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Neuropharmacology
We now focus here:
Don
He came for a consultation 5 weeks ago, and ropinirole was replaced with
a monoamine oxidase inhibitor drug. He now reports his interest in
gambling has disappeared.
Two Receptor
Subtypes
ionotropic metabotropic
Two Types of Synapses
ionotropic receptors
Glutamate – metabotropic receptors
Tre
Summary of glutamate’s actions
GABA
Symptoms appear within 20 minutes, starting with stiffness of the neck, twitching
muscles, and feeling of suffocation, then violent convulsions in which the body is arched
and the head bent backward. After a minute muscles relax, but a touch or noise causes
convulsions to recur, or they recur spontaneously, every few min.
Catecholamine Synthesis
Rate-limiting
Case
400 million cups of coffee are consumed every day in America. Mayo Clinic Proceed Aug.
2013: A study of 40,000 individuals found a greater than 50% increased mortality risk in
young men and women who drank more than 4 cups a day
Sites of drug action
Antipsychotic (neuroleptic) drugs
Class of drugs to treat schizophrenia and aggressive behavior
Typical neuroleptics are dopamine (D2) antagonists
Antidepressants
Monoamine oxidase inhibitors (MAOIs) prevent breakdown of monoamines at
the synapse
Accumulation of monoamines is the major action of antidepressants
Antidepressants – Two main modern classes
GABAA complex
Small head
Opiates
Opium and Morphine
Opium contains morphine, a potent analgesic
Binds to opioid receptors in the brainstem, especially locus coeruleus and the
periaqueductal gray
What is the origin of heroin?
Heroin is named for ‘heroic’
Bayer marketed the drug as a cure for codeine addiction before it was
quickly discovered that it rapidly metabolizes into morphine
Oops.
Case
53 y/o man is found down in the driveway of a house. EMS arrives and on exam
he is comatose and his pupils are tiny (2mm) and barely react to light. An IV is
inserted and he is given naloxone.
Within a minute he arouses and opens his eyes.
Diagnosis?
• Oxycontin overdose
Marijuana – active ligand is THC (tetrahydrocannabinoid)
Brain has cannabinoid receptors that bind anandamide and 2-AG (2 arachidonoyl
glycerol) (endocannabinoids) with many effects:
Synthesized 'on-demand‘
Smoking health risk is mostly due to other compounds in tobacco, not nicotine
But nicotine is the addictive component
• Only 5% of each attempt to stop are successful; about the same statistic for
heroin
Cocaine
Leaves from coca shrub alleviate hunger, enhance endurance and sense
of well-being. Not addictive.
Amphetamine and
methamphetamine are synthetic
stimulants
They block reuptake and increase
release of catecholamines
Adderall - dextroamphetamine
Ritalin – methylphenidate
Strattera - atomoxetine
Brain imaging studies show that stimulant medication increases activity in prefrontal
cortex, some subcortical regions, and cerebellum - all centers for executive function.
Cortico-thalamic networks control inhibitory attentional and impulse control systems and
process internal and external stimuli. ADHD medications stimulate these inhibitory
networks to function better.
Hyperactive behavior (leg tapping, fidgeting) stimulates those brain networks to work
better. When the medication stimulates these networks, the hyperactive behavior
becomes unnecessary and is reduced.
LSD resembles serotonin
Amphetamine analog:
Its primary effects in brain are on
neurons that use serotonin
• GHB and its analogues increase libido, suggestibility, passivity, and cause
amnesia - users are vulnerable to sexual assault
What's not trending?
Although the initial decision to take drugs is voluntary, brain changes that
occur over time challenge a person’s self-control and ability to resist
intense impulses urging them to take drugs
NIDA InfoFacts: Understanding Drug Abuse and Addiction
Addiction
Tolerance – decreased sensitivity to a drug as a result of taking it
Sensitization - increased sensitivity to a drug as a result taking it
Cocaine addicts:
nucleus accumbens
Addiction: Pharmacologic treatment strategies
1) Agonistic treatments mimic the drug’s effects, but are milder
• Methadone or buprenorphine for opiate addiction
• Nicotine patch
• Chantix stimulates nicotine receptors more weakly than nicotine does
(partial agonist)
These replace the drug, which helps with motivation