Chapter 4 Pharmacology


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Chapter 4 Pharmacology

  1. 1. Pharmacology Chapter 4
  2. 2. What Contributes to the Drug Experience? <ul><li>Emphasis of this chapter is on the characteristics of drugs and the role the body plays in producing drug effects </li></ul><ul><li>Series of interrelated factors contributes to a given drug effect </li></ul><ul><li>Importance of any one factor, or set of factors, for a given drug-taking occasion depends on the importance of the other factors </li></ul><ul><li>To evaluate the importance or contribution of any one factor, you must control the effects of other relevant factors </li></ul><ul><li>Control – In research, to be able to account for variables that may affect the results of a study </li></ul>
  3. 3. <ul><li>Not only are the contributory factors of a drug effect interdependent but feedback relationships may also occur. </li></ul><ul><li>Feedback – In this context, in a series of events, what happens in a later event alters events that preceded it </li></ul><ul><li>For example, a large quantity of a drug is taken and absorbed into the blood. </li></ul><ul><li>Absorbed – Drugs are absorbed by, or entered into, the bloodstream </li></ul><ul><li>It is carried to its site of action ( distributed ). </li></ul><ul><li>Distribution – Drugs are distributed, or transported, by the blood to their site(s) of action in the body </li></ul>
  4. 4. <ul><li>In some cases a large quantity of a drug may cause the body to slow absorption or quicken metabolism of the drug to defend itself against a toxic drug effect </li></ul><ul><li>Metabolism – The process by which the body breaks down matter into more simple components and waste </li></ul><ul><li>In this event, the distribution of the drug is information that the body “feeds back” to its regulators of absorption and metabolism to, in effect, reduce the drug quantity </li></ul>
  5. 5. “ Steps” in the Drug Experience <ul><li>A drug of a specified chemical structure is present </li></ul><ul><li>A certain quantity of this drug is measured </li></ul><ul><li>This quantity of the drug is administered in one of a number of possible ways </li></ul><ul><li>The drug is absorbed into the blood and distributed to site(s) of action </li></ul><ul><li>Some pharmacological effect is produced </li></ul><ul><li>In humans a drug’s pharmacological effects may be modified depending on characteristics of the person, such as genetic constitution, gender, age, personality, and drug tolerance </li></ul><ul><li>The setting or context of drug use also may modify a drug’s pharmacological effects </li></ul>
  6. 6. <ul><li>Two branches of pharmacology most relevant to understanding the drug experience are: </li></ul><ul><li>Pharmacokinetics – Concerns the absorption, distribution, biotransformation, and excretion of drugs. Drug absorption and distribution are essential for determining how much drug reaches its sites of action and therefore its effects </li></ul><ul><li>Pharmacodynamics – Concerns the biochemical and physiological effects of drugs and their mechanisms of action </li></ul>
  7. 7. Drug Dose <ul><li>The effect of a drug depends on how much of the drug is taken </li></ul><ul><li>A drug’s dose is computed according to a person’s body weight because heavier people have a greater volume of body fluid than lighter people </li></ul><ul><li>The drug is therefore less concentrated in a heavier person and less concentrated at the site of drug action, where generally the drug effect is the greater </li></ul><ul><li>The drug dose is expressed in milligrams of the drug per kilogram (mg/kg) of body weight </li></ul>
  8. 8. Routes of Administration <ul><li>Oral – Swallowing drugs in the form of pills, capsules, powders, or liquids is usually the safest, most convenient, and most economical way to administer a drug. </li></ul><ul><li>Examples: headaches medicines, cough syrups, and a variety of drugs available at any drug store </li></ul><ul><li>Drugs pass through the stomach and are absorbed through the small intestine </li></ul><ul><li>Food may encapsulate the drug so that it is passed out of the body in the feces </li></ul>
  9. 9. <ul><li>Food in the stomach delays absorption and decreases maximum drug level achieved </li></ul><ul><li>Even without the complications of food in the stomach, the drug is absorbed into the blood more slowly than other routes </li></ul><ul><li>With some drugs, such as heroin, stomach acids used in digestion break down the drug to some degree before it is absorbed into the blood and then the liver further metabolizes it so only a fraction of the drug dose reaches the brain. The outcome is a diminished drug effect </li></ul>
  10. 10. <ul><li>Injection – Three of the most common routes of drug administration involve injecting drugs into the body using a needle and syringe. When drugs are taken this way they are dissolved or suspended in some solution before injection </li></ul><ul><ul><li>Dissolved – A drug is dissolved as it changes from solid to liquid by mixing with a liquid </li></ul></ul><ul><ul><li>Suspended – A drug is suspended in solution if its particles are dispersed in solution but not dissolved in it </li></ul></ul><ul><li>Routes of administration for injecting drugs are subcutaneous, intramuscular, and intravenous </li></ul>
  11. 11. <ul><ul><li>Subcutaneous – Injecting the drug under the layers of the skin. Easiest of the injection routes, absorption rate slow but faster than oral and constant. Not for drugs irritating to body tissue </li></ul></ul><ul><ul><li>Intramuscular (“Within the muscle”) - Faster than oral but rate depends on blood flow to the muscle group the drug is injected into. Common muscle sites are the deltoid, thigh, and buttocks. Disadvantages include localized pain and risk of infection. </li></ul></ul>
  12. 12. <ul><ul><li>Intravenous (“Into the veins”) - Called “Mainlining”, most absorption problems are avoided when administered this way. Effects are immediate thus valuable in emergency medical situations. Both irritating drugs and vehicles can be taken due to the insensitivity of blood vessel walls and dilution with blood </li></ul></ul><ul><ul><li>Complications, such as overdose, are more likely to occur because large quantities of the drug reach the site of action so quickly, repeated use takes its toll on the body, and there is increased risk of infections (e.g. AIDS, hepatitis, tetanus) due to bypassing the body’s natural protections </li></ul></ul>
  13. 13. <ul><li>Inhalation – Fast and effective absorption through the lung’s membranes after inhaled as smoke, vapors, gaseous states, or fine liquid drops (tobacco smoke contains tiny drops of nicotine and the smoke from freebase cocaine contains droplets of cocaine). Disadvantage is that it is possible to absorb only a small amount of the drug in one administration </li></ul><ul><ul><li>Freebase – A substance may be separated, or “freed” from its salt base. The separated form of the substance is thus called “freebase”. </li></ul></ul>
  14. 14. <ul><li>Intranasal (“snorting”/”sniffing”) – Drug in powdered form is taken through the nose. </li></ul><ul><li>Examples of drugs commonly absorbed this way are cocaine, heroin, and powdered tobacco snuff </li></ul><ul><li>When drug is fat-soluble, it is a rapid and effective way to absorb it </li></ul><ul><li>If drug is irritating, it can cause damage, i.e., cocaine sniffing to nasal septum and lining of the nose </li></ul>
  15. 15. <ul><li>Sublingual – Drug tablet is placed under the tongue and dissolves in saliva </li></ul><ul><li>Examples are Nitroglycerin for angina and Nicotine in the form of chewing tobacco or snuff </li></ul><ul><li>Faster and more efficient than oral administration </li></ul><ul><li>Preferred for drugs that irritate the stomach and cause vomiting if taken orally </li></ul><ul><li>Disadvantage is that the unpleasant taste of many drugs prevents this type of administration </li></ul>
  16. 16. <ul><li>Transdermal (“through the skin”) – Usually administered in the form of patches at a site with a high rate of cutaneous blood flow </li></ul><ul><li>Examples include the Nicotine patch and Nitroglycerine </li></ul><ul><li>Alternative for when a drug causes unwanted gastrointestinal effects </li></ul><ul><li>Skin may act as a nonpermeable barrier for some drugs </li></ul>
  17. 17. <ul><li>Determining the preferred route of administration depends on the drug administered, goals of administration, and advantages and disadvantages of using a particular route with a particular drug under a particular circumstance </li></ul><ul><li>Table 4.2 – General considerations for the eight routes of drug administration </li></ul><ul><li>Table 4.3 – Summary of routes typically used with drugs taken for medical and nonmedical reasons </li></ul>
  18. 18. Drug Absorption <ul><li>Absorption may be defined as the rate and extent to which a drug leaves its site of administration. </li></ul><ul><li>Absorption and the factors that affect it are important because they influence bioavailability </li></ul><ul><ul><li>Bioavailability – The portion of the original drug dose that reaches its site of action or that reaches a fluid in the body that gives it access to its site of action </li></ul></ul><ul><li>Bioavailability is influenced not only by the route of administration but by numerous factors that influence absorption in general </li></ul>
  19. 19. <ul><li>For all routes of administration except oral, drugs must pass through at least one membrane before reaching the circulatory system. Body membranes consist largely of lipids (fats), therefore drugs that are more soluble in lipids are more readily absorbed. Solvents and alcohol are fat-soluble . </li></ul><ul><ul><li>Solubility – The ease with which a compound can be dissolved or entered into a solution </li></ul></ul><ul><li>Drugs taken in water solutions are absorbed more rapidly than drugs taken in suspension, oily solution, or in solid form because they are dissolved more readily at the site of absorption </li></ul>
  20. 20. <ul><li>Circulation at the site of absorption also influences it as more blood flow speeds absorption </li></ul><ul><li>Drugs are absorbed more rapidly from larger surface areas </li></ul><ul><li>Since each of these and other factors may singly or in combination affect absorption, you can see why it is so difficult to specify a drug effect for a person under specific conditions at a given time </li></ul>
  21. 21. Drug Distribution <ul><li>Biochemical properties of both the body and the drug influence a drug’s distribution to its sites of action </li></ul><ul><li>Because the blood transports the drug, parts of the body such as the heart, brain, kidney, liver, and other systems that receive a lot of blood get major portions of the drug shortly after absorption </li></ul><ul><li>The diffusibility of membranes and tissues also affects distribution with the more diffusible tissues receiving the drugs more rapidly </li></ul><ul><ul><li>Diffusibility – A more diffusible substance is more easily entered into or “receptive” of another </li></ul></ul>
  22. 22. <ul><li>Drugs that are highly fat-soluble are more able to penetrate the brain despite the blood-brain barrier designed to filter out toxins. Valium is a highly fat-soluble drug that passes easily into the brain </li></ul><ul><li>Some drugs such as marijuana have an affinity for fatty tissue where it can be stored and released slow enough that the psychoactive effects are negligible </li></ul><ul><li>Whether a drug selectively binds to elements of the body also affects distribution. Barbiturates bind to certain proteins in the plasma. The more “tightly” bound a drug is the slower its distribution to sites of action </li></ul>
  23. 23. Drug Elimination <ul><li>Drugs are excreted from the body directly or are metabolized into products that are less likely to be reabsorbed </li></ul><ul><li>Enzymes in the liver play the major part in drug metabolism </li></ul><ul><li>Same enzymes are also present in the kidneys and GI tract and thus drugs administered orally are subject to a “first-pass effect” where the enzymes in the GI tract break them down to some degree before they reach their sites of action </li></ul><ul><li>Metabolic by-products of drugs can still be pharmacologically active and cause side effects </li></ul>
  24. 24. <ul><ul><li>Side Effects – Effects of a drug other than those of central interest; used most often in reference to the other-than-therapeutic effects of medications, such as the side effect of drowsiness for antihistamines. Note that what are considered a drug's side effects depend on what specifically the drug is being used for </li></ul></ul><ul><li>Kidneys is the most important organ for excretion of both drugs and their metabolites </li></ul><ul><li>Drugs may also be excreted in feces, liver bile, mother’s milk, lungs, and perspiration </li></ul>
  25. 25. <ul><li>Rate of elimination obeys two general laws: </li></ul><ul><ul><li>Zero-order kinetics – Rate at which a drug is metabolized is independent of its concentration in the blood, (Ex. Alcohol) </li></ul></ul><ul><ul><li>First-order kinetics – Amount of drug metabolized in a unit of time depends on how much drug is in the blood </li></ul></ul><ul><li>Most drugs obey the law of first-order kinetics </li></ul><ul><li>Another common term related to drug elimination is half-life </li></ul><ul><ul><li>Half-life – The amount of time that must pass for the amount of drug in the body to be reduced by half </li></ul></ul>
  26. 26. Drug Testing <ul><li>Various methods of determining drug use, most commonly analyzing urine or blood samples </li></ul><ul><li>Analysis of urine is more sensitive because the drug metabolites may be detected in the urine </li></ul><ul><li>If the drug is detected in the blood directly, it is a sign of recent use </li></ul><ul><li>Validity of drug testing depends on dose of drug last taken, testing method, and laboratory quality control procedures used in testing </li></ul><ul><li>Detectability of a drug depends on its elimination time and detection time with detection time longer if the drug’s metabolites can be measured by the testing method </li></ul>
  27. 27. <ul><li>False-negative – Test shows a negative result when the person has actually used the drug </li></ul><ul><li>Three major methods have been used to get a false negative finding on a drug screen: </li></ul><ul><ul><li>Substitution – Exchanging a “dirty” urine for a clean one </li></ul></ul><ul><ul><li>Adulteration – Adding compounds that interfere with the mechanism the test uses to detect the drug or its metabolites </li></ul></ul><ul><ul><li>Dilution – Drinking large quantities of liquids to reduce the drug metabolite concentration below the level that the test can detect </li></ul></ul><ul><li>False-positive – Test shows a positive result for a drug the person has not used </li></ul>
  28. 28. Pharmacodynamics <ul><li>Dose-Effect Curve (formerly Dose-Response Curve) – Standard way to represent graphically drug effects that result from taking different drug doses. The vertical axis of the graph represents effect size and the horizontal axis represents the range of doses. When the effect is plotted for each dose, the resultant graph represents effect as a function of drug dose </li></ul><ul><li>As a Function Of – A term expressing correlation. In graphs of functional relationships between two variables, changes in one variable (for example, drug effect) associated with changes in another (drug dose) are represented </li></ul>
  29. 29. <ul><li>The dose-effect curve for a drug depends on the effect being measured </li></ul><ul><li>A typical dose-effect curve (Figure 4.2) is the S shape (sigmoid) curve showing that the drug produces a larger effect as the dose increases and then plateaus for the highest doses (Example: reaction time and alcohol) </li></ul><ul><li>Biphasic drug effect (Figure 4.3) – Effect of a drug may go in one direction - increase as the dose goes up - but then the effect changes direction (decreases) as the dose continues to go up (Example: heart rate for alcohol and marijuana) </li></ul>
  30. 30. Terms to Describe a Drug’s Action <ul><li>Slope – In a dose-effect curve reflects how much the drug dose changes before the effect gets larger </li></ul><ul><li>Efficacy – The most intense, or peak, level of a drug effect on the curve </li></ul><ul><li>Drug Potency – The minimum dose of a drug that is effective. </li></ul><ul><li>Effective Dose – The dose at which a given percentage of individuals show a particular effect of a drug </li></ul><ul><li>ED 50 – Dose at which 50% of the people who received the drug will experience the effect </li></ul>
  31. 31. <ul><li>Lethal Dose – The dose of a drug at which a given percentage of individuals are killed within a specified time </li></ul><ul><li>LD 50 – Dose at which 50% of animals/people administered a given dose of a drug died within a stated time </li></ul><ul><li>Therapeutic Index – A measure of a drug’s safety in medical care, it is computed as a ratio: LD 50 / ED 50. When the ED-LD difference is small, the greater the danger. The relationship between these two drug doses is essential information for medical and nonmedical drug use </li></ul>
  32. 32. Drug Interactions <ul><li>Interact – Two drugs interact if the effects of one drug are modified by the presence of the other </li></ul><ul><li>Synergism/Potentiation – Any enhancing drug interaction. When two drugs are synergistic, the effects of taking them together are greater than the effects of taking them alone, i.e., 2+2=4 can become 2+2=8 </li></ul><ul><li>Antagonism – The diminished or reduced effect of a drug when another drug is present. Amphetamines antagonize alcohol’s CNS depressant effects, however, they do not reduce alcohol’s impairment of motor skills like driving </li></ul>
  33. 33. <ul><li>An awareness of drug interactions is important because: </li></ul><ul><ul><li>Drugs are often used in combinations for more effective treatment of an illness </li></ul></ul><ul><ul><li>Several drugs could be taken for different illnesses that cancel each other out, or are detrimental or even lethal when taken together </li></ul></ul><ul><ul><li>Combinations of prescribed and nonprescribed drugs can cause problems </li></ul></ul>
  34. 34. <ul><li>Individuals also may intentionally combine drugs to achieve desired effects, either combining drugs with the same or similar actions to achieve a “super” high, or using drugs with opposite effects in a deliberate effort for one drug to modify the other. </li></ul><ul><li>Rather than focusing on the intensity (quantitative) of drug effects, drugs may also be combined to achieve qualitative interaction effects such as when they take a depressant drug with LSD to have a tranquil state while they experience the perceptual alterations that result from LSD </li></ul>
  35. 35. <ul><li>Adiós </li></ul><ul><li>Amigos ! </li></ul>