Pharmacology Final

drug used for non-medical purpose

drug is taken for a medical purpose incorrectly

• drug seeking behavior
• always comes first

signs of withdrawl

drug-class specific physiological changes

when use becomes excessive and difficult for the person to stop using the drug

• decreased response to effects of the drug over time
• marked increase in the amount of substance required to achieve the same effect

• increased metabolism of the drug
• ex. decreased half life of barbiturates

• a learned skill to reduce drug's influence
• ex. alcohol

• compensatory changes in receptor
• most common tolerance
• receptor internalization

• increased response with repitition of the same drug dose
• ex. amphetamine

• tolerance to other drugs
• ex. amphetamine vs. meth
• caffeine vs. nicotine
• psilocybin vs. mescaline

• treatment for drug dependance
• substitute a longer acting drug
• prevent withdrawl symptoms

acheive a complete withdrawal of drug while not inducing any withdrawal syndromes

• ventral tegamental area
• substantia nigra

• VTA
• mesolimbic pathway

L-Dopa

• mesolimbic pathway
• mesocortical pathway
• nigrostraital pathway
• tuberoinfundibular pathway

• drug dependance
• VTA-nucleus accumbens

• schizophrenia
• VTA-frontal cortex

• motor control
• parkinsons disease
• substantia nigra-striatum

• hormone secretion
• hypothalamus-pituitary

B. Nigrostriatal

• brain is hijacked during recreational use
• not true because only occurs in 32% of tobacco users

• postsynaptic molecule in dopamine signaling
• Genetic basis of adiction

cortical and thalamic

5-HT2A in prefrontal cortex

NMDA glutamate receptor

irreversible schizophrenia like psychosis

• Opioids
• Cannabinoids
• GHB
• LSD, mescaline, psilcybin

• MU-OR
• Agonist
• disinihibition of DA
• 4

• CB1-R
• Agonist
• Disinhibition of DA
• 2

• GABAb - R
• Weak agonist
• Disinhibition of DA

• 5-HT2A-R
• Partial agonist
• 1

• nicotine
• alcohol
• benzodiazepines
• phencyclidine, ketamine

• nACh - R
• Agonist
• Excitation of DA neurons
• 4

• GABAa, 5-HT3, nACh, NMDA, Kir3
• Excitation/disinhibition of DA neurons
• 3

• GABAa
• Positive modulator
• disinhibition of DA neurons
• 3

• NMDA
• antagonist
• 1

• Cocaine
• Amphetamine
• Ecstacy

• DAT, SERT, NET
• Inhibitor
• blocks DA uptake
• 5

• DAT,NET,SERT,VMAT
• reverses transport
• Blocks DA uptake, synaptic depletion
• 5

• SERT > DAT
• reverses transport
• blocks DA uptake

• high abuse potential
• no medical use

• High abuse potential
• Medical use with severe restriction
• Psychological and physical dependance

• Abuse potential less than I and II
• mediacl use
• moderate or low psyc and phys. dependance

• abuse potential less than III
• aceptable medical use
• Psyc and phys. dependance less than III

• Minimal abuse potential
• acceptable medical use
• limited dependance risk

• MDMA
• Ecstasy
• GHB
• heroin
• psilocybin/psilocyn
• mescaline
• LSD

• Cocaine
• Codeine

• anabolic steroids
• buprenorphine
• dronabinol
• ketamine

pams

codeine preparations

• natural
• semi-synthetic
• synthetic
• endogenous

• morphine
• codeine
• thebaine

heroin

• fentanyl
• methadone
• meperidine

• endorphin
• enkephalins
• dynorphin

• fentanyl
• heroin
• meperidine

• MU
• delta
• kappa

• morphine
• heroin

enkephalin

dynorphin and other endogenous

• heroin
• morphine

• fentanyl
• oxymorphone
• hydromorphone
• morphine

• codeine
• dihydrocodeine
• ethylmorphine

• loperamide
• difenoxin
• morphine

morphine

• oxymorphone
• dihydrocodeine

• sniffing
• orally
• smoking

3-5 hours

• lacrimation
• rhinorrhea
• yawning
• sweating

• hypothermia
• hypotension
• bradycardia
• mydriasis

antagonist

• Naloxone
• Methadone
• Clonidine

• acute toxicity by heroin
• short half life

longer acting

inhibit sympathetic overactivity like nausea, vomitting, cramps, hypertension

• 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)

tip of femal plant used for smoking

concentrated resin physically extracted by rubbing or with ice

sticky resin of the plant before pressed into hasish

ethanol extract of cannabis

bind cannabinoid receptor

• Phytocannabinoids
• endogenous cannabinoids
• synthetic cannabinoids

• analgesic
• appetite stimulant
• antiemetic
• schedule III

schedule 2

cannabinoid extract oral spray

rimonabant CB1 antagonist

• hallucinogens
• psychotomimetics
• GPCR 5-HT2A

5-HT2

5-HT1A & 5-HT1C

hallucinogenic potency

• distorted sensory perception
• colors seem bright & vivid
• objects appear distorted
• Auditory perception is enhanced
• time sense is distorted

• increased HR and BP
• n/v
• stomach pain

• cactus buds
• 1000-3000x less potent than LSD
• 30x less potent than psilocin

5-HT2A

• found in fungi
• a prodrug for psilocin

5-HT1A/2A/2C

• MAO in the liver
• MAOIs would inhance effects

• a neuroprotective drug for narcolepsy
• acts through GABAb
• date rape drug
• alcohol enhances sedative effects

cotinine

nAChRs

• most widely used substance
• third leading cause of death

• >4 femal
• >5 male

• >1 F
• >2 M

• 90% oxidized in the liver
• remainder is excreted in the lungs and urine

• alcohol dehydrogenase pathway
• Microsomal Ethanol Oxidizing System (CYP2E1)

• sedation and anxiolytic
• slurred speech
• ataxia
• impaired judgement

depressed myocardial contractility

• muscle relaxtion due to aldehyde
• hypothermia

less alcohol dehydrogenase

• decreas in:
• alveolar macrophage
• T cell & B cell
• aquired immune response
• Th1/Th2 switch

• congenital heart defects
• neurological deficits

• naltrexone
• acamprosate
• disulfiram

• orally active MU opioid receptor antagonist
• do not use in pt. on opioids

• reduces relaps when used with psychotherapy
• may cause GI discomfort and rash

• aldehyde dehydrogenase inhibitor
• acetaldehyde accumulates in the system
• no effects on non-drinkers
• causes flushing, throbbing, n/v, hypotension in alcoholics

• short term
• medium and long acting

• lorazepam
• diazepam

• bromazepam
• chlordiazepoxide
• clorazepate
• medazepam
• nordazepam

• flurazepam
• quazepam
• estazolam

• lormetazepam
• midazolam
• loprazolam
• brotizolam
• nitrazepam

• triazolam
• nimetazepam
• temazepam
• flunitrazepam
• flutoprazepam

• Diazepam
• Temazepam

• Diazepam
• Chlordiazepoxide
• Lorazepam
• Oxazepam

• pregnancy
• labor
• lactation
• mysthania gravis
• chronic psychosis driving

synergistic effect

slows down absorption

increases half life

increased half life

increase metabolism rate

worsening of parkinsonian symptoms

• both developed as anesthetics
• only ketamine is used

ketamine

• tropane alkaloid
• CNS stimulant
• appetite suppressant
• inhibits SET, DAT and NET reuptake

• reduced appetite
• increased/distorted sensations
• hyperactivity
• dilated pupils
• flushing
• ED, increased RR and BP

• anxiety/nercousness
• euphoria
• creative thinking
• increased energy/well being sense
• goal oriented thoughts

• Hyperthermia
• dehydration
• serotonin syndrome
• seizure