Drug Dependence

Front 1

Physical reward pathway in the human brain

Back 1

Rewarding stimulus results in information travelling from the VTA to the nucleus accumbens as well as up to the prefrontal cortex. Dopaminergic neurons projecting from the VTA to the nucleus acumbens seem to be the key element

Front 2

Shared physiological effects of abused substances

Back 2

Increase the release of DA in the nucleus accumbens

Front 3

D2 receptors

Back 3

It has been suggested that these receptors are involved in the reward aspect of addiction, but not the withdrawal aspects

Front 4

Difference between down-regulation and desensitization

Back 4

Down-regulation is the decrease in the # of receptors present on membrane. While desensitised receptors are still present on the membrane, but are inactive

vice versa with up regulation and sensitisation

Front 5

morphine/heroin mechanism

Back 5

morphine/heroin modifies the action of DA in the nucleus accumbens and the VTA. at µ opioid receptors, morphine inhibits the release of GABA, therefore reducing the inhibitory effect of GABA on DA neurones, which affects Ca2+ entry. The increased activation of DA neurones and the release of DA into the synaptic cleft results in sustained activation of the post-synaptic membrane. Continued activation leads to euphoria and feeling 'high'.

Front 6

What is involved in the tolerance of heroin/morphine that occurs in addicts

Back 6

It involves a decrease in adenylyl cyclase activity and a progressive uncoupling of receptor with 2nd messenger systems as well

Front 7

Cocaine mechanism

Back 7

cocaine binds to DA re-uptake transporters on the pre-synaptic membranaes of DA neurones, inhibiting the clearance of DA from the synaptic cleft and its degradation by MAO in the nerve terminal. DA remains in the synaptic cleft and is free to bind to its receptor on the post-synaptic membrane. Has the same results of morphine/heroin

Front 8

"speed-ball"

Back 8

combination of heroin and cocaine to produce an intense dopamine activation. This is a result of heroin and cocaine working via different mechanisms DA neurons. Obviously it is extremely dangerous

Front 9

Why is tobacco addictive.

Back 9

Although tobacco is composed of many toxic compounds, pharmacologically nicotine is the active agent in tobacco, which binds to nAChRs throughout the brain, including with the reward pathway. Sensitivity of nAChRs decreases in the presence of nicotine. Which leads to up-regulation of AChR, however it can also cause receptor desensitisation

Front 10

Nicotine mechanism

Back 10

The reward pathway is excited by nicotine, which results in increased DA release in the nucleus accumbens

Front 11

Nicotine Replacement Therapy

Back 11

The aim is to reduce general withdrawal symptoms. This is done by using a patch or chewing gum that stabilise nicotine levels within the blood, and allow users to begin the dissociation of smoking and the physical aspects of the habit

Front 12

Bupropion

Back 12

an antidepressant that inhibits neuronal reuptake of dopamine and noradrenaline. It is also a non-competitive nicotine antagonist at nAChR. It is effective as a nicotine-replacement drug, as it has fewer side effects than using nicotine itself

Front 13

Varenicline (Chantix)

Back 13

a partial agonist that is selective for alpha-4, beta-2 nAChRs. Varenicline blocks the nicotine receptors on the cell surface well enough to prevent withdrawal from the receptors being empty, but also blocks the binding of nicotine itself, which would feed the dependence on tobacco. Therefore, varenicline prevents withdrawal symptoms while moderate levels of dompamine are maintained in the brain.

Front 14

Disulfiram

Back 14

inhibits metabolism as acetaldehyde enters the blood. Used as aversion therapy. Leads to flushing, tachycardia, hyperventilation and stress.

Front 15

How is methanol poisoning treated

Back 15

With ethanol. This will saturate the alcohol dehydrogenase enzyme and prevent the formation of formate. Also ethanol has a greater affinity for the enzyme than methanol does.

Front 16

The effect of ethanol on the CNS

Back 16

It is a depressent, which enhances GABA(A)-mediated inhibition by (+) allosteric interaction; combination with BNZ may cause CNS depression. Also inhibits function of NMDA glutamate receptors and opening of voltage-dependent Ca2+ channels. Also associated with disinhibition of the reward pathways of the brain, with an increase in DA in nucleus accumbens

Front 17

Describe what happens during alcohol tolerance and dependence

Back 17

Decrease in GABA(A) receptor density. Increase in GLu and voltage dependent Ca2+ channels expression.Release of natural endorphins from the pituitary, and therefore alcohol has a mix of (+) and (-) effects, making it perhaps less "addictive" than other drugs.
Can be oxidised by CYP2E1, a cytochrome P450. Unlike alcohol dehydrogenase metabolism, CYP2E1 is induced by long-term alcohol use, contributing to tolerance

Front 18

Caffeine and xanthine alkaloids

Back 18

CNS stimulant that structurally resembles adenosine. At low concentration, caffeine blocks A2a adenosine receptors. While at high concentrations, the xanthines also inhibit phosphodiesterase (PDE), which increase intracellular cAMP

Front 19

Caffeine tolerance mechanisms

Back 19

Regular caffeine consumption increases the # of A2a receptors in the CNS, to compensate for their regular blockade. Which, contributes to tolerance over time - with more of these receptors present, a higher concentration of caffeine must be consumed to antagonise these receptors and to achieve these desired effects

Front 20

Cannabis

Back 20

psychomimetic and depressant drug that contain cannabanoids, of which THC is the most abundant and active.
Tolerance and drug dependence is relatively minor, even in heavy users compared to other drugs

Front 21

Cannabis mechanism

Back 21

Targets cannabinoid receptors (GPCRs) CB1 and CB2.
CB1 are found in the hippocampus, cerebellum, hypothalamus and mesolimbic DA pathway. Positioned pre-synaptically. Activation inhibits NT release.
CB2 exist in immune tissues, and may mediate cytokine release and modulate pain

Front 22

Anandamide

Back 22

endogenous ligand for CB1 and CB2. Although it is only a partial agonist at CB2

Front 23

difference between synthetic cannabis and cannabis

Back 23

synthetic cannabis contains no THC, but contains a synthetic cannabinoid which is 100x stronger than THC