Lecture 4 (Drugs) Flashcards
Ethnopharmacology
The study of substances use by society
ethopharmacology
the study of substances used by animals
dose
a single treatment
dosage
treatment regime
routes of drug ingestion:
1.) Ingestion
2.) Inhalation
3.) Dermal contact
4.) Injection
Dermal contact
patches that dissolve drug into skin. only for lipid soluble products
subcutaneous
injections into fat under the skin
intramuscular
injections into the muscle under the skin
intravenous
injections directly into the bloodstream
Intraperitoneal
Injections into the abdomen
intracerebroventricular
injections into the cerbral ventricles (into the CSF)
Intracerebral
Injections into a discrete location of the brain tissue that you are studying
intrathecal
injections into the spine
Blood brain barrier (why and how)
endothelial cells are much tighter together in CNS, drugs cannot diffuse past them
protects to neurons in brain from toxins (as they do not regenerate much)
Ways around:
* gases, small fat soluble drugs
* glymphatic system = astrocytes control blood flow in local regions move material form CSF to the brain
* specialized ultrasound
Ways around the Blood Brain Barrier:
- gases, small fat soluble drugs
- glymphatic system = astrocytes control blood flow in local regions move material form CSF to the brain
- specialized ultrasound
Ligand
Any substance that binds to a receptor
Types of Drug Actions (three:)
1.) Agonist = stimulates the action of an endogenous substance
2.) Antagonist = counters the action of an endogenous substance
3.) Inverse Agonist = acts oppositely to an agonist (blocks)
Some synaptic drug effects:
1.) alters axonal transport (such as blocking transport or signals)
2.) alterations in synthesis (such as more transmitter being produced)
3.) alterations in storage (reseperine = makes vesicles leaky, no transmitter when they rupture)
4.) re-uptake (such as prozac)
5.) Alterations in metabolic breakdown (such as inactivating enzymes that break down neurotransmitter)
Some post-synaptic drug effects:
1.) Inhibitors (such as MAOA’s, reduce breakdown of monamines in the cleft, more reuptake in pre-synaptic membrane)
2.) Direct effect on receptors (activate the receptors themselves, or a receptor sub-type)
3.) Block receptors (antagonists)
4.) Alter second messenger function
5.) Alter gene transcription (steroids?)
endogenous
made inside the the body
exogenous
made outside the body
“orphan receptor”
receptors inside the brain. We don’t yet know what endogenous substances interacts with it. But they must must exist…?
Three subtypes of Opioids + how many endogenous classes of opioids are there?
- mu, delta, kappa
- there are three classes
Antagonist to Opioids
Naloxone (reverse affects of overdose!)
Drug-receptor equilibrium means that?
drugs are binding and dissociating from receptors all the time at an equal rate
Receptor Affinity
A drug has varying infinity for different receptors (#1 favourite, #2 favourite ect.)
No drugs have only one receptor
Increase dosage (bind to more receptors)
Saturation
Drug binds to all high affinity receptors. Receptors are completely filled up with the drug.
Is saturation ever 100%?
No, drugs are always binding and dissociating
is 100% saturation necessary for best effects?
No, 60% for example saturation (for example) may be enough for good effects to be observed
Secondary binding
All higher affinity receptors are saturated. Drug bids to lower affinity sites and saturates them. Causes side effects.
why does secondary binding causes side effects?
Because the lesser affinity receptors may not be as directly related to the target process so they affect more bodily systems
Irreversible binding
Drug binds to receptor, and cannot detach. Not forever. The receptor waxes and wanes, breaks down fairly fast. (receptor metabolism!)
What does the dose response curve look like?
A flattened out S
LD50
Lethal dose for 50% of treatment subjects
ED50
effective dose for 50% of treatment subjects
therapeutic index
LD50 / ED50 = index
LD50 / ED50 = ?
The therapeutic index (want a big difference between lD and ED)
Alternative to the LD50?
TD50 (toxic dose for 50% of patients)
Effect of secondary saturation on the dose response curve?
dose réponse curve becomes non-monatomic (deviates from the s-shape) due to side-effects
Three types of tolerance?
1.) Metabolic tolerance = physiological changes that reduce the amount of drug that gets to to its target (body starts breaking down drug before it gets to the brain)
2.) Functional Tolerance = target tissue with successive exposure to drug may become less reactive (up or down regulation)
3.) Contigent Tolerance = drug effect must be experience for tolerance to occur (drug effect, need to have the drug before an experience? LOL help….)
Physiological changes that reduce the amount of drug that gets to to its target (body starts breaking down drug before it gets to the brain)
Metabolic tolerance
Target tissue with successive exposure to drug may become less reactive (up or down regulation)
Functional Tolerance
drug effect must be experience for tolerance to occur (drug effect, need to have the drug before an experience? LOL help….)
contigent tolerance
tolerance for one drug may generalized to similar drugs
cross-tolerance
Types of neurotoxins!
1.) Ion channel blockers (irreversible binding, agonist that binds permanently to a receptor)
2.)Ion channel openers (causes channels to stay open)
3.) Excito-toxins = amino acids variants cause cell to become hyper excitable (causes cell death)
4.) Metabolic = shut down metabolism or impair cell functioning
*mimic inappropriately an endogenous substance
Tetrodotoxin (TTX)
Animal toxin (pufferfish)
blocks voltage gated Na channels = no action potentials (OH NO, SO SAD) :(
Bungarotoxin (Banded krait)
Animal toxin
snake venom
blocks nicotinic Acetochcoline AHc channels irreversibly (paralysis)
Charybdotoxin
animal toxin
scorpion venom
irreversibly blocks potassium channels
stimulants
activate excitatory post-synaptic potentials
or block (IPSP)
depressants
reduce EPSP, or causes IPSP
examples of depressants:
opiates
alcohol
benzodiazepines (anxiety drugs)
MTPT (designer drug)
leads to Parkinson’s disease (kills dopamine receptors)
route of drug administration (5 stages):
1.) route of administration
* dermal contact
*inhalation
*injection
*ingestion
2.) Absorption (if applicable)
*gases
* dermal contact (lipid soluble)
3.) Binding
* drugs bind to receptors
*depot binding (binds to fat stores and deactivate, reactivate at some point)
4.) Inactivation
* enzymes breakdown drug via synapses
* mostly occurs in the liver
5.) Elimination
*urine
Set
Everything that someone brings with them (individually) to a drug experience
setting (drugs)
the physical setting/location of drug use
*known settings (body prepares, down regulation of receptors prior to even taking the drug)
