AGENDA Current News Quiz Review Chapter Five

Chapter 5 How and Why Drugs Work Instructor Ed Ramirez

Quiz Review Sumerians believed that the “Joy” plant was what? Review Gateway Drugs Sumerians believed that the “Joy” plant was what? Review why drugs are more serious today Why is addiction considered to be a disease

Quiz Review cont’d Review Addiction, i.e. physical and psychological dependency What is tolerance What are withdrawals Non drug addictions What are the birth defects caused by thalidomide

Quiz Review cont’d Review pharmacist Humphrey and what did he do Review Harrison Act

Introduction A common belief is that drugs can solve most of life’s serious physical, emotional, and medical problems. Although medications are essential to treatment for many diseases, excessive reliance on drugs causes unrealistic expectation that may lead to dangerous– even fatal consequences. We’ve covered this so far in the semester, relaxing, escaping, etc.

Celebrities Just because they're legal doesn't mean that prescribed drugs are any less dangerous than illicit drugs. They are potentially deadly when taken in large doses or when combined with alcohol or other drugs. Sometimes it takes high-profile cases to remind us of the dangers. Methaqualone, AKA Quaaludes (sedative) Secobarbital, AKA Seconal (sleeping pill) Pentobarbital and chloral hydrate (sleeping pills) As many as 14 different drugs, including codeine (painkiller) and methaqualone, AKA Quaaludes (sedative) Propofol

Some of the drugs used Elvis, On August 16, 1977, he suffered a heart attack in his Graceland estate, and died as a result. His death came in the wake of many years of prescription drug abuse. Jimi Hendrix-the cause of death as: "Inhalation of vomit due to barbiturate intoxication ( he took nine sleeping pills) Heath Ledger- (CNN) -- Heath Ledger died from an accidental overdose of prescription medications including painkillers, anti-anxiety drugs and sleeping pills, the New York City medical examiner's office said Wednesday. Actor Heath Ledger, 28, died January 22 at an apartment in Lower Manhattan.

What Killed Michael Jackson? Propofol Propofol is a potentially deadly drug in the wrong hands, and there is no room for error. "It's only designed for people trained to do advanced cardiac life support," Dombrowski says. "It induces a deep level of sleep and sedation, and it can cause your blood pressure to go down and your breathing to stop. You can die https://www.google.com/search?q=propofol Propofol is the generic name for Diprivan, which is a prescription, injectable drug. It's an anesthetic used to put people to sleep before surgery. It's also given for sedationin hospital intensive care units

Now Used In Missouri Executions https://deathpenaltyinfo.org/lethal-injection-missouri-intends-use-propofol-one-drug-lethal-injection http://www.foxnews.com/health/2012/05/24/missouri-to-use-same-drug-involved-in-michael-jackson-death-for-executions.html

Intended and Unintended Effects of Drugs When physicians prescribe drugs, their objective is usually to cure or relieve symptoms of a disease. However, drugs cause unintended effects that neither the physician nor the patient expected: THESE ARE CALLED SIDE EFFECTS

Side effects- Unintended drug responses

Side effects

Common Side Effects of Drugs Nausea or vomiting Changes in mental alertness Dependence Withdrawal Allergic reactions Changes in cardiovascular activity

Opiate withdrawal Withdrawal “Side Effects” Unpleasant effects that occur when use of a drug is stopped Withdrawal “Side Effects”

Withdrawal

Common Side Effects of Drug Figure 5-1: Common side effects with drugs of abuse. Almost every organ or system in the body can be negatively affected by the substances of abuse.

Dose-Response Dose Tolerance Potency Many factors can affect the way an individual responds to a drug, including the following: Dose Tolerance Potency

Dose-Response (continued) Additional factors Pharmacokinetic properties: Defined below Rate of absorption Manner distributed throughout the body Rate metabolized and eliminated Form of the drug Manner in which the drug is administered -the branch of pharmacology concerned with the movement of drugs within the body

Dose-Response Curve Figure 5-2: Dose-response curve for relieving a headache with aspirin in three users. User A is the most sensitive and has 100% headache relief at a dose of 600 mg. User B is the next most sensitive and experiences 50% headache relief with a 600-mg dose. The least sensitive is user C: with a 600-mg dose, user C has no relief from a headache.

Margin of Safety The range in dose between the amount of drug necessary to cause a therapeutic effect and a toxic effect.

Potency vs. Toxicity Potency: The amount of drug necessary to cause an effect Toxicity: The capacity of a drug to do damage or cause adverse effects in the body

Drug Interaction A drug’s effect can be dramatically altered when other drugs are also present in the body This effect is known as DRUG INTERACTION

Drug Interaction

Grapefruit and certain medications

Drug Interaction Cont’d Additive effects Effects created when drugs are similar and actions are added together Antagonistic (inhibitory) effects One drug cancels or blocks effects of another Potentiative (synergistic) effects Effect of a drug is enhanced by another drug or substance

OTC and Herbal drugs ae as likely to cause interactions problems. Public must be educated about the interactions most likely to occur with drugs that are prescribed, self-administered legitimately. OTC and Herbal drugs ae as likely to cause interactions problems. Example- Decongestant contains mild CNS stimulants. If taken with Illegal drugs such as cocaine or amphetamines, can cause fatally affect in the heart and brain. Page 155

Figure 05.B01A © Monkey Business/Fotolia.com

Pharmacokinetic Factors How does the drug enter the body? How does the drug move from the site of administration into body’s system How does the drug move to various areas (distribution) How and where does the drug produce its effects How is the drug inactivated, metabolized excreted from the body

Pharmacokinetics The study of factors that influence the distribution and concentration of drugs in the body Pathways Conjugation- 2 compounds resulting in the formation of another Adducts- draw towards

Adam Goldstein Better known as DJ AM Overdosed, August, 2009 CNS Depressants Six pills where found in his stomach. An OxyContin capsule was lodged in his throat.

Onset vary Figure 05.03: Relationship between the method of drug administration and drug effects.

Forms and Methods of Taking Drugs Half way Forms and Methods of Taking Drugs oral ingestion inhalation injection topical application Topical Application -made to be put on the skin topical lotions/creams a topical drug/treatment Half way Drugs can be introduced into the body using various methods, such as pills, capsules, oral liquids, topicals, or injections. © Oscar Knott/FogStock/Alamy Images

Oral ingestion One of the most common and convenient ways of taking a drug is orally It is difficult to control the amount of drug that reaches the site of action (Three Reasons)

Oral ingestion cont’d The drug must enter the bloodstream passing through the wall of the stomach or intestines without being destroyed or changed into an inactive form Materials in the stomach or intestines such as food may interfere with the passage The liver might metabolized orally ingested drugs to rapidly, before they are able to exert an effect.

INHALATION Some drugs are administered by inhalation into the lungs through the mouth or nose

Injection Intravenous (IV) Intramuscular (IM) Subcutaneous (SC) Drug injection beneath the skin

Topical application Drugs that readily pass though surface tissues such as the skin

Factors affecting Distribution Most drugs are distributed throughout the body in the blood. It takes approximately 1 minute for a drug to circulate throughout the body after it enters the bloodstream. Drugs have different patterns of distribution depending on their chemical properties. We have approximately 5 to 6 liters of blood

Factors affecting distribution Their ability to pass across membranes and through tissues Their molecular size (large versus small molecules) Their solubility properties Their tendency to attach to proteins and tissues throughout the body

Factors affecting distribution Cont’d Blood is carried to the nerve cells of the brain in a vast network of thin-walled capillaries. Drugs are soluble in fatty oily solutions are most likely to pass across these capillary membranes known as “the blood-brain barrier” THE BBB is defined as selective filtering between the cerebral blood vessels and the brain

The BBB

AGENDA For 3/8/18 Current News Short Film clip on Drugs Finish up with Chapter Five

Opioid Epidemic https://www.youtube.com/watch?v=s4LV0tBZncI https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis Every day, more than 115 Americans die after overdosing on opioids

Required Doses for Effects Threshold dose—the minimum amount of a drug necessary to have an effect Plateau effect—the maximum effect a drug can have regardless of the dose Example, aspirin, can effectively relieve your mild to moderate pain, but aspirin will not effectively treat your severe pains, regardless of the dose taken.

Time-Response Factors The closer a drug is placed to the target area, the faster the onset of action. Acute drug response: Immediate or short-term effects after a single drug dose Chronic drug response: Long-term effects after a single dose

Time-Response Factors Cont’d Important time factor that influences drug response is the interval between multiple administrations. If sufficient time for drug metabolism and elimination does not separate doses, a drug can accumulate within the body Cumulative effect—the buildup of drug concentration in the body due to multiple doses taken within short intervals

Inactivation and elimination of drugs from the body Half-life- Time required for the body to eliminate and/or metabolize half of a drug dose Metabolism- Chemical alteration of drugs by body processes Metabolites- Chemical products of metabolism Usually makes it possible for the body to inactivate, detoxify and excrete drugs and other chemicals. Exception: HEROIN becomes more active when it metabolizes.

Biotransformation Biotransformation—the process of changing the chemical or pharmacological properties of a drug by metabolism. The liver is the major organ that metabolizes drugs in the body. The kidney is the next most important organ for drug elimination.

Inactivation and elimination of drugs from the body Cont’d The body may eliminate small portions of drugs through perspiration and exhalation. Approximately 1% of consumed alcohol is eliminated in the breath and thus may be measured with a

Figure 05.B03: Family Matters: Genetics of Metabolic Enzymes and Alcoholism

Inactivation and elimination of drugs from the body Cont’d

Physiological Variables That Modify Drug Effects AGE Gender Pregnancy Changes in body size and makeup occur throughout the aging process Variations in drug responses due to gender usually relate to differences in body size, composition or hormones During pregnancy, unique factors must be considered when administering drugs.

Physiological Variables That Modify Drug Effects Cont’d The increase demand can make the woman more susceptible to the toxicity of some drugs As the fetus develops, it can be very vulnerable to drugs with Teratogenic- Something that causes physical defects in a fetus

Teratogenic Remember from chapter 3??

Adaptive Processes Figure 05.04: The relationship and consequences of adaptive processes to drug abuse. The processes discussed in the text are highlighted in the figure.

Adaptive Processes Your body systems are constantly changing Drugs sometimes interfere with the activity of the body’s systems and compromise their normal workings Stimulants can dangerously increase the heart rate, blood pressure and can cause heart attacks Depressants can diminish the brain activity, resulting in unconsciousness and loss of breathing reflexes

Figure 05.T02: Tolerance, Dependence, and Withdrawal Properties of Common Drugs of Abuse

Figure 05.HN01A: Here and Now: Drug Test Results Can be Flawed THE POPPY SEEDS Figure 05.HN01A: Here and Now: Drug Test Results Can be Flawed Data from Fiore, K. “APA: Drug Test Results Often Flawed.” MedPage Today. 23 May 2010. Available http://www.medpagetoday.com/MeetingCoverage?APA/20253. Accessed March 2, 2011.

Figure 05.HN01B: Here and Now: Drug Test Results Can be Flawed

Tolerance to drugs Reverse tolerance (sensitization): Enhanced response to a given drug dose; opposite of tolerance Cross-tolerance: Development of tolerance to one drug causes tolerance to related drugs

Drug Dependence Drug dependence can be associates with either physiological or psychological adaptations. Physical dependence reflects changes in the way organs and systems in the body respond to a drug, whereas psychological dependence is caused by changes in attitudes and expectations.

(e.g.,withdrawal and rebound) Drug Dependence Physical Dependence (e.g.,withdrawal and rebound) Psychological Dependence (e.g., craving)

Physical Dependence In general, the drugs that cause physical dependence also cause a drug withdrawal phenomenon called, “rebound effect” “This is a form of withdrawal; paradoxical effects that occur when a drug has been eliminated from the body” Physical dependence , drug withdrawal- two opposite things and that seems impossible but is actually true or possible

Physical Dependence Cont’d Cross Dependence- dependence on a drug can be relieved by other similar drugs Examples- Benzodiazepines and other CNS depressants can be used to treat the abstinence syndrome experienced by the chronic alcoholic Methadone, long acting narcotic, to treat heroin withdrawal

Psychological Factors Affecting Drug Effect Individual’s mental set The collection of psychological and environmental factors that influence an individual’s response to a drug Placebo effects Effects caused by suggestion and psychological factors independent of a pharmacological activity of a drug Placebo- From the Latin word meaning, “I shall please.”

Addiction and Abuse The use of the term addiction is sometimes confusing. It is often used interchangeably with dependence, either physiological or psychological in nature; other times, it is used synonymously with the term drug abuse. A more accurate definition is the compulsive drug use despite negative consequences.

Addiction and Abuse (continued) Factors affecting variability in dependence/addiction: Hereditary factors (genetic variants); responsible for 40–60% vulnerability Drug craving

Addiction and Abuse (continued) Other factors contributing to drug use patterns: Positive versus negative effects of drug Peer pressure Home, school, and work environment Mental state

Figure 05.B04: Family Matters: Family Addictions and Genetics

Addiction and Abuse (continued) Other factors contributing to drug use patterns Positive versus negative effects of drug (dysphoric is the opposite of euphoric) Peer pressure Home, school, work environment Mental state

Dysphoric Dysphoric is the opposite of euphoric Characterized by unpleasant mental effects Dysphoric is the opposite of euphoric Figure 5.4 again DYSPHORIA- a state of dissatisfaction, anxiety, restlessness, or fidgeting.

Questions Short Quiz on Wednesday, no Scantron needed