Drugs of Dependence, Addiction and Overdose Flashcards
define physical dependence
occurs when pharmacological adaptation and physiological changes in brain lead to tolerance in which more drug is needed to achieve same effect, withdrawal symptoms will ocurr if use ceased
define psychological dependence
emotional-motivational withdrawal symptoms, many daily drug users show both dependences
What variables work simultaneously to influence probability that user will develop physical/psychological dependence and/or addiction
agent, host and environment in which use occurs
Describe the physical reward pathway in the brain
natural systems reward actions that promote propagation of species producing slight mood elevation
what brain structures are involved in the reward pathways
VTA, nucleus accumbens and frontal cortex
describe the connection between the brain structures in the reward pathways and DA
DA is released in the VTA and is sent to many structures including the nucleus accumbens and frontal cortex
How does the brain cope with change?
CNS has plasticity where it can modify its hardware to best function in changing environments specifically change in receptor numbers
describe the reasons for an increase and decrease in receptor numbers on post-synaptic membranes
increase caused by up regulation due to the presence of an antagonist drug/molecule for a long period of time which significantly reduces the amount of NT released by the pre-synaptic membrane as well as blocking the post-synaptic receptors = more receptors present to try and collect as much of the NT as possible
decrease caused by presence of agonist for a long period of time resulting in down-regulation which blocks the reuptake of NTs causing too many available to post-synaptic membrane = less receptors present
What factors affect likelihood for drug abuse?
availability, cost, purity and potency, mode of administration, time of onset, level of addictiveness
What host factors affect likelihood for abuse?
heredity, metabolism, psychiatric symptoms, prior experiences, propensity for risk taking behaviour
Describe the relationship between morphine and heroin
morphine is synthetically acetylated to produce heroin, once heroin is injected it crosses the BBB and converts to morphine
Describe heroins effect on DA in the brain
heroin binds to and activates the mu opioid receptor inhibiting the release of GABA from the nerve terminal. This reduces GABAs inhibitory effect on DA neurons causing an increase in DA release in the nucleus accumbens. This causes sustained activation of the post-synaptic membrane lasting around 3-5 hours
List the effects of heroin
dry mouth, slurred speech, droopy eyelids, bradycardia, respiratory depression
Why is OD more common in long term drug users?
long term use of the drug causes down regulation of receptors when users tolerance increases and they can’t be sure which concentration they are receiving until its too late
describe cocaine’s effect on DA in the brain
cocaine binds to and blocks DA reuptake transporters on pre-synaptic membranes inhibiting clearance of DA from the synaptic cleft and degradation by the MAO in the nerve terminal, the DA then remains in the synaptic cleft and is free to bind to its receptors on post-synaptic membrane
why do cocaine and heroin together produce an even more intense DA activation?
because they work on different mechanisms on DA neurons of the reward pathway
List the effects of cocaine
talkativeness, physical energy, short term euphoria, tachycardia, HTN
What are the medical uses for amphetamines?
ADHD, obesity and narcolepsy
describe the MOA of amphetamines on DA in the brain
amphetamines have a similar structure to DA and competitively inhibit DA transport, once inside the neuron amphetamines interfere with vesicular monoamine transporter (VMAT) and impede the filling of synaptic vesicles and cytoplasmic DA concentration increases causing the reversal of DAT direction (into synapse instead of into neuron) and increased non-vesicular release of DA
what is the MOA of nicotine?
nicotine activates the nAChRs, stimulates sympathetic and parasympathetic ganglia, skeletal muscles and CNS= activates reward pathway increasing DA
what do vapes contain
nicotine, flavouring and humectant
what is the most dangerous dependence producing drug
nicotine
describe the absorption of ethanol
ethanol is rapidly absorbed in the GIT, first pass metabolism occurs in most cases but saturation of enzymes occurs quickly causing increased absorption into the bloodstream
what enzyme is induced by long term alcohol use and what does it relate to
CYP2E1, relates to tolerance
What nerve does methanol damage when ingested?
optic nerve
what is the antidote for methanol toxicity?
ethanol prevent the conversion of methanol into formate
What effects does ethanol have on the brain?
chronic exposure of ethanol in the brain alters GABA receptors expressed components (decrease alpha1 and increase alpha 4 subunits) resulting in positive allosteric effect reduction, down regulation of GABA a receptors, disinhibition of reward pathways in DA in nucleus accumbens increasing DA levels
What cross tolerance occurs with chronic ethanol use?
produces tolerance to alcohol and cross tolerance to benzodiazepines and other sedatives
Where is cannabis stored in body, how long until it reaches peak concentration here and how long does it take to clear?
cannabis is stored in body fats reaching peak concentration after 4-5 days, slowly released back into body and cleared after 30 days
what are some effects of cannabis
psychomimetic (hallucigen), depressant, relaxation, euphoria, increased appetite, anxiety, paranoia
describe the cannabinoid receptors
CB1Rs: abundant in hippocampus, cerebellum, activation of these Rs inhibits NT release (GABA, Glu)
CB2Rs: exist in immune tissue, modulate pain, explain why cannabis can act as pain relief
What effects can chronic cannabis use have on reproductive system?
can decrease testosterone and sperm count
List the medicinal uses of cannabis
nausea and vomiting, appetite stimulation, glaucoma treatment, treatment resistant epilepsy
Describe what happens in death by resp failure and the most common drugs that cause this
resp depression occurs after decrease in excitatory effect of Glu resulting in px passing out and having reduced breaths, px may inhale own vomit, most commonly caused by opioids and alcohol
Describe most common causes of death by stimulants and name the most common stimulants involved
burst blood vessels in brain, CV heart attack, hyperthermia, most commonly involves cocaine and amphetamines
Why does withdrawal often cause opposite effects of drug?
due to re-sensitisation and re-regulation of receptors in CNS and PNS
List some strategies used in detox and rehab
substitution therapy combined with symptomatic relief then weaning off, counselling, making drug experience unpleasant eg disulfiram for chronic alcohol abuse
What is the best type of opioid to prescribe in substitution therapy?
long acting opioid, avoids lows whilst maintaining “hit”
What is the most effective nicotine withdrawal treatment?
combining a nicotine patch with a self-administered form of nicotine replacement
What are the three phases involved in psychostimulant withdrawal?
crash, withdrawal, extinction
What drugs may be used for an opioid addict to avoid withdrawal symptoms whilst ceasing drug use?
methadone or buprenorphine
list the different monoamine NTs
dopamine, norepi and serotonin
