 degrees). The energy produced is harvested in ATP molecules. vii. In the mouth, we chew food to break it down. Saliva has enzymes. In the stomach the hydrochloric acid, trypsin, and pepsin. Trypsin and pepsin break the proteins into amino acids so they may be used for protein synthesis. In the small intestine, the amino acids are absorbed. 1. Starch molecule-made of hundreds of glucoses linked together. Break it down and absorb the glucoses. They are now available for energy. viii. Drugs taken orally: aspirin, penicillin, etc. Drugs not taken orally: preparation H, nasal decongestant, asthma drug, poison ivy creme, etc. 1. Sometimes it’s better to put a drug into a certain route because it will work better in that route. ix. Animals are necessary for testing drugs because sometimes it will do its function but may cause cancer or other adverse effects. III. Case #1 [S3] FUN2: 10:00-11:00 Scribe: Joan-Marie Manolakis Monday, December 1, 2008 Proof: Teresa Kilborn Dr. Pillion Pharmacology Page 2 of 5 a. Five students in the class have a headache this morning after a late night of partying. b. He proceeds with a dose response curve using Excedrin first. The active ingredient in Excedrin is aspirin. Dose is on the x axis and response is on the y axis. He also uses ibuprofen and Aleve (Naproxen) as examples. c. d. Note: He points out, “You take the lowest amount that works.” e. The cardinal rule of pharmacology: START LOW AND GO SLOW. Start with the lowest dose possible of a drug and then increase. f. Point of the curve: i. Potency vs. efficacy ii. Potency: what amount gives half the max response iii. Efficacy: what is the maximum response you can achieve iv. Our Graph: Efficacy of these drugs is the same because they have the same highest response. Potency is different, in 3rd drug you need two pills to get the ½ max response and in the 1st drug you only need to take one pill to get the ½ max response. It is not more efficacious, but it is more potent. v. If a drug never gets to the 100% maximum relief, it’ll have lower efficacy but may be more potent. vi. Saying a drug is more potent, really doesn’t say that much. Efficacy matters more g. Dosing: i. Two regular strength aspirin=650 mg (325 mg each). You take two every four hours =3900 mg through the day ii. Extra strength Tylenol: 500 mg each x 2=1000 mg every 6 hours so you take 4000 mg in a day iii. They give the same amount of drugs in a bigger dose less frequently or a smaller dose more frequently. iv. The level of the drug in the blood stream will look like a wave. It’ll jump rapidly and then fall. v. h. The level of the medication will fall below the threshold for it to work, so you must take another dose. Each time you take another dose, it’ll go higher than the last dose. You can’t take too much too fast. If you take more every six hours, the shape of the curve would go higher and last longer because there is more there. i. The drug is being metabolized and eliminated. If not, the level would remain very high in the blood. However, lead and DDT cause toxicity and stay in the body because they can’t be eliminated. j. Alcohol produces a straight line, not a curved line. It is a steady rate of decline. They can see how much you have metabolized and figure out your previous alcohol level. k. Dose-response relationship [S2] l. Toxicity m. Therapeutic level of drug n. Absorption o. Distribution p. Metabolism q. Elimination r. Potency FUN2: 10:00-11:00 Scribe: Joan-Marie Manolakis Monday, December 1, 2008 Proof: Teresa Kilborn Dr. Pillion Pharmacology Page 3 of 5 a. Efficacy II. SAMPLE CASE #2 [S6] a. Mrs. N is a 72 y.o. female with the following medical problems: i. Hypertension (HTN) ii. Hyperlipidemia iii. Diabetes mellitus (type 2), diet-controlled iv. Chronic obstructive pulmonary disease (COPD) v. Congestive heart failure vi. Non-ulcer dyspepsia vii. Insomnia viii. Glaucoma ix. Osteoarthritis x. History of tobacco abuse b. Consider: When selecting a drug, practitioners need to think about the full menu. There are several choices, but you must understand which is the most appropriate for the patient. III. The Menu Method [S8] a. Selecting drug treatment is like selecting a meal from a menu b. Kid’s Menu (only a few choices) vs. Full Menu (many choices) IV. Kid’s menu: (one drug for one problem) [S9] a. PROBLEM DRUG i. For high blood glucose: Insulin ii. For high cholesterol: Atorvastatin iii. For high blood pressure: Hydrochlorothiazide iv. For moderate pain: Aspirin v. For severe pain: Morphine V. Adult menu: (Select from a variety of drugs, tailor the choices to best fit the patient) [S10] a. Don’t memorize today. There are many drugs available, but you will be able to decide which is the right drug for the patient. b. For high blood glucose: Insulin Lyspro-insulin Glyburide Apidra insulin Metformin Regular insulin Rosiglitazone NPH insulin Pioglitazone 70:30 NPH:regular Acarbose 70:30 NPH:lyspro Avandamet 50:50 NPH:regular Exenatide Glargine insulin Amylin Levemir insulin Note: Know the abbreviations for the drugs. You will hear more about this later in the week. c. Some drugs may be taken only once a day (qam) because it may be metabolized more slowly or have a long lasting affect at its target site. [S14] A. Hydrochlorothiazide – thiazide diuretic – useful in the treatment of HTN (usually in combination with another agent) and edema secondary to CHF. It inactivates a sodium chloride channel and lasts a long time. You try a dose amount, and if it’s not affective then increase the dose. After raising the dose numerous times, you may have to switch the drug or add another drug in addition. B. Long-acting nifedipine – calcium-channel blocker – useful in the management of HTN C. Atorvastatin – HMG co-A reductase inhibitor – statin that lowers cholesterol, powerful anti-lipidemic medication D. Theophylline – a methylxanthine derivative – caffeine-like drugs used to open the lungs in a person with asthma and is useful in the management of COPD E. Combivent – contains albuterol (-adrenergic receptor agonist) and ipratropium (muscarinic cholinergic receptor antagonist) – useful in the treatment of COPD as a bronchodilator. These are given at the same time because they get a synergistic effect by working on two systems in opposite ways. a. You can’t put all of her drugs in the inhalant spray because it may not be a direct route for some of her maladies. F. Prednisone – a corticosteroid – many uses – here utilized to treat the inflammation resultant from COPD and osteoarthritis G. Ranitidine – an H2 histamine receptor antagonist – useful for the treatment of non-ulcer dyspepsia H. Pilocarpine – a muscarinic cholinergic receptor agonist – useful in the treatment of both narrow and wide-angle glaucoma FUN2: 10:00-11:00 Scribe: Joan-Marie Manolakis Monday, December 1, 2008 Proof: Teresa Kilborn Dr. Pillion Pharmacology Page 4 of 5 I. Timolol – a -adrenergic receptor antagonist – useful for the treatment of glaucoma J. Mylanta – an antacid - useful for the treatment of non-ulcer dyspepsia K. Diazepam – a benzodiazepine – useful in the treatment of insomnia L. Interval History M. Mrs. N falls [S12] a. Mrs. N reports having a fall 2 days ago. The patient states that she was walking across her living room when she slipped on a throw rug, fell to the ground and sustained an injury to her right ankle. There was no associated chest pain, palpitations, worsening of her baseline shortness of breath, headache, double vision, difficulty speaking, or loss of consciousness, and Ms. N injury to her eye or mouth. Anything here that may indicate a medication problem? N. Mrs. N is currently taking the following drugs: [S11, S14] 1. Hydrochlorothiazide 25 mg qam-changes the sodium reabsorption and causes a diarrhesis (urinate a lot which lowers blood pressure) 2. Long-acting nifedipine 30 mg qd-blocks calcium channels in smooth muscles and causes dilation in the blood vessels and falling blood pressure 3. Atorvastatin 10 mg qhs-inhibits HMG co-A reductase i. HMG co-A reductase is an enzyme involved in lipid synthesis and makes cholesterol. A drug inhibits an enzyme rather than an ion channel. ii. Aspirin-inhibitor of cyclo-oxygenase. Many drugs are enzyme inhibitors. 4. Theophylline SR 400 mg bid- inhibits phosphodiesterase. Phosphodiesterase takes cAMP and makes it AMP. cAMP is a second messenger (think fight or flight response). The lungs expand when the body has a fight or flight response. If you inhibit the enzyme that breaks down cAMP, the lungs open up long term. If you have COPD, the drug will cause a patient’s lungs to open up. Additionally, it will cause his/her heart rate to go up, and if he/she starts to have difficulty breathing, he/she needs to take more. This can lead to other problems. 5. Combivent (albuterol and ipratropium) metered dose inhaler 2 puffs qid.- contains albuterol (adrenergic receptor agonist) and ipratropium (muscarinic cholinergic receptor antagonist) – useful in the treatment of COPD as a bronchodilator i. A normal molecule that would bind to a beta-adrenergic receptor would be adrenaline (epinephrine). It is an agonist. It binds and has an effect. It opens up the lung. ii. Cholinergic and adrenergic (Acetylcholine and adrenaline) have opposite affects. iii .Adrenaline speeds up heart rate and acetylcholine slows it down, etc. iv. While sitting in class, acetylcholine is in control. Adrenaline may overtake the acetylcholine if you’re nervous about being called on. v. To open up the lungs, you can put in a molecule that looks like adrenaline or put in one that looks like acetylcholine but doesn’t do what it does (a cholinergic antagonist or adrenergic agonist). Both will open up the lungs. vi. A beta-adrenergic receptor blocker (antagonist) will lower heart rate. You could also give a cholinergic agonist. 6. Prednisone 10 mg qam.- steroid, causes an anti-inflammatory effect. Asthma improved but they were short and developed other complications. Now inhaled steroids are used for people with asthma because less gets into the bloodstream. 7. Ranitidine 150 mg qhs.-an antagonist of the histamine receptor. i. Nose and stomach-antihistamines are active. The histamine in the nose causes nasal congestion. ii. In the anti-histamines are a decongestant: H1 receptors. iii. The antihistamine receptor in stomach blocks the secretion of acid. The histamine in the stomach causes acid production. iv. Histamine binds to both receptors. v. The receptor in the nose can be blocked without affecting the one in the stomach. vi. Two systems have multiple receptors: the two receptors that both bind histamine and the cholinergic receptor (acetylcholine of different types) and the adrenergic receptors. 1. Adrenergic receptors are broken into alpha 1 and alpha 2 and beta 1 and beta 2 (others are coming) 2. The receptors in the heart are beta 1 that bind adrenaline and increases heart rate. 3. In the lung they are beta 2 receptors. It binds adrenaline and makes the lungs dilate. 4. That’s why we can make drugs that work on our heart and not on our lungs or vice versa. 5. If a beta adrenergic agonist in for the lungs and have problems breathing, so it’s taken over and over again, the level in the bloodstream goes up and starts to affect the heart because it looks like adrenaline and will bind to the beta-1 receptor in the heart. FUN2: 10:00-11:00 Scribe: Joan-Marie Manolakis Monday, December 1, 2008 Proof: Teresa Kilborn Dr. Pillion Pharmacology Page 5 of 5 6. When someone takes too much inhaler, their heart rate goes up because there is a receptor in the heart for the same molecule, it just has higher affinity for the receptor in the lungs. If the dose is very high, it’ll hit the lungs and the heart. 7. Side effect-what happens in other organs that you don’t want to happen. 8. When you think about side effects, you try to avoid them. You can make a therapeutic index and do a dose-response. a. When you take too many aspirins, you start to have more toxicity. b. Amount that gives 50% of toxicity= TD 50 (toxic dose 50) i. Measurement of toxicity: difference between affective dose and therapeutic dose. c. Exception: chemotherapy for a patient with breast cancer. The effective and toxic dose are very similar. The TD 50 for chemo may be lower than the effective dose. The therapeutic or safety range may be nill. We would only use this in exception cases. 8. Pilocarpine HCL eye drops 4% 1 gtt ou qid.-treatment of glaucoma. We put in an adrenergic antagonist and a cholinergic agonist. In the eye, the opposite is true from what was seen above. 9.Timolol eye drop 0.5% 1 gtt ou bid. 10. Mylanta 1 tablespoon, before meals, prn.-neutralizes acid 11. Diazepam 5 mg hs, prn, for sleep.-treats insomnia 12. Insulin 10 units 70:30 NPH: regular, bid A. Concern: she is taking a lot of drugs, there is a chance she is not taking all of them everyday or can’t afford the drugs, or have run out. B. You have two choices in practice for a patient who hasn’t responded well to therapy: either up the dose or ask if it was taken as directed C. Many of these drugs bind to albumin. It serves as a sink that these drugs can stick to. a. Example: Someone with epilepsy was given a pain reliever. Both the antiepileptic drug and pain medication bind to albumin. Thus she may have too much or too little antiepileptic drug in her blood. It was not about the way the drug worked, rather it was more about how it is carried in the blood stream. b. Example: A lady on a blood thinner. You give her pain medication and she has a stroke because you’ve displaced the blood thinner that’s bound to the albumin. [end 60:33]