Drug properties Flashcards
Dopamine projects from which area of the brain to each area?
Ventral Tegmental Area (VTA) to Nucleus Accumbens (NAcc)
All addictive drugs directly or indirectly…
Affect dopamine transmission
Serotonin is produced in and distributed from the…
The raphe nuclei (brain stem)
Serotonin depleted people are…
more irritable, and worse at stroop test
The serotonin’s precursor is _______. What does that mean?
tryptophan
It means, in our body: tryptophan -> chemical reaction -> serotonin
Hallucinogens act on ________ receptors
Serotonin
Serotonin receptors are…
Mostly Metabotropic - only one type of ionotropic
What are Selective serotonin Reuptake inhibitors (SSRIs) ?
Block serotonin from being removed from the synapse
Acts immediately but takes longer to actually make changes because what makes a difference are the chain reactions
SSRI efficacy mild to moderate depression
little difference between placebo and SSRIs
SSRI efficacy Severe depression
SSRIs help individuals, but the effect size is small: so should not be just used on their own. Also: Regression to the mean.
Acetylcholine
Neuromuscular junction
The first neurotransmitter that was ever discovered because it is released into the muscle tissue. Ionotropic receptors
Acetylcholine
Major function in the…
basal forebrain: Wakefulness, attention, arousal, etc.
Nicotine binds to ___________ receptors:
Acetylcholine
Agonist drug on acetylcholine (nicotinic) receptors
Endocannabinoids
How do they work on the synapse?
Travel from dendrite to axon, i.e. retrograde transmission (Endocannabinoid neurotransmitters come from postsynaptic and bind to the presynaptic terminal)
Weaken connection between two cells at synapse
Metabotropic receptors
Endocannabinoids
Function in the brain
Mechanism for forgetting or negative feedback mechanism, we are not sure
Weakens the synapse - Causes less neurotransmitters to be released
Adenosine
What is it?
Comes from ATP (cellular energy) - it’s its byproduct
ATP -> ADP -> AMP -> Adenosine
Our body accumulates adenosine as it breaks ATP down
Adenosine in the brain
Brain has adenosine receptors: when adenosine binds it inhibits
The more you are awake -> more adenosine -> more receptors inhibit neurons
Adenosine and caffeine
Caffeine is an adenosine receptor blocker (adenosine antagonist) -
but temporary - the NT builds up on the synapse
Your body creates more adenosine receptors (adaptation), which leads to tolerance
Endogenous opioids aka Endorphins
What are they?
Giant peptide neurotransmitters
System to block the pain - also involved with euphoric effects
Endogenous opioids aka Endorphins
Drugs
The neurotransmitter system that exogenous opioids (e.g. heroin) mimic
Fentanyl (opioid receptor agonist) and naloxone (opioid receptor antagonist)
Endogenous opioids aka Endorphins
Receptors (what and where)
Receptors are all GPCRs (G protein coupled receptors)
Receptors found in spinal cord, periaqueductal grey (PAG), nucleus accumbens, more.
Pharmacokinetic
What and steps
Drug’s passage through the body
Liberation, Absorption, Distribution (reach site of action), Biotransformation (Drug broken down by enzymes), Elimination
Absorption
Routes of administration
From high short effects to low long effects - Intravenous, intramuscular, subcutaneous, per os (by mouth) Also inhalation (smoke) or insufflation (snort, through mucous membranes)
Absorption
Environmental pH
If a drug is basic it is more likely to be absorbed in a basic area
If a drug is acidic it is more likely to be absorbed in a acidic area
Drug pKa
Drug level of acidity
Distribution
Bioavailability
- The ability for the drug to reach its site of action (target)
Things that affect bioavailability
Blood-brain barrier and Nonspecific binding
Blood-brain barrier - molecules that have more chance to pass: lipid soluble, small and not have a lot of polarity
Nonspecific binding - When chemicals get lost along the way, before binding to the site of action. It binds in other places.
First-pass metabolism
Drug starts breaking down before it reaches site of action
Active metabolites
Some drugs, as they are metabolized, turns into other drugs
Prodrugs
Are not drugs, but once metabolized they become a drug.
Example: L-DOPA crosses the blood brain barrier and then is converted into dopamine, while dopamine cannot cross the barrier
Pharmacodynamics
How the drug works
Agonism, antagonism, etc
Binding affinity - cf. Dissociation constant, Ka
Receptor efficacy
Tolerance
The need for a higher dose for the same effect. Is not fix, it is usually dependent on the environment.
Tolerance and environments
Most people overdose in novel environments, even with the same usual dose. Higher mortality rate in novel environments. Our bodies get ready for the drug to be present when it feels that it is coming. A new environment gets your body off guard.
Sensitization
Opposite of tolerance. increased effect of drug following repeated doses
Dependence
An adaptation has developed such that our body expects the drug to be there.
It is a feature of addiction but is not addiction. Can have dependence without addiction.
Leads to withdraw if drug not there.
