Week 3 Flashcards
The two major aspects of drug influences
Drug effects (observable changes)
sites of action (binding sites)
Pharmacokinetics
What the body does to the drug
Endogenous vs exogenous
Endogenous: made in our body
Exogenous: produced outside our body
Pharmacokinetics vs pharmacodynamics
Pharmacokinetics: how drug moves through body
pharmacodynamics: biological response to drug
Four processes of pharmacokinetics
ADME
Absorption (how get in body)
Distribution (how moves trough body)
Metabolism (how is drug changed to an inactive form my enzymes)
Excretion (drug is excreted in urine by kidneys)
IV: fastest b/c it goes straight into your bloodstream
intraperitoneal: to your stomach (e.g., tubefeeding)
subcutaneous: into your fat
intracerebral: directly into your brain; bypass the blood-brain barrier; not really done in humans but on research animals
intracerebroventricular: straight into CSF
oral: one of the slowest ways; first pass metabolism (broken down in saliva, down to GI tract, etc); most common way for
psychotherapeutic drugs
sublingual: absorbing through capilaries below your tongue
intrarectal: bypassess “first pass” metabolism
inhalation: into your lungs
insufflation: absorbed by the mucous membrane in your nose (e.g.,
snorting cocaine)
Inhalation vs insufflation
inhalation: into your lungs - EX. weed
insufflation: absorbed by the mucous membrane in your nose (e.g.,
snorting cocaine)
- EX. cocaine
Blood flow
Entire volume of blood supply circulates every minute
Where do drugs exert their effects?
Sits of action
Most important factor in determining rate of absorbtion?
Lipid solubility – Lipid soluble materials pass through the most rapidly (pass through BBB)
heroin is more addictive b/c it has higher lipid solubility than morphine
Metabolism of drugs
most drugs are metabolized and deactivated by enzymes.
Enzymes sometimes transform molecules into more active versions
than the initial molecule. THIS INCREASES DURATION
- Ex. Prozac: body changes it to be more active, why takes two weeks to kick in (enzymatic activation)
LIVER: plays big role in enzymatic deactivation
Excretion of drugs
kidney is the primary organ of excretion
(GI, skin, lungs, and liver too)
Effictiveness of a drug is impacted by
sites of action
affinity at its site of action
Affinity: the capacity of a drug molecule to bind to a key site of action.
Affinity ratio for most desirable drug
Most desirable drug has high affinity for sites of action producing
therapeutic effects and low affinity for sites of action producing toxic side
effects
Dose Response Curve
Determines the point of maximum effect of a drug
After point of maximum effect of drug, increasing the dose does not produce a stronger effect
Margin of safety
The difference between therapeutic/desired effect of a drug and undesired effect
want the largest margin of safety
Therapeutic Index
A commonly used margin of safety
Two numbers obtained:
- Effective Dose 50 (ED50) = the dose that produces the desired effects in 50
percent of the individuals
- Toxic Dose 50 (TD50) = the dose that produces toxic effects in 50 percent of the individuals
Want ratio of TD/ED to be bigger than 10
Ex.
Low TI
ex. Lithium, Clozapine, Tricyclic antidepressants
have to get blood tested often
Neurotransmitter vs neuromodulator
Neurotransmitter: a chemical used for a neuron-to-neuron communication
Neuromodulator: a chemical that affects the neurotransmission of a whole group of neurons
GROUP VS INDIVIDUAL
Termination of a neurotransmitters
Through reuptake or enzymatic deactivation/degradation
Ligands
Neuromodulators that bind to a complementary receptor site
Agonists vs antagonists
Agonist a molecule that by binding to the receptor stimulates a
response = ↑ postsynaptic effects
Antagonists a molecule that by binding to a receptor blocks or
inhibits the response = ↓ postsynaptic effects
Is a drug that blocks the re-uptake or enzymatic degradation of a
neurotransmitter an antagonist or agonist?
Agonist! because re-upatake is blocked, the neurotransmitters are jsut hanging in the cleft, still sending signals
If the activation of a receptor causes vasoconstriction, what would happen if someone took an antagonist for that receptor?
Decreases vasoconstriction
Direct vs indirect
Indirect: attatched to alternative binding site
Direct: attaches to direct binding site
Neuromodulators are associated with… (direct or indirect)
Indirect
(b/c they bind to an alternative sites)
Amino acid neurotransmitters in the brain
Glutamate - excitatory
GABA - inhibitory
Amino acid neurotransmitters in the spinal chord and brain stem
Glutamate - excitatory
Glycine - inhibitory
4 main glutamate receptors
NMDA, AMPA, Kainate, Metabotropic Glutamate
NMDA Receptor
Receptor for glutamate!
Has 6 binding sites
Requirements for glutamate to bond:
- glycine must be attatched
- Mg must not be attatched (need it to be depolarized)
When channel opens, Na and Ca –> cell depolarizes
Ca is the secondary messenger
Alteration of the synapse (synaptic plasticity) =
building block of a newly formed memory
Acetylcholine
PNS: central role in muscle contraction
CNS: Found in specific locations and pathways in CNS. Key role in REM sleep, perceptual learning, and memory.
Facts about monoamines
Neuromodulators derived from a single amino acid.
Produced by several systems of neurons in the brain; mainly brainstem with widespread distribution around brain.
Mediate a variety of CNS fxns (e.g.,motor control, cognition, emotion, memory processing, and endocrine modulation)
Three classes of monoamines and their chemicals (examples)
Catecholamines: dopamine, norepinephrine/noradrenalin, epinephrine/adrenalin
Indolamine: serotonin
Ethylamine: histamine
Synthesis of catecholamines
Tyrosine -> L-dopa -> dopamine -> norepinephrine
Precursors
Substances that can be chemically altered to become neurotransmitters
What is the primary effect of dopamine?
movement, attention, learning, and reinforcing effects of substances
What is the primary effect of norepinephrin?
Primary effect = vigilance/attentiveness
PNS: ANS regulation (heart rate, etc.)
(Dopamine in vesicles is converted to norepinephrine by a special enzyme)
Locus Coeruleus (nucleus in the pons)
Where most noradrenergic systems begin
noradrenergic: involved in the body’s “fight or flight” response
What are the primary effects of serotonin?
CNS: mood and pain regulation
control of eating, sleeping, arousal, and dreaming
PNS: involved in digestive tract
Precursor = Tryptophan
What are the precursors of dopamine, norepinephrine, and serotonin?
Dopamine: tyrosine
Norepinephrine: dopamine
Serotonin: tryptophan
Are dopamine, serotonin, and norepinephrine excitatory or inhibitory?
dopamine: excitatory and inhibitory
serotonine: inhibitory
norepinephrine: excitatory
What are surplus and deficit effects of dopamine?
Surplus: Sz, substance addiction
Deficit: Parkinson’s, anxiety, memory, challenges, ADHD
What are the surplus and deficit effects of serotonin?
Surplus: autism, mania
Deficit: depression and other mood d/os
What are the surplus and deficit effects of Norepinephrine?
Surplus: anxiety
Deficit: several psychiatric conditions
Primary effects of histamine
CNS: wakefulness
PNS: immunse response
Primary effects of opiods
CNS: reinforcement, pain modulation
PNS: pain modulation
Primary effects of Endocannabinoids
CNS: appetitie regulation
PNS: immune response
Tolerance
A decrease in the effectiveness of a drug that is administered repeatedly. It is the body’s attempt to maintain homeostasis.
Sensitization
An increase in the effectiveness of a drug as it is administered repeatedly.
(becasue your reward system gets so excited, the anticipation is so exicting and great)
Pharmacokinetic tolerance
body breaks down drug preventing it from reaching
receptors.
Pharmacodynamic tolerance
Decrease in receptor affinity for drug.
Damaged receptors
Receptor down-regulation (decrease in receptor)
Dependence
The physical or psychological symptoms that occur that make someone feel like they must continue taking a substance; lack of substance results in withdrawal
Placebo
an inactive/inert substance given as a control in substance
experiments.
Responses can be the result of motivation, expectation, classical conditioning
Viewing injection of placebo = ↓ post-operative pain
Informing participants, a placebo is a stimulant = ↑ HR and BP
