Pharmacology Study Guide1. Introduction to Pharmacologya. Pharmacology i. Study of medicines ii. The core of patient care, no matter the nursing specialtyiii. Four Basic Terms of Pharmacology 1. Drug: any chemical that can affect living processes 2. Pharmacology: the study of drugs and their interactions with living systems. Encompasses the study of the physical and chemical properties of drugs as well as their biochemical and physiological effects. It includes the knowledge of drug absorption, distribution, metabolism, and excretion3. Clinical Pharmacology: the study of drugs in humans. Includes the study of drugs in patients as well as in healthy volunteers (during new drug development)4. Therapeutics: also known as pharmacotherapeutics; known as the use of drugs to diagnose, prevent, or treat disease or to prevent pregnancy. Or simply the medical use of drugs iv. Responsibility of the Nurse1. Know the drug being administereda. Expected therapeutic reactionb. Possible side effects and adverse reactions 2. Any known allergies to drugs3. 6 rights (patient, drug, dose, route, time, documentation) 4. What other drugs are contraindicated 5. Understand condition being treated 6. Drug/drug or drug/food interactions 7. Manage toxicity v. It is ethically and legally unacceptable for the nurse to administer a drug that is harmful to the patient, even though the medication has been prescribed by a licensed provider and dispensed by a licensed pharmacist b. The Big Three: Effectiveness, Safety, and Selectivity i. Effectiveness is the most important property a drug can have ii. Safety: a safe drug is defined as one that will not cause harmful effects even if administered in high doses and for prolonged periods of time. There is no such thing as a safe drugiii. A selective drug is one that elicits only the response for which it is given and would not produce side effects. There is no such thing as a selective drug: all medications cause side effects c. The Therapeutic Objectivei. The objective of drug therapy is to provide maximum benefit with minimum harm d. Legal Terminologyi. Misfeasance negligence; giving the wrong drug or the wrong dose resulting in the clients deathii. Nonfeasance omission; omitting a drug dose which results in the clients death iii. Malfeasance giving the correct drug, but the wrong route, which results in the clients death e. Application of Pharmacology in Patient Care i. Preadministration Assessment 1. Three basic goals:a. Collect baseline data needed to evaluate therapeutic and adverse responses b. Identify high-risk patientsc. Assess the patients capacity for self-care ii. Dosage and Administration1. Must know that:a. Certain drugs have more than one indication, and dosage may differ depending on which indication the drug is used forb. Many drugs can be administered by more than one route, and dosage may differ depending upon the route selected c. Certain intravenous agents can cause severe local injury if the line through which they are being infused becomes extravasated d. Basic Guidelines:i. Read med order carefully. If unclear verify with the prescriber ii. Verify identity of patient by comparing the name on wristband with name on drug order or MARiii. Read med label carefully. Verify identity of drug, amount of drug, and suitability for administration by intended routeiv. Verify dosage calculations v. Implement any special handling the drug may require vi. Dont administer any drug if you dont understand the reason for its use f. Drug Namesi. Chemical1. Exact description of the drugs composition 2. Chemical structure ii. Generic1. Official name (nonproprietary name) 2. Given by the manufacturer who first develops the drug before the drug is approved 3. Only one generic nameiii. Trade/Brand1. Name in which the manufacturer markets the drug (also known as the proprietary name) 2. Created with the intention that they be easy for nurses, physicians, pharmacists, and consumers to recall and pronounce g. Federal Legislation: public is protected from drugs that are impure, toxic, ineffective, or not tested before public salei. Recent study estimated the cost to bring a new drug to market at $800 million ii. Takes an average of 6-12 years to get FDA approval for new drugs h. Food and Drug Administration (FDA) : Stages of Approval i. Preclinical Testing (in animals): Toxicity, Pharmacokinetics, Possible Useful Effects Investigational New Drug (IND) Status Clinical Testing (in humans): Phase 1 (Subjects: healthy volunteers. Tests: metabolism, pharmacokinetics, and biologic effects) Phase 2 (Subjects: patients. Tests: therapeutic utility and dosage range) Phase 3 (Subjects: patients. Tests: safety and effectiveness) Conditional approval of New Drug Application (NDA) Phase 4 (postmarketing surveillance) 1. Preclinical Investigationa. Extensive laboratory research b. Studies done on human and microbial cells cultured in the labc. Studies performed on animals to look at drugs effectiveness at different doses and to look for adverse effectsd. May take up to 5 yearse. For every 5,000 agents that are submitted for preclinical testing, only 5 will make it for clinical review 2. Clinical Investigation a. Longest part of the drug approval processb. Consists of clinical phase trialsi. Researchers try to determine:1. Proper dosage2. Effectiveness3. Possible adverse effects4. If the drug worsens other medical conditions5. Drug interactionsa. At the conclusion of the clinical trials, the company will write a NDA c. Studies are first done on healthy volunteers d. Studies are then done on a select group of people with a particular disease e. Takes 2-10 years to complete this step 3. Review of the New Drug Application a. FDA is permitted 6 months to initially review the application i. If approved, the application moves to the final stageii. If there are concerns, the pharmaceutical company will be required to address them b. The average NDA Review time is 17-24 monthsi. The NDA may contain over 100,000 pages 4. Post Marketing Surveillance a. Purpose is to survey for harmful drug effects in a larger population over a longer period of timei. History of Drug Regulation and Standardsi. 1906: The Pure Food and Drug Act gave the government the power to control the labeling of medicines ii. 1912: Sherley Amendment prohibited the sale of drugs labeled with false therapeutic claims iii. 1938: Food, Drug and Cosmetic Act 1. Prevented marketing of drugs not thoroughly tested2. Required a New Drug Application be submitted to the FDA prior to marketing 3. Required all new drugs undergo testing for toxicity iv. 1962: Harris-Kefauver Amendment1. Drugs must be proved effective before marketing 2. First law to actually demand that drugs offer some benefit 3. Established rigorous procedures for testing new drugs v. 1970: Controlled Substance Act1. Set rules for manufacture and distribution of drugs considered to have potential for abuse 2. Defines categories into which controlled substances are placeda. Schedule I, II, III, IV, and V i. Schedule I: no accepted medical use in the US and high potential for abuse (Heroin and LSD) ii. Schedules II-V: have acceptable use but also potential for abuse 1. Schedule V drugs have less potential for abuse than Schedule II drugs vi. 1992: Accelerated Approval for Drugs for AIDS and Cancer 1. FDA recognized the need to permit accelerated approval of Drugs for AIDS and cancer2. Drugs could be approved for marketing prior to completion of phase III trials 3. Rigorous follow-up studies must be in place during phase IV vii. 1994: Dietary Supplement Health and Education Act 1. Requires clear labeling of dietary supplements viii. 1997: FDA Modernization Act 1. Allowed the FDA to hire more employees and restructure its organization to more efficiently handle the processing of huge numbers of new drug applications 2. FDA hired nearly 700 new employees 3. Modernization Act among with other issues, granted financial incentives to do pediatric research on existing drugs a. However they did not demand pediatric research 4. Allowed fast track approval for other serious and life-threatening illness (besides just AIDS and cancer)5. Allowed drug companies to give prescribers journal articles and information regarding off-label uses of drugs a. Prior to the Modernization Act, companies could not discuss off-label use ix. 2002: Best Pharmaceuticals for Children Act (BPCA)x. 2003: Pediatric Research Equity Act (PREA) 1. Both laws were designed to promote much-needed research on Pediatric Drug Research 2. BPCA offers a 6-month patent extension to manufacturers who evaluate a drug already on the market for its safety, efficacy and dosage in kids 3. PREA gives the FDA the power to require drug companies to conduct pediatric clinical trials on new medications that might be used on kids j. FDA Pregnancy Categories i. Category A: no risk to fetus ii. Category B: assumed little or no risk. Adverse effect may have been evident on animals, but not on humans iii. Category C: adverse effect on animals, but not adequate studies on humansiv. Category D: risk to human fetus has been proven 1. Used in life threatening conditions2. Risk versus benefit of the drug must be determined v. Category X: drug should be avoided during pregnancy k. New Drug Patent i. The original drug developer has exclusive rights to name and market a drug for 17 years after a new drug application is submitted to the FDA ii. The amount of time spent in approval is subtracted from the 17 years l. Brand Name vs. Generic Drugsi. Generic drugs (store brands) are cheaper because manufactures dont have to do all the clinical development and testing ii. Generic drugs have the same active ingredient. However, generic drugs may have different fillers and binders that alter the drugs efficacy by altering the absorption rate and therefore the generic may require more time to take effect iii. Generic drugs have to be FDA approved:1. If the serum concentration falls within 80% and 125% of the brand drug, it is considered equivalent iv. Brand Name Drugs should be preferred when ordering:1. Anticonvulsants 2. Anticoagulants 3. Lanoxin for CHF 4. Large doses of aspirin for Rheumatoid Arthritis m. Classification of Drugsi. Drugs are categorized by similar characteristicsii. Drug classification may indicate:1. The effect of the drug on the body system 2. The symptoms the drug relieves3. The drugs desired effect iii. Drugs may be in classifications such as:1. Cardiovascular agents2. Respiratory agents 3. Gastrointestinal agentsiv. Each class of drugs contains agents that are prescribed for similar types of health problems:1. Cardiovascular agents:a. Antianginalb. Antihypertensives c. Anticoagulants v. The physical and chemical composition of drugs within a class is not necessarily the same: 1. The drug may do the same thing, but may have a different mechanism of actiona. To treat hypertension, you may use: diuretics, calcium channel blockers, or beta blockers vi. A drug may be in more than one category:1. Ibuprofen is categorized as: antipyretic, anti-inflammatory agent, and analgesic n. Over The Counter Medicationsi. Americans spend about $20 billion annually on OTC drugs ii. More than 60-95% of all illnesses are initially treated with OTC products iii. The average home medicine cabinet contains 24 OTC preparations iv. FDA is in the process of making many drugs OTC v. FDA is working to standardize the labels and provide better information for OTC drugs o. Terminologyi. Addiction: continued use of a specific psychoactive substance despite physical, psychological, or social harm ii. Physical Dependence: nervous system adapts to the continual presence of the drug. Body begins to believe that it is normal and necessary for the drug to be present and withdrawal will result if the agent is not present iii. Withdrawal (abstinence syndrome): physical effects such as nausea, convulsions that result from a drug being stoppediv. Psychological Dependence: intense, overwhelming desire or craving for a drug1. Not a physical addiction, no physical discomfort after the agent is discontinued2. The intense craving may continue for months or even years after the agent is discontinued 3. Relapses are common v. Tolerance: body adapts to a substance1. Over time higher doses of the agent are required to produce the same initial effect 2. Tolerance is not a sign of addiction or abuse, but rather a natural consequence vi. Cross-Tolerance: possible with drugs that are closely related1. People who have developed a tolerance to alcohol, will show tolerance to other CNS depressants 2. Pharmacokinetics and Pharmacodynamics a. Nature of Drug Actions:i. Two Phases:1. Pharmacokinetic Phasea. Absorption i. Passage of the drug molecule into the bloodstreamii. Drugs are absorbed through the: 1. Skin 2. Mucous membranes3. GI tract lining 4. Respiratory tractiii. Bioavailability:1. The percentage of the administered drug dose that reaches the systemic circulation a. Bioavailability of oral drugs is always less than 100% 2. Oral doses may need to be 3-5x larger than the IV dose of the same drug due to the bioavailability iv. Factors that will affect absorption: 1. IV drugs are already there2. Enteric coated drugs:a. Resist disintegration in the gastric acid of the stomachb. Disintegration does not occur until these drugs reach the small intestine i. More alkaline environment c. Enteric coating is used for:i. Protecting drugs from acid and pepsin in the stomach ii. Protecting the stomach from drugs that can cause gastric discomfort d. Disadvantages of enteric coating:i. Absorption time will varyii. onset of these drugs will be reliant on the gastric emptying timeiii. may be within minutes, or hours iv. Enteric coatings may fail to dissolvev. medications will pass right through the GI system vi. Is the stomach is alkaline the medication may dissolve while in the stomach 3. Sustained Release preparationsa. Tablets or capsules filled with tiny spheres that contain the actual drug b. The spheres have coatings that dissolve at variable rates c. Some spheres dissolve more slowly, releasing the medication throughout the day 4. Rate of dissolutiona. Elixirs and syrups will absorb faster than pills and tabletsb. Disintegration: breakdown of a tablet into smaller particles c. Dissolution: dissolving of the smaller particles in the GI fluid before absorption d. Rate limiting: the term used to define the time it takes for the drug to be available for absorption e. Tablets are not 100% drug ----- they contain fillersi. Fillers allow drugs to have various colors, sizes, and shapesii. Fillers have ingredients that allow for better dissolution and absorption 5. Body surface areaa. There is a greater surface area in the small intestine than the stomach b. Most drugs given po will absorb from the small intestine 6. Blood flowa. Drugs are absorbed faster from sites where blood flow is high b. There is more blood flow to the deltoid muscle than the gluteal muscle c. Subcutaneous tissue has fewer blood vessels than muscle d. Sublingual, buccal, and rectal medications absorb fast 7. pH partitioninga. drugs will have a greater desire to move across the membrane is they will be ionized on the other side b. for example: a weak acid will move faster over to an area that is alkaline 8. Drug-Drug or Drug-Food interactions a. Tetracycline will not be absorbed is given with food b. Some drugs are destroyed by digestive enzymes in the small intestine i. Insulin and growth hormones ii. These drugs are given by injection c. Some drugs are inactivated by hydrochloric acid i. Penicillin G ii. Given IM v. Time of administration will affect absorption: 1. Most po meds will absorb more rapidly when given between meals 2. Food, milk, and antacids may alter the pH, thus altering absorption 3. Dont usually give milk or antacids 2 hours before and 1 hour after medication administration a. Unless otherwise directed from drug book4. Conditions at the absorption site: a. Poor circulation as a result of shock or vasoconstriction drugs will decrease the blood flow b. Thus absorption will be hampered vi. Digestive motility will affect the speed of absorption:1. If the function of the small intestine is altered by drugs/diseases.then absorption will be altered a. Such as hypermotility of the GI tract 2. Pain, stress, and foods that are solid, hot and fatty will slow down gastric emptying time 3. Drugs remain in the stomach longer 4. If drugs remain in the longer, than more of the drug may be absorbed 5. Exercise will decrease blood flow to the stomach a. Blood will be shunted to the peripheral muscles 6. Decreased blood flow to the stomach will decrease absorption of po medications b. Distribution i. The rate and extent of distribution depends on the:1. Blood flow to tissues and organsa. Abscesses and solid tumors i. Difficult to deliver medication to either ii. No blood supply to the inner mass of an abscess iii. Solid tumors have a huge blood supply to the outer edges but very little blood supply to the core iv. Poor circulation to the feet of a diabetic patient will alter the availability of a drug to that sitev. Poor circulation to an area of a badly burned area will alter the availability of a drug to that site 2. Ability of the drug to exit the vascular system a. Drugs in the vascular system leave the blood in capillary beds b. Most drugs leave the vasculature by passing through the pores in the capillary wall i. Passing between capillary cells 3. Ability of a drug to enter the cells ii. Protein Binding:1. Most drugs bind to the protein (albumin) somewhat in your bloodstream2. The percentage of the drug molecules that will bind to the protein is determined by the strength of the attraction between the albumin and the drug 3. The free drug is the drug that creates the action desired 4. As the free drug is metabolized and excreted, the protein bound drug is then released into the blood stream 5. Decreased albumin level is expected in:a. Elderly, those with liver disease, and those with malnutrition 6. Potential for increased drug activity or toxicity 7. Plasma protein/albumin levels are checked8. When two highly protein bound drugs are given together (Lasix and Ibuprofen) they compete for the protein sites 9. This causes more free drug to be released than anticipated a. Thus you get higher blood concentrations of one of the drugs -----i. possible toxicity iii. Anatomical Barriers to Distribution:1. The brain and the placenta provide an anatomical barrier that inhibits many chemicals and medications from entering 2. Blood-Brain Barrier a. Tight junction between the cellsb. So tight that they prevent drug passagec. Only drugs that are lipid soluble, or have a transport mechanism can passd. Some meds such as sedatives and anticonvulsants readily pass the BBBe. Most antitumor meds will not pass the BBB making brain cancer difficult to treat 3. Fetal-Placental Barriera. The membranes of the placenta separate the maternal circulation from the fetal circulation b. This membrane does NOT constitute an absolute barrier c. Lipid soluble and non-ionized agents easily pass across the membrane iv. Accumulation of Medications:1. Some tissues have the ability to accumulate and store drugs after absorption a. Bone marrow teeth eyes adipose tissue 2. Valium and lipid soluble vitamins (A, D & K) will store in the adipose tissue 3. Tetracycline binds to calcium salts and will accumulate in the bones and teeth c. Metabolism i. Biotransformation enzymatic alteration of drug structure 1. When drugs are biotransformed, the consequences may be:a. Accelerated renal excretion of drugsi. Most drugs are inactivated by the liver enzymes and are then transformed to inactive metabolites or water soluble substances for excretion ii. The kidneys cannot excrete lipid soluble drugs so if the drugs are lipid-soluble, the liver will metabolize the lipid-soluble drug to a water-soluble substance for renal excretion b. Drug inactivationc. Increased therapeutic action i. Some drugs are transformed into active metabolites ii. They now have an increased pharmacologic response iii. Codeine undergoes transformation to morphine greater pain relief after transformation d. Activation of prodrugs i. Prodrugs a compound that is pharmacologically inactive as administered and then undergoes conversion to its active form within the body ii. Lotensin & Cozaar e. Increased toxicity i. Metabolism can change relatively safe drugs into forms that may be toxic ii. Acetaminophen when metabolized results in a toxic metabolite to the liver f. Decreased toxicity i. Most drugs are converted into inactive forms and thus decrease risk of toxicity ii. The primary site of metabolism is the liver iii. Cytochrome P450 Enzymes:1. Most drug metabolism in the liver is performed by the P450 enzyme system2. Cytochrome P450 is not a single molecular entity, but rather a group of 12 closely related enzymes 3. Three of the P450 enzymes are responsible for drug metabolism a. CYP1, CYP2, and CYP3 b. Each type metabolizes certain drugs iv. Special considerations for metabolism: 1. AGE:a. Infants have decreased ability to metabolize drugsi. Liver does not mature until about 1 year after birth 2. NUTRITIONAL STATUS:a. Malnourished patients may have deficient hepatic enzymes essential cofactors v. First-Pass Effect:1. Remember: in the liver, most of the drug is metabolized to an inactive form, thus reducing the amount of active drug 2. Remember: that after oral drugs are absorbed, they go first to the liver via the portal vein 3. Certain drugs are completely inactivated on this first pass though the liver therefore they can have no therapeutiv effect 4. Drugs that have a first-pass effect: Lidocaine and Nitroglycerine (Not given PO b/c most of the drug would be inactivated) as well as Coumadin and Morphine 5. Drugs that have a first-pass effect will usually have a lower bioavailability such as 20 40% 6. Higher doses are prescribed knowing that the first pass affect will reduce the amount of active drug a. Patient with cirrhosis or hepatitis:i. Will have altered liver function ii. Metabolism will be affectediii. Patient will end up with drug toxicity b/c the drug cannot be metabolized to an inactive form iv. Drug accumulation occurs v. Nurses should watch lab values for liver enzymes d. Excretion i. Elimination 1. Exits: kidneys, bowel, lungs, saliva, sweat, and breast milk ii. Steps in Renal Drug Excretion:1. Glomerular Filtrationa. Blood flows through the glomerualr capillaries, fluids and small molecules are forced through the pores of the capillary wall b. Blood cells and large molecules will not passc. Protein (and protein bound drugs) will not pass2. Passive Tubular Reabsorption a. Lipid soluble drugs that are in the renal tubule after entering the glomerular then undergo passive reabsorption from the tubule back into the blood stream b. b/c they are lipid soluble, they easily pass through the membranec. the drug concentration is less in the blood stream than in the tubule, so the drug passes due to the concentration gradient d. this is why lipid soluble drugs are not excreted from the kidneys 3. Active Tubular Secretion a. There are certain active transport systems in the kidney tubules that pump drugs from the blood to the tubular urineb. P-Glycoprotein will be one pump that will work to pump certain agents into the urine iii. Factors that Modify Excretion:1. Urine pH affects drug excretion a. Acidic urine eliminates weak base drugs (ionized)b. Alkaline urine eliminates weak acid drugs (ionized)c. Remember, that if an acid is exposed to alkaline environment, it becomes ionizedd. If it becomes ionized, it will not pass as a lipid soluble e. Therefore passive tubular reabsorption will not occur f. Aspirin is a weak acid drugi. More readily excreted in alkaline urineg. If a person takes an overdose of aspirin, sodium bicarbonate will be given h. This will make the urine more alkaline and will readily excrete the aspirin i. Large quantities of cranberry juice will decrease the pH causing acidic urine inhibiting elimination of aspirin j. Diazepam (Valium) is excreted faster with a slightly more acidic urine pH k. An overdose of valium can be treated with the administration of ammonium chloride this will acidify the filtrate l. If pt has renal disease, drug excretion is slowed or impairedm. If blood flow to the kidneys is decreased, then elimination will be decreased n. If pt has altered kidney function, the doses of medication for pt should be reduced 2. iv. Plasma Half-Life:1. Time it takes for a medication to decrease concentration in the plasma by one-half after administration 2. Metabolism and elimination affect the half-life of a drug 3. For the patient with liver or kidney dysfunction: a. The half-life will be prolongedb. Less drug is metabolized and eliminated 4. A drug has several half-lives5. The first half life is the time it takes for the drug concentration to reduce in half6. The second half life is the time it takes for the second half of the drug concentration to be reduced by half again 7. Typically takes about 4 half lives for any drug to be almost out of the blood stream 8. A drug with a long half life, such as Valproic Acid (15 hrs) will take days for the drug to be completely out of the system 9. Drug doses are determined by the half life of the drug10. A drug with a short half life will have to be given more frequently in order to maintain a constant blood serum level 2. Pharmacodynamic Phasea. The study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which effects are produced i. what drugs do to the body, and how they do it b. Therapeutic Effect:i. Also called the primary effect; is the expected or predictable physiological response, the reason the drug was intended c. Adverse Drug Reactions:i. Side Effects1. Predictable secondary effecta. Sometimes harmlessb. Sometimes causes injuryc. Sometimes beneficial 2. May outweigh the benefit ii. Toxicity1. When a drug accumulates in the blood above a therapeutic level (overdose of insulin causes blood sugar levels to decrease) iii. Allergic Reaction1. Unpredictable immune response; mild or severe a. Urticaria hivesb. Eczema rashc. Pruritus itching of the skind. Rhinitis swelling and clear drainage from nose e. Wheezing constriction of the smooth muscles surrounding the bronchioles iv. Idiosyncratic Effect1. Unpredictable; client overreacts or underreacts to a drug v. Physical Dependencevi. Carcinogenic Effect 1. Ability of medications, environment and chemicals to cause cancervii. Teratogenic Effect1. Drug induced birth defects d. Onset Peak Duration of Action:i. Goal: constant blood level within a safe therapeutic range ii. Repeated doses are required to achieve a constant therapeutic concentrationiii. MEC: minimum effective concentrationiv. MTC: minimum toxic concentration v. Onset of Action: period of time it takes after the drug is given to create a response 1. Minimum effective concentration vi. Peak Action: time it takes for a drug to reach its highest blood concentration 1. The highest concentration, peak, occurs just before the last of the drug is absorbed vii. Duration of Action: length of time during which the drug is present in a concentration great enough to produce a response viii. Drug Dosing:1. Based on the Onset, Peak, and Durationa. If you are not maintaining the MEC, than the dosing is incorrect if you are dipping into the MTC than the dosing is incorrect 2. Remember the Serum Half Lifea. The time it takes for excretion processes to lower the serum drug concentration by half b. In order to maintain a therapeutic dose, the next dose should be given about the time of the first half life e. Therapeutic Index:i. Aka the Therapeutic Rangeii. The ratio of a drugs LD to its ED 1. ED: average effective dosea. The dose that is required to produce a defined therapeutic response in 50% of the population 2. LD: average lethal dose a. The dose that is lethal to 50% of the animals treated iii. Estimates the margin of safety of a drug iv. Drugs with a low therapeutic index have a narrow margin of safety1. With these drugs, serum levels need to be monitored v. Drugs with high therapeutic index, have a wide margin of safety 1. Less danger of toxic effects with high therapeutic index drugs vi. Calculating the Therapeutic Index1. ED = average effective dose for a particular medication; LD = average lethal dose for a particular medication a. to determine therapeutic index the LD is compared to the EDi. therapeutic index = LD/ED ii. if TI is 2, it means that it would take an error of 2x the average dose to be lethal to a patient f. Cellular Receptors i. Many drugs work because they bind to a particular receptor ii. These receptors exist normally in the body to bind with endogenous hormones, growth factors and neurotransmitters iii. A drug attaches to its receptor in a specific manner, similar to a lock and key 1. Meds effecting the autonomic nervous system may trigger the alpha or beta receptors g. Peak and Trough Serum Levels i. Peak: highest plasma concentration1. Peak time will vary depending on drug and routea. May be 10 minutes for drugs given IV or 4 hours if given PO2. Drug guide will tell you the proposed peak time 3. Blood sample is drawn at the proposed peak time 4. Measures the rate of absorption indicates the MTC ii. Trough: lowest plasma concentration 1. Blood is drawn before the next dose is due 2. Measures the rate of elimination indicates the MEC iii. Peak and trough levels are drawn on drugs with a narrow therapeutic index (such as Gentamycin) 1. If the peak is too high the patient may become toxic2. If the trough is too low the patient is not getting a constant therapeutic level of the drug b. Movement of Drugs Across the Membranes i. Drugs have to move from site of administration to the blood stream to the site of action to the kidneys for elimination ii. Three ways to cross a cell membrane:1. Pass through channels or poresa. Only very small ions such as potassium and sodiumb. Go around the cells2. Pass with the aid of a transport systema. Different transport mechanismsb. Most transport systems are selective for the drug c. P-Glycoprotein i. A protein that transports a wide variety of drugs out of cellsii. Present in the liver, kidneys, placenta, intestine and capillaries of the brain iii. Transports the drug out of the cell, so that it can be eliminated iv. Pumps drugs out of the cells in the kidney, into the urinev. Pumps drugs out of the cells in the brain into the bloodstream 3. Direct penetration of the membrane a. Most common b. Lipid soluble drugs can directly penetrate membranes c. Membranes are primarily composed of lipids d. The drug will dissolve into the lipid membrane and cross to the other side e. Molecules that are not lipids, will not be able to penetrate the membrane i. Water soluble medications and ionized agents cannot dissolve into the lipid membrane of cells 1. Water soluble drugs need a carrier a. Lipids and water separate 2. The carrier will either be an enzyme or a protein that will help the drug molecules pass through the membrane 3. Basically: a. Lipid soluble across the membraneb. Non-ionized agents move across the membrane c. Water soluble agents and ionized agents do not move across the membraneiii. Transport of Ions 1. Molecules that have a net electrical charge 2. Except for very small molecules, ions are unable to cross membranes 3. Certain drugs can exist in either a charged or uncharged forma. The pH of the surrounding area, will determine if the molecule has an electrical charge 4. Aspirin is a weak acida. When aspirin (weak acid) is in the stomach (acidic environment) it is not ionized ------ can pass because it is nonionized b. Is aspirin is in the small intestine (more alkaline environment) it would not be able to pass ------ cannot pass because it is ionized c. Aspirin will ionize in an alkaline environment i. Become an ionii. Cannot cross cell membranes5. An amphetamine agent is a weak base a. Amphetamines will ionize in an acidic environment i. Become an ion 6. Nonionized drugs can pass through membranes c. Drug Interactionsi. Drug Drug Interaction1. An altered effect of a drug as a result of an interaction with another drug 2. Not to be confused with an adverse drug reaction a. Adverse drug reaction:i. Undesirable drug effect, includes hypersensitivity and anaphylaxis 3. Categories of Drug Interactions:a. Direct Chemical or Physical Interactionsi. Drugs interact due to their chemical or physical properties ii. Usually both drugs are inactivated iii. Often called a Drug Incompatibility 1. A chemical or physical reaction that occurs among two or more drugs 2. Most commonly will occur in the IV container or tubing 3. Never administer an IV drug that is discolored/cloudy b. Pharmacokinetic Interactions i. Absorption1. The rate of absorption of one or both drugs can change 2. One drug can block, decrease, or increase the rate of absorption of the other drug a. Decreasing/Increasing gastric emptying timei. The longer the drug stays in the stomach or in the intestines, the greater the amount of drug absorption ii. Drugs that increase gastric emptying such as laxatives, increase the gastric and intestinal motility and decrease absorptioniii. Drugs that decrease gastric emptying such as narcotics, cause an increase in absorption b. Changing the gastric pH i. When the gastric pH is decreased, a weak acid drug, such as aspirin is absorbed faster ii. Drugs that increase the pH of gastric juices decrease the absorption of weak acid drugs iii. Antacids such as Maalox and Amphojel, raise the gastric pH and block or slow absorption iv. increase in pH = alkaline c. Forming drug complexes i. Some drugs can react chemically to other drugs ii. tetracycline, if given with antacids, will form a complex and will not be absorbed iii. tetracycline also forms complexes with dairy products ii. Distribution 1. When 2 drugs are given together that are highly bound to protein (albumin) sites in the plasma, they compete for the albumin sites 2. When one drug takes all of the albumin spots, it leaves the other drug free floating so more is distributed and can lead to drug toxicity 3. When two highly-bound albumin drugs need to be given together, doses may need to be decreased 4. Coumadin and NSAIDS are both highly protein bound drugs iii. Metabolism (Biotransformation) 1. Certain drugs can stimulate liver enzymesa. Enzyme inducers b. Drugs that stimulate the synthesis of the CYP enzymes are inducers i. Enzyme inducers will increase the metabolic rate of other drugs ii. Increase in metabolism will cause more rapid drug excretion and a decrease in drug concentration in the blood 2. Certain drugs can inhibit hepatic enzymes a. Enzyme inhibitors b. Drugs that inhibit the CYP enzymes are inhibitors i. Enzyme inhibitors will decrease the metabolic rate of other drugs ii. If metabolism is decreased, the plasma concentrations of the other drugs will be increased toxicity is likely iv. Excretion 1. Changing urine pH affects drug excretiona. Alkaline urinei. Promotes the excretion of drugs that are weak acids, such as aspirin and barbiturates b. Acidic urinei. Promotes the excretion of drugs that are weak bases such as Quinidine c. Sodium bicarbonate (antacid) causes the urine pH to be alkaline 2. Drugs that decrease cardiac output, will decrease blood flow to the kidneys and decrease glomerular filtration a. Will delay or decrease drug excretion 3. Drugs that increase or decrease renal excretion, have an effect on the excretion of other drugs a. Diuretics promote water and sodium excretion from the renal tubules b. Diuretics decrease reabsorption of water, sodium, and potassium

c. Pharmacodynamic Interactionsi. Onset, Peak, Duration of Action ii. The combined effect of the drugs will have a:1. Additive Effecta. The sum of the effect of the two drugs i. When two drugs with similar action are administered, the drug interaction is called an additive effect ii. The effect can be desirable or undesirable iii. Tylenol and Codeine = desirable effect iv. Apresoline (antihypertensive) given with Nitroglycerine = undesirable hypotensive effect 2. Synergistic Effecta. One drug can potentiate another b. Greater than the combined effect of the two drugs c. The effect can be desirable or undesirable i. Demerol and Phenergan given together = phenergan enhances the effects of Demerol so less Demerol is needed = desirable effect ii. Alcohol and Demerol = increases the CNS depression and leads to decreased respirations = undesirable effect 3. Antagonistic Effecta. Drugs that block a response i. When two drugs are combined that have opposite effects ii. May be desirable or undesirable iii. Isuprel (beta adrenergic stimulant) given with Inderal (beta adrenergic blocker) = cancel each other out d. Combined Toxicity (p. 60) ii. Drug Food Interaction 1. Food can increase, decrease or delay drug absorption 2. Food can bind with drugs, causing less or slower drug absorptiona. TCN binds with food (dairy products) 3. Some drugs have increased drug absorption with fooda. Lopressor and Macrodantin 4. MAO Inhibitors, such as Marplan, should not be taken with Tyramine-rich foods a. Cheese, wine, organ meats, beer, yogurt, sour cream, bananas b. More norepinephrine is released and the result could be hypertensive crisis c. Avoid these foods for 2 weeks following taking this drug 5. Theophylline cannot be taken with caffeine a. Will produce exaggerated CNS excitation 6. Grapefruit Effect a. Grapefruit juice can inhibit the metabolism of certain drugs b. In one study, coadministration of grapefruit juice produced a 406% increase in blood levels of Felodipine (Plendil) a calcium channel blocker c. The more grapefruit juice that the patient drinks, the greater the inhibition d. Inhibition can persist for up to 3 days after the last glass iii. Drug Laboratory Interaction 1. Abnormal plasma or serum electrolyte concentrations can affect certain drug therapies 2. Patient with a decreased serum potassium level or an increase in serum calcium level will be more prone to Dig Toxicity 3. Frequently patients on Digoxin, will also be taking a potassium-wasting diuretic d. Pediatric and Geriatric Implications i. b/c of the immature organs in infants, the changing metabolic rate in the preschool and school-aged child, and the declining organ function in the elderly, the effect of drug therapy should be closely monitored ii. many drugs are not approved by the FDA for pediatric patients iii. not much research is done on pediatric patients 1. difficult to get a large enough study sample due to informed consent 2. fewer financial resources put forth by pharmaceutical companies due to the decrease in numbers of prescriptions for kids compared to adults and elderly 3. some people think that pediatric research is unethical iv. doctors will prescribe these meds for kids anyways 1. of all medications carry federally approved indications for kids 2. Whereas of all meds are used on kids a. Marketed for adults only v. Dosing of pediatric medications 1. Pediatric doses are often calculated according to BSA or BW 2. Pediatric dose ranges have been established for many drugs and can be found in the Drug Reference guides vi. Pharmacokinetics: Pediatrics1. Absorption: a. Reduced gastric acid production/ higher gastric pH i. Infants under 1 year of age have alkaline gastric juices ii. The pH of gastric juices drops to the adult normal level at age of 2 iii. The difference in pH may hinder or enhance drug absorption iv. Some drugs such as PCN absorb faster in higher pH1. Lower drug doses may be required for kids v. Acidic pH favors absorption of acidic drugs 1. Therefore in infants, these drugs would absorb slower because they have alkaline gastric juices b. Slow or irregular peristalsis i. Gastric emptying is prolonged in infants, but speeds up as kids get older ii. Delayed emptying in kids, although will allow for more absorption, resulting in decreased PEAK concentrations iii. Irregular peristalsis, associated with diarrhea or vomiting will decrease absorption time for meds 1. Thus less absorption

c. Topical drugsi. May be absorbed faster and in greater concentration in kids ii. The skin is thinner and more porous iii. Kids also have a proportionally greater body surface area iv. Be careful with topical drugs: kids can get a systemic effect that is unwanted 2. Distribution: a. Lower blood pressure affects the blood flow to tissues i. Liver and brain are proportionally larger and receive more blood flow ii. Kidneys and peripheral tissues receive less blood flow b. Infants are composed of 70% wateri. Premature infants are about 85% water ii. As kids grow, the percentage decreases to about 50 60% water iii. Water soluble drugs are diluted in the large volume of their body fluid iv. A larger drug dose may be needed to achieve the desired plasma concentration 1. Due to the drug dilution 2. Until the age of 2 c. Infants have less albumin than older kids i. With less albumin, there will be fewer protein binding sitesii. Protein bound drugs will have to be given in lower doses iii. If an infant has a high bilirubin level, the bilirubin molecules will bind with the protein sites that are available, thus they wont be available for the medications that rely on protein-binding 3. Metabolism: a. Infants have an immature liver and kidneys i. This will lead to a decrease in the metabolism and excretion of drugs ii. The liver and kidneys will mature by the age of 1 1. At age 1-2 months, these organs are more mature than with the neonate iii. Before the age of 1 year, the liver enzymes are decreased 1. With decreased metabolism, there will be a prolonged half-life and possible toxicity if not dosed correctly b. Metabolism in older children is faster than with adults i. Drug half-life in the older child can be shorter due to the increased metabolic rate ii. Higher doses for the older child might be needed to off-set the increased metabolic rate 4. Excretion: a. Drug elimination via the kidneys is decreased until 9 months of age i. This happens due to a lower blood pressure that reduces the blood flow to the kidneys ii. This may lead to a (shorter/longer) half- life of the drug vii. Pharmacodynamics: Pediatrics 1. Peak, onset and duration will be affected by the pharmacokinetics discussed 2. Immaturity of the organs in the infant will affect the drug action and drug dose frequently 3. Receptor site sensitivity will differ with the neonate, infant and young child 4. Some tissues are more sensitive to certain drugs 5. Some drugs are more toxic to adults than to children viii. Geriatric Pharmacology 1. Growing number of older people in society coupled with the number of meds that they each take, has led to serious problems with drug interactions and drug misuse/abuse 2. Approximately 70% of clients older than 65 years of age take at least one to two prescribed drugs daily 3. The other 30% of older adults take 5 or more prescribed drugs daily 4. Besides just taking the prescription drugs, problems arise due to: a. The older patient also takes a lot of OTC drugs b. The older client may take too much or too little of their medication due to memory problemsc. Taking many drugs together can lead to confusion, falls, malnutrition, renal and liver dysfunction and nonadherence 5. Physiological changes in the elderly that have an effect on drug therapy: a. p. 97 Table 11-1b. Gastrointestinal:i. Alkaline gastric secretions1. Acidic drugs are poorly absorbed ii. Decreased peristalsis 1. Delayed gastric emptying time c. Cardiac and Circulatory:i. Decreased cardiac output1. Decreases blood flow to all parts of the body including the liver and kidneys d. Hepatic:i. Decreased enzyme function1. Decreases the livers ability to metabolize and detoxify drugs 2. Increases the risk of drug toxicity e. Renal: i. Decreased blood flowii. Decreased functioning nephronsiii. Decreased glomerular filtration rate 1. Will prolong the drug half-life2. Will increase the risk of drug accumulation and drug toxicity 6. Pharmacokinetics: Geriatrics a. Absorption: i. Decrease in gastric acid alters absorption of weak acid drugs such as aspirin ii. Enteric coated meds are made to break down in alkaline fluids, so they more readily break down in the stomach of an elderly person iii. Decreased blood flow to the GI tract1. Caused by decreased cardiac output 2. Slows down absorption iv. Reduction in GI motility rate may delay onset of action b. Distribution: i. Decrease in body water1. So water soluble drugs are (more/less) concentrated ii. Increase in fat-to-water ratio, so fat-soluble drugs are stored and likely to accumulate iii. Decreased serum-protein (albumin) levels 1. Fewer protein binding sites resulting in more free drug 2. Increased drug interactions due to lack of available protein sites c. Metabolism: i. Decrease in hepatic enzyme production ii. Decrease in hepatic blood flow and total liver function iii. These physiologic changes lead to an (increase/decrease) in drug metabolism iv. Reduction in the metabolic rate will: 1. (increase/decrease) the drug half-life2. An increase in the drug half-life will (increase/decrease) the risk of drug toxicity d. Excretion: i. Decrease in renal blood flowii. Decrease in glomerular filtration rate by 40 50% iii. These changes will (increase/decrease) the drug half-life

3. Integumentary a. Topical Glucocorticoids i. Used for numerous inflammatory or pruritic dermatoses 1. Atopic and Contact dermatitis2. Psoriasis3. Eczema4. Insect bite reactionsii. Mechanisms of Action1. Topical corticosteroids diffuse across cell membranes and induce cutaneous vasoconstriction 2. The vasoconstriction inhibits the migration of macrophages and leukocytes into the area3. The degree of vasoconstriction is commensurate with the potencyiii. Topical Corticosteriods1. Topical corticosteroids are ranked according to potencya. Group I is the most potent b. Group VII as the least potentc. Group VII is often the OTC agents2. Potency is the most important variable when a topical steroid is choseniv. Absorption varies depending on:1. The vehicle useda. Ointments are more occlusive, thus more potent than creams and lotions2. The amount of skin surface area covered3. Location of the skina. Face, scrotum have thinner skin layers4. Condition of the skin5. Temperature of the skin6. Use of occlusive dressingv. Occlusive Dressings1. Use of plastic wrap2. Increases skin penetration 10-fold3. May be beneficial in resistant cases4. May lead to increased adverse effects and possible adverse systemic effectsvi. Dosing and Special Considerations1. Apply sparingly!2. Preparations of mild to intermediate strength should be considered when large areas are treated because of the likelihood of systemic absorption3. After long term use of with high potency agents, Topical Corticosteroids should not be abruptly discontinueda. May lead to rebound effect4. Treatment should be discontinued when the skin condition has resolved. Tapering the corticosteroid will prevent recurrence of the skin conditionvii. Topical Corticosteroids: Geriatric Client1. Geriatric patients are more susceptible to secondary infection when steroids are used2. Geriatric patients are more susceptible to the systemic effects because their skin tends to be thinnerviii. Topical Corticosteroids: Pediatric Client1. May be more susceptible to systemic adverse effects2. The least-potent strength compatible with effective treatment should be used3. Potent corticosteroids should typically not be used in children4. May lead to delays in growth and development in childrenix. Monitoring the Patient1. With Mid to High Potency Products, monitor for:a. Superinfection b. Adverse Effects (Cushing Symptoms)c. Growth and development in childrend. Blood glucose and serum potassium levelsx. Patient Education1. Use exactly as prescribed2. Demonstate the amount of the medication to applya. Pea size, spread thinly over the area3. Instructions on occlusion if it is warranted4. Report any adverse effectsb. Acne Preparationsi. Acne1. Inflammatory disorder of the sebaceous glands2. Sebacious glands remain small throughout childhood3. During Puberty, hormone levels (specifically androgens) rise and cause an increase in sebum secretion4. The face, chest back and upper arms have the largest and most numerous sebaceous glands5. Acne is further be exaggerated by Propionibacterium Acnes.a. Propionibacterium Acnesi. (P. Acnes) ii. A normal skin residentiii. A microbe that converts sebum into an irritant fatty acids iv. P. Acnes promotes inflammation by attracting leukocytesii. Classifaction System1. Treatment is based on severity and type of lesion present2. Milda. Comedones (Blackheads)b. Noninflammatory lesion of acne3. Moderatea. Papules and Pustules4. Severea. Cystic Acneiii. Benzoyl Peroxide1. Bactericidal agent against P Acnesa. Does not promote resistance of P Acnes2. Used for mild to moderate acne3. Available OTC and by prescriptiona. Most common OTC medication4. Available as a cream, lotion, gel or wash5. Has a keratolytic effecta. Helps to dry out and shed the outer layer of the epidermis6. Client should be instructed to:a. Apply once a day in the beginningb. Increase frequency of application to a maximum of three times daily as tolerated.c. Wear sunscreen when outdoors.iv. Topical Clindamycin or Erythromycin1. For mild to moderate acne2. Works by suppressing P Acnes3. Antibacterial and antiimflammatory action4. Therapeutic response seen in 6-12 weeks5. Combination products available with Benzoyl Peroxidea. Monotherapy with either antibiotic will quickly lead to resistancev. Topical Retinoids1. Considered 2nd or 3rd line therapy2. Derivatives of vitamin A (retinol)3. Retinoids are used against both inflamed and noninflamed acne lesions4. Can be used alone or in combination with antibiotics5. Effect may not be seen for 2 to 3 weeks6. Can be extremely irritating to the skin7. Patient should use a small amounta. Pea size8. Wait for 20 30 minutes after washing face to apply9. Will cause severe sun sensitivitya. Avoid the sun, or wear sunscreen10. Avita and Retin-A Micro are newer formulations of the original Retin-Aa. The newer formulations may have less intense localized effects.vi. Systemic Antibiotics1. Used for moderate to severe acne that does not respond to topical treatment2. Works by suppressing the growth of P. Acnes and decreasing inflammation3. Usually used in combination with a topical retinoid4. Minocycline and Doxycycline are the agents of choicea. Tetracycline and Erythromycin are alternativesb. Resistance to Tetracycline and Erythromycin is common5. Good results with systemic antibiotics, but takes 3 6 months to reach maximum benefit6. After symptoms have controlled with an oral antibiotic, patients should be switched to a topical antibiotic for long-term maintenancevii. Isotretinoin (Accutane)1. Derivative of vitamin A2. Very potent and effective3. Reserved for severe cystic acnea. Due to severe side effects4. Treated for 20 weeks5. If a second course of treatment is necessary, the client should wait 8 weeks before starting again6. Accutane:a. Decreases sebum productionb. Decreases inflammationc. Causes Keratinization d. Lowers the skin population of P. acnes7. Side Effects:a. Dry skin & mucous membranesb. Nasal irritation/ nose bleedsc. Dry eyes/ Photosensitivityd. Elevated blood triglyceride levelsi. Etoh intake escalates triglyceride levelse. Teratogenic effectsi. Not to be taken by sexually active femalesii. Category Xf. Arthralgia g. Rare: Mood changes/ Depression/ Suicide tendenciesh. Risk of Toxicityi. Tetracyclines and Vitamin A supplements increase risk of toxicityii. Should be discontinued before starting Isotretinoin (Accutane)i. Risk of Teratogenic Effectsi. Fetal abnormalities include:1. Hydrocephalus, microcephaly, facial malformation, cleft palate, cardiovascular defects and abnormal formation of the outer ear

8. iPLEDGEa. Name of a very strict risk management programb. Went into effect in December, 2005c. The iPLEDGE program has rules that apply to the physician, patient, and pharmacistd. All transactions involving Isotretinoin (Accutane) must be processed through a central automated systeme. Pregnancy must be ruled out prior to prescribing and again before each monthly refilli. Two negative pregnancy tests are required before the first dosef. Each patient must use two effective forms of birth control, even if one is a tubal or vasectomyg. Birth control measures must be implemented at least 1 month before starting isotretinoin (Accutane), and continue for one month following the last administrationh. Informed consent must be signedi. Patient must register with iPLEDGE j. Physician must be registered with iPLEDGE k. Pharmacist must be registered with iPLEDGE and obtain the drug from a registered iPLEDGE wholesalerc. Treatment of Burnsi. Topical Sulfonamides1. Used to suppress bacterial colonization in patients with 2nd and 3rd degree burns. ii. Agents:1. Silver Sulfadiazine (Silvadene)2. Mafenide (Sulfamylon)iii. Administration:1. Premedicate with analgesic before application2. Cleanse and debride prior to administration3. Use sterile technique to apply4. Burn should be coated at all times with thin layeriv. Adverse Effects:1. Nephritisa. Monitor Renal function i. Creatinine and BUNii. Urine output2. Leukopenia a. Monitor CBC3. Silver Sulfadiazine may cause skin discoloration

4. Neurological Agentsa. Peripheral Nervous Systemi. Consists of Two Divisions:1. Somatic Motor Systema. Voluntaryb. Acts on Skeletal Muscles2. Autonomic Nervous Systema. Involuntaryb. Controls or regulates the functions of the heart, respiratory system, smooth muscles, GI system and glandsb. Autonomic Nervous System i. Consists of two divisions:1. Sympathetic Nervous Systema. Fight or Flighti. Also Called Adrenergicii. Main neurotransmitter is Norepinephrine iii. 2. Parasympathetic Nervous Systema. Rest and Digesti. Also called Cholinergicii. Main neurotransmitter is Acetylcholineiii. c. Receptors of PNS i. Two Basic Categories of Receptors1. Cholinergic Receptorsa. Respond to Acetylcholine2. Adrenergic Receptorsa. Respond to Norepinephrine and Epinephrined. Subtypes of Cholinergic & Adrenergic Receptorsi. Subtypes of Cholinergic Receptors1. Nicotinic and Muscarinic ii. Subtypes of Adrenergic Receptors1. Alpha 1, Alpha 2, Beta 1 and Beta 2e. Adrenergic Receptors: Alpha 1 and Alpha 2i. Alpha 1 is located on the blood vessels and causes vasoconstrictionii. Alpha 2 is located on the postganglionic nerve endings and cause decrease in vasoconstriction (dilation)

f. Adrenergic Receptors: Beta 1 and Beta 2 i. Beta 1: Located primarily in the heartii. Beta 1 = 1 heartiii. Beta 1 is also located in the kidney1. Causes the release of renin into the bloodiv. Beta 2 located primarily in the lungsv. Beta 2 = 2 lungsvi. Beta 2 is also in the arterioles and uterus1. Relaxes uterine smooth muscles2. Dilates arterioles in the heart, lungs and skeletal muscles

g. Adrenergic Agonistsi. Stimulates the Sympathetic Nervous System1. Also Called:a. Adrenergics b. Adrenergic Agonistsc. Sympathomimetics h. Adrenergic Drugsi. Most Sympathomimetics act by directly binding to and activating adrenergic receptors1. Some Sympathomimetics act by causing a release of norepinephrine 2. Some Sympathomimetics act by inhibiting the reuptake or destruction of norepinephrine i. Chemical Classification of Adrenergic Agonistsi. Adrenergics are divided into two chemical classifications: 1. Catecholamines and Noncatecholamines a. Catecholamines i. Epinephrine, Norepinephrine, Isoproterenol, Dopamine and Dobutamine ii. Cannot be taken orallyiii. Short half lifeiv. Do not cross the blood brain barrier b. Noncatecholamines i. Ephedrine, Phenylephrine, and Terbutaline ii. Half life is longer than the catecholamine groupiii. Can be taken orallyiv. Does cross the blood brain barrierii. Adrenergics: work on one or more of the receptor sitesiii. Alpha 1 Receptor Agonists1. Used for:a. Vasoconstriction in blood vessels of the skin, viscera and mucous membranesi. Treatment of nasal congestionii. To stop bleeding (nose bleeds)iii. To elevate blood pressure1. Not the primary medication usedb. Mydriasis during ophthalmic examinationsi. Not used often for this purposeii. If applied topically to the eye, should not lead to vasoconstriction or elevation in blood pressureiv. Adverse Effects of Alpha 1 Activation1. Hypertension2. Bradycardia a. Reflex slowing of the heart triggered from a response by the baroreceptors responding to hypertension3. Necrosis at IV site with infiltration into tissuesa. Due to vasoconstrictionv. Alpha 2 Receptor Agonists1. Used for Hypertension2. Also used via an Epidural for management of cancer pain unresponsive to opioids 3. Example:a. Clonidine (Catapres)4. Be careful in Geriatric populationa. May lead to orthostatic hypotensionvi. Beta 1 Receptor Activation1. Treatment of cardiac arresta. Can initiate contraction in a heart that has stopped2. Treatment of shocka. Increases heart rate, force of contraction and cardiac output vii. Adverse Effects of Beta 1 Activation1. Altered heart rate or rhythma. Tachycardia and dysrhythmias may result2. Angina Pectorisa. Increases cardiac oxygen demandviii. Beta 2 Receptor Activation 1. Treatment of Asthmaa. Promotes bronchodilation 2. Treatment of Preterm Labora. Relaxes uterine smooth muscles (give beta 2 agonist) ix. Adverse Effects of Beta 2 Activation 1. Hyperglycemiaa. Promotes breakdown of glycogen into glucoseb. Is a problem only in patients with diabetesc. Insulin doses may need to be increased2. Tremorsa. Enhances contraction of the receptors in skeletal musclesb. This effect generally fades over timex. Adrenergic Agonist Agents:1. Epinephrine:a. Alpha 1b. Beta 1c. Beta 2d. Catecholamine2. Administered topically, by injection and by inhalationa. Cannot be given orallyb. Catacholamines undergo destruction before reaching the systemic circulation3. Because it activates so many receptors, expect side effectsa. Hypertension, Angina, Necrosis following IV Extravasation, Hyperglycemia (Beta 2), Dysrhythmias (Beta 1) 4. The Epi Penxi. Isoproterenol Hydrochloride (Isuprel)1. Activates Beta 1 and Beta 22. Used for Bronchospasms with anesthesia3. Used for Cardiovascular Disordersa. AV heart block, cardiac arrest and increase cardiac output4. Undesirable effects of Isuprel:a. Can lead to tachydysrhythmias and Anginab. Can cause Hyperglycemia in Diabetic clients5. Terbutaline (Brethine)a. Primarily Beta 2, Minimal Beta 1i. If administered in large doses, will have beta 1 activationb. Primary reaction is bronchodilation and uterine relaxationc. Noncatecholamine d. Stops preterm labor and respiratory problems 6. Dopaminea. Catecholamineb. Binds to Beta 1and Dopamine receptorsc. At high doses, will also bind to alpha 1d. Used to treat:i. Shock (Increases cardiac output and dilates renal blood vessels)ii. Heart Failure (increases myocardial contractility)iii. Acute Renal Failure (Increases renal blood flow and urine output.7. Dobutamine a. Causes selective activation of beta 1 receptorsb. The only indication is for treatment of heart failurexii. Adrenergic Antagonists 1. Also called:a. Adrenergic Blockersb. Sympatholytic Agentsxiii. Alpha Blockers1. Drugs that Block Alpha 1will be used in the:a. Treatment of Hypertensioni. Through Vasodilation b. Treatment of Peripheral Vascular Disease (Raynauds Disease)c. Treatment of Pheochromocytoma i. Catecholamine secreting tumor usually located in the adrenal medullaii. Treatment of choice is removal of the tumor, but Alpha 1 Blockers can be given with inoperable tumors or preopertively d. Treatment of Benign Prostatic Hyperplasiai. Decreases contraction in smooth muscle in the bladder necke. Reversal of Toxicity form Alpha 1 Agonisti. In the event of an overdose or intravenous extravasation, an Alpha 1 blocker can be administeredii. If an IV line containing an alpha agonist infiltrates, necrosis can occuriii. Alpha 1 blocker (Phentolamine) can be injected into the region and will prevent injuryxiv. Adverse Effects of Alpha Blockers 1. Orthostatic Hypotensiona. Alpha Blockers reduce the muscle tone in the venous wallb. Blood tends to pool when the patient stands up2. Reflex Tachycardiaa. Increases heart rate by triggering the baroreceptor reflexb. Can be suppressed by use of beta blockers3. Nasal Congestiona. Dilates the blood vessels of the nasal mucosa4. Inhibition of Ejaculationa. May lead to impotenceb. Reversible when the alpha blocker is stoppedxv. Adrenergic Alpha Blockers 1. Prazosin (Minipress)a. Selective for Alpha 1 Receptorb. Causes dilation of arterioles and veins (orthostatic hypotension) c. Causes relaxation in the bladder neck and prostatic capsuled. Used for hypertension, and BPHe. Watch out for orthostatic hypotension!!f. Can lead to impotence and nasal congestion2. Phentolamine a. Blocks Alpha 1 and Alpha 2b. Used in the treatment of Pheochromocytoma c. Used to prevent tissue necrosis following extravasation of drugs that produce alpha 1 vasoconstrictioni. Norepinephrine d. Can cause orthostatic hypotension, nasal congestion and inhibition of ejaculation3. Terazosin (Hytrin)a. Selective antagonist for alpha 1 receptorsb. Approved for use with hypertension and BPH4. There is minimal recognizable therapeutic application to blocking alpha 2xvi. Adrenergic Beta Antagonists 1. Also calleda. Beta Blockersb. Beta Adrenergic Blockersc. Sympatholytic Agentsd. Beta Blockers end in lol e. Drugs that block the beta receptorsi. Beta 1 and/or Beta 2f. Practically all of the therapeutic effects of the beta adrenergic antagonists result from blockade of the Beta 1 receptor. i. Reduces heart rateii. Reduces the force of the cardiac contractioniii. Reduces the velocity of the impulse conduction through the AV nodeg. Beta Blockers will be used to treat: i. Angina pectoris1. Decreases cardiac workloadii. Hypertension1. Reduces peripheral vascular resistanceiii. Cardiac Dysrhythmias iv. Myocardial Infarction1. Can reduce pain, infarct size and mortalityv. Hyperthyroidism1. Will decrease the heart ratevi. Migraine Headaches 1. When taken prophylactically 2. Will not treat the headache itselfvii. Pheochromocytoma 1. Can prevent the cardiac stimulation caused from the catecholamine secretionviii. Stage Fright1. Help prevent the fear associated with a generalized discharge from the Sympathetic Nervous Systemxvii. Adverse Effects of Beta Blockers: Beta 11. Bradycardia 2. Reduced Cardiac Outputa. Reduces heart rate and force of contractionb. Extreme caution in patients with heart failure3. Precipitation of Heart Failurea. Due to suppression of heart functionxviii. Adverse Effects of Beta Blockers: Beta 2 1. Bronchoconstriction a. Be careful with COPD or asthmab. Lopressor is selective for Beta 1, therefore will not have an effect on bronchioles2. Inhibition of Glycogenolysis a. Insignificant effect for patients who arent Diabeticb. Beta 1 Selective Blocker should be used for Diabetics who require a Beta Blocker xix. Beta Blocker Agents1. Propranolol Hydrochloride (Inderal)a. Nonselective for Beta 1 and Beta 2b. Treats angina, cardiac dysrhythmias, hypertension, and MIi. Contraindicated with respiratory patientsc. See the similarity in namesInderal and Isuprel Be careful!!2. Metoprolol (Lopressor, ToprolXL)a. Blocks Beta 1 Receptors onlyi. At higher doses, it will also block beta 2 3. Atenolol (Tenormin)a. Blocks Beta 1 Receptor onlyb. These are the preferred Beta Blocking agents for patients with asthma or diabetesc. Primarily used to treat Hypertensionj. Cholinergicsi. Stimulates the Parasympathetic Nervous Systemii. Also Called:1. Cholinergic Agonists2. ParaSympathomimetics 3. Muscarinic Agonistsiii. Two Types of Cholinergic Receptors:1. Muscarinic Receptorsa. Stimulates the parasympathetic responses2. Nicotinic Receptorsa. Contraction of the Skeletal Musclesiv. Major uses of Cholinergic Drugs: 1. Stimulate the Bladder and GI Tone2. Constrict the Pupilsv. Other Effects of Cholinergic Drugs:1. Decreases heart rate/ blood pressure2. Increased salivary and bronchial secretionsvi. Adverse Effects: Parasympathomimetics 1. Profuse salivation2. Increased muscle tone3. Urinary Frequency4. Abdominal cramping and diarrhea5. Bronchoconstriction 6. Bradycardia 7. Hypotensionvii. Bethanechol (Urecholine) 1. Cholinergic agent that elicits all of the parasympathetic responsesa. Activates muscarinic receptor activation2. Therapeutic Usea. Relieves urinary retention3. Adverse Effectsa. With oral dosing, side effects are rareb. Could have full range of parasympathomimetic responsesviii. Anticholinergics 1. Inhibits the action of Acetylcholine2. Also called a. Parasympatholytics b. Antimuscarinic Agents3. Major Responses include:a. Increase in the pulse rateb. Decrease in GI motilityc. Relaxation of the bronchid. Decrease in salivatione. Dilation of the pupilsix. Anticholinergic Agents: Atropine1. Used as:a. Preop med to decrease salivary secretions and maintain heart rateb. Increase heart rate when bradycardia is presentc. Dilate pupils for eye exams/eye surgery2. Adverse Effects: Anticholinergicsa. Tachycardiab. Urinary retentionc. Dry mouth/ Dry eyesd. Blurred visioni. Increase in intraocular pressure1. Contraindicated in patients with glaucomae. Constipationx. Other common uses of Anticholinergics 1. Oxybutynin (Ditropan) a. Urinary Tract Antispasmodicb. Treats an overactive bladderc. Used for Incontinence2. Tolterodine (Detrol)a. Used for overactive bladder only3. Scopolaminea. Motion sickness and eye examinations4. Ipratropium (Atrovent)a. Used for asthma, COPD and rhinitisb. Administered by inhaler5. Dicyclomine (Bentyl)a. Used for irritable bowel syndrome6. Exposure to nerve agents in a bioterrorism attacka. All manifestations of nerve gas exposure are due to the over-stimulation of Acetylcholinei. Increase salivationii. Increase sweatingiii. Muscle twitchingiv. Involuntary urination and defecationv. Confusion vi. Convulsionsvii. Respiratory Distress & Respiratory Failure7. Treated with anticholinergic agenta. Injector kits are carried which contain Atropinek. Drugs for Neurodegenerative Disordersi. Parkinsons Disease1. A Disease of the Extrapyramidal System2. The most common neurodegenerative disorder after Alzheimers Disease3. Incidence increases with age4. No cure ii. Extrapyramidal System1. The functional system that is important in maintenance of equilibrium and muscle toneiii. Diseases that effect the extrapyramidal system result in symptoms such as:1. Tremors2. Rigidity3. Postural instability4. Slow movementsl. Parkinsons Diseasei. Caused by death of neurons that produce the neurotransmitter Dopamine1. Between 70 80% of these neurons must be lost before symptoms of Parkinsons are obviousii. Results in an imbalance between Dopamine and Acetylcholine in the basal ganglia1. Decreased amount of dopamine and normal amount of acetylcholine iii. Parkinsonism Drugs1. Antiparkinsonims agents are given to restore the balance of dopamine and acetylcholinea. Dopaminergics increase dopaminei. Increase Dopamine levels in the Corpus Striatum of the Brainii. Used more commonly than Anticholinergics iii. Levodopa1. Traditionally has been the drug of Choice for Parkinsons Diseasea. Newer recommendations lead to Dopamine Agonists instead2. Levodopa will increase Dopamine (chatecholamine cannot pass BBB) levels in the braina. Will turn into Dopamine after biosynthesis in the brain3. Levodopa can pass the blood-brain barriera. Dopamine, if administered, will not cross the blood-brain barrier4. Levodopa is thought to be more effective than the Dopamine Agonists, but with long term use, may end up with disabling dyskinesias and decrease in effectivenessa. Dyskinesia: A defect in the ability to perform voluntary movement5. With long term use of Levodopa, adverse effects tend to increase, and therapeutic effects tend to diminish6. Great results during the first 2 yearsa. By the 5th year, many patients are back to pre-treatment symptomsb. May be more of a sign of disease progression and not tolerance to the drug7. Adverse Effects: a. Dyskinesias b. Postural hypotensionc. Psychosisi. Develops in about 20% of clientsii. Hallucinations, nightmares, paranoid ideationd. Darkened color of sweat and/or urinee. On-Off Phenomonon i. Abrupt loss of effectii. Occurs even when drug levels are highiii. Off times may last from minutes to hoursiv. Over the course of the treatment, Off hours will occur more and more frequentlyf. Food Interactionsi. High protein foods can reduce therapeutic responsesii. Reduces amount of levodopa absorbediii. Reduces amount transported into the brainiv. May be the cause of the off phenomenonv. Patients are advised to spread their protein consumption evenly throughout the dayg. Drug Holidaysi. Drug Holidays may be recommendedii. Brief interruption of treatment iii. @10 daysiv. Must be hospitalized during the drug holidayv. May lead to severe psychologic distress, immobility, aspiration pneumonitis, decubitus ulcersiv. Levodopa/Carbidopa1. Combination drug2. Carbidopa enhances the effect of Levodopa (synergistic effect)a. Carbidopa has no therapeutic effect by itselfb. Allows the dosage of Levodopa to be reduced by about 75%3. Examples: Sinemet and Paracopa v. Dopamine Agonists (younger pts or beginning stages) 1. Stimulate Dopamine receptors directly2. Recommended as the initial drug of choice for patients with mild to moderate symptomsa. May be supplemented with Levodopa b. Levodopa is still the drug of choice for elderly and those with advanced disease3. Examples: Pramipexole (Mirapex) and Ropinirole (Requip)vi. Advantages/Disadvantages of Dopamine Agonists 1. Advantagesa. Dont compete with dietary proteins for absorption and transport across the blood-brain barrierb. Lower incidence of response failure if used long term2. Disadvantagesa. Hallucinationsb. Daytime sleepinessb. Anticholinergics decrease acetylcholine i. Blocks the effects of Acetylcholine in the brain, decreasing symptoms1. Remember, the symptoms of Parkinsons is due to an imbalance of Dopamine and Acetylcholinea. Low Dopamine compared to Acetylcholineii. Examples:1. Tihexphenidyl (Artane)2. Benztropine (Cogentin)iii. Anticholinergics are not as effective as levodopa in treating Parkinsons1. Used early in the course of the disease2. Used in patients who cannot tolerate Levodopa iv. What are the side effects of Anticholinergics?1. Constipation, tachycardia, urinary retention, dry mouth, blurred visionv. Selegiline or Rasagiline1. Newer agents2. MAO-B Inhibitors (parkinsons disease) a. Inactivates MAO by irreversibly binding to it at type B (brain) sitesb. MAO-B is an enzyme that inactivates dopaminec. Leads to increased amounts of dopamine available in the CNSd. Nonselective (depression) MAO inhibitors used for depression inhibit serotonin, norepenephrine and Dopaminevi. MAO B Inhibitors1. May be used as drug of choice for patients with mild symptoms 2. May also be given during off times with Levodopa therapy2. Pharmacotherapy will not cure Parkinsons, but rather will reduce symptomsm. Alzheimers Disease i. Degenerative Disorder characterized by progressive memory loss, confusion and inability to think or communicate effectivelyii. Associated with cerebral atrophyiii. Treatment of AD1. Acetylcholine is the neurotransmitter responsible for learning and memorya. In patients with advanced Alzheimers Disease, levels of acetylcholine are 90% below normal2. Choline Acetyl Transferase a. Enzyme responsible for Acetylcholine Synthesis3. Acetylcholinesterase a. An enzyme that stops the action of acetylcholine4. Acetylcholinesterase Inhibitors are the most widely used agents for Alzheimers Disease5. When Acetylcholinesterase is inhibited, Acetylcholine levels become elevatediv. Acetylcholinesterase Inhibitors 1. These agents are Parasympathomimetics 2. These agents are only used in the early stages of Alzheimers a. They only work if there are functioning neuronsb. As the disease progresses, these agents are usually discontinued3. Examples:a. Donepezil hydrochloride (Aricept)i. Once a day scheduleii. Best toleratedb. Galantamine (Reminyl)c. Tacrine (Cognex) 4x day dosing4. What side effects would you expect to see? Diarrhea, abdominal cramping, pupil constriction, bronchi constriction 5. Should this drug be use by patients with asthma or COPD? NO constriction of bronchi 6. Should this agent be used in a patient that has a history of peptic ulcer disease? NO increases gastric motility v. Memantine1. Newest Drug approved for Alzheimers Diseasea. Approved in 2003b. In use in Germany since 19832. Indicated for moderate to severe disease3. Thought to slow the cognitive decline4. Works by slowing/controlling the influx of calcium into the cells n. Drugs for Seizures i. Called Antiepileptics ii. Seizures: 1. Caused from abnormal electrical discharge from the Cerebral Neuronsiii. Antiepileptics suppress the Abnormal Electrical Impulses iv. Suppress seizures, but do not treat the cause of the seizuresv. Goal of antiepileptic agents:1. Suppress neuronal activity to prevent abnormal firingvi. Four mechanisms by which Antiepileptics act:1. Potentiating GABA2. Blocking the receptors for Glutamate3. Delaying an influx of Sodium4. Delaying an influx of calciumvii. Drugs that Potentiate GABA1. GABA:a. An inhibitory neurotransmitter that is widely distributed throughout the brain2. These agents decrease neuronal excitability3. Drugs that potentiate GABA work by:a. Directly binding to GABA receptors and thus increase the effectivenessi. Benzodiazepines and Barbiturates4. Promote GABA release5. Inhibit GABA reuptake6. Inhibiting the enzyme that degrades GABAviii. Blocking the Receptors of Glutamate 1. Glutamic acid (Glutamate)a. Primary excitatory transmitter in the CNS2. If receptor is blocked, will decrease the neuronal excitationa. Felbimate b. Topiramate ix. Suppression of Sodium and Calcium Influx 1. When sodium ions and Calcium ions are delayed from moving across the neuronal membrane, the CNS activity will be suppressedx. Types of Seizures 1. Partial (focal) Seizuresa. Localized symptomsb. Discrete symptoms that are determined by the brain region involved2. Generalized Seizuresa. Seizure activity is caused from abnormal electrical activity that is conducted widely throughout both hemispheres of the brain3. Absent Seizuresa. Zone out stay awake but do not respond for 10-30 seconds, do not remember what happened4. Pharmacologic choice will be dependent on type of seizure activity5. Phenytoin is effective with Partial and Tonic-Clonic, but not with absence seizures6. Valproic Acid seems to be effective with all types of seizuresxi. Special Considerations 1. Plasma Drug Levelsa. Monitored on most Antiepileptics (narrow therapeutic range) b. To establish a safe and effective plasma level2. Promoting patient Adherencea. Extremely important on these agentsb. Narrow therapeutic range3. Discontinuance of the agentsa. These agents must be withdrawn slowly over a period of 6 weeks to several months4. Most anticonvulsants are cytochrome P450 Inducersa. Many drug-drug interactions5. May reduce the effectiveness of birth control pillsxii. Two Categories of Antiepileptic Agents1. Traditional Agentsa. Last agent approved in 1978b. Cost lessc. More extensive experienced. Troublesome side effectse. Complex drug interactionsf. Phenytoin (Dilantin)i. Most widely used antiepileptic agentii. Works through inhibition of sodium channelsiii. Used to treat all forms of seizures except absence seizuresg. Narrow therapeutic rangei. Doses of phenytoin needed to produce therapeutic effects are only slightly smaller than the doses that may cause toxicityii. As doses rise slightly, the drug will saturate the liver and overwhelm the livers ability to metabolizeiii. According to your text small changes in dosage produce large changes in drug levelsh. Therapeutic Rangei. 10 20 mcg/mLii. Doses must be individualized based on careful serum monitoringi. Gingival hyperplasiai. Excessive growth of gum tissuesii. Side effect in about 20% of clientsiii. Nurses must teach patients about good oral hygiene including gum massagej. Teratogenic effects to the fetus if used during pregnancyi. Pregnancy Category Dii. Can lead to:1. Cleft palate, heart malformations, motor or mental deficiency, microcephaly2. Also causes bleeding tendencies in the newborn because it decreases the synthesis of vitamin Kk. Drug interactionsi. Liver Enzyme Inducer1. Decreases the effect of other drugs such as Warfarin, Oral contraceptivesii. Highly Protein Bound1. Valproic Acid elevates levels of free phenytoin by displacing it from protein binding sitesl. Carbamazepine (Tegretol) i. Effective against tonic-clonic and partial seizures, but not absence seizuresii. Works by suppressing sodium influxiii. May be used for Bipolar Disorderiv. Liver Enzyme Inducer1. Increases its own metabolism over time2. Half life will decrease over timea. Initial treatment: Half life of 40 hoursb. With continue treatment: Half life of 15 hoursv. Adverse Effects1. Minimal effect on cognitive functiona. Often the drug of choice for younger childrenvi. Hematologic Effects1. Bone marrow suppressiona. Leukopenia, anemia and thrombocytopeniab. CBC should be monitoredvii. Teratogenic Effects1. Category D m. Valproic Acid (Depakene, Depakote) i. Will treat all major seizure typesii. Also used in the treatment of Bi-Polar Disorder and migraine headachesiii. Works by three mechanisms:1. Suppresses sodium and calcium influx, also augments GABAiv. Causes minimal sedation and cognitive impairmentv. Teratogenic Effects1. Category D2. Neural Tube defectsa. Women are encouraged to take a folic acid supplementvi. May be hepatotoxic 1. Raren. Ethosuximide (Zarontin)i. Drug of choice for absence seizuresii. Will not work for other types of seizuresiii. Does not require serum level monitoring1. Dose is determined by watching the incidence of the seizure activityo. Phenobarbital i. One of the oldest antiepileptic agentsii. Considered a barbiturate1. Can cause physical dependencyiii. Significant side effects1. Learning impairment, Lethargy, Depressioniv. Not used as commonly as it once was p. Oxcarbazepine (Trileptal) i. Newer Antiepileptic Agentsii. Most commonly prescribed of the newer agentsiii. A derivative agent of Carbamazepine 1. As effective2. More expensive3. Better toleratediv. Adverse Effects1. Dizziness and Drowsiness 2. Hyponatremia a. Sodium levels are monitored if patient is on any other medications that effect sodium concentration (diuretics)3. Does not cause the severe hematologic problems seen with carbamazepine 4. Pregnancy category Ca. Women should use effective contraceptivesq. Management of Status Epilepticusi. Continuous tonic-clonic seizure that lasts at least 20 - 30 minutes1. Patient develops tachycardia, hypertension, hypoxia, acidosis and hypoglycemia2. Can lead to permanent neurologic injury or deathii. Goal of treatment:1. Maintain airway2. Correct hypoglycemia3. Stop the seizureiii. IV started1. Glucose solution infused 2. Antiepileptic agent infusediv. Lorazepam (Ativan) or Diazepam (Valium) are the agents of choice1. These drugs are Benzodiazepines2. Effects of Ativan can last for 72 hours, so it is now the drug of choicev. Benzodiazepines are usually prescribed for short term control of seizuresvi. If prescribed for long term therapy, the client will develop a tolerance vii. Once the seizurs have been stopped, Phenytoing (Dilantin) or Fosphenytoin (Cerebyx) may be given for long term suppression2. Newer Agentsa. Approved in 1993 or laterb. Cost morec. Less experience, therefore, prescribed less frequentlyd. Smaller risk of teratogenic effectse. Fewer drug interactions3. Both groups appear equally effective4. Both groups have their advantages and disadvantageso. Psychotherapeutic Drugsi. Schizophrenia1. Chronic psychotic illness2. Characterized by disordered thinking and difficulty comprehending realityii. Symptoms of Schizophrenia:1. Hallucinations, delusions, agitation and paranoia2. Lack of motivation, blunt affect, social withdrawal3. Disordered thinking, memory and learning difficulties, inattentivenessiii. Cause of Schizophrenia1. Exact etiology is unknown2. Thought to be caused from an excess of Dopamine in the braina. All antipsychotic drugs work by competing with the Dopamine receptor sitesb. Thus, they block Dopamine receptors in the braini. Thought to be Dopamine Antagonists3. DISEASE CAUSED FROM LACK OF DOPAMINE iv. Two Major Categories of Antipsychotic Agents1. First Generation (Conventional) Agentsa. Further classified as low potency, medium potency or high potencyb. Block receptors for Dopaminec. EPS symptoms likelyd. Two chemical categories of Conventional Agentsi. Phenothiazines 1. Chlorpromazine (Thorazine)2. Thioridazine (Mellaril)ii. Butyrophenones (Phenothiazine-Like)1. Haloperidol (Haldol)e. Adverse Effects of Conventional Antipsychotic Agentsi. Drowsinessii. Anticholinergic Effects iii. Orthostatic Hypotensioniv. Extrapyramidal Symptomsf. Extrapyramidal Symptoms (EPS) i. Acute Dystonias 1. Severe muscle spasms2. Tongue, neck, face or back3. Opisthotonic Posturingii. Akathisia 1. Inability to rest or relax2. Pacing and squirmingiii. Parkinsonism1. Tremors 2. Mask Like Face3. Stooped posture4. Rigidity5. Shuffling Gait6. Pill-Rolling7. Bradykinesia iv. Tardive Dyskinesia 1. Develops in 20% of patients with long-term therapy2. Serious Side Effect3. Protrusion of tongue is accompanied by sucking, smacking lips, involuntary movements of the body and extremities4. Med should be stopped immediately if symptoms are exhibited5. For many patients, the symptoms are not reversible6. Results in speaking and nutritional difficulties2. Second Generation (Atypical) Agentsa. Moderately block receptors for Dopaminei. Lower risk of EPS symptomsb. Stronger block of receptors for Serotoninc. Newer drugs on the marketd. Have become the drug of choice for treatment of Psychosese. Greater therapeutic Effectsf. Not likely to cause EPS Symptomsg. Also called: Second Generationv. Atypical Antipsychotic Agents1. Mechanism of Actiona. Block Dopamine Receptors (loosely)b. Also block Serotonin and Alpha-adrenergic receptors2. Examples:a. Risperidone (Risperdal)b. Olanzapine (Zyprexa)c. Dibenzodiazepine (Clozapine)vi. Side Effects of Atypical Antipsychotics1. Weight Gaina. May quickly lead to obesityb. Especially Clozapine (Clozaril) and Olanzapine (Zyprexa)2. Increase in prolactin levelsa. Leads to menstrual disorders, sexual dysfunction and osteoporosis3. Teratogenic effects a. Contraindicated during pregnancy and lactation4. Diabetesa. New onsetp. Depressioni. Three Types of Depression1. Reactivea. Sudden onset with precipitating factorsb. Normal grief/sadnessc. Appropriate reaction to a major life stressor2. Unipolar a. Major depressionb. Loss of interest in work and homec. Considered an illness3. Bipolara. Manic and depressiveii. Depression is most common psychiatric disorderiii. Affects 30% of populationiv. Only 30% of population with depression are treated with medication1. Depression is under-diagnosed and under-treatedv. Theory of Depression1. Caused from insufficient amount of monoamine neurotransmittersa. Norepinephrine b. Serotoninvi. Antidepressants 1. St Johns Wort:a. Herbal Supplementb. Decreases the reuptake of the neurotransmitters:i. Serotonin, Norepinephrine & Dopamine2. Conflicting study results regarding effectiveness3. Thought to be as effective as the Tricyclic antidepressants in treating mild to moderate depression4. Not shown to be effective in treating severe depression5. Known to interact adversely with many other drugsa. Induces cytochrome P450 enzymesb. Induces P- Glycoproteinc. Intensifies the serotonin effectsi. May lead to fatal serotonin syndromevii. Five Groups of Antidepressants 1. Tricyclic (TCAs)a. Available in the late 1950sb. Blocks the uptake of norepinephrine and serotoninc. Less expensive than the SSRIsd. Therapeutic response takes 2-6 weekse. Gradually withdrawn when discontinuingf. Used most commonly for major Depressiong. Examples:i. Amitriptyline (Elavil)ii. Imipramine (Tofranil)h. Side Effects:i. Sedationii. Anticholinergic effectsiii. Orthostatic Hypotension1. Blocks Alpha 1 receptorsiv. Increase risk of suicide early in treatment1. Could overdose on the medication2. Supply should be limited to one week in the beginning of therapy2. Selective Serotonin Reuptake Inhibitors a. Introduced in 1987b. Most commonly prescribed antidepressantc. $3 Billion in annual salesd. SSRIs Block the reuptake of serotonini. Do not block the uptake of dopamine or norepinephrine e. More expensive than the Tricyclics f. Do not block cholinergic and alpha 1 adrenergic receptorsi. Fewer side effectsg. Used for major Depressionh. Also used to treat:i. Obsessive/Compulsiveii. Paniciii. Phobiasiv. PTSDv. Anxietyi. Examples of SSRIs:i. Fluoxatine (Prozac)ii. Fluxovamine (Luvox)iii. Sertraline (Zoloft)iv. Paroxetine (Paxil)v. Citalopram (Celexa)vi. Escitalopram (Lexapro)j. Side Effectsi. Sexual dysfunction1. Up to 70% of men and women may experience decreased libido and lack of ability to reach an orgasm2. May result in noncompliance with medicationii. Insomniaiii. Headacheiv. Weight gain v. Serotonin Syndrome (SES) 1. May occur when taking SSRIs along with other medications that increase serotonin levelsa. MAOIs, Tricyclics, Lithium2. Occurs if Serotonin levels accumulate in the body3. Symptoms include:a. Confusion, anxiety, restlessness, hypertension, tremors4. Recommended treatment is supportive and discontinue the SSRI.a. If untreated, may result in deathvi. Withdrawal Syndrome1. Abrupt discontinuation of SSRIs can cause a withdrawal syndrome. 2. Symptoms include: a. Headacheb. Dizzinessc. Nausead. Tremorse. Anxiety3. Symptoms can last for 1 3 weeks4. Drug must be tapered slowly3. Serotonin/Norepinephrine Reuptake Inhibitors (S/NRIs)a. Block reuptake of serotonin and norepinephrine b. Similar effect to SSRIsi. SSRIs seem to be better toleratedc. Two drugs in this category:i. Venlafaxine (Effexor)ii. Duloxetine (Cymbalta)iii. Desvenlafaxine (Pristiq)4. Monoamine Oxidase Inhibitors (MAOIs)a. The first drug approved to treat depression in the 1950s.b. Inactivates Monoamine Oxidase c. Monoamine Oxidase is an enzyme found in the liver, the intestine & the braini. The function of Monamine Oxicase is to:1. inactivates the three neurotransmitters2. Inactivates tyramine in foodsd. Examples:i. Tranylcypromine (Parnate)ii. Isocarboxazid (Marplan)iii. Phenelzine (Nardil)e. Used to treat reactive or unipolar depressionf. Very effectiveg. Due to severe side effects, not used oftenh. Only used when other antidepressants are not effectivei. Drug Food Interactionsi. Normally, dietary Tyramine is metabolized by MAO in the intestinal wall and in the liverii. Tyramine, if not metabolized, will promote the release of norepinephrine from the sympathetic systemiii. MAOIs inactivate the enzymes that detoxifies Tyramine 1. will cause a hypertensive crisis due to a drastic release of norepinephrine into the blood streamiv. Tyramine Rich Foods1. Cheese, cream, yogurt, bananas, raisins, coffee, chocolate, Italian green beans, liver, sausage, soy sauce, beer, red winej. Drug Drug Interactions i. MAOIs used concurrently with other antidepressants or sympathomimetic drugs1. Can cause a hypertensive crisis2. Due to the drastic increase in norepinephrine ii. MAOIs used concurrently with SSRIs1. Serotonin Syndromeiii. MAOIs will potentiate the hypoglycemic effect of insulin and oral hypoglycemic agents5. Atypical Antidepressantsa. Available in the 1980sb. Used for major and reactive Depressionc. They affect one or two of the three neurotransmittersd. Examples:i. Trazadone (Desyrel)ii. Bupropion (Wellbutrin)iii. Mirtazapine (Remeron)q. Mood Stabilizers i. Used to treat Bi Polar Disorderii. Effective in controlling the Mania and Depressioniii. Mood Stabilizers:1. Lithium2. Valproic Acid3. Carbamazepine iv. Many patients also receive an antipsychotic, and some may require an antidepressantv. Lithium1. Approved in the US in 19702. Drug of choice for controlling acute manic episodes and for long-term prophylaxis against recurrence3. Narrow Therapeutic Rangea. 0.6 to 1.5mEq/Lb. Death has resulted from Lithium levels > 2.5mEq/L4. Serum Lithium levels should be monitored frequentlya. Every 1 to 3 days when beginning therapyvi. Lithium/Sodium Relationship1. Lithium is a salt2. Low serum sodium level will increase risk of lithium toxicity3. Important that serum sodium levels remain normal 4. Sodium levels will be affected by:a. Vomiting/ Diarrheab. Sweatingc. Use of diuretics.5. Lithium is excreted by the kidneys6. Renal excretion of lithium is affected by blood levels of sodium7. Lithium excretion is reduced when blood levels of sodium are low8. When the kidneys sense that sodium levels are inadequate, it retains lithium in an attempt to compensate9. If the sodium levels are low, the lithium will be retained and accumulate rapidly to toxic levelsvii. Valproic Acid and Carbamezapine1. These antiepileptic drugs can suppress mania and stabilize mood in patients with Bi-Polar Disorder2. Valproic Acid is very effective and gaining popularity as drug of choicer. Sedative Hypnotic Agents i. CNS Depressantsii. Used to treat anxiety1. Anxiolytic agents2. Antianxiety agentsiii. Used to treat insomnia1. Called Hypnoticsiv. Terms: Sedative Hypnotic 1. Sedative Effect: Depresses physical and mental responses