Chapter 2: Pharmacokinetics & Pharmacodynamics PDF

PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS PHARMACOLOGY Ex. Aluminum (Antacid), Flouride (dental cavities), Iron...

PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS PHARMACOLOGY Ex. Aluminum (Antacid), Flouride (dental cavities), Iron Is the study of the biological effects of chemicals. (Anemia) DRUGS AND MEDICINES 4. SYNTHETIC SOURCES Drug/s Drugs that are developed synthetically. o Comes from the Dutch word “droog”, which means dry. Altered chemical with proven therapeutic effectiveness to make o Are chemicals that are introduced into the body to cause it better (more potent, more stable, less toxic). some sort of change. The first Synthetic Drug is Chloral hydrate, as a sedative Medicines hypnotic medication (induced sleep) and is still available today. o Are those drugs used in the prevention or treatment of THREE PHASES OF A TABLET OR CAPSULE diseases. A tablet or capsule taken by mouth goes through three phases: 1. Pharmaceutic 2. Pharmacokinetic 3. Pharmacodynamic 1. PHARMACEUTIC PHASE In the Pharmaceutic phase, the drug becomes a solution so that it can cross the biologic membrane. When the drug is administered parenteraly by subcutaneous (subQ), intramuscular (IM), or intravenous (IV) routes, there is no pharmaceutic phase. In the GI tract, drugs need to be in solution so they can be absorbed, a process known as dissolution. Excipients are fillers and inert substances used in drug preparation to allow the drug to take on a particular size and shape and to enhance drug dissolution. Some additives in drugs, such as the ions potassium and sodium in penicillin potassium or penicillin sodium, increase the absorbability of the drug. Drugs in liquid form are more rapidly available for GI absorption than are solids. Generally, drugs are both disintegrated and absorbed faster in acidic fluids with a pH of 1 or 2 rather than in alkaline fluids. Both the very young and older adults have less gastric acidity; therefore, drug absorption is generally slower for those drugs absorbed primarily in the stomach. o Stomach pH is 1.5 to 3.5 and the fluid of is 20 – 100 ml. CLINICAL PHARMACOLOGY Fillers are inactive substance used to make the active The branch of pharmacology that uses drugs to treat, prevent, medicine easier to measure. Usually use in tablets and and diagnose disease. capsules. 2 Key Concerns: PHARMACOKINETICS 1. The drug’s effects on the body (Pharmacodynamics) 2. The body’s response to the drug (Pharmacokinetics) 2. PHARMACOKINETIC PHASE THERAPEUTIC REGIMEN Once a drug is administered, it goes through two phases, the pharmacokinetic phase and the pharmacodynamic phase. Refers to all methods to be used for treatment of disease. In addition to drug therapy, this may include plans for special The pharmacokinetic phase, or what the body does to the diets; use of hot packs, whirlpools, counselling, psychotherapy. drug, describes the movement of the drug through the body. It is composed of four processes: SOURCES OF DRUGS 1. Absorption 1. PLANTS 2. Distribution Plants are an important source of chemicals that are developed 3. Metabolism (biotransformation) into drugs. 4. Excretion (elimination) Ex. Quinidine (for malaria) 3. PHARMACODYNAMIC PHASE 2. ANIMAL PRODUCTS Once a drug is administered, it goes through two phases, the Are used to replace human chemicals that are not produced pharmacokinetic phase and the pharmacodynamic phase. because of disease or genetic problems. The pharmacodynamic phase, or what the drug does to the Ex. Insulin (from the pancreas of cows and pigs) body, involves receptor binding, postreceptor effects, and 3. INORGANIC COMPOUNDS chemical reactions. Salts of various elements can have therapeutic effects in the A biologic or physiologic response results from the human body. pharmacodynamic phase.  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS After absorption of oral drugs from the GI tract, they pass from the intestinal lumen to the liver via the portal vein. o In the liver, some drugs are metabolized to an inactive form and are excreted, thus reducing the amount of active drug available to exert a pharmacologic effect. This is referred to as first-pass metabolism. o Lidocaine and some nitroglycerins, for example, are not given orally because they have extensive first-pass metabolism, and most of the drug is inactivated. o Drugs that are delivered by other routes (IM, IV, SQ, nasal, sublingual, buccal) do not enter the portal circulation and are not subjected to first-pass metabolism. Bioavailability refers to the percentage of administered drug available for activity. o For orally administered drugs, bioavailability is affected by absorption and first-pass metabolism. o The bioavailabilty of oral drugs is always less than 100% DRUG ABSORPTION and varies based on the rate of first-pass metabolism. Drug absorption is the movement of the drug into the o The bioavailability of intravenous (IV) drugs is 100%. bloodstream after administration. o Factors that alter bioavailability include the (1) drug form; Approximately 80% of drugs are taken by mouth (enteral). (2) route of administration; (3) gastric mucosa and For the body to use drugs taken by mouth, a drug in solid form motility; (4) administration with food and other drugs; (tablet or capsule) must disintegrate into small particles and and (5) changes in liver metabolism caused by liver combine with a liquid to form a solution, a process known as dysfunction or inadequate hepatic blood flow. dissolution (drugs in liquid form are already in solution), to be o A decrease in liver function or a decrease in hepatic blood absorbed from the GI tract into the bloodstream. flow can increase the bioavailability of a drug, but only if o Unlike drugs taken by mouth, eyedrops, eardrops, nasal the drug is metabolized by the liver. sprays, respiratory inhalants, transdermal drugs, DRUG DISTRIBUTION sublingual drugs, and parenteral drugs do not pass Distribution is the movement of the drug from the circulation through the GI tract. to body tissues. Tablets are not 100% drug. Fillers and inert substances – such Drug distribution is influenced by vascular permeability and as simple syrup, vegetable gums, aromatic powder, honey, and permeability of cell membranes, regional blood flow and pH, various elixirs – called excipients are used in drug preparation cardiac output, tissue perfusion, the ability of the drug to bind to allow the drug to take on a particular size and shape and to tissue and plasma proteins, and the drugs lipid solubility. enhance drug dissolution. Drugs are easily distributed in highly perfused organs such as Disintegration is the breakdown of an oral drug into smaller muscle, fat, and peripheral organs, result in decreased drug particles. distribution. The rate of dissolution is the time it takes the drug to disintegrate and dissolve to become available for the body to absorb it. Drugs in liquid form are more rapidly available for GI absorption than are solids. Enteric-coated (EC) drugs resist disintegration in the gastric acid of the stomach, so disintegration does not occur until the drug reaches the alkaline environment of the small intestine. o EC tablets can remain in the stomach for a long time; therefore their effect may be delayed in onset. o EC tablets or capsules and sustained-release (beaded) capsules should not be crushed because crushing alters the place and time of absorption of the drug. o AFFINITY can be defined as the extent or fraction to which Aspirin works in stopping the production of certain natural a drug binds to receptors at any given drug concentration substances that cause fever, pain, swelling and blood clots. or the firmness with which the drug binds to the receptor. o BISACODYL (Dulcolax) is an example here in the o EFFICACY describes the maximum response that can be Philippines. achieved with a drug. Drugs given rectally are absorbed slower than drugs Protein Binding administered by the oral route. o As drugs are distributed in the plasma, many bind with o Absorption is slower because the surface in the rectum is plasma proteins (albumin, lipoproteins, and alpha-1-acid- smaller than the stomach, and it has no villi. glycoprotein (AGP). o Additionally, the composition of the suppository base o Acidic drugs (such as aspirin and methotrexate) and affects drug absorption. neutral drugs (such as nortriptyline) bind with albumin or  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS lipoproteins; however, basic drugs (morphine, DRUG METABOLISM amantadine) bind to AGP. Metabolism, or biotransformation, is the process by which the o Drugs that are more than 90% bound to protein are body chemically changes drugs into a form that can be known as highly protein-bound drugs (warfarin, excreted. furosemide, and diazepam); drugs that are less than 10% The liver is the primary site of metabolism. bound to protein are weakly protein-bound drugs Liver enzymes – collectively referred to as the cytochrome (gentamicin, metformin, metoprolol, and lisinopril). P450 system, or the P450 system, of drug metabolizing o The portion of the drug bound to protein is inactive enzymes – convert drugs to metabolites. because it is not available to interact with tissue receptors A large percentage of drugs are lipid soluble, thus the liver and therefore is unable to exert a pharmacologic effect. metabolizes the lipid-soluble drug substance to a water-soluble o The portion that remains unbound is free, active drug. substance for renal excretion. Free drugs are able to exit blood vessels and reach their Liver diseases such as cirrhosis and hepatitis alter drug site of action, causing a pharmacologic response. metabolism by inhibiting the drug-metabolizing enzymes in the o When two highly protein-bound drugs are administered liver. together, they compete for protein-binding sites, leading When the drug metabolism rate is decreased, excess drug to an increase in free drug being released into the accumulation can occur and can lead to toxicity. circulation. Prodrugs - If warfarin (99% protein bound) and furosemide (95% o A prodrug is a compound that is metabolized into an active protein bound) were administered together, warfarin pharmacologic substance. – the more highly bound drug – could displace o Prodrugs are often designed to improve drug furosemide from its binding site. bioavailability; instead of administering a drug directly, a - In this situation, it is possible for drug accumulation to corresponding prodrug might be used instead to improve occur and for toxicity to result. pharmacokinetics (absorption, distribution, metabolism, or o Another factor that may alter protein binding is low excretion), decrease toxicity, or target a specific site of plasma protein levels (patients with liver or kidney action. disease), which potentially decrease the number of o An example of prodrug is codeine. available binding sites and can lead to an increase in the o Codeine itself has very little intrinsic activity in amount of free drug available, resulting in drug endogenous opioid receptors. However, drug-metabolizing accumulation and toxicity. enzymes in the liver convert codeine into morphine. o Blood vessels in the brain have a special endothelial lining Morphine, in turn, exhibits greater affinity for opioid where the cells are pressed tightly together (tight receptors. junctions); this lining is referred to as the blood-brain o The drug half-life (t ½) is the time it takes for the amount barrier (BBB). of drug in the body to be reduced by half. o The BBB protects the brain from foreign substances, which o The amount of drug administered, the amount of drug includes about 98% of the drugs on the market. remaining in the body from previous doses, metabolism, o Some drugs that are highly lipid soluble and of low and elimination affect the half-life of a drug. molecular weight (benzodiazepines) are able to cross the o With liver or kidney dysfunction, the half-life of the drug is BBB through diffusion, and others cross via transport prolonged, and less drug is metabolized and eliminated. proteins. o A drug goes through several half-lives before complete o Water-soluble drugs (atenolol and penicillin) and drugs elimination occurs, and drug half-life is used to determine that are not bound to transport proteins (free drugs) are dosing interval. not able to cross the BBB, which makes it difficult for these - Ibuprofen has a half-life of about 2 hours. If a person drugs to reach the brain. takes 200 mg, in 2 hours, 50% of the drug will be o During pregnancy, drugs can cross the placenta much as gone, leaving 100 mg. two hours later, another 50% of they do across other membranes, and this affects both the the drug will be gone, this time leaving 50 mg; in fetus and the mother. another 2 hours, 50% more will be gone, so only 25 o Drugs taken during the first trimester can lead to mg will remain. This process continues such that 10 spontaneous abortion, teratogenesis, or other subtler hours after 200 mg of ibuprofen has been taken, if no defects. additional doses are administered, 6.25 mg of the o During the third trimester, drugs may alter fetal growth drug remains. and development. o By knowing the half-life, the time it takes for a drug to o The risk-benefit ratio should be considered before any reach a steady state (plateau drug level) can be drugs are given during pregnancy. determined. o During breastfeeding, drugs can pass into breastmilk, o A steady state occurs when the amount of drug being which can affect the nursing infant. administered is the same as the amount of drug being o Nurses must teach women who breastfeed to consult their eliminated; a steady state of drug concentration is health care provider before taking any drug – whether OTC necessary to achieve optimal therapeutic benefit. This or prescribed – or any herb or supplement. takes about 4 half-lives, if the size of all doses is the same. - For example, digoxin – which has a half-life of 36 hours with normal renal function – takes approximately 6 days to reach a steady state concentration.  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS Loading Dose the patient drives a car, but at bedtime it could be desirable o However, in the case of drugs with long half-lives, it may because it causes mild sedation. not be acceptable to wait for a steady state to be achieved. DOSE-RESPONSE RELATIONSHIP - Take for example, the case of a person with seizures The dose-response relationship is the body’s physiologic receiving phenytoin. The half-life of phenytoin is response to changes in drug concentration at the site of action. approximately 22 hours; if all doses of the drug were Two concepts further describe this relationship: the same, steady state would not be achieved for o Potency refers to the amount of drug needed to elicit a about 3½ days. By giving a large initial dose, known specific physiologic response to a drug. A drug with high as a loading dose, that is significantly higher than potency, such as fentanyl, produces significant therapeutic maintenance dosing, therapeutic effects can be responses at low concentrations; a drug with low potency, obtained while a steady state is reached. After the such as codeine, produces minimal therapeutic responses loading dose, maintenance dosing is begun; this is the at low concentrations. dose needed to maintain drug concentration at o Then point at which increasing a drug’s dosage no longer steady state when given repeatedly at a consistent increases the desired therapeutic responses is referred to dose and constant dosing interval. as maximal efficacy. DRUG EXCRETION Closely related to dose-response and efficacy is the therapeutic The main route of drug excretion, elimination of drugs from index (TI), which describes the relationship between the the body, is through the kidneys. therapeutic dose of a drug (ED50) and the toxic dose of a drug Drugs are also excreted through bile, the lungs, saliva, sweat, (TD50). and breast milk. o ED50 is the dose of a drug that produces a therapeutic The kidneys filter free drugs, water-soluble drugs, and drugs response in 50% of the population; TD50 is the dose of a that are unchanged. drug that produces a toxic response in 50% of the The lungs eliminate volatile drug substances, and products population. metabolize carbon dioxide (CO2) and water (H2O). o The therapeutic index is the difference between these two The urine pH influences drug excretion. Normal urine pH varies points. from 4.6 to 8.0. Acidic urine promotes elimination of weak base o If the ED50 and TD50 are close, the drug is said to have a drugs, and alkaline urine promotes elimination of weak acid narrow therapeutic index. drugs. o Drugs with a narrow TI – such as warfarin, digoxin, and Prerenal, intrarenal, and postrenal conditions affect drug phenytoin – require close monitoring to ensure patient excretion. safety. o Prerenal conditions, such as dehydration, or hemorrhage, o To be safe, plasma drug levels of drugs with a narrow reduce blood flow to the kidney and result in decreased therapeutic index must fall within the therapeutic range glomerular filtration. (also known as the therapeutic window). o Intrarenal conditions, such as glomerulonephritis and o The therapeutic range is a range of doses that produce a chronic kidney disease (CKD), affect glomerular filtration therapeutic response without causing significant adverse and tubular secretion and reabsorption. effects in patients. o Postrenal conditions that obstruct urine flow – such as ONSET, PEAK, AND DURATION OF ACTION prostatic hypertrophy, stones, and neurogenic bladder – Onset is the time it takes for a drug to reach the minimum adversely affect glomerular filtration. effective concentration (MEC) after administration. o With any of these situations, drug accumulation may The MEC is the minimum amount of drug required for drug occur, resulting in adverse drug reactions. effect. o Common tests used to determine renal function include A drug’s peak occurs when it reaches its highest concentration creatinine and blood urea nitrogen (BUN). in the blood. - Creatinine is a metabolic by-product of muscle Duration of action is the length of time the drug exerts a excreted by the kidneys. therapeutic effect. - Urea nitrogen is the metabolic breakdown product of Some drugs produce effects in minutes, but others may take protein metabolism. hours or days. PHARMACODYNAMICS If the drug plasma concentration decreases below the MEC, Pharmacodynamics is the study of the effects of drugs on the adequate drug dosing is not achieved; too high of a drug body. concentration can result in toxicity. o Drugs act within the body to mimic the actions of the THERAPEUTIC DRUG MONITORING body’s own chemical messengers. Once a steady state has been achieved, drug concentration can o Drug response can cause a primary or secondary be determined by measuring peak and trough drug levels. physiologic effect or both. o Peak and trough levels are requested for drugs that have a A drug’s primary effect is the desirable response, and the narrow therapeutic index and are considered toxic. secondary effect may be desirable or undesirable. Peak drug level is the highest plasma concentration of drug at An example of a drug with a primary and secondary effect is a specific time, and it indicates the rate of drug absorption. If diphenhydramine, an antihistamine. The primary effect of the peak is too low, effective concentration has not been diphenhydramine is to treat the symptoms of allergy; the reached. secondary effect is a central nervous system depression that causes drowsiness. The secondary effect is undesirable when  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS If the drug is given orally, the peak time is usually 2 to 3 hours after drug administration. If the drug is given IV, the peak time is usually 30 to 60 minutes after the infusion is complete. If the drug is given IM, the peak time is usually 2 to 4 hours after an injection. Trough drug level is the lowest plasma concentration of a drug, and it measures the rate at which the drug is eliminated. RECEPTOR THEORY Drugs act by binding to receptors. Binding of the drug may activate a receptor, producing a response, or it may inactivate a receptor, blocking a response. The activity of many drugs is determined by the ability of the drug to bind to a specific receptor. The better the drug fits at the receptor site, the more active the drug is. Most receptors, which are protein nature, are found on cell surface membrane or within the cell itself. Drug-receptor interactions are similar to the fit of the right key in a lock. MECHANISMS OF DRUG ACTION Mechanisms of drug action include (1) stimulation, (2) depression, (3) irritation, (4) replacement, (5) cytotoxic action, (6) antimicrobial action, and (7) modification of immune AGONISTS, PARTIAL AGONISTS, AND ANTAGONISTS status. Drugs that activate and produce a desired response are called o A drug that stimulates enhances intrinsic activity agonists. (adrenergic drugs that increase HR, sweating, and RR Partial agonists are drugs that elicit only moderate activity during fight-or-flight response). when binding to receptors; partial agonists also prevent o Depressant drugs decrease neural activity and bodily receptor activation by other drugs. functions (barbiturates and opiates) Drugs that prevent receptor activation and block a response are o Drugs that irritate have a noxious effect, such as called antagonists. Blocking receptor activation either astringents. increases or decreases cellular action, depending on the o Replacement drugs such as insulin, thyroid drugs and endogenous action of the chemical messenger that is blocked. hormones replace essential body compounds. Nonspecific and Nonselective Drug Effects o Cytotoxic drugs selectively kill invading parasites or o Many agonists and antagonists lack specific and selective cancers. effects. Receptors produce a variety of physiologic o Antimicrobial drugs prevent, inhibit, or kill infectious responses, depending on where the receptor is located. organisms. o Cholinergic receptors are located in the bladder, heart, o Drugs that modify the immune status modify, enhance, or blood vessels, stomach, bronchi, and eyes. depress the immune system. o Drugs that affect multiple receptor sites are considered SIDE EFFECTS, ADVERSE DRUG REACTIONS, AND DRUG TOXICITY nonspecific. Side effects are occur(?) that can be effects of drug therapy. - Betanechol may be prescribed for postoperative urinary retention to increase bladder contraction. All drugs have side effects. Even with correct dosage, side However, because betanechol is nonspecific, other effects occur that can be predictable and range from cholinergic sits are also affected; the HR decreases, BP inconvenient to severe or life theratening. decreases, gastric acid secretion increases, the Adverse drug reactions (ADRs) are unintentional, unexpected bronchioles constrict, and the pupils constrict. reactions to drug therapy that occur at normal drug dosages. o Some drugs affect multiple receptors, and these are The reactions may be mild to severe and include anaphylaxis considered nonselective drugs. (cardiovascular collapse). - Epinepherine affects multiple body systems.  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS o ADRs are always undesirable and must be reported and o Alteration of bacteria normally found in the GI tract can documented because they represent variances from affect drug pharmacokinetics. planned therapy. Metabolism Drug toxicity occurs when drug levels exceed the therapeutic o A drug can increase the metabolism of another drug by range; toxicity may occur secondary to overdose (intentional or stimulating liver enzymes. unintentional) or drug accumulation. o Increased metabolism promotes drug elimination and o Factors that influence drug toxicity include disease, decreases plasma concentration of the drug; the result is a genetics, and age. decrease in therapeutic drug action. TOLERANCE AND TACHYPHYLAXIS o The use of tobacco and alcohol may have variable effects Tolerance refers to a decreased responsiveness to a drug over on drug metabolism. Chronic cigarette smoking leads to an the course of therapy; an individual with drug tolerance increase in hepatic enzyme activity and can increase requires a higher dosage of drug to achieve the same theophylline clearance. Asthmatics who smoke and take therapeutic response. theophylline to manage their disease may require an Tachyphylaxis refers to an acute, rapid decrease in response to increase in theophylline dosage. a drug; it may occur after the first dose or after several doses. o Natural or herbal products can also affect drug metabolism. Flavanoids, a group of naturally occurring PLACEBO EFFECT compounds found in the juice and pulp of citrus fruits, are Placebo effect is a drug response not attributed to the chemical potent inhibitors of the metabolism of certain drugs properties of the drug. (carbamazepine, calcium channel blockers, and drugs for The response can be positive or negative and may be erectile dysfunction). influenced by the beliefs, attitudes, and expectations of the Excretion patient. o Drugs can increase or decrease renal excretion and can Although the placebo effect is psychological in origin, the have an effect on the excretion of other drugs. response can be physiologic, resulting in changes in HR, BP, and o Drugs that decrease cardiac output decrease blood flow pain sensation. to the kidneys; decreased blood flow results in decreased DRUG INTERACTIONS GFR, which can decrease or delay drug excretion. Drug-drug, drug-nutrient, drug-disease, and drug-laboratory o Diuretics promote water and sodium excretion from the interactions are an increasing problem. renal tubules. The renal loss of potassium can result in Patients at high risk for interactions include those who have hypokalemia, which can alter the action of some drugs; for chronic health conditions, take multiple medications, see example, it can enhance the action of digoxin and can lead more than one health care provider, and use multiple to toxicity. pharmacies. o With decreased renal or hepatic function, there is usually Older adults are at especially high risk for drug interactions an increase in free drug concentration. It is essential to because 20% of older adults take five or more medications. closely monitor these patients for drug toxicity when they A drug interaction is defined as an altered or modified action or take multiple drugs. effect of a drug as a result of interaction with one or multiple PHARMACODYNAMIC INTERACTIONS drugs. Additive Drug Effects Drug interactions can be divided into two categories: o When two drugs are administered in combination, and pharmacokinetic and pharmacodynamic interactions. the response is increased beyond what either could PHARMACOKINETIC INTERACTIONS produce alone, the drug interaction is called an additive Pharmacokinetic interactions are changes that occur in the effect. absorption, distribution, metabolism, and excretion of one or o Additive effects can be desirable or undesirable. more drugs. o Diuretic and a beta blocker for the treatment of Absorption hypertension have a more pronounced BP lowering effect. o When a person takes two drugs at the same time, the rate o Hydralazine for hypertension and nitroglycerin for angina of absorption of one or both drugs can change. A drug can could result in a severe hypotensive response. block, decrease, or increase the absorption of another Synergistic Drug Effects and Potentiation drug. It can do this in one of three ways: (1) by increasing o When two or more drugs are given together, one drug can or decreasing gastric emptying time, (2) by changing the have a synergistic effect on another. gastric pH, or (3) by forming drug complexes. o An example of this is the use of two cytotoxic drugs to o Drugs that increase the speed of gastric emptying, such as reduce individual drug dosing, thereby decreasing side laxatives, may cause an increase in gastric and intestinal effects. motility and a decrease in drug absorption. o An example of an undesirable effect occurs when alcohol o Opioids and anticholinergic drugs such as atropine and a sedative-hypnotic drug such as diazepam are decrease gastric emptying time and GI motility, causing an combined. The resultant effect is increased CNS increase in absorption rate. depression. o GI bacteria account for 70% of the body’s microbes. They Antagonistic Drug Effects play a major role in the absorption of drugs and nutrients o When drugs with antagonistic effects are administered and in the metabolism of bilirubin, bile acids, cholesterol, together, one drug reduces or blocks the effect of the and steroid hormones as well as the synthesis of vitamins other. B and K.  PHARMACOLOGY | NCM 106 CHAPTER 2: PHARMACOKINETICS & PHARMACODYNAMICS o In some situations, antagonistic effects are desirable. o In morphine sulfate overdose, naloxone is given as an antagonist to block the narcotic effects of morphine sulfate. o Likewise, in the case of heparin overdose, protamine sulfate is administered to block the effects of heparin. DRUG-NUTRIENT INTERACTIONS Food may increase, decrease, or delay the body’s pharmacokinetic response to drugs. A classic drug-food interaction occurs when a monoamine oxidase inhibitor (MAOI) antidepressant (phenelzine) is taken with tyramine-rich foods such as cheese, wine, organ meats, beer, yogurt, Vour cream, or bananas. o Tyramine is a potent vasoconstrictor, and when taken in conjunction with a MAOI, the result could be a hypertensive crisis. Nutritional deficiencies such as protein-energy malnutrition (PEM) like kwashiorkor and marasmus may alter pharmacokinetic processes and drug responses, resulting in toxicity. Persons with either form of PEM may have decreased drug absorption and decreased protein binding, altered volume of distribution and biotransformation, and decreased drug elimination. DRUG-LABORATORY INTERACTIONS Drugs often interfere with clinical laboratory testing by cross- reaction with antibodies, interference with enzyme reactions, or alteration of chemical reactions. Drug-laboratory interactions may lead to misinterpretation or invalidation of test results, resulting in additional health care costs associated with unnecessary repeat laboratory testing or additional testing. Drug-laboratory interactions may also lead to missed or erroneous clinical diagnosis. DRUG-INDUCED PHOTOSENSITIVITY A drug-induced photosensitivity reaction is a skin reaction caused by exposure to sunlight. It is caused most often by the interaction of a drug and exposure to ultraviolet A (UVA) light, which can cause cellular damage; however, ultraviolet B (UVB) light may also contribute to drug-induced photosensitivity reactions. The two types of photosensitivity reactions are photoallergic and phototoxic. A photoallergic reaction occurs when a drug (sulfonamide) undergoes activation in the skin by UV light to a compound that is more allergenic than the parent compound. Because it takes time to develop antibodies, photoallergic reactions are a type of delayed hypersensitivity reaction. With a phototoxic reaction, a photosensitive drug undergoes photochemical reactions within the skin to cause damage. o This type of reaction is not immune mediated. The onset of a phototoxic reaction with erythema can be rapid, occurring within 2 to 6 hours of sunlight exposure. Most photosensitive reactions can be avoided by using sunscreen with a sun protection factor (SPF) greater than 15; avoiding excessive sunlight, especially at the height of daylight hours; and wearing protective clothing. Decreasing the drug dose may decrease the risk of photosensitivity if treatment is required.