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Basic Biopharmaceutics

Presenters: Judy Riffee Arthur Wharton

Learning Objectives
Explain the differences between pharmacodynamics and pharmacokinetics. Understand the ways in which cell receptors react to drugs. Describe mechanism of action and identify and understand its key factor. Explain how drugs are absorbed, distributed, metabolized, and cleared by the body. Explain the difference between fat-soluble and water soluble drugs and give examples of each. Identify and explain the effect of bioavailability and its relationship to drug effectiveness.

Learning Objectives
Understand addiction and addictive behavior. Describe the role of the pharmacy technician in identifying drug-abusing patients. List and identify some drugs that interact with alcohol.

Pharmacodynamics and Pharmacokinetics


Pharmacodynamics is the study of the biochemical and physiologic effects of drugs and their mechanisms of action; it is the study of how drugs affect the body. Pharmacokinetics is the study of the time course of a drug and its metabolites in the body following drug administration; it is the study of how the body handles drugs, how the body changes a drug from its original form into something that the body can use, and how the body secretes and eliminates metabolized drugs.

Pharmacodynamics and Pharmacokinetics


Pharmacologic principles have Pharmaceutic and therapeutic implications: For action, a drug must be absorbed, transported to the target tissue or organ, and then it must penetrate into the cell membranes and their organelles and alter the ongoing process. The drug may be distributed to a number of tissues, bound or stored and metabolized to inactive or active products. Then, it must be excreted

Pharmacodynamics
The study of the biochemical and physiologic effects of drugs The study of the mechanisms of action of drugs The study of how drugs affect the body

Pharmacokinetics
The study of the time course of a drug and its metabolites in the body following drug administration The study of how the body handles drugs The study of how the body changes a drug from its original form into something that the body can use The study of how the body secretes and eliminates metabolized drugs The study of how the body affects drugs

Pharmacodynamics - Receptors
Most drugs affect the cells in the body by interacting with specific drug receptors. This process is likened to a lock and key. Each cell in the body has receptors (locks) that require a specific key to produce an effect. Specific drugs are developed to unlock certain receptors in the body, producing the desired effect.

Pharmacodynamics - Receptors
A- Drugs act by forming a chemical bond with specific receptor sites, similar to a key and lock. B- The better the fit, the better the response. Those with complete attachment and response are called agonists. C- Drugs that attach and do not elicit a response are called antagonists. D- Drugs that attach, elicit a response, and also block other responses are called partial agonists.

Pharmacodynamics - Receptors
Most drugs affect the body by interacting with specific drug receptors they alter the normal function of the cells in and tissues in the body correct cells are chose due to the specific affinity for a particular cell-called the receptor this process is likened to a lock and key Each cell in the body has receptors (locks) requiring a specific key to produce an effect

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Pharmacodynamics - Receptors
Specific drugs are developed to unlock certain receptors in the body, producing the desired effect The drug that has the affinity for the receptor and causes a functional change in the cell is called an agonist Not all drugs that bind to a specific cell causes a change in function in the cell and act as antagonists antagonists block a sequence of biochemical events some drugs act by affecting the enzyme functions of the body antimetabolites some drugs build up metabolites-stored and will not have an immediate effect until some time later

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Pharmacodynamics - Receptors
Receptors are located on the surfaces of cell membranes and inside cells Most receptors can be found throughout the body but some occur only in a few places The place where a drug causes an effect is called the site of action

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Pharmacodynamics - Mechanism Of Action


Mechanism of action is a term that refers to how a drug works and produces its desirable (and sometimes undesirable) effects. The key factor is the drugs ability to bind to cell receptor sites. Once a drug binds to a receptor site, it may stimulate or prevent cellular activity. Drugs that are agonists bind to receptor sites on a cell and cause some action to occur. Drugs that are antagonists bind to receptor sites on a cell and prevent other chemicals or drugs from affecting the cell.

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Pharmacodynamics - Mechanism Of Action


Refers to how a drug works and produces its desirable (and sometimes undesirable) effects Key factor is the drugs ability to bind to receptor sites Once a drug binds to a receptor site, it may stimulate or prevent cellular activity

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Pharmacodynamics - Mechanism Of Action


Types of Action when drugs interact with the site of action, they can: act through physical action, such as with the protective effects of ointments upon topical application react chemically, as with antacids that reduce excess gastric activity modify the metabolic activity of pathogens, as with antibiotics

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Pharmacodynamics - Mechanism Of Action


Types of Action change the osmolarity of blood and draw water out of tissues and into the blood incorporate into cellular material to interfere normal cell function join with other chemicals to for a complex that is more easily excreted modify biochemical or metabolic process of the body's cells or enzyme systems

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Pharmacodynamics - Mechanism Of Action


Other drug actions change the ability of ions to move into or out of cells. sodium or ion channels can open and allow movement of the ions into nerve cells, stimulating their function. potassium channels can open and allow the movement of potassium ions out of nerve cells, obstructing their function

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Pharmacodynamics - Mechanism Of Action


Other drug actions modify the creation, release, or control of nerve cell hormones that regulate physiological processes Agonistdrug binds to receptor sites and causes some action to occur Antagonistdrug binds to receptor sites and prevents other chemicals or drugs from affecting the cell

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Concentration and Effect


Dose-response curve The dose-response relationship is the relationship between the size of a dose and the intensity of the response produced one way to monitor the amount of drug in the body and its effect at the site of action a certain effect is different for every person-some people respond to low doses while others require larger doses for an equal response to be produced

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Concentration and Effect


Dose-response curve due to human variability (covered under section of this lecture called "Other Factors Affecting Drug Action even though some differences are due to the product itself, dose response curves are not ideal for relating the amount of drug in the body to its effects

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Concentration and Effect


Dose-response curve A typical dose-response curve shows that a typical response increases as the dose is increased There are 3 phases to a dose-response curve: 1. the curve us relatively flat-doses are too low to elicit a significant response 2.the curve climbs upward as bigger doses elicit a corresponding increase in response 3. the curve levels off; bigger doses are unable to elicit a further increase in response

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Concentration and Effect

Dose Response Curve


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Concentration and Effect


Potency Potency is rarely an important characteristic of a drug. the fact that morphine is more potent than meperidine for pain relief, does not mean that morphine is a superior drug. Just that morpine can be given in smaller doses. The difference between providing pain relief with morpoine versus meperidine is like the difference between purchasing a Snickers candy bar with a dime instead of two nickels; the purchasing power is identical.

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Concentration and Effect


Potency The potency of a drug implies nothing about its maximal efficacy efficacy is defined as the clinical effect that a drug can produce

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Concentration and Effect

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Concentration and Effect


Blood-Concentration-Time profiles a better way to relate the amount of a drug in the body to its effect is to determine the drug concentration in the body's fluids blood used because of its rapid equilibrium between site of action and site of administration

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Concentration and Effect


Blood-Concentration-Time profiles Practical Applications data analyzed by manufacturers of their drug products pharmacy professionals use data to visualize the consequences of incorrectly compounding a formulation or of using the wrong route of administration researchers and clinicians use the data to measure human variability in the drug product performance physicians and pharmacists use the data to monitor drug therapy regimens in patients

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Concentration and Effect


a typical blood concentration time-profile for a drug given orally would normally start at zero at the time the drug is administered (before it has been absorbed into the blood). With time, the drug leaves the formulation and enters the blood, causing concentrations to rise. To produce an effect, the concentrations must achieve a minimum effective concentration (MEC).

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Concentration and Effect


MEC is when there is enough drug at the site of action to produce a response. The time this occurs is called the onset of action. With most drugs, when blood concentrations increase, so does the intensity of effect Some drugs have an upper concentration limit beyond where there are undesired or toxic effects-Minimum toxic concentration (MTC)

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Concentration and Effect


The range between minimum effective concentration and minimum toxic concentration is called the therapeutic window. When concentrations are in this range, most patients receive the maximum benefit from their drug therapy with minimum of risk. The last part of the curve shows the blood concentrations declining as absorption is complete and elimination is proceeding. The time between the onset of action and the time when the minimum effective concentration is reached by the declining blood concentrations is called duration of action. This is the time when the drug should produce the desired effect

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Concentration and Effect


In the first part of a concentration-time curve, absorption is the primary process and concentrations rise. As absorption nears completions, metabolism and excretion become the primary processes, causing the concentrations to decline. Distribution occurs throughout. The colored lines show the parts of the profile most influenced by the various ADME processes.
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Concentration and Effect


Half-life the half-life of a drug is the time it takes for the plasma concentration to be reduced by 50% When a patient ceases using a drug, the combination of metabolism and excretion will cause the amount of the drug in the body to decline-the half-life of drug is an index of just how rapidly that decline occurs In defining half-life, a percentage-not a specific amount of a drug is lost during one half-life Expressed as t(1/2)

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Concentration and Effect


Half-life Half-life does not specify that 18mg will leave the body at a given time. Rather, it tells us that no matter how much drug is in the body, half (50%) will leave the body at a given time. The more drug is in the body, the larger the amount lost in one half-life the half-life of each drug may be different it is the most common method to explain drug actions a drug with a short half-life, such as 2-3 hours will need to be administered more often than a drug with a longer half-life, such as 8 hours half-life determines the dosing intervals

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Concentration and Effect


Half-life The time required for a drug concentration to reach steady state is determined by the drug's half-life. It takes one half-life to reach 50% 2 half-lives to reach 75% 3 half-lives to reach 87.5% 3.3 half-lives to reach 90% 4 half-lives to reach 93.75% of steady state In most clinical situations, the attainment of steady state can be assumed after 3-5 half-lives

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Concentration and Effect


Half-life The time required for a drug concentration to reach steady state is determined by the drug's half-life. It takes one half-life to reach 50% 2 half-lives to reach 75% 3 half-lives to reach 87.5% 3.3 half-lives to reach 90% 4 half-lives to reach 93.75% of steady state In most clinical situations, the attainment of steady state can be assumed after 3-5 half-lives

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Concentration and Effect


Half-life If we take Klonopin's longest half-life number, which is 50 hours, that would be 50hours x 5 = 250 hours = 10.42 days. it takes around 10 days for Klonopin to build to full strength in the blood stream and likewise it takes about that time for the drug to be eliminated. build up and elimination of all drugs can be calculated in the same way. build up and elimination happen most at the beginning and less at the end of the time frame.

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Age newborns and the elderly will show the greatest effects of drugs. They are more sensitive to medications that affect the CNS and are at risk of developing toxic drug levels. Drug dosages for these two groups must be carefully calculated and treatment starts with very small doses.

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Drug-related problems in young patients are encountered most frequently in newborn infants. They do not have a fully developed system of enzymes called cytochrome P-450 (the enzymatic factor that contributes to many drug interactions).

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action cytochrome P-450 plays a key role in the oxidative biotransformation of many drugs. grapefruit itself and grapefruit juice are known to contain certain chemicals that inhibit a form of cytochrome P-450 found in the intestines. This will increase the possibility of an overdose, even at normally prescribed levels because much of the absorbed drug by-passes the first-pass metabolism and is absorbed right into the circulatory system

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action sex men and women respond to drugs differently. Some medications pose risks for pregnant women because of the damage they can do to the developing fetus. Some drugs have side effects that may stimulate uterine contractions causing premature delivery. IM drugs stay in men's tissues longer than in women

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action body weight the same dosage has less effect in a patient who weighs more than another patient who weighs less. Pediatric medications are designed for the body weight or body surface areas of children

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action diurnal body rhythms- daytime rhythms play an important part in the effects of some drugs sedatives given in the morning will not be as effective as those administered before bedtime. On the other hand, the preferred time for corticosteroid administration is in the morning because this mimics the body's natural pattern of corticosteroid production and elimination

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Illness patients with liver or kidney disease may respond to drugs less favorably because the body is not able to detoxify and excrete chemicals properly psychological factors involves how patients feel about the drugs prescribed for them and the different ways they respond to them

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Drug Toxicity nearly all drugs are capable of producing toxic effects. The range between therapeutic and toxic doses, is measured by the therapeutic index, which is used to explain the relative safety of a drug. This range is expressed as a ratio: TI= LD50/ED50 LD50 is the lethal dose of a drug that will kill 50% of animals tested ED50 is the effective dose that produces a specific therapeutic effect in 50% of animals tested.

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Drug Interactions Defined as the effects of medications taken together. One of the following results may be seen: The drugs have no effects on the others actions The drugs increase each others effects-synergism The drugs decrease each others effects-antagonism One drug prolongs the effects of another-potentiation

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Food-Drug interactions-food may affect the rate and the extent of absorption from the GI tract. many antibiotics should be administered at least 1 hour before or two hours after each meal to achieve the appropriate levels of absorption. Dairy products contain calcium and may decrease the absorption of tetracycline and fluorquinolone derivatives by forming a complex (when molecules of different chemicals bind together-protein binding)

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Pharmacodynamics - Mechanism Of Action


Other Factors that Influence Drug Action Food-Drug Patients on MAOs (antidepressant) should avoid wine, cheese and yogurt because the potential for toxic effects exists. Broccoli, cabbage and Brussels sprouts contain vitamin K in sufficient levels to inactivate anticoagulants (warfarin)

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ADME Process (Pharmacokinetics)


Blood concentrations are the result of four simultaneously occurring processes: Absorption, Distribution, Metabolism, and Excretion. 1. Drug absorption refers to how a drug enters the body and eventually enters the bloodstream. largely dependent upon the type of drug, how designed, and the reason the type of drug was used. 2. Once a drug is absorbed, it then is distributed throughout the body by way of the circulatory system. Some of the drug binds to plasma proteins. The amount of the drug that does not bind to plasma proteins floats through the bloodstream and may interact with receptors, producing a therapeutic effect.

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ADME Process (Pharmacokinetics)


3. Once distributed, the drug is broken down or metabolized for use, typically but not always in the liver. The body metabolizes or digests drugs into usable products that cause desired effects. 4. After being metabolized and used, the drug becomes a waste product that must be cleared from the body. Ideally, drugs metabolize and are cleared at a steady rate, ensuring that the patient has a stable, consistent amount of medication in the body.

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ADME Process (Pharmacokinetics)


Drug absorption How a drug enters the body and eventually enters the bloodstream When a drug is first administered, absorption is the primary process while the other three processes have a much less amount of drug available to them, therefore having little effect. As more drug is absorbed into the blood, it is available to undergo the DME process.

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ADME Process (Pharmacokinetics)


Drug absorption The process of absorption is achieved through diffusion or active transport. The barriers to movement are largely lipid. A drug must be transported across one or more membranes to reach the blood circulation.

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ADME Process (Pharmacokinetics)


Drug absorption Diffusion the most common and important mode of transport of drugs through membranes. Defined, diffusion is the process in which particles in a fluid move from an area of higher concentration to an area of lower concentration, resulting in an even distribution of particles in the fluid. Takes place mainly through digestive system unless a drug is injected directly into the bloodstream

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ADME Process (Pharmacokinetics)


Drug absorption Weak acids and lipid-soluble drugs absorbed well through the stomach Weak bases not absorbed from stomach generally Small intestine the primary site for absorption due to large surface area for drugs to diffuse Largely dependent upon the type of the drug and reason for use Based on route of administration (oral, parenteral, etc.)

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ADME Process (Pharmacokinetics)


Drug absorption Weak acids and lipid-soluble drugs absorbed well through the stomach Weak bases not absorbed from stomach generally Small intestine the primary site for absorption due to large surface area for drugs to diffuse Largely dependent upon the type of the drug and reason for use Based on route of administration (oral, parenteral, etc.)

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ADME Process (Pharmacokinetics)


Factors influencing Absorption Physiochemical properties Acidity of the stomach Drugs with acidic pH absorbed easily from stomach Alkaline drugs absorbed more readily from small intestine Presence of food in stomach Food decreases absorption rate May be used as a buffer for irritating drugs Routes of Administration

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ADME Process (Pharmacokinetics)


Drug distribution Once absorbed, drug is distributed throughout the body by circulatory system Molecules leave the bloodstream and enter the tissues of the body Travels through blood, lymphatics and other fluids to site of action

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ADME Process (Pharmacokinetics)


Some of the drug binds to plasma proteins Particularly albumin (principle protein of plasma in terms of drug binding Drugs bound to albumin are inactive drugs Protein-bound drugs cannot be filtered by the kidneypharmacologically inert These large complexes prevents bound drug from entering sites of action, metabolism, and excretion-only unbound drugs can move through tissue membranes and cellular openings

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ADME Process (Pharmacokinetics)


Some of the drug floats through the bloodstream Initial rate of distribution of a drug is heavily dependent on the blood flow to various organs Organs with high blood flow rates are the heart, liver and kidneys Distribution to muscle, fat and skin is usually slower due to lower blood flow Floating drug may interact with receptors, producing therapeutic effects

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ADME Process (Pharmacokinetics)


Drug metabolization Once distributed, drug is broken down or metabolized for use Most drugs are acted upon by enzymes in their body and are converted to metabolic derivatives during metabolism Metabolites are the reaction products that are produced by the action of enzymes Majority of metabolites are inactive and toxic and are excreted

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ADME Process (Pharmacokinetics)


Drug metabolization Typically but not always metabolized in the liver The body metabolizes or digests drugs into usable products that cause desired effects Metabolism influences drug action, such as duration of effects, drug interactions, drug activation, and drug toxicity or side effects

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ADME Process (Pharmacokinetics)


Drug metabolization In response to chronic administrations of certain drugs, the liver will increase its enzyme production Called enzyme induction and results in greater metabolism of a drug requiring larger doses to produce a therapeutic effect Some drugs decrease or may delay enzymatic activity and is called enzyme inhibition and smaller doses of a drug would be needed to avoid toxic effects of drug accumulation

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ADME Process (Pharmacokinetics)


Drug metabolization The liver may secrete drugs or their metabolites into bile that is stored in the gall bladder Gall bladder empties bile into intestine in response to food and drugs or metabolites may be reabsorbed or eliminated with the feces. Enterohepatic cycling is the reabsorption of drugs or metabolites back into the blood circulation

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ADME Process (Pharmacokinetics)


Drug excretion After being metabolized and used, drug becomes a waste product Most drugs and their metabolites are excreted in the urine by the kidneys Some orals are not easily absorbed from the GI tract and as a result are significantly excreted in the feces Excretion can also occur through the bile (if no enterohepatic cycling occurs) Certain drugs are removed through the lungs

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ADME Process (Pharmacokinetics)


Drug excretion The kidneys filter the blood and remove waste materials (including drugs and their metabolites) Some of the plasma water from the blood flowing through the kidneys are filtered into the nephron ( kidneys functional unit) This process is called glomerular filtration Urinary excretion is much faster than fecal excretion Ideally, drugs metabolize and are cleared at a steady rate Steady metabolism and excretion ensure that the patient has a consistent amount of medication in the body

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ADME Process (Pharmacokinetics)


Factors Affecting Urinary Excretion If the kidneys functions become impaired- must decrease drug dosage or dosing interval lengthened Some drugs affect the excretion of others- dosage of affected drug must be decreased or interval lengthened to avoid accumulation pH of urine can affect reabsorption of some drugs

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Fat and Water Soluble Drugs


Solubility is the ability of a material to dissolve in a given medium. Water-soluble drugs dissolve in the presence of water fat (lipid) soluble drugs dissolve in the presence of fats Drug solubility affects the ability of the body to absorb the medication Fat-soluble drugs are very quickly absorbed into the body Water-soluble drugs are usually only partially soluble, preventing the product from being absorbed too rapidly.

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Bioavailability
The amount of drug that is available for use Determined by the bodys ability to absorb the drug Several factors influence absorption: Solubility of the medication How the drug is manufactured Presence of different buffers Salt forms vs. nonsalt forms Rate and volume of distribution Clearance from the body

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Addictions
The communication between a pharmacy technician and a patient may determine the treatment outcome. If a patient comprehends why it's important to take medication in the exact manner prescribed, they are more likely to comply. Many times patients who have not been properly communicated to will alter dose or duration of the medication based on how they feel if they are not fully aware of the reactions behind the specific directions. A pharmacy technician who understands their role in communication and treatment, will also understand the crucial role they play in patient care and will maintain knowledge through education.

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Addictions
Addiction Defined as both a psychological and a physiological dependency Specific withdrawal symptoms must present following abrupt change in use Some signs of addictive behavior include: Absorbing focus on the substance Increased tolerance Painful withdrawal

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The Role of the Pharmacy Technician in Addictions


Although it is not within the pharmacy technicians jurisdiction to undertake prescription counseling, it is the pharmacy technicians responsibility to bring possible drug abuse situations to the attention of the pharmacist. Identifying drug-abusing patients Always bring possible drug abuse situations to the attention of the pharmacist!

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