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How and Why
Drugs Work
Chapter 5
Wednesday: Would you rather….
A. Find true love
B. Find $10,000,000.00
Find
true
love
Find
$10,000,000.00
68%
32%
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.
Common Side Effects of Drugs
• Nausea or vomiting
• Changes in mental alertness
• Dependence
- Withdrawal
• Allergic reactions
• Changes in
cardiovascular activity
Common Side Effects of Drug
Dose-Response
• 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:
• 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
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
• 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
Pharmacokinetic Factors
That Influence Drug Effects
• Administration
• Absorption
• Distribution
• Inactivation
• Biotransformation and elimination
Forms and Methods
of Taking Drugs
• Oral ingestion
• Inhalation
• Injection
• Topical
application
Distribution
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.
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 single dose
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
© 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
Adaptive Processes
Tolerance
• 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
Physical
Dependence
(e.g.,withdrawal
and rebound)
Psychological
Dependence
(e.g., craving)
Psychological Factors Affecting
Drug Effect
• Individual’s mental set
• Placebo effects
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

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Accessible design: Minimum effort, maximum impact
 
social pharmacy d-pharm 1st year by Pragati K. Mahajan
social pharmacy d-pharm 1st year by Pragati K. Mahajansocial pharmacy d-pharm 1st year by Pragati K. Mahajan
social pharmacy d-pharm 1st year by Pragati K. Mahajan
 

Chapter 5 How and Why Drugs Work

  • 1. How and Why Drugs Work Chapter 5
  • 2. Wednesday: Would you rather…. A. Find true love B. Find $10,000,000.00 Find true love Find $10,000,000.00 68% 32%
  • 3. 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.
  • 4. Common Side Effects of Drugs • Nausea or vomiting • Changes in mental alertness • Dependence - Withdrawal • Allergic reactions • Changes in cardiovascular activity
  • 6. Dose-Response • Many factors can affect the way an individual responds to a drug, including the following: - Dose - Tolerance - Potency
  • 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
  • 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 • Toxicity: The capacity of a drug to do damage or cause adverse effects in the body
  • 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
  • 12. Pharmacokinetic Factors That Influence Drug Effects • Administration • Absorption • Distribution • Inactivation • Biotransformation and elimination
  • 13. Forms and Methods of Taking Drugs • Oral ingestion • Inhalation • Injection • Topical application
  • 15. 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.
  • 16. 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
  • 17. 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
  • 18. 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.
  • 19. Physiological Variables That Modify Drug Effects • Age • Gender • Pregnancy © Pixtal/SuperStock
  • 20. 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
  • 22. Tolerance • 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
  • 24. Psychological Factors Affecting Drug Effect • Individual’s mental set • Placebo effects
  • 25. 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.
  • 26. Addiction and Abuse (continued) • Factors affecting variability in dependence/addiction: - Hereditary factors (genetic variants); responsible for 40–60% vulnerability - Drug craving
  • 27. 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

Notas do Editor

  1. Dose-response relationship = correlation between the response and the quantity of drug administered Threshold = the dose at which an effect is first observed Some response systems have higher thresholds than others, so dose-response curves can be created for different drug effects Some drugs have an all-or-none dose-response relationship The effects of drugs on behavior depend on one’s attitudes toward drugs, emotional state, and previous experiences Set The psychological state, personality, and expectations of an individual while using drugs (internal environment) Setting The physical and social environment in which drugs are used (external environment)
  2. Drugs vary in the timing of the onset, duration, and termination of their effects The time course of a drug depends on how the drug is administered, how rapidly is it absorbed, and how it is eliminated from the body Drug effects can be prolonged by taking additional doses at intervals determined by the time course of the drug Taking multiple doses too close together will increase the maximum blood level of the drug (cumulative effects) An estimated 25% of admissions to emergency rooms result from interactions between alcohol and medications The effects of combining drugs and food can be additive, antagonistic, or synergistic Taking certain antidepressants with certain foods can result in hemorrhaging and stroke More than 150 prescription and over-the counter medications interact negatively with alcohol Dose-response relationship = correlation between the response and the quantity of drug administered Threshold = the dose at which an effect is first observed Some response systems have higher thresholds than others, so dose-response curves can be created for different drug effects Some drugs have an all-or-none dose-response relationship The effects of drugs on behavior depend on one’s attitudes toward drugs, emotional state, and previous experiences Set The psychological state, personality, and expectations of an individual while using drugs (internal environment) Setting The physical and social environment in which drugs are used (external environment)
  3. Safety Many problems arise from impurities rather than from the drugs themselves The purity of drugs varies greatly among illegal drugs – heroin has varied from 4% to 69% Potency refers to a drug’s ability to produce an effect relative to other drugs – some drugs vary naturally in potency y of drug is determined by levels of dosing. A drug that has a lethal dose that is close to the effective dose is more dangerous.
  4. Potency = measured by the amount of a drug required to produce a given effect Toxicity = capacity of a drug to do damage or cause adverse side effects Safety margin = difference between: Dose that produces the desired therapeutic effect in most patients Lowest dose that produces an unacceptable toxic reaction Most drugs have an LD1 well above the ED95
  5. Routes of Administration: Oral Ingestion Absorption from the gastrointestinal (GI) tract is a complicated process Drugs must withstand the digestive processes and pass through the cells lining the GI tract into the bloodstream Drugs from the GI tract travel through veins first to the liver, where they may be metabolized Oral Ingestion Drugs can be consumed in the form of pills, liquids, tablets, or capsules Convenient and safe Not appropriate in emergencies Slow absorption rate may reduce the amount of the drug to an insufficient level Can choke on a drug if not conscious Some ingested drugs cause nausea and vomiting Because conditions in the gastrointestinal tract change constantly, drug absorption is variable Intravenous (IV) injection involves putting the drug directly into the bloodstream Effects are rapid High concentrations can be delivered Irritating material can be injected this way Veins can be damaged over time Infections can be directly introduced into the bloodstream Subcutaneous injection (under the skin) “Skin popping” Can cause necrosis Intramuscular injection (into a muscle) Absorption is more rapid from intramuscular injection due to the greater blood supply in muscles Injection (parenteral drug use) Reach the brain quickly but carry many risks In intravenous injection, or mainlining, drugs are administered directly into the bloodstream In intramuscular injection, drugs are injected into muscle tissue Injecting drugs just below the layers of the skin is called subcutaneous injection Unsterile needles pose risk for infectious diseases such as AIDS Inhalation The drug moves from the lungs into the bloodstream through capillary walls Effects are rapid because blood moves quickly from the lungs to the brain Inhalation Drugs absorbed into the bloodstream via the lungs Fast and efficient Irritates the lungs Inhaled drugs include volatile anesthetics such as glue, paint thinner, and gasoline, in addition to cigarettes, marijuana, and crack cocaine Topical Absorption through the skin can provide slow, steady drug delivery Absorption through the mucous membranes occurs more rapidly When a user snorts cocaine, the drug is absorbed through the mucous membranes in the nose. Topical application (transdermal method) Drugs applied to the skin and absorbed into the bloodstream by placing small disks or patches behind the ear or on the arm or chest Introduces drugs into the body slowly Drugs are absorbed directly into the bloodstream at programmed rates Used to relieve motion sickness, angina pectoris, and nicotine dependency
  6. Routes of Administration: Oral Ingestion Absorption from the gastrointestinal (GI) tract is a complicated process Drugs must withstand the digestive processes and pass through the cells lining the GI tract into the bloodstream Drugs from the GI tract travel through veins first to the liver, where they may be metabolized Oral Ingestion Drugs can be consumed in the form of pills, liquids, tablets, or capsules Convenient and safe Not appropriate in emergencies Slow absorption rate may reduce the amount of the drug to an insufficient level Can choke on a drug if not conscious Some ingested drugs cause nausea and vomiting Because conditions in the gastrointestinal tract change constantly, drug absorption is variable Intravenous (IV) injection involves putting the drug directly into the bloodstream Effects are rapid High concentrations can be delivered Irritating material can be injected this way Veins can be damaged over time Infections can be directly introduced into the bloodstream Subcutaneous injection (under the skin) “Skin popping” Can cause necrosis Intramuscular injection (into a muscle) Absorption is more rapid from intramuscular injection due to the greater blood supply in muscles Injection (parenteral drug use) Reach the brain quickly but carry many risks In intravenous injection, or mainlining, drugs are administered directly into the bloodstream In intramuscular injection, drugs are injected into muscle tissue Injecting drugs just below the layers of the skin is called subcutaneous injection Unsterile needles pose risk for infectious diseases such as AIDS Inhalation The drug moves from the lungs into the bloodstream through capillary walls Effects are rapid because blood moves quickly from the lungs to the brain Inhalation Drugs absorbed into the bloodstream via the lungs Fast and efficient Irritates the lungs Inhaled drugs include volatile anesthetics such as glue, paint thinner, and gasoline, in addition to cigarettes, marijuana, and crack cocaine Topical Absorption through the skin can provide slow, steady drug delivery Absorption through the mucous membranes occurs more rapidly When a user snorts cocaine, the drug is absorbed through the mucous membranes in the nose. Topical application (transdermal method) Drugs applied to the skin and absorbed into the bloodstream by placing small disks or patches behind the ear or on the arm or chest Introduces drugs into the body slowly Drugs are absorbed directly into the bloodstream at programmed rates Used to relieve motion sickness, angina pectoris, and nicotine dependency
  7. Safety Many problems arise from impurities rather than from the drugs themselves The purity of drugs varies greatly among illegal drugs – heroin has varied from 4% to 69% Potency refers to a drug’s ability to produce an effect relative to other drugs – some drugs vary naturally in potency y of drug is determined by levels of dosing. A drug that has a lethal dose that is close to the effective dose is more dangerous.
  8. Transport in the blood Some drug molecules attach to protein molecules; they are inactive in this state Free (unbound) drug molecules can move to sites of action in the body Drugs vary in their affinity for binding with plasma proteins Blood-brain barrier Some drugs can’t cross the blood-brain barrier; they act only on peripheral nerves Only lipid-soluble substances can leave capillaries in the brain Many brain capillaries are covered with glial cells, also increasing the difficulty for compounds to pass out of the capillaries Active transport systems may be needed to move chemicals in and out of the brain Trauma and infections can impair the blood-brain barrier Effects on all neurons Used to be believed that drugs worked by influencing some characteristic common to all neurons, such as the cell membrane which is semi-permeable. By influencing the permeability of the membrane, the drug can alter the electrical characteristics of the neuron. With new research, this theory is in dispute, most scientists cite the specific effects on neurotransmitters as the primary way a drug influences the brain/neurons. Effects on specific neurotransmitter systems Drugs may alter the availability of a neurotransmitter by changing the rate of synthesis, metabolism, release, or reuptake Drugs may activate or prevent the activation of a receptor Combining depressants can cause respiratory depression Stimulants + antidepressants can lead to overexcitement, high blood pressure, and arrhythmia Stimulants + depressants can lead to explosive and dangerous behaviors Cocaine + alcohol produces a potent and toxic substance called cocaethylene Enzyme induction When the body’s cells detect the presence of a foreign drug, they trigger production of more of the specific metabolizing enzyme Causes tolerance Causes interaction of drugs broken down by the same enzyme Enzyme activity returns to normal some time after the inducing drug is no longer being used Enzyme induction and tolerance can occur after use of prescription and OTC drugs, dietary supplements, or illicit drugs Deactivation: A drug ceases to have an effect when it is excreted unchanged from the body or is chemically changed The key drug-metabolizing liver enzymes are a group known as CYP450 The resulting metabolite no longer has the same action as the drug The resulting metabolite can be excreted by the kidneys
  9. TUTORIALS ON CANVAS Tolerance Progressively decreasing responsiveness to a drug Pharmacological tolerance Adjustment or compensation of the body to the presence of a given drug Drug disposition (pharmacokinetic) tolerance Increased metabolism reduces the effect of the subsequent dose May relate to enzyme activity or alteration of urine pH Pharmacodynamic tolerance Sensitivity of neurons change after repeated use of a drug Can cause withdrawal reactions Behavioral tolerance Adjustment or behaviors learned by an individual to compensate for the presence of drugs Behavioral tolerance Drug may have the same biochemical effect but a reduced behavioral effect as a drug user learns to compensate for nervous system impairment Cross-tolerance Transference of tolerance to a drug to chemically similar drugs Reverse tolerance A drug user’s experiencing of the desired effects from lesser amounts of the same drug https://www.youtube.com/watch?v=8-Qtd6RhfVA
  10. Video is available on Canvas At the ends of axons are saclike vesicles containing neurotransmitters which cross the synapse to receptor sites Chemicals in the receptor sites generate electrical impulses Drugs that influencing the release, storage, and synthesis of neurotransmitters are classified as presynaptic Drugs affecting neurotransmitters after they cross the synapse are classified as postsynaptic Neurotransmitters linked to addiction include dopamine, norepinephrine, GABA, and serotonin Some drugs increase activity and excitation nerve cells (e.g. caffeine) Sedative-hypnotic drugs make nerve cells less sensitive Many nerve cells contain autoreceptors that alter the synthesis of neurotransmitters (e.g. LSD)
  11. Nonspecific effects derive from the user’s unique background, expectations, perceptions, and environment (setting) Specific effects depend on the presence of a chemical at certain concentrations Placebo effects are those produced by an inactive chemical that the user believes to be a drug Especially important in treating pain and psychological depression The effects of drugs on behavior depend on one’s attitudes toward drugs, emotional state, and previous experiences Set The psychological state, personality, and expectations of an individual while using drugs (internal environment) Setting The physical and social environment in which drugs are used (external environment) Placebos are inert substances capable of producing psychological and physiological reactions Placebo prescriptions are effective because of expectations for the drug The notion of a drug being euphoric or dysphoric depends a great deal on set To a large extent, setting determines set Gender: Women are more sensitive to drugs because fat stores drugs and water dilutes drugs in the bloodstream Females are especially affected by drugs during the premenstrual phase of the menstrual cycle and pregnancy Teratogenic drugs damage the developing fetus Use of tobacco, coffee, and alcohol during pregnancy increases the risk of miscarriages Gender: Women are more sensitive to drugs because fat stores drugs and water dilutes drugs in the bloodstream Females are especially affected by drugs during the premenstrual phase of the menstrual cycle and pregnancy Teratogenic drugs damage the developing fetus Use of tobacco, coffee, and alcohol during pregnancy increases the risk of miscarriages