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Chapter 12: Pharm
Chapter 12: Human Variability
| Question | Answer |
|---|---|
| What can human variability do? | Significantly alter blood concentration-time profiles and affect drug efficacy. |
| What are the variables that influence the differences in disposition and response to medications? | Differences in age, weight, genetics, and gender are the variables. |
| What are the six stages of human life? | Neonate, infant, child, adolescent, adult, and elder. |
| Neonate | up to 1 month after birth |
| Infant | Between the ages of 2 and 12 years |
| Adolescent | Between the ages of 13 and 19 years |
| Adult | Between 20 and 70 years |
| Elder | Older than 70 years |
| Adults experience a decrease in many physiological functions between what ages? | 30 to 70 |
| What does the drug distribution, metabolism, and excretion look like in neonate and infants? | Different functions than adults because their organ systems have not been fully developed, so not able to metabolize or eliminate drugs as efficiently as adults. |
| Children metabolize drugs faster than adults, what age does the rate of metabolism increase? | Between 1 and 12 (depending on the child and the drug) |
| What are four drugs that become eliminated faster in children? | Clindamycin, valproic acid, ethosuximide, and theophylline. |
| Which age group consumes more drugs? | The Elderly |
| What are some physiological changes that elderly go through that significantly affect drug interactions? | Changes in gastric emptying, increased gastric pH, intestinal motility, GI blood flow slows the rate of absorption, decreased cardiac output = slow distribution of drug, metabolism, and excretion. Also decreased kidney functions. |
| What was one reason to exclude women from clinical drug investigations? | To avoid exposing a fetus or potential fetus to unknown risks. |
| What are some differences shown in male or women with drug investigations? | Shows differences in drug disposition, drug response appears to be related to hormonal fluctuations in women during their menstrual cycle, and differences in body composition (men more muscle, women more fat). |
| What are some physiological changes that can occur in women that are preganat? | Delayed gastric emptying and decreased gastrointestinal tract motility. These changes tend to reduce the rate of absorption. |
| True or false: Drug plasma protein binding may be reduced and metabolism increased in pregnant women for a number of drugs. | True |
| True or false: Drug concentrations may be greater in mother than the fetus. | False. The drug concentration tends to be more in the fetus than the mother due to the fetus having underdeveloped mechanisms to handle drug exposure. |
| What is pharmacogenomics? | A field of study that defines the hereditary basis of individual differences in absorption, distribution, metabolism, and excretion (ADME processes). |
| What is the largest contributing factor to inherited variability? | Metabolism |
| Dosage adjustments based on weight is considered on what types of patients? | Infants, children, or unusually small or obese patients. |
| What does adverse drug reaction (ADR) mean? | An unintended side effect of a medication that is negative or in some way injurious to a patient's health. |
| What are some situations called "side effects"? | Some ADRs can occur with a usual dose drug which is a side effect situation. |
| What is anaphylactic shock? | A potentially fatal hypersensitivity reaction producing severe respiratory distress and cardiovascular collapse. Only last within minutes. |
| What are some immediate drugs required for anaphylactic shock? | Epinephrine, antihistamines, or bronchodilator drugs is required. |
| What does idiosyncrasy mean? | An unexpected reaction the first time a drug is taken, generally due to genetic cause that alters a patient's drug metabolizing enzymes. |
| What is carcinogenicity? | The ability of a substance to cause cancer. |
| What is teratogenicity? | This is the ability of a substance to cause abnormal fetal development when given to pregnant women. |
| What are some drug groups that are considered teratogenic? | Analgesics, diuretics, antihistamines, antibiotics, and antiemetics. |
| What is hepatotoxicities? | (Liver toxicity) Include hepatitis, hepatic necrosis, and biliary tract inflammation or obstruction. |
| What are some commonly used hepatotoxic drugs? | Acetaminophen, methotrexate, phenytoin, and aspirin. |
| What are some ways renal toxicity could occur? | With gentamicin and other aminoglycosides, with ibuprofen and other nonsteroidal anti-inflammatory drugs, and with many other drugs like celecoxib, omeprazole, and acyclovir. |
| What are some life threatening hematological effects that could be caused by drugs? | Blood coagulation, bleeding, and bone marrow disorders. |
| What class of drugs can cause excessive bleeding? | Anticoagulants |
| What can be given to reduce severe bleeding? | Vitamin K (phytonadione) |
| What are the most common gastrointestinal effects to drugs? | Anorexia, nausea, vomiting, constipation, pain, heartburn, and diarrhea. |
| What can aspirin or potassium chlorides cause? | Esophageal ulcer |
| What can NSAIDs, theophylline cause? | Esophageal reflux |
| What can NSAIDs cause? | Gastritis |
| What can aluminum containing antacids cause? | Constipation |
| What can clindamycin, amoxicillin cause? | Diarrhea |
| CNS effects may result from what? | CNS Stimulation (confusion, agitation, delirium) and CNS depression (drowsiness, dizziness, sedation). |
| What does it mean when someone has a physiological dependence on a drug? | Accompanied by unpleasant physical symptoms when the drug is discontinued or the dose is reduced. |
| What does it mean when someone has a psychological dependence on a drug? | Involves getting an emotional or mental fixation on drug usage. |
| What drugs could cause a physiological or psychological dependence when used chronically? | Chronic usage of narcotic analgesics, sedative hypnotic agents, antianxiety agents, and amphetamines. |
| What does tolerance to a drug mean? | When the body becomes overly adapted to the drug and fails to respond to the drug at the cellular level. |
| What is drug resistance? | The reduction in effectiveness of an antimicrobial, anthelmintic, or antineoplastic drug. Need to change medication because increasing the dose will not help. |
| What is acute viral hepatitis? | An inflammatory condition of the liver caused by viruses. |
| What is obstructive jaundice? | An obstruction of the bile duct that causes hepatic waste products and bile to accumulate. |
| What is cirrhosis? | A chronic liver disease causing loss of function. Occurs with long term alcohol abuse. Large amounts of blood with drug bypasses the liver and circulates directly into the intestine. |
| What is hyperthyroidism? | A condition in which thyroid hormone secretions are above normal, often referred to as an overactive thyroid. |
| What is hypothyroidism? | A condition in which thyroid hormone secretions are below normal, often referred to as an underactive thyroid. |
| Which two diseases appear to decrease hepatic metabolism and thereby diminish the first-pass metabolism of some drugs? | Cirrhosis and obstructive jaundice. = bioavailability increases |
| What are the selected drugs with decreased elimination in cirrhosis and obstructive jaundice? | Caffeine, diazepam, encainide, erythromycin, lidocaine, meperidine, metronidazole, metoprolol, theophylline, and verapamil. |
| What are the selected drugs with decreased elimination in renal disease? | atenolol, digoxin, gentamicin, lithium, piperacillin, ranitidine, vancomycin |
| What should happen to the dosage of the drug when renal function decreases? | The dosage of a drug that is eliminated by the kidneys should be reduced to avoid accumulation of the drug in the body. |
| What is a major plasma and tissue protein that is responsible for acidic drug binding? | Albumin |
| In chronic renal disease, why is albumin allowed by the kidneys? | Normally the kidneys do not allow the elimination of albumin, but in these circumstances, excessive protein filtration may occur which leads to loss of albumin from the body. |
| What is orosomucoid? | A plasma protein that is rapidly produced when the body is injured. It is also a protein that many basic drugs bind to in the body. |
| What happens to orosomucoid during chronic renal disease? | Orosomucoid blood concentrations are higher than normal, which results in increased basic drug binding. |
| Decreases in renal function can be measured by what? | By monitoring the amount of creatinine excreted in the urine. |
| What is creatinine? | It is produced by muscles in the body and excreted at a constant rate primarily by glomerular filtration. |
| What happens to the rate of creatinine in disease kidneys? | The rate of creatinine excretion decreases. |
| Circulatory disorders causes what? | Cause a diminished blood flow to the organs of the body, which affects the drug absorption, distribution, and elimination. This influences the drug's effect. |
| What are some effects on absorption? | Delayed gastric emptying time, decreased intestinal motility, or changes in GI pH. The changes lead to a delayed or erratic drug absorption. |
| What are other effects of decreased blood flow? | Affect how drugs are metabolized by the liver, ability of certain drugs moving from the blood into the hepatic cells, and decrease the clearance of drugs that are eliminated in proportion to hepatic blood flow. |
| The rate of metabolism is controlled by what? | By the levels of circulating thyroid hormones. |
| Lower plasma of blood is observed in what? (this is the only one that is opposite) | Hyperthyroidism |
| Higher levels of blood is observed in what? (only one that is opposite) | Hypothyroidism |
| What is complexation? | When two different molecules associate or attach to each other. By the drugs binding together and forming nonabsorbable complexes, it results in decreased absorption. |
| What is displacement? | A drug that is bound to a plasma protein is removed when another drug of greater binding potential binds to the same protein. |
| What is enzyme induction? | The increase in hepatic enzyme activity that results in greater metabolism of drugs. |
| What is enzyme inhibition? | The decrease in hepatic enzyme activity that results in reduced metabolism of drugs. |
| What is a problem with reducing gastric emptying time? | Drugs that are degraded by gastric acid have a longer time to degrade, resulting in a decreased amount of drug availability for absorption from the intestine. |
| What are some factors affected by pH? | The amount of unionized drug available for absorption, the rate of dissolution, intestinal motility, and degradation. |
| What do antibiotics do to the GI tract? | Kills the normal bacterial flora in the GI tract, which disrupts the enterohepatic recycling of the oral contraceptive's estrogens. |
| What is the biggest consequence of displacement interactions? | The change in pharmacological effect. If drugs are highly protein bound, displacement tends to have greater effect than with drugs that are not highly bound. |
| What are other things can be influenced by enzyme induction? | Age, genetics, or liver disease. |
| When does enzyme inhibition usually occur, and what happens to one of the drugs? | Usually occurs when two drugs compete for binding sites on the same metabolizing enzyme. This increases the plasma concentration ( and pharmacological effect) of at least one of the drugs. |
| Which one is slower, enzyme induction or enzyme inhibtion? | Enzyme induction is much slower, while enzyme inhibition has a rapid onset within 24 hours, and disappears quickly once the inhibitor is discontinued. |
| Which one is easier to predict, enzyme induction or inhibition? | Enzyme inhibition is easier to predict since it appears to be dose related. |
| True or False: Drugs that share a similar chemical structure often share the potential for enzyme inhibition. | True |
| What happens between two basic and two acidic drugs? | They may compete for the same transport system and this can cause one or both of the drugs to accumulate in the blood. |
| Urinary reabsorption is influenced by what? | Influenced by the pH of the urine and the extent of ionization of the drug. |
| What happens in acidic urine? | Acidic drugs tends to be reabsorbed while basic drugs do not, as a result basic drugs are excreted into the urine. |
| What happens in alkaline urine? | Acidic drugs will not be reabsorbed but will instead be excreted in urine, while basic drugs will be reabsorbed. |
| What is additive effects? | Occurs when two drugs with similar pharmacological actions result in an effect equal to the sum of the individual effects. |
| What is an example of a additive effect? | Trimethoprim + sulfamethoxazole for antibiotic effect |
| What is synergism? | Occurs when two drugs with similar pharmacological actions produce greater effects than the sum of individual effects. |
| What is an example of synergism? | Aspirin + warfarin = increased anticoagulation |
| Why is knowing the time course of an interaction important? | Allows quick identification and treatment of potential interactions. Also allows clinicians to evaluate the relative importance of an interaction from two drugs compared to their therapeutic effects. |
| What is potentiation? | Occurs when one drug with no inherent activity of its own increases the activity of another drug that produces an effect. |
| What is an example of potentiation? | Amoxicillin + clavulanic acid = increased duration of amoxicillin's antibiotic effect. |
| What is an antidote? | An antidote to a particular drug is given to block or reduce its toxic effects. This sometimes called an antagonistic interaction. |
| What is an example of an antidote? | Naloxone + morphine = relief of morphine induced respiratory depression. |
| What are drug-diet interactions? | When elements of ingested nutrients interact with a drug and this affects the disposition of the drug. |
| How can the physical presence of food in the GI tract alter the absorption? | Interact chemically, improve the solubility of some drugs by increasing the bile secretion, affect the performance of the dosage form, alter gastric emptying, alter intestinal motility, and alter liver blood flow. |
| When food is present and slows absorption, what happens to bioavailability ? | Bioavailability of a drug is generally decreased when the presence of food slows absorption. Ex: Tablets taken with food is dissolved more slowly, decreased absorption. |
| Interactions that alter drug absorption can be minimized by what? | Separating the administration of drugs and food intake by about 2 hours. |
| What is the difference with undernourished people and the plasma protein binding of certain drugs? | With low albumin levels they have fewer binding sites available for highly bound drugs. |
| What is the difference between high protein and high carbohydrate diets ? | High protein diets accelerates metabolism while high carbohydrates decrease metabolism. Substituted fat calories for carbohydrates show no affect of drug metabolism rates. |
| Increasing protein in diet causes what ? | Appears to increase glomerular filtration, decrease reabsorption, and decrease secretion in the kidneys. |
| What do high sodium diets do? | Tend to increase the excretion of sodium and they also increase the excretion of lithium bcs it shares the same reabsorption site in the nephron as sodium. |
| Why are adolescents are excluded from clinical trials? | Puberty affects ADME, so excluded due to many variations. |
| What declines with age? | Metabolism |
| What happens when pregnant women have more blood volume? | The blood volume can go to the kidneys more, which means more drug is being excreted. |
| What is an disadvantage for pregnant womens taking drugs? | Might cross over in the bloodstream of the fetus, which causes an effect. Most drugs are teratogenic due to this. |
| What does genetics determine? | Determines type and amounts of proteins. |
| What is the thing that affects variability the most? | Genetics |
| What is a common drug that can cause complexation? | Iron salts (iron supplements) and antacids |
| What happens if a drug delays or increase gastric emptying time? | If it delays, then it delays absorption, if it increases, it increases the absorption. |
| Drugs are degraded by what when gastric emptying is delayed? | It is degraded by hydrochloric acid (less drug available for absorption), Most drugs cannot stay in the stomach for too long. |
| What happens with distribution and elimination if a drug becomes displaced? | When some drugs can displace other drugs from a plasma protein increases the amount of free drug available for distribution thereby increasing the drug's effect. Also faster elimination because more drug is available for metabolism and excretion. |
| What is the biggest complication with displacement? | Change in drug effect |
| Which type of drug has greater effect when displaced? | Highly bound protein drug is usually have a greater effect when displaced. |
| What is the capillary network that filters the blood? | Glomerulus |
| What type of transport is urinary reabsorption? | Passive transport |
| What is urinary reabsorption affected by? | Affected by the urinary pH and ionization of drug. |
| Vitamin K reverses what (antidote)? | Reverses the effect of warfarin |
| Protamine sulfate reverses what (antidote)? | Heparin |
| Naloxone + morphine reverses the effect of what (antidote)? | The effect of morphine or other narcotics |
| Flumazenil reverses the effect of what (antidote)? | Benzodiazepines |
| If you eat something in high in protein but low in carbs then what happens? | Higher metabolism rate |
| If you eat something high in carbs what happens? | Slower metabolism rate of certain drugs |
| What happens to someone's metabolism if they are severely malnourished? | Slow metabolism |
| Increased protein diets means what happens in excretion? | Increase glomerular filtration, decrease reabsorption, and decrease secretion in the kidneys. |
| Diet in high in sodium means what with excretion? | You excrete more sodium |
| For patients taking Warfarin, what foods should they limit to take? | Limit spinach, cabbage, and dark greens that contain Vitamin K because it might decrease the drug's effect. |
| For patients taking statins, what should they not consume? | Do not consume grapefruit or its juice because this blocks the enzymes and free drug increased. |
| What is absorption? | Transfer of drug into the bloodstream |
| What is distribution? | How the drug travels in the body to its site of action |
| What is metabolism? | How the drug is broken down |
| What is excretion? | How the drug leaves the body |
| Older infants have what equal levels compared to adults? | Older infants have almost equal levels of protein binding and kidney function as adults. |
| What is unfunctional or immature in older infants? | Liver function and blood brain barrier is immature. |
| Due to the decreased kidney functions in elderly, what happens to urinary excretion? | Leads to slow urinary excretion of drugs. |
| How does pregnancy affect absorption? | Delayed gastric emptying and decreased GI movement = decrease in absorption. |
| How is plasma protein binding affected in pregnant women? | Plasma protein binding decreased for some drugs (pregnant women have decreased levels of albumin). |
| How is metabolism and urinary secretion affected in pregnant women? | Metabolism is increased for most drugs and urinary secretion is greater in some drugs. |
| What percent of human variability is due to genetics? | 20-50 percent |
| What is acute viral hepatitis? | An inflammation condition of the liver caused by viruses-- can lead to cirrhosis. |
| How is bioavailability affected by hypothyroidism? | Increase bioavailability of some drugs, so it stays in the intestines longer for absorption. |
| How is bioavailability affected by hyperthyroidism? | Decrease bioavailability of some drugs, so it stays in the intestines shorter amount of time for absorption. |
Created by:
imaliha2003
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