Drugs Use and Abuse Chapter 5, 6, 7, 8, 14 Flashcards
How many people are sent the hospital a year because of side effects?
700,000
Dose-response
correlation between the amount of a drug given and its effects
Factors that affect responses to drugs
- size of the individual,
- stomach contents,
- different levels of enzymatic activity in the liver,
- acidity in the urine,
- time of the day,
- and state of person’s health
Margin of safety
range in dose between the amount of drug necessary to cause a therapeutic effect and that needed to create a toxic effect
Does a magic bullet drug exist?
None found yet (perfect drug)
Potency
amount of drug necessary to cause an effect
• The smaller the dose the greater the potency
Toxicity
– capacity of one drug to damage or cause adverse effects in the body
• Toxic compounds = poisons
o 3 types of drug interactions:
- 1) Additive
- 2) Antagonistic (inhibitory)
- 3) Potentiative (synergistic)
Additive interactions
summation of effects of drugs taken concurrently; happens when drugs are similar and actions are added together
Antagonist interactions
– effects created when drugs cancel one another
Synergism
– ability of one drug to enhance the effect of another; also called potentiation
PHARMACOKINETIC FACTORS THAT INFLUENCE DRUG EFFECTS (5)
- Administration (how the drug enters the body)
- Absorption
- Distribution
- Activation (where does the drug produce its effects)
- Biotransformation and elimination (How inactivated or metabolized)
Pharmocokinetics
Study of factors that influence the distribution and concentration of drugs in the body
4 Principal forms of drug administration
- 1) Oral ingestion
- 2) Inhalation
- 3) Injection
- 4) Topical application
Oral ingestion
o Most common and convenient ways
o Introduces drug into the body by way of stomach or intestines
o Difficult to control amount of drug that reaches the site of action for 3 reasons:
• 1) Drug must enter bloodstream after passing through the wall of the stomach or intestines without being destroyed or changed to an inactive form, the drug must diffuse to the target area and remain there in sufficient concentration to have effect
• 2) Materials in the stomach like food can interfere with the passage of some drugs through the gut lining and thus prevent drug action
• 3) Liver might metabolize orally ingested drugs too rapidly, before they are able to exert an effect
Inhalation
o Through mouth or nose
o Because of large capillaries in lungs, chemicals can enter the blood rapidly as they can via IV and can be equally dangerous
o One serious problem is the potential for irritation to the mucous membrane lining of the lungs
o Drug may have to be continually inhaled to maintain the concentration necessary for an effect
o Common to prevent contracting AIDS which can be contracted via injection with a contaminated needle
Injection
o Intervenous (IV) (in the vain), intramuscular (IM) (into the muscle, or subcutaneous (SC) (drug injection been the skin)
o Advantage is the speed of action, delivered rapidly and direction and often less drug is needed
o Impurities may irritate the vein (needle sharing)
• Same site injection elasticity of the vein is reduced causing the vessel to collapse
o Intramuscular can damage the muscle
• If nerve is destroyed, the muscle will degenerate (atrophy)
o Subcutaneous may damage skin
o Needle sharing common problem
Topical application
o Skin, lining of the nose, and under the tongue for systemic (whole-body) effects
4 Factors affecting drug distribution
o 1) Ability to pass across membranes and through tissues
o 2) Their molecular size
o 3) Their solubility properties
o Drugs that are soluble in fatty solutions are most likely to pass across these capillary membranes
o 4) Their tendency to attach to proteins and tissues throughout the body
Threshold dose
minimum drug dose necessary to cause an effect
Plateau effect
- maximum drug effect, regardless of dose
- o OTC drugs have a limit on their effect
- o Other drugs may cause distinct or opposite effect (ex: small dose of alcohol stimulant, large doses sedative effects)
Half-life
time required for the body to eliminate and/or metabolize half of a drug dose
o Body eliminates the drug either directly without altering it chemically or in most instances after it has been metabolized or modified
Biotransformation
process of changing the chemical properties of a drug usually by metabolism
Primary organ for metabolism of drugs
o Liver primary organ that metabolizes drugs in the body
• Contains hundreds of enzymes that continually synthesize, modify, and deactivate biochemical substances
• Metabolizing enzymes highly regulatable
• Genetic variations on their structures can account for a wide variations in their activity, influencing onset, duration, and potency of drug effects
o Kidneys next most important organ for drug elimination because they remove metabolites and foreign substances from the body
• Kidneys constantly eliminate substances from the blood
• Rate of excretion of some drugs by the kidneys can be altered by making the urine more acidic or more alkaline
o Body may eliminate small portions of drugs through perspiration and exhalation
Metabolites
chemical products of metabolism
3 Physiological variables that modify drug effects
- Age
- Gender
- Pregnancy
Tetratogenic
something that causes physical defects in a fetus
Dependence
physiological and psychological changes or adaptations that occur in response to the frequent administration of a drug
Reverse Tolerance
enhanced response to a given drug dose, opposite of tolerance
o Same response to a lower dose than an original higher dose
o Some researchers believe that its development depends on how often, how much, and in which setting the drug is consumed
o May reflect adaptive changes in the nervous tissues
Rebound effect
form of withdrawal; paradoxical effects that occur when a drug has been eliminated from the body
• Paradoxical because symptoms are nearly opposite to the direct effects of the drug
Cross-dependence
dependence on a drug can be relieved by other similar drugs
Psychological dependence
dependence that results because a drug produces pleasant mental effects
o Does not produce the physical discomfort, rebound effects, or life-threatening consequences that can be associated with physical dependence
o Psychological aspects may be more significant that physical dependence in maintaining chronic drug use
o Fact that their dependence does not typically induce antisocial and destructive behavior distinguishes them from most forms of dependence-producing drugs (ex: tobacco or coffee)
Mental set
the collection of psychological and environmental factors that influence an individual’s response to drugs
Drug craving (3 assessments)
- 1) Questioning patients about the intensity of their drug urges
- 2) Measuring physiological changes such as increases in heart and breathing rates, sweating, and subtle changes in the tension of facial muscles
- 3) Determining patients’ tendency to relapse into drug-taking behavior
o Distinct from the phenomenon of withdrawal
o Not likely that craving itself causes drug addiction
Dysphoric
characterized by unpleasant mental effects; the opposite of euphoric
4 Other Factors affecting drug abuse
o 1) Peer pressure
o 2) Home, school, and work environments
o 3) Mental state
o 4) Excessive stress
o 30% - 60% of drug abusers have some underlying psychiatric illness
2nd only to narcotic medications as the most frequently abused group of prescription medications
CNS depressants
Why are CNS depressants so problematic
- Prescription
- Use of CNS depressants can cause alarming, even dangerous behavior if not monitored closely
- Several seemingly unrelated drug groups have some ability to cause CNS depression and all too frequently are the cause of death by drug overdoses (Drugs mix and can be deadly)
- CNS depressants can cause disruptive personality changes that are unpredictable and sometimes very threatening
History of CNS depressants
1800s introduce bromides
1900s Barbiturates
1950s benzodiazepines
1970s and 1980s epidemic of prescription CNS depressants
Sedatives
CNS depressants used to relieve anxiety, fear, and apprehension
• Anxiolytic – drug that relieves anxiety
• Many have muscle-relaxing properties that enhance their relaxing effects
Hypnotic
CNS depressants used to induce drowsiness and encourage sleep
• Produce amnesiac effect as well
• Amnesiac – cause the loss of memory
Most frequently prescribed CNS depressant?
Benzodiazepines (like Valium)
o Large margin of safety
o Were originally referred to minor tranquilizers
o 1st benzodiazepine, chlordiazepodxide, 1960
• Valium came around the market the same time
o Valium 1972-1978 was the top-selling prescription drug in the US
o Benzodiazepine Schedule IV drugs because of dependence problems
Benzodiazepines affect what receptors of neurontransmitters
Neurotransmitter GABA (gamma aminobutyric acid)
GABA
o GABA is a very important inhibitory transmitter in several regions of the brain: the limbic system, the reticular activating system, and the motor cortex
o Benzodiazepines the inhibitory effects of GABA are increased
o Alter mood (limbic function), cause drowsiness (reticular activating system function), relax muscles (cortical function)
o Flumazenil, highly selective antagonist drug used to treat benzodiazepine overdoses
How many benzodiazepines available in US
15
Side effects of benzodiazepines
o Drowsiness, lightheadedness, lethargy, impairment of mental and physical activities, skin rashes, nausea, diminished libido, irregularities in the menstrual cycle, blood cell abnormalities, increased sensitivity to alcohol and other CNS depressants
o Only very high doses have a significant impact on respiration unlike barbiturates
o Serious suppression occurs when drugs combined with other depressants most often alcohol
o Used 50% of the time to treat persistent disorders such as chronic insomnia
o Have less effect on REM sleep than do barbiturates
• REM sleep – the restive phase of sleep associated with dreaming
o On rare occasion, cause paradoxical effects, like nightmares, anxiety, irritability, sweating, and restlessness
o These drugs should be prescribed at the lowest dose possible and for the shortest time possible or withdrawal problems can result
o Relatively new for insomnia, Ambien and Sonata Schedule IV
Barbiturates History
First synthesized by Bayer in 1864
o 1st barbiturate, barbital (Veronal) was used in 1903
o Since then more than 2500 barbiturates have been synthesized ; only 50 actually approved for human use
o Due to serious side effects only a few are still prescribed for medical purposes
o Names of barbiturates traditionally end in –al
Mechanisms of action and elimination of Barbiturates
o Precise mechanism of action for barbiturates is unclear
o Likely interfere with activity in the reticular activating system, limbic system, and motor cortex
o Do not seem to act at a specific receptor site; probably generally effect the inhibitory transmitter GABA
o Benzodiazepines and barbiturates have overlapping effects
o Different pharmacological features
o Fat solubility of barbiturates is another important factor in the duration of their effects
o Move rapidly in and out of tissues and are likely to be shorter acting
o Fat-soluble barbiturates are likely to be stored in fatty tissue, fat content of the body can influence the effects on the user
• Therefore men and women differ
Barbiturate-like drugs
o All of these drugs cause substantial tolerance, physical and psychological dependence, and withdrawal symptoms
o Likely replaced by safer benzodiazepines
o Safety closer to barbiturates
o Significant abuse potential
o Methaqualone – Schedule II
o Glutethimide and Methyprylon – Schedule III
o Chloral Hydrate – Schedule IV drug
Chloral hydrate
o Noctec of “knock-out drops)
o Slipping into people’s drinks to make them unconscious
o In 1800s mix of chloral hydrate and alcohol given name Mickey Finn when sailors short on supply on Barbary Coast of San Francisco
• Drink, wake up as a crew member
o Good hypnotic
o Narrow margin of safety
o Stomach irritant especially if given repeatedly and in fairly large doses
o Schedule IV
Glutethimide
o Doriden
o Can be abused and that causes severe withdrawal symptoms
o Induces blood abnormalities (anemia and abnormally white cell counts)
o If taken regularly in moderate doses, can cause nausea, fever, increased heart rate, and convulsions
o Schedule III
➢ Methyprylon
o Noludar
o Short-acting nonbarbiturate
o Used as a sedative and hypnotic
o Similar to Doriden
o Schedule III
Methaqualone
o Schedule II
o Few drugs have become so popular so quickly as methaqualone
o Sedative-hypnotic
o Introduced in India in the 1950s as an antimalarial agent
o Available in US as Quaalade, Mequin, and Parest
o Since 1985 not manufactured in the US
o Side effects: fatigue, dizziness, anorexia, nausea, vomiting, diarrhea, sweating, dryness of moutn, depersonalization, headache, and paresthesia of the extremities (pins and needles sensation of the extremities)
o Hangover
Antihistamines
o Both nonprescription and prescription medicinal products
o Relieve symptoms associated with the common cold, allergies, and motion sickness
o Many antihistamines cause significant CNS depression are used both as sedatives and hypnotics
o Exact mechanism of CNS depression cause by these agents not totally known
o Seems to relate to their blockage of acetylcholine receptors in the brain (antagonize the muscarinic receptor types)
o Anticholinergic activity helps cause relaxation and sedation
Propofol, An Abused General Anesthetic
o Diprivan
o Initially made available in 1986 and used intravenously for rapid sedation, analgesia, and general anesthesia in hospital or outpatient clinics
o Used off-label to relieve severe chronic or migraine headaches in pain clinics or for sleep induction in patients suffering from insomnia
o Initially thought to be free of abuse
o Physical dependence is rare
o Drug can cause euphoria and relive stress and pain, and has been abused and involved in suicides and accidental deaths
o Recent abuse problems have particularly involved droctos and nurses who have access to this anesthetic
o Not a scheduled substance, so easy to obtain and its effects wear off in a matter of minutes
GHB (Gamma-hydroxybutrate): The Natural Depressant
o GHB is colorless, tasteless, and odorless found naturally in the body resulting from metabolism of the inhibitory neurotransmitter GABA
o Some evidence that GHB is itself a neuromodulator with its own receptor targets in the brain
o Has been used in Europe as an adjunct for general anesthetic, a treatment for insomnia, and narcolepsy, treatment for alcoholism and alcohol withdrawal and narcotic dependence
o During 1980s, GHB became available OTC in health food stores and was used by body builders to stimulate the release of growth hormone to reduce face and build body muscle
o More recently, became popular for recreational use due to pleasant, alcohol-like, hangover-free high with aphrodisiac properties
o Because of abuse potential, GHB restricted by DEA in 2000
o Became known as a club drug
Substance abuse can be diagnosed when 3 of the following 8 criteria met
- 1) Person need greatly increased amounts of the substance to achieve the desired effect
- 2) Characteristic withdrawal occurs when drug use is stopped, encourages continued use of the substance
- 3) Substance is consumed in larger amounts over a longer period of time than intended
- 4) Person shows persistent desire or repeated unsuccessful efforts to decrease substance use
- 5) Great deal of time is spent obtaining and using the substance or recovering from its effects
- 6) Daily activities revolve around the substance
- 7) Person withdraws from family activities and hobbies to use substance privately or spend more time substance-using friends
- 8) Person continues use of the substance despite recognizing that it causes social, occupational, legal, or medical problems
Those who chronically abuse the CNS depressants prefer 3 things
- 1) Short-acting barbiturates such as pentobarbital and secobarbital
- 2) Babiturate-like depressants such as glutethimide, methyprylon, an d methaqualone
- 3) Faster acting benzodiazepines such as Valium, Xanax, or Ativan
Treatment of CNS depressant withdrawal
o Withdrawal symptoms include: anxiety, tremors, nightmares, insomnia, anorexia, nausea, vomiting, seizures, delirium, and maniacal activity
o Duration and severity of withdrawal dependent on the particular drug taken
o Approach to detoxifying a person who is dependent on a sedative-hypnotic depends on the nature of the drug, the severity of dependence, and the duration of action of the drug
o General objective to eliminate drug dependence in a safe manner while minimizing discomfort
o In reality, detoxification is rarely sufficient by itself to assure long-term abstinence from the drug
o Often basic approach is substitution with either pentobarbital or the longer-acting Phenobarbital then gradually reduced
o Using a substitute is necessary because abrupt withdrawal for a person who is physically dependent can be dangerous
o Problem of psychological dependence maybe more difficult to handle
• These types of patients require intense psychological counseling and must be trained to deal with their difficulties in a more constructive and positive fashion
• Without such psychological support, benefits from detoxification will only be temporary
Natural depressants
o Some plants that contain naturally occurring CNS depressants are included in herbal products or made into teas for relaxation or a treatment for sleep problems
o Best known – kava kava plan (piper methysticum)
• Belong to the pepper family and grows on South Pacific islands
• Popular in Polynesian populations and sometimes used in religious ceremonies
• Extract prepared from the part of the kava kava plant beneath the surface of the ground
• Small amounts cause euphoria and increased sociability, large doses cause substantial relaxation, lethargy, relaxed lower limbs, and eventually sleep
o 2nd type of common herb that contains CNS depressants is the Datura family of plants
• Typically associated with hallucinogenic effects
• Smaller amounts can cause sedation and even induce sleep
• Ex: Devil’s trumpet (Datura inoxia) and Jimson weed or thornapple (Datura Stramonium)
• Active ingredient typically anticholinergic drugs such as atropine or scopolamine
• Actions of the herbs are somewhat similar to the OTC antihistamine-containing sleep aids
• Higher doses cause hallucinogenic effects
• Cause constipation, dry mouth, blurred vision
Most consumed drug in the world
Alcohol (ethanol)
Only alcohol used for human consumption
Ethanol
Lethal level of alcohol dose
between 0.4% and 0.6% BAC