Pharmacology-Drugs of Abuse Flashcards
A 20 year old man with a heavy history of heroin use presents to the ED with an 8 hour history of nausea, vomiting, diarrhea, muscle aches and anxiety. He reports that he is trying to quit and had his last hit 24 hours ago. Physical exam reveals a fidgety man with elevated temp, HR, BP, and extreme sensitivity to touch (painful). How might you start to manage his symptoms?
High dose methadone to suppress withdraw symptoms. This can be done because of opiate cross-dependence. He should then be enrolled in a 28 day detox program with decreasing doses of methadone (note that as you decrease the dose, he will feel very uncomfortable). Physical addiction will be gone by 7 days, psychologic addiction may continue for much longer.
Relapse rate for heroin abuse
80.00%
When you take opiates, what effect do they have when they bind to their receptor?
Opiate binds u-opoid receptor -> Gai/o subunit activated -> hyperpolarization (disinhibits DA release) and inhibition of Ca entry (reduced NT release)
When you take cannabinoids, what effect do they have when they bind to their receptor?
Cannabinoids bind CB receptor -> Gai/o subunit activated -> hyperpolarization (disinhibits DA release) and inhibition of Ca entry (reduced NT release). Note that there are many more cannabinoid receptors than opioid receptors.
When you take LSD or mescaline, what effect do they have when they bind to their receptor?
LSD/mescaline are partial agonists at 5HT2 receptors -> activates Gq subunit -> increases IP3 -> Depolarization of neurons -> hallucinations.
When you take caffeine, what effect does it have when it binds to its receptor?
Caffeine antagonizes adenosine-1 receptor -> A1R inhibits Gi/o, A2R activates Gs -> adenosine is displaced from receptors and you get less tired.
What effect does nicotine have once it is bound to receptors?
Nicotine binds nACH receptor (alpha4-beta2) -> cation conductance is increased -> depolarization of neurons facilitates DA release
What effect do benzodiazepines have once bound to their receptors?
Benzodiazepine binds GABA-a receptor -> potentiates GABA -> hyperpolarization and DA release -> Sedation, euphoria
What effect does alcohol have when it binds to its receptor?
Alcohol binds GABA-a -> increases GABA release -> hyperpolarization -> sedation. It also binds NMDA receptors and inhibits glutamate release -> DA release -> Euphoria.
What effect do ketamine and PCP have when they bind to their receptors?
They block the NMDA receptor release of glutamate -> DA release -> Disorientation, hallucinations, euphoria
What are the effects of huffing?
Disorientation and mild euphoria.
How does cocaine cause a euphoric high?
Blocks DAT, NET and SERT -> prevents reuptake of DA, NE and 5HT -> Euphoria from excess DA, NE and 5HT
How do amphetamines cause a euphoric high and neurotoxicity?
Blocks VMAT -> displaces DA, NE and 5HT -> Euphoria from displacement of DA, NE and 5HT. Note that this depletes neuronal stores of these monamines.
How does MDMA cause euphoria and neurotoxicity?
Blocks SERT -> Displaces 5HT -> Euphoria. Note that this depletes neuronal stores of 5HT.
Stimulants of drug abuse.
Cocaine, amphetamines, MDMA, bath salts (weak amphetamines) and nicotine
What are the physiologic changes that occur with chronic stimulant abuse?
Excess release of NE, DA and 5HT causes down regulation of their respective receptors because the receptors are being over activated. Neuronal stores also become depleted of the monamines. This results in decreased stimulatory effects (less NE = less focus), depression (DA & 5HT are mood elevating), anxiety, hunger and weight gain.
What are the DA, NE and 5HT pathways?
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A patient presents to the ED with tachycardia, arrhythmia, HTN, MI, hyperthermia and intracranial hemorrhage. What will differentiate this as a cocaine overdose vs. an amphetamine overdose?
Cocaine: SEIZURES, coma and death. Amphetamine: PSYCHOSIS, paranoia, aggression, skin lesions, tooth/gum disease. Other than these aspects, they both stimulate the sympathetic nervous system and have similar presentations.
Symptoms of cocaine and amphetamine withdraw?
Dysphoria, depression, hunger and drug craving. Note that cocaine withdraw is typically more mild and amphetamine withdraw may include drowsiness and irritability.
A patient presents to the ED with an elevated HR, BP and level of alertness. He is dehydrated and having mild hallucinations. What symptoms might he have if he overdosed on MDMA?
Marked hyperthermia leading to myonecrosis, renal and CV failure. MI, stroke, seizures can occur. 5HT depletion can lead to memory impairment. MDMA is an amphetamine, but hallucinations are more mild than that of normal amphetamines.
Why is it easy for the user to control how much nicotine is absorbed?
Lipophilic droplets are inhaled in the lungs and it rapidly crosses the alveolar membrane and diffuses into the blood where it can travel to the NAc and VTA to initiate DA release.
What would you look for on a drug test if you wanted to know that someone was a smoker?
Cotinine.
Who overdoses on nicotine? What symptoms do they experience?
Tobacco workers. They get green tobacco sickness from elevated nicotine levels in the air. They get sick from overstimulation of the sympathetic nervous system (increased BP, HR and MI). People who smoke often have elevated levels of carboxyhemoglobin and risk for cancer.
How is ethanol metabolized? What drug can inhibit it?
1st to acetaldehyde by alcohol dehydrogenase. 2nd to acetic acid by aldehyde dehydrogenase. The minor pathway involves CYP2E1. Fomepizole inhibits alcohol dehydrogenase.
What happens if an alcoholic decides to drink methanol instead of ethanol?
Methanol -> formaldehyde. Formaldehyde -> formic acid. These are toxic, can cause blindness and you must give ethanol or fomepizole to saturate alcohol dehydrogenase to prevent formation of the toxic intermediates of methanol metabolism.
