Lec #4 Drugs from Nature Flashcards
ethanol
product of yeast metabolism, in which complex carbohydrates and sugars from grains are used as an energy source
how does alcohol integrate quickly into the brain?
- very small molecule with chemical features that allow it to be soluble in both water and oik
-through fats and cell membranes to rapidly move from the stomach to the blood and the blood to the brain
How is alcohol soluble in water
hydroxyl group (OH)
to what receptors is alcohol an agonist to?
- agonist at GABA-A receptors
- acts in a manner that is similar to barbiturates to keep the channel open longer.
- allows more chloride into the neuron, so the neuron is hyperpolarized and less likely to fire.
to what receptors is alcohol an antagonist to?
- antagonist to NMDA receptors for the main excitatory neurotransmitter in the brain, glutamate
-allow sodium and calcium into the neuron - promote neuron activation
What is the two-step process in the liver in which alcohol is metabolized by enzymes?
- alcohol dehydrogenase (ADH)
- aldehyde dehydrogenase (ALDH)
What is the toxic intermediate of alcohol metabolism that causes flushing, vomiting, and cancer?
acetaldehyde
what happens with people with slow variants of ADH?
intermediate builds up and takes time to become acetate
§ Increased risk for alcohol-induced cancers and addiction, as the intermediate remains longer in their system; they enjoy It more
why alcohol a powerful depressant of neurons?
blocks the excitatory message of glutamate and it amplifies the inhibitory message of GABA
why is there an increase of dopamine when consuming alcohol?
- the first neurons to become quiet are the ones that normally keep dopamine neurons from firing
- contribution to the feeling of wellbeing and reduction of anxiety
what are the symptoms of acute alcohol poisoning?
- impaired motor coordination
- decreased activity in neurons (causes people to do things they wouldn’t normally do)
- amnesia
- vomiting
- loss of consciousness
- breathing suppression
- increased vasodilation (flushed, feeling of warmth) can lead to loss of body heat
- increased GI ulceration/ gastric secretion
what are the symptoms of chronic heavy alcohol consumption?
- dependence
- addiction
- wernicke-korsakoff syndrome
- fetal alcohol syndrome
- endocrine effects
- increased risk of heart failure and liver cancer
what are 3 neurotransmitter systems affected by alcohol
- GABA (agonist and facilitate its action)
- glutamate ( Antagonist of NMDA; Alcohol acts to inhibit a subset of glutamate receptors (N- methy-D- aspartate, NMDA), thus diminishing the excitatory actions of glutamate.
- dopamine (alcohol stimulated its action and firing of neurons)
what are the low-dose effects of nicotine (nicotiana tabacum)?
serenity, reduced agitation, increased attention and focus
what are the effects of overexposure of nicotine?
- vomiting
- delirium
- difficulty breathing
- excessive mucus production
to what receptor does nicotine act as an agonist to?
- agonist to the nicotinic acetylcholine receptor
- receptor allows sodium ions into neurons, so it causes the neuron to fire (excitatory)
where are nicotinic receptors located?
neuromuscular junction and autonomic nervous system
what happens when the nicotinic receptors are continually activated by excessive nicotine poisoning?
desensitization:receptors actually stop working and become desensitized and muscles become flaccid
what are the negative effects of smoking?
- hardening of the treaties
- increases the risk for heart attack and stroke
what makes cocaine (erythxylum coca) stimulant?
blockade of the transporters that clear dopamine, norepinephrine and serotonin
what transporters does cocaine block the actions of?
- dopamine transporter, causing dopamine levels to accumulate in the synapse
- norepinephrine and serotonin transporter, so increases the number of neurotransmitters when ingested
how are cocaine and lidocaine anaesthetic?
- prevent the nociceptive sensory neuron and other neurons from firing
- blockade of sodium channels that are needed to propagate the action potential
how is cocaine a psychomotor stimulant?
- increases the level of alertness and arousal
- induces a state of euphoria and grandiose with paranoid thoughts
- increase heart rate and blood pressure
what receptors do hallucinogens (psilocybin and mescaline) activate?
5HT2A serotonin receptors inducing vivid hallucinations
what receptor is salvanorin A an agonist to?
- agonist of the kappa opioid receptor causing brief but intense hallucinations that can be disturbing
which drug is the most harmful to society?
alcohol
what are the factors that help determine the legal status of drugs?
- liability
- medical utility
- safety profile
- international agreements
Salvinorin A
pain reliever that causes unpleasant hallucinations.
to what receptor is Salvinorin A
(Salvia divinorum) an agonist to?
- kappa opioid receptor (in the same family of receptors as mu opioid receptor). The endogenous
ligand for kappa OR is dynorphin. - analgesic
Serotonergic hallucinogens- entheogens
Drugs that directly activate serotonin receptors (5HT2A- serotonin and 5HT2C and 5HT3) cause large increases in synaptic serotonin are often hallucinogenic
what are the common and adverse effects of serotonergic hallucinogens?
- state-dependence (environment and user’s state of mind)
- feelings of peace and serenity
- lucid thoughts and time alteration
- excessive activation of serotonin receptors (serotonin syndrome)
Mescaline from Peyote cactus
(Lophophora williamsii)
- Found only in Chihuahuan desert of southern Texas and northern Mexico.
- Dried tops of cactus are ingested. Used for shamanic rituals and induces mainly visual hallucinations. Often causes nausea and vomiting.
- 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 the active ingredient in the Peyote cactus to produce drugs?
mescaline
what receptors does mescaline activate on as an agonist?
- 5HT2A receptors, a subtype of serotonin receptors, causing hallucinations
- also activated by LSD (lysergic acid diethylamide) and psilocybin (mushrooms)
- not addictive
ayahuasca
tea made using P. viridis (a shrub) and B. caapi (a
vine).
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 ayahusca.
