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Phases of Drug Action Pharmaceutical phase Pharmacokinetic phase Pharmacodynamic phase
Pharmaceutical Characteristics of Drugs Physical Properties of the Drug: Drug Composition Tablet Capsule Powder Suspension Solution Excipients Coatings
Routes of Administration 1. Enteral Routes: Oral Gastric Rectal 2. Parenteral Routes: Skin (topical) Lungs (inhalation) Nasal cavity Injection sites Subcutaneous (3-5 min) Intramuscular (3-5 min) Intravenous (15-30 sec) Intraperitoneal Intrathecal
Rate-Limiting in Pharmaceutical Phase Tablets: Capsules (slower speed) Disintegration Powders (medium speed) Dissolution Suspensions & Solutions (fastest speed) Absorption
Pharmacokinetics A mathematical model of drug disposition in the body
Steady State quantity of drug in the body remains constant (rate in = rate out)
Half-life the amount of time required to reduce the blood-drug concentration to one half the original value
Therapeutic Range Blood drug concentrations which generally have little toxicity & are highly effective
Determinants of the Pharmacokinetic Phase Drug Absorption: from fastest to slowest Inhaling 7- 10 sec Injecting 15-30 sec Snorting 3-5 min Orally 20-30 min Transdermal 1-2 days
Determinants of the Pharmacokinetic Phase Drug Distribution: Tissue Mass Percentage of body fat Blood volume to tissue Drug acceptors Tissue barrier mechanisms --Blood-brain barrier --Placental barrier
Determinants of the Pharmacokinetic Phase Drug Biotransformation: Inactive Drug– Active Metabolite Active Drug– Less Active Metabolite Active Drug – Equipotent Metabolite
Pharmaceutical Characteristics of Drugs  Chemical Properties of the drug Drug concentration Molecular size Lipid/ water solubility Degree of ionization
Biological Fate of Psychoactive Drugs Psychobiological Effect (STEPS A DRUG TAKES THROUGH THE BODY) 1. Absorption 2. Distribution 3. Accumulation at Receptors 4. Receptor Occupancy 5. Biotransformation to Inactive Metabolites 6. Redistribution 7. Elimination
biological factors Body weight/ size Age Gender Genotype Health condition Nutritional status Pharmacological state Environmental setting Psychological disposition Personality variables Expectations (set) about drug effects
how does gender effect drug use women and men have different chemicals and hormone levels that affect drugs absorption (ex: more chemicals present in men’s stomach than women’s that allow alcohol to be processed) women have more body fat (factors into metabolization )
anadamide effects Sensory experiences, controls learning, memory, analgesic
Dopamine effects Fine motor regulation, reinforcement, olfaction, mood, concentration, hormone control
Serotonin effects Emotional processing, mood, appetite, temperature control, sleep, pain processing, hallucinations, reflex regulation
GABA Major inhibitory neurotransmitter in CNS, muscle relaxation
Endorphins effects Regulation of pain, mitigation of stress, physiological function
Epinephrine: effects Function as a stimulant, demands energy for body, motivation, hunger, attention span, confidence & alertness
what are Neurotransmitters classified as excitatory or inhibitory according to their effects on postsynaptic membranes.
A neurotransmitter is called excitatory (ex: ACh) if activation of the receptor causes depolarization of the membrane and promotes action potential generation.
A neurotransmitter is called inhibitory (ex: GABA) if the activation of the receptor causes hyperpolarization of the membrane and depresses action potential generation.
Schedule I abuse potential use medical value ex Abuse potential: high Use:? Medical value (USA): none, unsafe without proper supervision Ex: heroin, LSD, THC, PCP
Schedule 2 abuse potential use medical value ex Abuse potential: high Use: may lead to severe dependence Medical value: yes Ex: opium, , cocaine, codeine,
Schedule 3 abuse potential use medical value ex Abuse potential: less than I & II Use: may lead to moderate physical or high psychological dependence Medical value: yes Ex: Tylenol with codeine,
Schedule 4 abuse potential use medical value ex Abuse potential: low Use: may lead to limited physical or psychological dependence Medical value: yes Ex: Valium,
Schedule 5 abuse potential use medical value ex Abuse potential: lower than IV Use: may lead to limited physical or psychological dependence Medical use: yes ex. cough medicine
what part of the brain do most drugs effect Most drugs effect the reward/pleasure center of the brain
Nicotine One of the 4000 active ingredients in T obacco n The most important neurotransmitter with respect to Nicotine: ̈ Dopamine
whats the most active ingredient in tabacco and what is its neurotransmitter nicotine dopamine
Four of the most important Neurotransmitters with respect to alcohol: Glutamate GABA dopamine seratonin
what does alcohol control in the brain Controls reasoning and judgment Controls mood and emotions
Most important Neurotransmitters with respect to Cannabis: Anandamide
Anandamide binds with cannabinoid receptors and activates neurons, which causes adverse effects on the mind and body
what is the Active ingredient in Cannabis delta-9- tetrahydrocannabinol (THC).
Stimulants (2) n Cocaine n Methamphetamines
Cocaine Cocaine prevents the reabsorption of neurotransmitters thus increasing their concentration in the synapse and intensifying the effects
Most important Neurotransmitters with respect to Cocaine: ̈ Dopamine ̈ Serotonin ̈ Norepinephrine
Increase in Dopamine, serotonin, and Norepinephrine levels in Nucleus accumbens and Amygdala do what? the reward pathway
Methamphetamines Methamphetamines causes these neurotransmitters to stay in the synapse longer than Cocaine does ( Norepinephrine ̈ Epinephrine ̈ Dopamine)
Most important Neurotransmitters with respect to Methamphetamines: Norepinephrine ̈ Epinephrine ̈ Dopamine
Methamphetamines does what to the brain? will increase the concentration of Dopamine causing pleasure and in turn activating the pleasure circuit of the brain
Hallucinogens (2) n MDMA n LSD n Psilocybin
Major neurotransmitter with respect to MDMA: ̈ Serotonin
Serotonin what does it do and whats it controlled by? plays an important role in the regulation of mood, sleep, pain, emotion, appetite, and other behaviors controlled by the Limbic system
Major neurotransmitters with respect to LSD: Serotonin - involves in emotions and the senses ̈ Norepinephrine – a sudden release causes an over sensitization of senses
Psilocybin Active ingredient in a number of psychedelic mushrooms
Major neurotransmitters with respect to Psilocybin Serotonin - involves in emotions and the senses ̈ Norepinephrine - a sudden release causes an over sensitization of senses
Cerebral cortex controls what controls mood, cognition, and perception
Environmental & developmental influences are reasons for leading a person into drug abuse what are some examples Stress Anger Peer pressure Boredom
Psychoactive Drugs: Can cause addiction even to those not made susceptible by: Heredity Environment -Excessive, frequent, prolonged use can modify neurochemistry
Compulsive Behaviors -Gambling, compulsive sex, eating disorders -Dysfunctions of brain chemistry -Unlike OCD since actions are associated with pleasure
Addiction characterized by: Tolerance Tissue dependence Withdrawal syndrome Psychological dependence
Addiction occurs when the body adapts to the toxic effects of drugs Given enough of a drug, a person will become addicted
The Diathesis-Stress Theory of Addiction genetics, environment, availability, behaviors (risk taking)
Compulsion Curves heredity, environment, & drug use Different for every person & every substance
Hereditary susceptibility: Inherited brain structure Inherited neurochemical composition
Environmental Factors: Can increase susceptibility to habituation, abuse, & addiction examples of these Childhood experiences Friends Nutrition Heredity + Environment Levels of Use Addiction Abuse Habituation Social/recreatio nal Experimentation Abstinence Levels of susceptibility Susceptibility Stress Media/ads
Long-term or heavy drug use: person to person Might take those with low susceptibility 10 years or more of heavy drinking to become alcoholics. Might take someone with high susceptibility less than a year
Abstinence & detoxification: (addiction/detox) Once people have become addicted, they have changed their brain chemistry. When they stop using, their susceptibility will drop somewhat but never to their starting point.
someone with an ADDICTION: Practices addiction most of the time Continues use despite adverse consequences Denies there
levels of use: abstinence(not using) experimentation (infrequent use, curious) social/recreational habituation (regular patter of use, loss some control over drug) drug abuse: continued use despite negative consequences addiction (compulsive use, loss of control)
Factors Affecting Physiological Dependence Social Economic Drug characteristics Drug user characteristics
Factors affecting actions of drugs Drug Potency Drug Receptors --Agonist Drugs --Antagonist Drugs
Pharmacodynamic model of drug withdrawal: Acute phase -Physical withdrawal Latent phase -Cravings -Depression -Mood alterations
addiction triangle organism, drug, environment (addiction center) Organism: personality, genetics, health Drug: hedonic effects, withdrawal reactions, physiological impact Environment: legal factors, social, stress, availability
Addictive Disease Model AKA medical model a disease that is: Chronic Progressive Relapsing Incurable Potentially fatal Heredity- more important than environment Triggered by drug use & reacts biochemical & neurological irregularities
Addictive Disease Model Heredity: Passes susceptibility to alcoholism, drug addiction, & compulsive behaviors from generation to generation
The alcoholism-associated gene (DRD2A1 allele gene) Gene found in twice the number of severe alcoholics than social drinkers or abstainers (70% vs. 30%) This compulsivity gene-found in people susceptible to alcoholism, addiction, & other compulsive behaviors.
Compulsion Curves Interplay among: heredity, environment, & drug use Different for every person & every substance
Relapse: Recovery from addiction is possible if stress is reduced and alternative coping strategies are adopted but any use will lead to rapid relapse
How do drugs work? Mimic or disrupt natural chemicals Dopamine reward pathway Pat Pathway
Dopamine reward pathway -Released from the amygdala even after only anticipating the drug -After drug is used -> more dopamine is released -> do it again signal -Stop/satiation pathway -damaged in addicts
ADH Alcohol Dehydrogenase A fast ADH or a slow ALDH enzyme can cause acetaldehyde to build up in the body. This may affect an individual’s risk level for alcholism.
ALDH Acetaldehyde Dehyrogenase A fast ADH or a slow ALDH enzyme can cause acetaldehyde to build up in the body. This may affect an individual’s risk level for alcholism.
The major psycho-active ingredient of the marijuana plant is delta-9-tetrahydrocannabinol (THC)
Cannabis Most popular illicit psychoactive drug Major psychoactive ingredient is delta-9-tetrahydrocannabinol (THC) Magnifies the existing personality traits of the user Effects depend on mind-set of the user and setting
pure food and drug act 1906: Pure Food and Drug Act required the labeling of any cannabis in any Over-The-Counter remedies
controlled substance act 1970: Controlled Substance Act reported Marijuana had no potential for medical use
The Harrison Narcotics Act The Harrison Narcotics Act 1914 required those who dispensed "narcotics" to register with the Bureau of Internal Revenue (predecessor to the IRS), pay a tax, and keep records of the drugs they dispensed.
Spectrum of Pharmacological Effects1 1. Disruption in mechanism of attention 2. Impairs short term memory 3. Altered interpretation of sensory info 4. Analgesia 5. Decrease control of motor movement 6. Immunosuppressant 7. Ptosis 8. Increased heart rate 9. Sleepiness . Relaxation
How THC Affects the Body High concentrations of cannabinoid receptors in the hippocampus, cerebellum and basal ganglia. The hippocampus is important for short-term memory.
Inhalation:Factors Affecting Smoked Marijuana Potency: Concentration of THC in plant Amount Smoked Time period for drug ingestion Depth of inhalation
half life of weed ( inhalation) Half life about 30 hours
Oral: marijuana intake Absorption slow & incomplete Onset of action takes 30-60 min & peaks at 2 – 3 hours THC is about 3 times more effective when smoked versus oral
THC Usage Acute Use: Impairs ability to perform complex function requiring attention & mental coordination
Effects of THC on the body Reproductive System: Chronic use by males: can reduce testosterone levels & sperm count Chronic use in females: can reduce hormones FSH & LH can affect menstrual cycles Infants born of marijuana-smoking mother: display withdrawal
Tolerance to Cannabis sativa occurs by 2 separate mechanisms: 1. desensitization of brain cannabinoid receptors 2. rapid receptor internalization followed by agonist binding & receptor activation
tolerance occurs fairly rapidly, even though initially smokers become more sensitive, not less to desired effects.
Dependence ( 3 elements) 1. Preoccupation with acquisition of the drug 2. Compulsive use of the drug 3. Relapse to or recurrent use of the drug (emotionally driven dependence)
Indole Psychedelics LSD & Psilocybin
Catecholamine Psychedelics Peyote (mescaline) & MDMA
Cannabinoids: Marijuana
Other Psychedelics: Ketamine & PCP
hallucinogens general effect Delusions • Hallucinations • Stimulations • Impaired judgment • Distorted reasoning
LSD LSDbindstotheserotonin receptors in the brain. • Affectstheraphenuclei, the center of serotonin activity. – This filters the incoming sensory stimuli. – LSDdisruptsthisprocess, leading to the surge of sensory data.
Dr. Albert Hoffman 1st extracted LSD in 1938 • Was used as therapy for mental illness & alcoholism • 1st discovered Psilocybin in 1959
LSD • Physical Effects: • Rise in heart rate & blood pressure • Higher body temperature • Dizziness • Dilated pupils • Glassy eyes • Some sweating like amphetamines
LSD after effects no dependece • Flashbacks – Short term LSD – One feels the same as they did on the initial trip, which could be pleasant or unlikeable. • Hallucinogen persisting perception disorder (HPPD) long term symptoms similar to Schizophrenia
Psilocybin & Psilocin Activeingredientsin“magic mushrooms” • Bindstotheserotoninreceptors in the brain • Alsoaffectstheraphenucle
Ketamine (originally used?) • Dissociativegeneral anesthetic • used in human & veterinary medical procedures • SimilartoPCP
pcp how was it originally used and what forms does it come in? • Originally used as a general anesthetic in humans but caused hallucinations & was discontinued Forms: Liquid, Crystal, Powder
MDMA • Releases reservoirs of serotonin in brain • More serotonin induces feelings of happiness
Opium Opium - the exuded substance from the poppy Papaver Somniferum which is harvested to make opiates and opioids
opiate Opiate - a drug naturally extracted from opium sap; used to make morphine and codeine; bind to endogenous opiate receptors in the human body
Opioids Opioids - natural and semi-sythetic opium- derivatives as well as wholly synthetic opium-like compounds that also bind to the opiate receptors and have agonistic (activating) properties
Endorphins - Endorphins - naturally occurring internal analgesic peptides which induce morphine- like effects (antagonists of the opioid receptors)
Most Common collegiate Opioids Abused + Relative Strengths § Codeine: 1 unit (of strength) § Vicodin/Norco (Hydrocodone): 4-6x’s (codeine) § Morphine: 7-10x’s § Percodan/OxyContin (Oxycodone): 15-20x’s § Heroin: 20-30x’s
Codeine Commonly prescribed as an analgesic, antitussive (cough suppressant), and antidiarrheal
Vicodin and Norcos Opioid: semi-synthetic derivative from/of codeine (though it is far more powerful) § Active ingredients: Hydrocodone and acetaminophen (Tylenol)
OxyContin and Percodan Activeingredient:Oxycodone § Semi-sythetic (derived from a stimulant poison in opium called Thebaine) § Treatmentforsevere-to-intolerablelong-termpain HIGHLY addicting, quick development of dependence, and EXTREMELY potent § Tolerance develops rapidl
Heroin: Routes of Administration § Injection: commonly found in the hydrochloride salt form, which can be mixed with water and injected with a syringe § Oral: ingestion into gastrointestinal tract § Insufflation (snorting): crushed and absorbed into sinus cavity § Inhalation:
most widely abused substance in the whole world caffine
Created by: channingkahn