Lecture 6 Flashcards
drug name for alcohol
ethanol
alcohol is soluble in both
water and oil
- this allows it to be quickly absorbed into the bloodstream and cross the blood brain barrier
alcohol is metabolized
in a two-step process in the liver by the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are genetic variants of these two enzymes that cause fast or slow metabolism.
if you metabolize alcohol fast then
then you don’t get to enjoy alcohol
- It makes you sick, you will never develop alcohol use disorder
if you metabolize alcohol slow
- the metabolization stops at acetaldehyde
- you get to enjoy alcohol
- Slow is a risk factor, fast is protective
alcohol is a
CNS depressant (reduces neuronal activity) with numerous central and peripheral effects
acute effects of alcohol
- Euphoria, disinhibition, reduced anxiety, impaired reaction time, balance, speech, vision, hearing, motor coordination.
- Increased vasodilation (flushed, feeling of warmth) can lead to loss of body heat.
- Increased gastric secretion (GI ulceration).
- Vomiting, unconsciousness, coma, death from respiratory depression.
chronic alcohol consumption can lead to
- Dependence – abrupt withdrawal can cause seizures and death.
- Addiction – compulsive use despite adverse consequences.
- Wernicke-Korsakoff syndrome – amnesia and cognitive impairment due to thiamine deficiency that accompanies alcohol use disorder.
- Fetal alcohol syndrome – in utero exposure causes craniofacial abnormalities, cognitive and behavioural deficits, stunted growth.
- Endocrine effects: reduced production of testosterone and increased production of glucocorticoids (corticosterone).
- Fatty liver, alcoholic hepatitis, and cirrhosis of the liver.
- Hypertension, increased risk of heart failure.
- Liver cancer and increased risk of several cancers including breast and colon cancer.
how is GABA affected by alcohol
GABA is the major inhibitory neurotransmitter in the brain. Alcohol acts primarily at the GABA receptor to facilitate its action, thus in essence creating enhanced inhibition.
how is glutamate affected by alcohol
GLUTAMATE is the major excitatory neurotransmitter in the brain. Alcohol acts to inhibit a subset of glutamate receptors (N- methy-D-aspartate, NMDA), thus diminishing the excitatory actions of glutamate.
how is dopamine affected by alcohol
DOPAMINE is involved in reward processes and thus seems to be responsible for the rewarding aspects of alcohol consumption. Other things that people find rewarding such as food, sex, and other drugs of abuse also act to release DA in the brain. Alcohol stimulates dopamine action by inhibiting inhibitory neurons, increasing the firing of dopamine neurons.
what are the three neurotransmitter systems affected by alcohol
GABA, Glutamate, and Dopamine
cocaine MOA and its effects
- Stimulant (increases wakefulness), motor stimulant (increases activity), euphoric, hallucinations, delusions, appetite suppressant, increased heart rate and blood pressure.
- These effects are due to blockade of the transporters that clear dopamine, norepinephrine, and serotonin.
- Cocaine is also a local anaesthetic (was used before development of lidocaine).
- Local anaesthetic effects are due to blockade of sodium channels that propagate the action potential. Sensory neurons can’t fire & release neurotransmitter. At high doses, cocaine blocks the sodium channel that is needed for action potentials – local anesthetic
psychoactive ingredient for tobacco
nicotine
MOA and effects for tobacco
○ Nicotine is an agonist of the nicotinic acetylcholine receptor.
○ The receptor allows sodium ions into neurons, so it causes the neuron to fire (excitatory).
○ Activating these receptors will increase focus and attention and improve cognitive performance. Activation also induces a feeling of serenity, and smokers often need a cigarette to calm themselves.
○ Nicotine receptors are located on dopamine neurons, and when they are activated by nicotine the dopamine neurons fire more.
- Nicotinic receptors are also located in the body (peripheral nervous system), so there are major effects on organ systems like lungs, heart, blood vessel dilation, GI tract.
what happens when there is a lot of nicotine in the system
The nicotine receptors are activated: in the peripheral nervous system it causes an overactivation of the parasympathetic nervous system. This is what produces nausea, vomiting, difficulty breathing, and blurred vision
overactivation leads to a process called
desensitization, where the receptor no longer opens and stops working altogether
nicotine has different effects depending
on the dose – it activates the receptors at a low dose, but because of desensitization it causes a reduction in receptor function at high doses.
what is Salvinorin A
a hallucinogen, originally used by shamans for rituals
MOA and effects of Salvinorin A
- Salvinorin A is the active ingredient. It is a very selective agonist of the kappa opioid receptor (in the same family of receptors as mu opioid receptor). The endogenous ligand for kappa OR is dynorphin.
- Dynorphin and other kappa agonists are analgesic, but they also cause dysphoria and hallucinations. They reduce firing rate of dopamine neurons.
- They induce conditioned place aversion in animals.
- Animals will avoid going to locations where they have been given these drugs.
what are serotonergic hallucinogens (entheogens)
Drugs that directly activate serotonin receptors or cause large increases in synaptic serotonin are often hallucinogenic. There are 14 different types of serotonin receptors, but important for hallucination are 5HT2A and 5HT2C. Important for vomiting (emesis) is 5HT3.
what does serotonin affect
Addiction, Aggression, Anxiety, Appetite, Arousal, Blood Pressure, Cardiovascular Function, Cognition, Emesis, GI Motility, Heart Rate, Impulsivity, Memory, Mood, Nausea, Nociception, Penile Erection, Pupil Dilation, Respiration, Sensory Perception, Sexual Behavior, Sleep, Sociability, Thermoregulation
common affects for serotonic hallucinogens
- State-dependent effects – the effects depend on the environmental setting and the users state of mind.
- Feeling of peace/serenity/well-being/connected to others or to nature (**or fear/paranoia)
- Lucid thought and contemplation
- Ego dissociation – separation from body and dissolving of self/non-self boundaries
- Enhanced sensation (visual, tactile, auditory etc) and synesthesia – for example seeing colors with music.
- Time distortion – altered sense of time
adverse effects for serotonic hallucinogens
- Serotonin syndrome – caused by excessive activation of serotonin receptors.
- Adverse effects at hallucinogenic doses: nausea & vomiting, bruxism (clenched teeth), hyperthermia, sweating, dry mouth, increased blood pressure, muscle twitching & convulsions. Injuries (falls) can occur while user is hallucinating.
- Overdose can cause death from hyperthermia, high blood pressure leading to cardiovascular event
hallucinogens that activate serotonin receptors
- Natural products – psilocybin, mescaline, DMT – agonism at 5HT2A receptor.
- Lysergic acid diethylamide (LSD) – semisynthetic – derived from a fungus (Ergot). Agonist of 5HT2A receptor.
- MDMA (3,4- enedioxy – synthetic – similar to amphetamine & methamphetamine but acts more selectively on the serotonin transporter (SERT). Ecstasy is a reverse transporter of serotonin so all serotonin receptors are activated.
Mescaline LSD origin
from the top of the Peyote Cactus
- found only in the chihuahuan desert in South Texas and Northern Mexico
MOA and effects of Mescaline LSD
- The active ingredient in the cactus is the drug mescaline. It causes hallucinations by activating the 5HT2A subtype of serotonin receptors.
- The 5HT2A receptors are located throughout the cortex, hippocampus, and basal ganglia. Other activators of this receptor includes LSD (lysergic acid diethylamide) and psilocybin (found in mushrooms).
- 5HT2A agonists are not considered addictive, and have been investigated for treating OCD, anxiety, and PTSD. Psilocybin, LSD, and mescaline are all controlled substances. (Peyote plant is legal)
What is Ayahuasca
hallucinogenic preparation of two plants.
- A tea made using P. viridis (a shrub) and B. caapi (a vine)
MOA and effects of Ayahuasca
- Active ingredient in leaves of P. viridis is N,N dimethyltryptamine (DMT), which activates 5HT2A receptor. On its own, DMT is quickly metabolized by monoamine oxidase and effects last for 15 minutes or less.
- The tea is brewed with the B. caapi vine, which contains an MAO-A inhibitor (harmine) that extends effects to last 2-3 hours.
- It is because the brew has harmine in it that people taking SSRIs should not take ayahusc
