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
8. 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
9. Margin of Safety
• The range in dose between the amount of
drug necessary to cause a therapeutic effect
and a toxic effect.
10. 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
14. 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.
15. 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
16. 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
17. 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. 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
• Physiological or Pharmacological tolerance: Changes
causing decreased response to a set dose of a drug
• 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
23. 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.
24. Addiction and Abuse (continued)
• Factors affecting variability in dependence/addiction:
• Hereditary factors (genetic variants);
responsible for 40–60% vulnerability
• Drug craving
25. 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
Hinweis der Redaktion
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)
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)
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.
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
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
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
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.
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
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)
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
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
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