lecture 20 Flashcards
How is cocaine metabolized?
Metabolized via hydrolysis and CYPs, so metabolites are found in urine
What are four psychostimulants street drug?
Amphetamines
cocaine
ecstasy
methamphetamine
what are some opioid derivatives
hydrocodone
codeine
hydromorphone
meperidine
oxycodone
fentanyl
heroin
What are the physiological effects of taking morphine (opioids)?
Increase threshold of pain tolerance
respiratory depression and sedation
euphoria
pupil constriction, nausea
constipation since GI mobility is decerased
What are the two mechanims of opiod misuse?
1: Tolerance&withdrawal: patient who used opiod to manage pain for a long time got addicted to it, having withdrawl effect if stop using
2: Activate opiate reward pathway: Stimulate the release of dopamine throught disinhibition of GABA
WHat are the two types of tolerance that can be deceloped from benzo misuse?
1: relapse= return of the original symptoms
2: rebound= return of the original symptoms at a greater intensity than before
What happen if cocaine is mixed with alcohol?
Toxic cocaethylene byproduct is formed, which is more cardio toxic than using cocaine itself
What is Amphetamines? What does it do and how does it do it?
Amphetamines is a CNS stimulant that induce fight or flight response, by increasing the relase of dopamine and norepinephrine
Norepinephrine hyperactitivity causes wakefulness, alertness, increase speed of response, euphoria and energetic
Dopamine hyperactivity causes reinforcement, sterotypy, paranoia, hallucianations
What is crack? What is the difference between crack and coke in terms on effect? Why is it even worse?
Crystal rocks that was made with cocaine and alkaline solution such as baking soda
It is heated to give off vapour that is inhaled, so crack is “smoked” by user
Crack is absorped faster, and has shorter duration of action, so more intense euphoria is achieved
It is more cardiotoxic due to the impurities adulteration, and it is more addicting due to it shorter duration of action
What is ecstasy? What is the mechanism of action and the effect?
It is large class of drug that are MDMA derivatives
It has affinity for 5HT2 receptor, increase the release of dopamine and serotonin, and block serotonin reuptake
It causes increase in energy and alertness, increase calmess, decrease anger and hostility, increase sensory awarensess
What is heroin in terms of production? What is significant about its potency?
It a semi-synthetic opioid, and it is 3 times more potent than morphine
It is rapidly converted into morphine by DME
highly addictive, short acting and more rewarding
More euphoric effect
What is ketamine? What is it used for and its mechanism of action
It is a analgesic/ anaesthetic drug, which is a NMDA non-compepetitive antagonist. It blocks the NMDA, causing disociative anaesthetic
It increase DA efflux and inhibit DAT, causing positive reinforcement effect
What is methamphetamines? What is the effect and mechanism of action? Compare to amphetamines
It is CNS stimulant drug, that increase the release of amines (DA, NE, 5HT), and makes them not as readily removed or degraded
Similar effect as amphetamines but it has more pronouced CNS effect, since its more lipid soluble
WHat is the acute toxic effects of ecstatsy? How is it fatal?
It is fatal as it can cause dehydration and hyperthermia
It can cause seotonin syndrome, memory loss, and amphetamine like effect such as hypertension, loss of appetite, nausea and vomiting, and ventricular arrhythmia
What is the bioavailability of THC? What is the effect of the bioavailability?
What is THC solublity? What is the effect?
What is the half life?
It has high oral bioavailability, and slow absorption, and therefore a long duration whe THC is consumed orally
It is lipid soluble, so it reach the brain easier and faster, causing quick onset and effect
Half life : 56 hours
What is the clincial use of benzodiazepines? How does it work?
It is clincally used for anxiety, sedative, anti seizure, muscle relaxant, hypnotic
It can be used to assist in alcohol cessation
It is positive allosteric modulator of the GABA receptor, enhacing GABA effect, depressant and BLUNT CNS excitability
What is the dopamine reward? What does positive reinforcement drug do?
Mesolimbic system is a area in the brain, which scan for reward situation
Positive reinforcement drug increase dopamine in this area, inappropriately, which leads to reinforcement (europhia)
What is the effect of cocaine? talk about acute, high does, OD, and chronic effect
Acute effect: induce fight or flight response, increase mental awareness, euphria, hallucination, delusion and paraonia
High dose: delusion and hallucination, paranoid psychosis, erratic behaviour, convulsion
OD: hyperthermia, , cardiac arrthymia, convulsions, coma, death
Chronic: decrease appetite, hyperactivity and insomnia (difficult to sleep)
What is the mechanism of action of cocaine?
it blocks the reuptake of dopamine, norepinephrine and serotonin, sp DA will stay around for longer to directly activate DA receptor on neurons
It blocks the voltage gated sodium channel, causing anesthetic and cardiovascular effect
What is the mechanism of action of opiates?
It mimics endogenous peptides and bind to opioid receptor, reducing the neuronal excitability via g protein inhibition
Neurotransmission is inhibited, so the pain signal is turned off
Disinhibtion: Opioid inhibit the release of GABA, so doapamine release cannot be supressed, and more dopamine is released
What is the morphine PK?
It has a siginificant first pass metabolism
What is the neurotoxicity of meth?
It increases the release of serotonin as well as doapmine, which damage neuron and cause neronal death
What is the original purpose of synthetic opioids? Name 3 examples
Prescription meication used for chronic and breakthrough pain
1) Oxycontin
2) fentanyl : 100X more potent than morphine, given through patch
3) carfentanil : 10000X more potent, man made illicit high potency opioids, very deadly, intended for use in large animals only
What is the pharmacodynamic of THC? in terms of receptor binding and the mechanism of binding
1: Bind to CB1 presynaptic and CB2 receptor, activate CB1 and inhibit the release of specfic neurotransmitters, causing increase of dopamine (disinhibition)
TO bind to recpetor, it mimics endogenous ligands
