Pharmacology Packet Review What is a drug? A drug is something intended to affect the structure of the body, whether it be good or bad. Define pharmacology: the study of drugs Define pharmacodynamics: the effect of drugs on the body; in lecture we discussed how drug molecules bind onto receptors such as beta 1, beta 2, or beta 3 and then act as either antagonists or agonists for that receptor depending on the drug. Define pharmacokinetics and its primary components. The effect of the body on the drugs. The four components are: absorption HOW the drug is taken; distriubtion: WHERE the drug goes; metabolism: how the drug works/pharmacodynamics; excretion: how it turns into something soluble to be exreted (kidneys) Provide 2 definitions for polypharmacy: >5 medications More drugs prescribed than warranted 3 reasons why polypharmacy is a problem: Adverse drug reactions Medication adherence Unnecessary healthcare costs 3 main risks of OTC medications: Increased adverse drug reactions Delay use of more efffective medications Decreased awareness of recommended dosages (tylenol like tic tacs) List all routes of drug administration available: Enteral: involving GI system o Oral o Sublingual/buccal o Rectal Paraenteral: everything BUT GI system o Para-: prefix: alongside of, beside, near, apart from o Inhalation o Injection Intrathecal Intraarticular Intramuscular Intravenous Intraarterial Subcutaneous o Transdermal Patches o Topical Skin Mucous membranes Which drug routes are systemic routes of administration: Oral, sublingual/buccal, rectal, intramuscular, intravenous, intraarterial, subcutaneous, transdermal, mucous membrane topical Which 4 routes of drug administration are considered “less systemic?” Rank them from least systemic to most systemic. Least: skin-topical, intraarticular, intrathecal, inhalation What factors affect the rate of GI absorption of oral medications? Blood flow: increased blood flow=increased abosrption Gastric motility: increased peristalsis=increased absorption o This is decreased in people with parkinsons and diabetes Food: if there is lots of food in the stomach, there will be a slower absoprtion rate since a shit ton of other things are trying to ge absorbed as well For drugs taken PO, list 2 conditions that would decrease the rate of absorption: Parkinsons and diabetes Define first-pass inactivation (list its other names) first pass metabolism; first pass inactivation; first pass effect First-pass inactivation: Only pertains to oral drugs: the amount of drug that is bioavailable after becoming metabolized by the liver to actually produce an affect Ex: If a drug has 100% first pass inactivation, then that drug will have become completely metabolized in the liver before ever reaching the systemic system. List the 6 compartments that drugs can be injected into: Paraenteral: anything but the GI tract o Injection: Intraarticular, intramuscular, intravenous, intraarterial, intrathecal, subcutaneous For topical administration, where are drugs applied? Topical: Skin or mucous membranes o Skin: on the epidermis: neosporin: local effects: superficial absorption, metabolism occurs by skin enzymes o Mucous membranes: cocaine: systemic effects: rapid systemic absorption What degree of systemic absorption occurs with each of these? Skin: local Mucous membranes: systemic What is the difference between topical and transdermal drug application? Intended goal. Topical skin application has the goal of a local effect. Topical mucous membrane application has the goal of a systemic effect. Transdermal application has the goal of a systemic effect. It also requires some modality or device such as a patch to push medications through the skin. For transdermal patches, what is the clinical relevance of heat modalities? (Include the drug release membrane in answer.) Transdermal patches are applied purposefully to areas where there is no friction. They consist of a drug release membrane that is applied to the skin with the intended effect of a steady state dosage of whatever the drug needed is. Unfortunately, drug patches increase the rate at which the drug is dispersed when they are heated up or damaged. That is why it is critical to not use heating modalities on patients with drug patches. Too much heat can be cause from external sources such as modality like heat pack, OR from internal sources such as a fever. Define bioavailability: How much of a drug is available for use in the systemic system Define drug distriubtion: WHERE the drug travels for its target tissue receptors What factors influence where in the body a drug is distributed? Blood flow Adiposity Where the drug is designed to bind to How would hypoalbuminemia affect the bioavailability of a drug that is taken PO? Albumin not only functions as maintaining oncotic pressure, but it also works to bind drug molecules to itself. This limits the drugs from crossing to its target tissues because the drug molecule HAS to be free in order to cross through the membrane. If you have low amounts of albumin, there will be excessive amounts of drug molecules abailable for the tissues. This needs to be accounted for in the dosage parameters for individuals with hypoalbuminemia, as they will have an increased effect from the drug. For drugs that are lipophilic, list 2 patient characteristics that will prolong the drugs effect: Drugs are distributed in areas based on blood flow: Blood-brain-viscera-muscle-fat: This means that the drug arrives at the fat last, and leaves the fat last. If drugs are lipophilic then individuals with increased adiposity will have prolonged effects from the drug molecules because it takes a long time for that drug to leave the system. Older individuals have increased adiposity, as well as obese indiviudals? Define drug metabolism: Pharmacodynamics: \ What organ is primarily responsible for drug metabolism and why? The liver is the primary organ that is responsible for drug metabolism. It creates almost all drug metabolizing enzymes (CYP450) What is the name of the enzyme system responsible for the majority of drug metabolism? CYP450 What is a CYP450 inducer? A CYP inducer is an enzyme that acts as an agonist on a cell membranes receptor. In other words, it mimics what an endogenous NT, hormone, etc. Would do if it had binded to the receptor instead. It is stated that an inducer as an agonist has both efficacy because it produces a change in the cell structure/function, and also affinity. We used albuterol as an example of an agonist. It searches for a beta 2 adrenergic receptor of the lungs, binds to it, and causes vasodilation in order to breathe better. HOWEVER, it is important to note that although albuterol is technically a selective agonist, that it it is not completely perfect, and some of the drug is going to bind to beta 1 receptors on the heart and cause vasodilation and therefore an increased heart rate. That is one of the most common ADRs for albuterol. Give an example of a drug-drug interaction that involves a CYP450 inducer What is a CYP450 inhibitor? An inhibitor or antagonist is something that binds to a receptor because it has affinity for it, but DOES not have efficacy, so it does not cause any change to the structure or affect of the cell it is binding to. All it is doing is blocking endogenous hormones/NT/etc. From binding there and causing an effect on the cells. Metropolol is the drug example for an antagonist adregenic beta 1 blocker. OMG beta blocker! I get it now. Once it finds the heart receptors, it blocks things from activating them, so vasoconstriction occurs in the heart. If we think of how these drugs are not perfectly selective, we can assume that some of this beta blocker makes its way to beta 2 receptors, and the metopolol also works there as well. That means that the lungs will constrict, and an adverse drug reaction of dyspnea could occur. Give an example of a drug-drug inercation that involves a CYP450 inhibitor: Define excretion: What organ is primarily responsible for drug excretion? Kidneys turn metabolites into a soluble substance that can be excreted. How are drugs eliminated from the body? Metabolism and excretion=elimination Define half-life in words: A half life is the amount of time it takes for HALF of the drug to be eliminated from the body. For most drugs, how many-half lives are required for the majority of the drug to be eliminated from the body? For the majorit of drugs, about 5 half lives are required for 95% of the drug to be eliminated from the body. o In other words, once you know a drugs half life, you can multiply that number by 5, and that should be the amount of time it takes for that drug to be 95% eliminated. Give 2 examples of characteristics that would increase the half life of a drug in a specific individual (consider the equation for ½ life) EquationL T0.5= Volume of distribution / Clearance of drug o We can increase the half life of a drug by increasing the volume of distribution, or by decreasing the clearance of a drug. If an individual has more adiposity (such as an older adult) the Vd will increase. Additonally, the liver and kidneys are not as functional in an older adult, so the clearance of the drug will be reduced. Both of these factors will increase the drugs half life. What is the therapuetic index? The therapeutic index is a dose-response curve that is based off of the effective dose for 50% of the population, and the toxic dose of 50% of the population. It is meant to figure out what the best dose is with the intended effect without having toxic adverse drug reactions. The closer the two ratios are together the more likely you are to be sick. Chemotherapy drugs are a great exmaple of a drug tat has a low therapuetic index. Over the counter drugs have very high therapuetic indexes. Do OTC drugs have low or high therapuetic indices? High Over the counter drugs needs to be deregulted under specific circumstances of safety. One of those being having a very high therapeutic index so this now easily accessible drug does not cause everyone to experince adverse drug reactions. What is the clinical relevance of a drug that has low therapuetic index? If a drug has a low TI, then there is a larger probablility that they will experience an adverse drug reaction. Even a slight change in medication or any of the factors mentioned could have an effect. Drugs with low TI are usually very carefully monitored and prescribed. Warfarin is an anticoagulant for DVT and clotting disorders. It also has a low TI. This is the reason that INR levels needs to be mointored very closely for patients taking warfarin, so they stay within the therapuetic range of 2-3? What is the INR range for therapuetic anticoagulation? 2-3: therapeutic anticoagulation Define adverse drug reaction. Specifically, how is an ADR different from an overdose or distinct from a side effect? An adverse drug reaction is something other than the intended effect of the drug that occurs at a therapeutic dose. For each organ system, define: Dermatologic toxicity: What is the drug toxicity? Drug + light Give an example of drug/drug class that is associated with this toxicity. NSAID Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) Wear sunscreen, clothing, etc. Ototoxicity: What is the drug toxicity? Damaging the otoliths/vestibular system Give an example of drug/drug class that is associated with this toxicity. Lasix Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) monitor balance, fall risk GI toxicity: What is the drug toxicity? Damages stomach lining nausea/vomiting Give an example of drug/drug class that is associated with this toxicity. NSAIDS Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) ulcers, Nephrotoxicity: What is the drug toxicity? Damage to kidneys Give an example of drug/drug class that is associated with this toxicity. NSAIDS Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) identify risk factors, decrease NSAID consumption Hepatotoxicity: What is the drug toxicity? Damage to liver Give an example of drug/drug class that is associated with this toxicity. Acetimenaphon (tylenol) Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) CNS toxicity: What is the drug toxicity? Central nervous system Give an example of drug/drug class that is associated with this toxicity. Antihistamine Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) Cardiovascular toxicity: What is the drug toxicity? Give an example of drug/drug class that is associated with this toxicity. Antihypertensives, antiarrhythmics Provide clinical relevance (how can we as PTs monitor, education, or mitigate this toxicity?) Which pharmacokinetic parameter is most important in the association of increasing age and incidence of ADRs? Excretion: decreased renal function is the most important PK factor resulting in ADRs in adults because no excretion What is the PT’s role in managing medications? A PT is responsible for helping with medication adherence and education. TAKING DRUG HISTORY, recongize ADRs, What are key questions/considerations when reviewing a patient's medication list? What are the interactions between the drugs? When did they last take a drug? MAIN: Could their current clinical presentation have something to do with a drug? What do the drugs they are taking tell us about the patient that was not mentioned in the subjective? WHAT HAS CHANGED?
