How and Why Drugs Work Chapter 5

Intended and Unintended Effects of Drugs Intended responses: Reason for using the drug Unintended responses: Side effects The main distinction between intended responses and side effects depends on the therapeutic objective. (what is the purpose of taking the drug)

Common Side Effects of Drugs Nausea or vomiting Changes in mental alertness Dependence Withdrawal Allergic reactions Changes in cardiovascular activity © fred goldstein/ShutterStock, Inc.

Common Side Effects of Drug (continued)

Side Effects of Drugs – Risk, Cost, vs. Benefit Are the therapeutic benefits of the drug greater than the risk of the drug? Does the benefit of the drug outweigh the potential amount of cost the drug may cause in side effects? Is the cost of not taking the medication greater than the alternative medical treatment?

Dose-Response Many factors can affect the way an individual responds to a drug, including the following: Dose – Amount of the drug taken Tolerance – Changes in the body that decrease response to a drug even though the dose remains the same Potency – The amount of drug necessary to cause an effect

Dose-Response (continued) Additional factors Pharmacokinetic properties: Rate of absorption Manner distributed throughout the body Rate metabolized and eliminated Form of the drug Manner in which the drug is administered

Dose-Response Curve (see Fig. 5-2, p.159) Figure 5.0.2: Dose–response curve for relieving a headache with ibuprofen in three users. User A is the most sensitive and has 100% headache relief at a dose of 400 milligrams. User B is the next most sensitive and experiences 50% headache relief with a 400-milligram dose. The least sensitive is user C: with a 400-milligram 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. The smaller the drug amount required to perform the desired therapy, the greater the potency. Toxicity: The capacity of a drug to do damage or cause adverse effects in the body. A high potency drug has a greater capacity for toxicity

Drug Interaction Additive effects Summation of effects of drugs taken concurrently 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. (synergism)

Pharmacokinetic Factors That Influence Drug Effects Administration - How does the drug enter the body? Absorption – How does the drug move from the site of administration? Distribution – How does the drug move to the various areas in the body? Activation – How and where does the drug produce its effects? Biotransformation and elimination – How is the drug inactivated, metabolized, and/or excreted from the body?

Forms and Methods of Taking Drugs Oral ingestion Rate and Stomach contents Must pass through liver following digestion Inhalation Injection Intravenous Intramuscular Subcutaneous Topical application © Oscar Knott/FogStock/Alamy Images

Forms and Methods of Taking Drugs

Distribution Most drugs are distributed throughout the body in the blood. It takes approximately one 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. Their ability to pass through membranes Their molecular size Their solubility properties Their tendency to attach to proteins and tissues throughout the body.

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 Cumulative effect: The buildup of drug concentration in the body due to multiple doses taken within short intervals

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 repeated doses Cumulative Effects – buildup of a drug in the body after multiple doses taken at short intervals

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.

Physiological Variables That Modify Drug Effects Age Gender Pregnancy Underlying causes in each are changes that occur in body composition, physiology, and organ changes © Pixtal/SuperStock

Adaptive Processes Tolerance: Changes causing decreased response to a set dose of a drug Dependence: The physiological and psychological changes or adaptations that occur in response to the frequent administration of a drug Withdrawal (see diagram on following slide, Fig 5.4, p. 172)

Adaptive Processes (continued) Figure 5.4 The relationship and consequences of adaptive processes to drug abuse.

Tolerance Reverse tolerance (sensitization): Enhanced response to a given drug dose; opposite of tolerance. If sensitized, you would have the same response to a lower dose of a drug as you initially did to the original higher dose Cross-tolerance: Development of tolerance to one drug causes tolerance to related drugs. This may be due to altered metabolism resulting from chronic drug use. (usually same type of drug category)

Tolerance

Discussion Why would a drug with a relatively narrow margin of safety be approved by the FDA for clinical use? Give an example. Discuss in your group what might be examples when a high potency drugs could be self-medicated and low potency drugs that must be given under medical supervision.

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

Psychological Factors Affecting Drug Effect Individual’s mental set – The setting, or total environment, in which a drug is taken may modify its effect (Individual’s personality, past history of drug use, social experience, attitudes toward the drug , etc) Placebo effects – The psychological factors that influence the responses of drugs independent of their pharmacological properties

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. More recently the term “substance use disorder” has been used. A common definition for all of these terms 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 – the intense desire for drugs, considered a distinct phenomenon of withdrawal.

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

End of Presentation