-
drug abuse
drug used for non-medical purpose
-
drug misuse
drug is taken for a medical purpose incorrectly
-
Psychological dependance
- drug seeking behavior
- always comes first
-
Physiological dependance
signs of withdrawl
-
Drug withdrawl results in
drug-class specific physiological changes
-
Drug addiction
when use becomes excessive and difficult for the person to stop using the drug
-
Tolerance
- decreased response to effects of the drug over time
- marked increase in the amount of substance required to achieve the same effect
-
metabolic tolerance
- increased metabolism of the drug
- ex. decreased half life of barbiturates
-
Behavioral tolerance
- a learned skill to reduce drug's influence
- ex. alcohol
-
Functional tolerance
- compensatory changes in receptor
- most common tolerance
- receptor internalization
-
Reverse tolerance
- increased response with repitition of the same drug dose
- ex. amphetamine
-
Cross tolerance
- tolerance to other drugs
- ex. amphetamine vs. meth
- caffeine vs. nicotine
- psilocybin vs. mescaline
-
Detoxification
- treatment for drug dependance
- substitute a longer acting drug
- prevent withdrawl symptoms
-
Goal of detoxification
acheive a complete withdrawal of drug while not inducing any withdrawal syndromes
-
Areas in the brain that produce dopamine
- ventral tegamental area
- substantia nigra
-
most important area in the brain for drug abuse
-
Therapeutic form of dopamine
L-Dopa
-
4 major dopaminergic pathways
- mesolimbic pathway
- mesocortical pathway
- nigrostraital pathway
- tuberoinfundibular pathway
-
Mesolimbic pathway
- drug dependance
- VTA-nucleus accumbens
-
Mesocortical pathway
- schizophrenia
- VTA-frontal cortex
-
Nigrostriatal pathway
- motor control
- parkinsons disease
- substantia nigra-striatum
-
Tuberoinfundibular Pathway
- hormone secretion
- hypothalamus-pituitary
-
Which one of the following dopamine pathway is associated with PD?
B. Nigrostriatal
-
Hijacked brain hypothesis
- brain is hijacked during recreational use
- not true because only occurs in 32% of tobacco users
-
FosB/DFosB
- postsynaptic molecule in dopamine signaling
- Genetic basis of adiction
-
Nonaddictive drugs act on this area of the brain
cortical and thalamic
-
LSD acts on this receptor
5-HT2A in prefrontal cortex
-
PCP and ketamine act on
NMDA glutamate receptor
-
Long term effects of chronic PCP use
irreversible schizophrenia like psychosis
-
Drugs taht bind and activate G-protein coupled receptors
- Opioids
- Cannabinoids
- GHB
- LSD, mescaline, psilcybin
-
Opioids
- MU-OR
- Agonist
- disinihibition of DA
- 4
-
Cannabinoids
- CB1-R
- Agonist
- Disinhibition of DA
- 2
-
Y-Hydroxybutyric acid (GHB)
- GABAb - R
- Weak agonist
- Disinhibition of DA
-
LSD, Mescaline, Psilocybin
-
Drugs that bind to ionotropic receptors and ion channels
- nicotine
- alcohol
- benzodiazepines
- phencyclidine, ketamine
-
Nicotine
- nACh - R
- Agonist
- Excitation of DA neurons
- 4
-
Alcohol
- GABAa, 5-HT3, nACh, NMDA, Kir3
- Excitation/disinhibition of DA neurons
- 3
-
Benzodiazepines
- GABAa
- Positive modulator
- disinhibition of DA neurons
- 3
-
-
Drugs that bind to biogenic amines
- Cocaine
- Amphetamine
- Ecstacy
-
Cocaine
- DAT, SERT, NET
- Inhibitor
- blocks DA uptake
- 5
-
Amphetamine
- DAT,NET,SERT,VMAT
- reverses transport
- Blocks DA uptake, synaptic depletion
- 5
-
Ecstasy
- SERT > DAT
- reverses transport
- blocks DA uptake
-
Schedule I
- high abuse potential
- no medical use
-
Schedule II
- High abuse potential
- Medical use with severe restriction
- Psychological and physical dependance
-
Schedule III
- Abuse potential less than I and II
- mediacl use
- moderate or low psyc and phys. dependance
-
Schdule IV
- abuse potential less than III
- aceptable medical use
- Psyc and phys. dependance less than III
-
Schedule V
- Minimal abuse potential
- acceptable medical use
- limited dependance risk
-
Schedule I drugs
- MDMA
- Ecstasy
- GHB
- heroin
- psilocybin/psilocyn
- mescaline
- LSD
-
-
Schedule III drugs
- anabolic steroids
- buprenorphine
- dronabinol
- ketamine
-
-
scheduel V drugs
codeine preparations
-
4 major types of opioids
- natural
- semi-synthetic
- synthetic
- endogenous
-
-
Semi-synthetic opioids
heroin
-
synthetic opioids
- fentanyl
- methadone
- meperidine
-
Endogenous opioids
- endorphin
- enkephalins
- dynorphin
-
Drugs abused by healthcare professionals
-
-
Drugs that bind the MU receptor
-
drugs that bind the delta opioid receptor
enkephalin
-
drugs that bind the kappa opioid receptor
dynorphin and other endogenous
-
drugs that have poor oral bioavalibility
-
drugs used to treat acute and chronic pain
- fentanyl
- oxymorphone
- hydromorphone
- morphine
-
drugs used to treat cough
- codeine
- dihydrocodeine
- ethylmorphine
-
drugs used to treat diarrhea
- loperamide
- difenoxin
- morphine
-
Drugs used to treat severe diarrhea
morphine
-
drugs used to treat anxiety due to shortness of breath
- oxymorphone
- dihydrocodeine
-
-
Typical heroin dose produces effec within
3-5 hours
-
Early withdawal symptoms
- lacrimation
- rhinorrhea
- yawning
- sweating
-
Later symptoms of withdrawal
- hypothermia
- hypotension
- bradycardia
- mydriasis
-
Withdrawal syndrom can be precipitated by administereing an
antagonist
-
Treatment for addiction
- Naloxone
- Methadone
- Clonidine
-
Naloxone
- acute toxicity by heroin
- short half life
-
-
clonidine
inhibit sympathetic overactivity like nausea, vomitting, cramps, hypertension
-
Morphine and disease/pregnancy
- enhances HIV replication
- accelerates HIV/AIDS
- reduces IFN-alpha expression
- increases HCV replication
- Increases bacterial infection (morph and codeine)
- low birthweight & development delay (heroin, MSO4)
-
Marijuana
tip of femal plant used for smoking
-
Hasish
concentrated resin physically extracted by rubbing or with ice
-
kief
sticky resin of the plant before pressed into hasish
-
Hash oil
ethanol extract of cannabis
-
tetrahydrocannabinol (THC)
bind cannabinoid receptor
-
three types of cannabinoids
- Phytocannabinoids
- endogenous cannabinoids
- synthetic cannabinoids
-
marinol (dronabinol)
- analgesic
- appetite stimulant
- antiemetic
- schedule III
-
Nabilone (cesamet)
schedule 2
-
Sativex
cannabinoid extract oral spray
-
Treatment for marijuana addiction
rimonabant CB1 antagonist
-
LSD, Mescaline & Psilocybin
- hallucinogens
- psychotomimetics
- GPCR 5-HT2A
-
LSD is an antagonist for
5-HT2
-
LSD is an Agonist for
5-HT1A & 5-HT1C
-
5-HT2 activity has good correlation with
hallucinogenic potency
-
Effects of LSD
- distorted sensory perception
- colors seem bright & vivid
- objects appear distorted
- Auditory perception is enhanced
- time sense is distorted
-
physical effects of LSD
- increased HR and BP
- n/v
- stomach pain
-
Mescaline
- cactus buds
- 1000-3000x less potent than LSD
- 30x less potent than psilocin
-
Receptor that mescaline acts on
5-HT2A
-
Psilocybin
- found in fungi
- a prodrug for psilocin
-
psilocybin acts on the ____ receptor
5-HT1A/2A/2C
-
Psilocybin is metabolized by
- MAO in the liver
- MAOIs would inhance effects
-
GHB
- a neuroprotective drug for narcolepsy
- acts through GABAb
- date rape drug
- alcohol enhances sedative effects
-
Active metabolite of nicotine
cotinine
-
Nicotine acts on the ____ receptors
nAChRs
-
Alcohol
- most widely used substance
- third leading cause of death
-
-
-
Alcohol metabolism
- 90% oxidized in the liver
- remainder is excreted in the lungs and urine
-
Two major pathways of alcohol metabolism
- alcohol dehydrogenase pathway
- Microsomal Ethanol Oxidizing System (CYP2E1)
-
CNS effects of alcohol consumption
- sedation and anxiolytic
- slurred speech
- ataxia
- impaired judgement
-
CV effects of alcohol
depressed myocardial contractility
-
Smooth muscle effects of alcohol
- muscle relaxtion due to aldehyde
- hypothermia
-
Women are more susceptible to alcohol effects because
less alcohol dehydrogenase
-
Immune system effects of alcohol
- decreas in:
- alveolar macrophage
- T cell & B cell
- aquired immune response
- Th1/Th2 switch
-
Not so common Fetal Alcohol Syndrome abnormalities
- congenital heart defects
- neurological deficits
-
Treatment for alcoholism
- naltrexone
- acamprosate
- disulfiram
-
Naltrexone
- orally active MU opioid receptor antagonist
- do not use in pt. on opioids
-
Acamprosate
- reduces relaps when used with psychotherapy
- may cause GI discomfort and rash
-
Disulfiram
- aldehyde dehydrogenase inhibitor
- acetaldehyde accumulates in the system
- no effects on non-drinkers
- causes flushing, throbbing, n/v, hypotension in alcoholics
-
Three types of benzodiazepines
- short term
- medium and long acting
-
BZDs for anticonvulsant use
-
BZD for anxiolytic
- bromazepam
- chlordiazepoxide
- clorazepate
- medazepam
- nordazepam
-
BZDs for mild insomnia
- flurazepam
- quazepam
- estazolam
-
BZDs for moderate insomnia
- lormetazepam
- midazolam
- loprazolam
- brotizolam
- nitrazepam
-
BZDs for severe insomnia
- triazolam
- nimetazepam
- temazepam
- flunitrazepam
- flutoprazepam
-
BZDs used to premedicate for procetures
-
BZDs used for ETOH dependancy
- Diazepam
- Chlordiazepoxide
- Lorazepam
- Oxazepam
-
Contraindications for BZDs
- pregnancy
- labor
- lactation
- mysthania gravis
- chronic psychosis driving
-
BZD interaction with ETOH
synergistic effect
-
BZD with antacid
slows down absorption
-
BZD with oral contraceptives
increases half life
-
BZDs + Isoniazid
increased half life
-
BZDs+Rifmpacin
increase metabolism rate
-
BZDs with L-Dopa
worsening of parkinsonian symptoms
-
Ketamine and PCP
- both developed as anesthetics
- only ketamine is used
-
shows neuroprotective against ischemic brain injury
ketamine
-
Cocain
- tropane alkaloid
- CNS stimulant
- appetite suppressant
- inhibits SET, DAT and NET reuptake
-
Physical effects of amphetamines
- reduced appetite
- increased/distorted sensations
- hyperactivity
- dilated pupils
- flushing
- ED, increased RR and BP
-
Psychological effects
- anxiety/nercousness
- euphoria
- creative thinking
- increased energy/well being sense
- goal oriented thoughts
-
Ecstasy (MDMA) results in
- Hyperthermia
- dehydration
- serotonin syndrome
- seizure
|
|
