1. How and Why Drugs Work Chapter 5

2. 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)

3. Common Side Effects of Drugs
Nausea or vomiting
Changes in mental alertness
Dependence
Withdrawal
Allergic reactions
Changes in cardiovascular activity
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4. Common Side Effects of Drug (continued)

5. 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?

6. 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

7. 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

8. Dose-Response Curve (see Fig. 5-2, p.151)

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

10. 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

11. 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)

13. 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?

14. 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
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15. Forms and Methods of Taking Drugs

16. 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.

17. 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

18. 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

19. 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.

20. Biotransformation

21. Physiological Variables That Modify Drug Effects
Age
Gender
Pregnancy
Underlying causes in each are changes that occur in body composition, physiology, and organ changes
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22. 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. 152)

23. Adaptive Processes (continued)

24. 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)

25. Tolerance

26. 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.

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

28. 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

29. 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

30. 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.

31. 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

32. End of Presentation