Drugs of Abuse Flashcards
(29 cards)
Characteristics of Drug Dependence
Tolerance,
Withdrawal symptoms
Compulsive drug use
Reward Pathway
Dopaminergic ventral tegmental area neurons increasing dopamine release in the nucleus accumbens (striatum).
Drug Effect on Reward Pathway
- Inhibitory neuron, GABA, synapses onto excitatory dopaminergic neuron in VTA.
- Dopaminergic neuron travels through to nucleus accumbens via mesolimbic pathway, release dopamine there.
- Stimulating reward will activate another neuron.
Opioids (or alcohol) will bind Mu OR on GABA which will inhibit GABA (less Ca2+), decreasing inhibitory signalling on dopaminergic neuron, allowing more dopamine to be released.
Alcohol absorption
-highly lipid soluble
-rapidly passes into small intestine
-absorbed rapidly into blood by diffusion (high fat food slow)
-peak levels in 30-60 mins or 1-2hrs with food-
Alcohol distribution
Distributed to total body water Vd= 0.7 litres per kg.
Alcohol metabolism
0 order kinetics (constant).
15 mg/100ml per hour
ethanol to acetaldehyde (alcohol dehydrogenase)
acetaldehyde to acetic acid (aldehyde dehydrogenase)
cofactor nicotinamide adenine dinucleotide (NAD) [limits rate]
Hangover
Accumulation of acetaldehyde, nausea, vomiting, headache. When too much to convert to acetic acid.
Disulfiram
Inhibits aldehyde dehydrogenase big hangover if drink.
Prevent alcohol abuse for those serious about quitting.
Polymorphisms in alcohol metabolising enzymes
ADH1B*2 and *3 = faster ethanol metabolism to acetaldehyde, bigger hangover, less abusive behaviour. [ Japanese]
ALDH*2 slowed aldehyde dehydrogenase activity. Alcoholism risk down. Cancer risk if do.
Treatments for alcohol abuse?
Acamprosate (NMDA antagonist) - reduces cravings in patients with alcohol disorder. (maintains sobriety).
Naltrexone (Mu opioid antagonist) - reduce pleasurable effects of drinking alcohol (induce opioid withdrawal effects, opioid history no)
Blood Alcohol Concentration Equation
= (alcohol intake in grams / weight of individual (g) x gender constant) x 100 [in grams/per 100ml]
Gender Constant for BAC Equation
Men = 0.68, Women = 0.55 (lower percentage of total body water)
Conversion of Alcohol in ml to grams
multiply by 0.789.
Long Term effects of alcohol (7)
-Fatty liver, fatty acids kill hepatocytes, fibrosis (scarring), cirrhosis (permanent damage).
-dementia risk increase
-foetal alcohol syndrome
-Iron & folate deficiency
- cardiomyopathy
-peripheral neuropathy
- Wernick - Korsakoff encephalopathy
Foetal Alcohol Syndrome
Growth retardation, face and head abnormal features, CNS abnormalities.
Behavioural issues.
Reward pathway of Cannabis
Activates CB1 receptors on GABAnergic neurons disinhibiting dopaminergic neurons of VTA.
Opioids Receptors Endogenous Agonists
Endorphins, encephalin
Mu Opioid Receptor locations
Brainstem, spinal cord, limbic system
Mu Opioid Receptor Action
Analgesia, euphoria, respiratory depression, constipation, physical dependence.
Kappa Opioid Receptor Location
Spinal cord, brainstem, limbic system
Kappa Opioid Receptor Action
Analgesia, dysphoria, sedation, psychotomimetic effects.
Delta Opioid Receptor Location
Peripheral tissue
Delta Opioid Receptor Action
Mood modulation, analgesia, antidepressant effects.
Opioids M.O.A
E.g. morphine. heroin, fentanyl
Mu Receptor agonists.
GPCRs of Ga(i) subtype.
Inhibit adenylate cyclase, reduce Ca2+ channels opening more inward rectifying K+ channels. Less action potentials reached.
Less NT released. Inhibitory response. e.g GABA inhibited allows more excitation.
