Pharmacokinetics Pharmacology Pharmacology Chapter 2

How Does medication Work in our Bodies? Pharmacokinetic Model Pharmacokinetic Model Different cells are targeted to evoke a desired response Different cells are targeted to evoke a desired response Via chemical messangers. Via chemical messangers. Can you name some? Can you name some?

Receptors Cells communicate through the action of chemical messengers Cells communicate through the action of chemical messengers “Target cell”-(the cell that responds to the communication). “Target cell”-(the cell that responds to the communication). Receptor is a protein molecule on the surface of or within a cell that recognizes and binds with specific molecules, thereby producing some effect within the cell. Receptor is a protein molecule on the surface of or within a cell that recognizes and binds with specific molecules, thereby producing some effect within the cell. Specificity- the messenger has the same receptor structure as the target cell. Specificity- the messenger has the same receptor structure as the target cell. Affinity- the strength by which a messenger binds to a receptor site. Affinity- the strength by which a messenger binds to a receptor site.

Mechanisms of Drug Action How a drug produces its effects. How a drug produces its effects. Agonist is a drug that binds to a particular receptor site and triggers the cell’s response in a manner similar to the action of the body’s own chemical messenger. Agonist is a drug that binds to a particular receptor site and triggers the cell’s response in a manner similar to the action of the body’s own chemical messenger. Antagonists- Drugs that bind to a receptor site and block action of chemical messengers. Antagonists- Drugs that bind to a receptor site and block action of chemical messengers. Other drugs Other drugs interact with non specific lipids interact with non specific lipids combine with proteins combine with proteins Use Osmosis -how water is reabsorbed by the kidneys Use Osmosis -how water is reabsorbed by the kidneys

Pharmacokinetics The action of drugs in the body over a period of time. The action of drugs in the body over a period of time. Pharmacokinetic Processes Pharmacokinetic Processes ADME Scheme of kinetics (Pharmacokinetic Modeling) ADME Scheme of kinetics (Pharmacokinetic Modeling) Absorption Absorption Distribution Distribution Metabolism Metabolism Elimination Elimination Considerations such as: Considerations such as: Levels of the drug in blood and tissues Levels of the drug in blood and tissues Overall distribution Overall distribution Reaction of the drugs with other drugs Reaction of the drugs with other drugs Patient compliance Patient compliance Life of the drug that includes bioavailability, half-life, bioequivalence Life of the drug that includes bioavailability, half-life, bioequivalence

Pharmacokinetics

Absorption The process whereby a drug enters the circulatory system. The process whereby a drug enters the circulatory system. Rate depends on ROA, solubility and physical properties. Rate depends on ROA, solubility and physical properties. Dissolution –the time necessary drug to be dissolved. Dissolution –the time necessary drug to be dissolved. Rate of dissolution depends on the chemistry, surface area, and mnf variables. Rate of dissolution depends on the chemistry, surface area, and mnf variables. Primary site of absorption- Small Intestine Primary site of absorption- Small Intestine GI motility can affect the rate of absorption GI motility can affect the rate of absorption

Distribution The process by which a drug moves from the blood into other body fluids and tissues. The process by which a drug moves from the blood into other body fluids and tissues. Factors that affect distribution Factors that affect distribution Binding to Plasma Proteins Binding to Plasma Proteins Binding to Cellular Constituents Binding to Cellular Constituents Blood Brain Barrier Blood Brain Barrier Blood flow is the rate Blood flow is the rate The distribution is not necessarily equal throughout the whole body The distribution is not necessarily equal throughout the whole body

Metabolism The process of converting drugs to compounds that are useful in the body. The process of converting drugs to compounds that are useful in the body. Factors that can alter metabolism Factors that can alter metabolism Other medications Other medications Disease states, age, genetics Disease states, age, genetics

Metabolism Most metabolism takes place in the liver Most metabolism takes place in the liver Metabolism changes the chemical structure of the original drug Metabolism changes the chemical structure of the original drug There are different influences that can alter metabolism such as age, gender, genetics, diet, and other chemicals digested There are different influences that can alter metabolism such as age, gender, genetics, diet, and other chemicals digested

Excretion Occurs primarily in the kidney and bowel. Occurs primarily in the kidney and bowel. Also exhalation, sweat glands, breast milk Also exhalation, sweat glands, breast milk Clearance - rate at which a drug is eliminated from a specific volume of blood per unit of time. Clearance - rate at which a drug is eliminated from a specific volume of blood per unit of time. Excretion is the last phase of a drug’s life in the body Excretion is the last phase of a drug’s life in the body

Important Pharmacokinetic Parameters Safe and effective drug therapy requires that drugs be delivered in concentrations that will treat the disease without toxicity. Safe and effective drug therapy requires that drugs be delivered in concentrations that will treat the disease without toxicity. Bioavailability how much of the drug administered becomes active in the body. Bioavailability how much of the drug administered becomes active in the body. First Pass effect- drugs must first pass through the intestines and the liver before reaching target site. First Pass effect- drugs must first pass through the intestines and the liver before reaching target site. Ceiling effect -Greater doses are given until a point is reached when no improved clinical response occurs and increasing beyond this point can cause side effects, toxicity and death. Ceiling effect -Greater doses are given until a point is reached when no improved clinical response occurs and increasing beyond this point can cause side effects, toxicity and death.

Pharmacokinetics Dose-Response Curve

Therapeutic window - optimum response with the least probability of toxicity. Therapeutic window - optimum response with the least probability of toxicity. Therapeutic level/Range -amount of drug in the blood that produces the desired effect. Therapeutic level/Range -amount of drug in the blood that produces the desired effect. Duration of Action -The amount of time a drug is at this level Duration of Action -The amount of time a drug is at this level Loading dose, the amount of drug needed to bring blood quickly to desired response. Loading dose, the amount of drug needed to bring blood quickly to desired response.

Pharmacokinetics Therapeutic Range

Pharmacokinetics Duration of Action

Maintenance Doses Given to maintain therapeutic levels Given to maintain therapeutic levels

Half Life The time it takes for the body to eliminate half the drug The time it takes for the body to eliminate half the drug T1/2 T1/2 It takes a drug 5-7 times longer than it’s half life to be considered removed from the body It takes a drug 5-7 times longer than it’s half life to be considered removed from the body 1000mg of Drug a has t ½ of 2 hours 1000mg of Drug a has t ½ of 2 hours 12 am Take first dose 12 am Take first dose 2am = 500 mg left 2am = 500 mg left 4am = 250 mg left 4am = 250 mg left 6 am = 125 mg left 6 am = 125 mg left 8 am = 62 mg left 8 am = 62 mg left 10 am 31 mg left 10 am 31 mg left 12pm = 15 mg left 12pm = 15 mg left 2 pm = 7 mg left 2 pm = 7 mg left 4 pm = drug eliminated 4 pm = drug eliminated 14 hours to rid the body of the medications 14 hours to rid the body of the medications

Half Life

Discussion How is a drug’s volume of distribution, clearance, and half-life used in dosing drugs? How is a drug’s volume of distribution, clearance, and half-life used in dosing drugs? Answer: Volume of distribution is important for calculating the loading dose, clearance for calculating the maintenance dose, and half-life for determining the dosing interval. Answer: Volume of distribution is important for calculating the loading dose, clearance for calculating the maintenance dose, and half-life for determining the dosing interval.

Bioequivalence This is the comparison between drugs either from different manufacturers or in the same company but from different batches of a drug This is the comparison between drugs either from different manufacturers or in the same company but from different batches of a drug Generic drug manufacturers strive to achieve the same equivalence as brand name manufacturers for competition Generic drug manufacturers strive to achieve the same equivalence as brand name manufacturers for competition

Drug Effects Effects of drugs can be beneficial or detrimental and dangerous. Effects of drugs can be beneficial or detrimental and dangerous. Site of action- location in the body where a drug exerts its therapeutic effect. Site of action- location in the body where a drug exerts its therapeutic effect. Beneficial Responses Beneficial Responses Therapeutic Effect Therapeutic Effect effect-The desired action of a drug in treatment or symptom of a disease. effect-The desired action of a drug in treatment or symptom of a disease. Local Effect Local Effect Confined to a specific part of the body Confined to a specific part of the body Systemic Effect Systemic Effect Generalized, all-inclusive effect on entire body Generalized, all-inclusive effect on entire body

Drug Effects When choosing a drug for a patient, a healthcare practitioner considers: When choosing a drug for a patient, a healthcare practitioner considers: Indications Indications diseases, symptoms, and conditions for which the drug is known to be of benefit diseases, symptoms, and conditions for which the drug is known to be of benefit Contraindications Contraindications conditions for which the drug will not be beneficial and may do harm conditions for which the drug will not be beneficial and may do harm

Drug Effects Side Effects Side Effects secondary responses to a drug other than it’s intended effect. secondary responses to a drug other than it’s intended effect. Allergic responses Allergic responses Drug dependence, addiction, abuse, and tolerance Drug dependence, addiction, abuse, and tolerance

Harmful Responses An allergic response can be a local or general immune response. An allergic response can be a local or general immune response. an overreaction to a harmless substance. an overreaction to a harmless substance. Can be mild to severe Can be mild to severe Anaphylactic response- characterized by respiratory distress, vascular collapse and shock. Anaphylactic response- characterized by respiratory distress, vascular collapse and shock. Idiosyncratic reactions- unusual or unexpected reactions to a medication. Idiosyncratic reactions- unusual or unexpected reactions to a medication. Drug dependence- physiological and/or psychological need for a drug Drug dependence- physiological and/or psychological need for a drug Addiction- A perceived need for a drug Addiction- A perceived need for a drug Abuse –The use of a drug for purposes other than prescribed and or in amounts not directed. Abuse –The use of a drug for purposes other than prescribed and or in amounts not directed. Tolerance -Decreased response to the effects of a drug do to its continued use. Tolerance -Decreased response to the effects of a drug do to its continued use.

Drug Interactions Combined effect of two or more drugs. Combined effect of two or more drugs. Common Drug relationships Common Drug relationships Addition Addition = = 2 Antagonism Antagonism = = 1 Potentiation Potentiation > > 1 Synergism Synergism > > 2

Discussion Name a common drug-food interaction. Name a common drug-food interaction. Answer: Grapefruit juice can affect drugs for up to a day following ingestion. Answer: Grapefruit juice can affect drugs for up to a day following ingestion.

Discussion Why is it important for the pharmacy to have a complete list of all of the prescription drugs, OTC medications, vitamins, and herbal remedies that a patient is taking? Why is it important for the pharmacy to have a complete list of all of the prescription drugs, OTC medications, vitamins, and herbal remedies that a patient is taking? Answer: Such a list will help healthcare professionals identify potential drug interactions. Answer: Such a list will help healthcare professionals identify potential drug interactions.

Factors that Influence Drug Effects Age Age Gender Gender Disease/Medical condition Disease/Medical condition Other-psychological, genetics, allergies. Other-psychological, genetics, allergies.

Geriatric Pharmacology Factors that affect the rate of aging Factors that affect the rate of aging Genetics Genetics Nutrition Nutrition exercise exercise injury injury disease disease environment environment Geriatric = over 65, Geriatric = over 65, Most elderly patients will take 4 different RX’s. Most elderly patients will take 4 different RX’s. This increases the chance of adverse reactions or drug-drug interactions. This increases the chance of adverse reactions or drug-drug interactions.

Physiological Effects of Aging on Pharmacokinetic Process Loss of lean body mass Loss of lean body mass Decrease in % of body water Decrease in % of body water Increased of body fat Increased of body fat Absorption- is slowed and a delay in the onset of drug action occurs. Absorption- is slowed and a delay in the onset of drug action occurs. Distribution - drugs can become more concentrated within the system. Increased body fat can slow the excretion of fat soluble drugs. Distribution - drugs can become more concentrated within the system. Increased body fat can slow the excretion of fat soluble drugs. Metabolism-is reduced and there is an increase in the duration of drug actions Metabolism-is reduced and there is an increase in the duration of drug actions Elimination - Reduced blood flow and surface area can cause delays in excretion. Elimination - Reduced blood flow and surface area can cause delays in excretion.

Drug Compliance in the Elderly The elderly can easily become confused by their dosing regiments and can have difficulty remembering what meds are for what. The elderly can easily become confused by their dosing regiments and can have difficulty remembering what meds are for what. Polypharmacy- multiple drug prescriptions. Polypharmacy- multiple drug prescriptions. Increased side effects, Increased side effects, Forgetting to take prescribed dose Forgetting to take prescribed dose Continuing to take D/C Meds Continuing to take D/C Meds Difficult dosage form Difficult dosage form Small print on drug labels Small print on drug labels Look alike pills Look alike pills An average of six diseases coexist in older persons. An average of six diseases coexist in older persons.

Pediatric Patients Children undergo constant physiologic changes that can affect the ADME scheme of Kinetics. Children undergo constant physiologic changes that can affect the ADME scheme of Kinetics. Could cause over or under dosing, resulting in failure of therapy, adverse reactions and death. Could cause over or under dosing, resulting in failure of therapy, adverse reactions and death. Age and or weight is the least reliable guideline for dosing, Age and or weight is the least reliable guideline for dosing, BSA BSA

Lets Try it! Child weighs 13.9 kg and is 85 cm tall Child weighs 13.9 kg and is 85 cm tall What is the BSA? What is the BSA? 13.9 x 85 = 13.9 x 85 = /3600 = (hit the = before next step!) /3600 = (hit the = before next step!) √ = √ = m m2

Once More with Feeling! Child weighs 12.2 lb and is 24 inches tall Child weighs 12.2 lb and is 24 inches tall What is the BSA? What is the BSA? 12.2 x 24 = 12.2 x 24 = /3131 = (hit the = before next step!) 292.8/3131 = (hit the = before next step!) √ = √ = m m2

Discussion What can the pharmacy technician do to help patients manage their medications properly?

Teaching Patients To Manage Their Medications Patients failure to follow drug regimen is often caused by a lack of understanding or unclear information. Patients failure to follow drug regimen is often caused by a lack of understanding or unclear information. The pharmacy technician can positively affect patient compliance by providing clearly written instructions and aids. The pharmacy technician can positively affect patient compliance by providing clearly written instructions and aids. Techs are responsible for gathering and maintaining patient information such as medical history and possible allergies to prevent drug interactions and duplications. Techs are responsible for gathering and maintaining patient information such as medical history and possible allergies to prevent drug interactions and duplications. Obtain information about OTC medications. Obtain information about OTC medications.

Techs should type full, clear directions on the prescription label this includes. Techs should type full, clear directions on the prescription label this includes. Name and strength of medication ( Brand and Generic if applicable) Name and strength of medication ( Brand and Generic if applicable) Qty ( 1 tablet, 5 ml, 1 teaspoonful) Qty ( 1 tablet, 5 ml, 1 teaspoonful) Route ( po, pr) Route ( po, pr) Time ( tid, qid ) Time ( tid, qid ) Any extra information. ( dx) Unwrap etc) Any extra information. ( dx) Unwrap etc) Axillary labels Axillary labels 1 qd 1 qd Take 1 every day? Take 1 every day? Take 1 tablet orally every day. Take 1 tablet orally every day. NO!!!

Teaching Patients Medication Management