midterm #1 Flashcards
median effective dose ED50
dose that’s effective in 50% of individuals tested
median lethal dose LD50
dose that’s lethal in 50% of individuals tested
ionized molecules (3 + what percentage depends on (3))
- when drug dissolved in a liquid, some of its molecules become ionized
- ions not lipid-soluble, cannot cross membranes
- percentage of ionized molecules depends on: drug acid/base, liquid acid/base, drug pKa (pH at which half its molecules are ionized)
- faster absorption with lower percentage of ionized molecules!
first-pass metabolism
metabolism of drugs in the liver before the drug is distributed throughout the body
- ingested drugs reach liver before arriving at the heart
- only applies to drugs absorbed by the intestines
rates of elimination
first-order elimination:
- half-life, asymptotic elimination rate
- low toxicity
zero-order elimination:
- constant elimination rate
- as soon as toxicity is hit (e.g. alcohol, overdose response)
kidneys
- maintain balance of water and salt
- excrete unwanted molecules (e.g. liver metabolites)
- filter out everything, then allow re-absorption of all that’s required
oral administration
stomach: impermeable, no distribution
intestines: permeable, distribution
- much easier absorption for lipid-soluble drugs
combination of absorption and elimination
rate of elimination (half-life) for any drug stayconstant, but absorption differs depending on administration route
-> resultant curve depends on administration
upregulation vs downregulation
upregulation:
- increase in receptors/sensitivity/transmitter production
- response to drugs blocking receptors
downregulation:
- decrease in receptors/sensitivity/transmitter production
- response to drugs activating receptors
blood-brain barrier: active vs passive diffusion
active:
- transport, also against concentration gradients
- requires energy
passive:
- diffusion through channel protein
- attaching to carrier protein
urinalysis and blood sampling
+ problems (3)
urinalysis: looks for metabolites
blood sampling: looks for drug itself
problems:
- elimination time > detection time (cannot say when drug’s been taken)
- length of drug use (metabolic deposits)
- individual differences
tempering with drug tests
substitution: put in someone else’s urine
adulteration: change molecules, e.g. attach to fat
dilution: decrease concentration
potency
efficacy
effectiveness
potency: amount required to produce a given effect
efficacy: maximum response achievable for a given dose
effectiveness: ability to produce the therapeutic effect, taking into account secondary and side effects
therapeutic index
LD50/ED50 -> safety ratio, how safe a drug is
protective index
TD50/ED50 -> safety ratio
TD50: dose at which 50% of people have complaints
- reserved for humans
certain safety factor
LD1/ED99 -> where 99% have effect and 1% dies
- pertains to instant and not long-term use
pharmacological antagonism (2)
reduced effect due to presence of another drug
(1) competitive:
- at site of action
- need more drug to achieve max result (curve shifted to right)
(2) non-competitive:
- drug B binds to receptor or allosteric site, reduces receptor activity
- reduces max achievable result (decreased efficacy)
physiological antagonism
when substances produce different effects counteracting each other, via different binding sites and mechanisms
additive effects (2)
combined drug effects
(1) synergistic: combined effects are greater than their sum
(2) potentiation: ineffective drug becomes (more) effective in presence of another drug
pharmacodynamic tolerance (2)
tolerance in CNS (number of receptors/neurotransmitters)
(1) protracted:
- after several exposures
- need more drug for same psychological effect (graded)
(2) acute / tachyphylaxis:
- after only one exposure
- psychological effects during intake, not elimination
- reduced subjective effect (threshold)
pharmacokinetic tolerance
changes in metabolism resulting from constant concentrations in body
increases in rates of:
- enzymes (enzyme induction)
- elimination from body
cross-tolerance + factors (2)
tolerance that extends to another drug
factors:
- enzymes
- CNS: site of action (downregulation), similar reward-feedback mechanism (upper limit for DA release)
behavioural tolerance + factors (2)
adjustment and compensation as a result of experience
factors:
- self-awareness
- determination
homeostasis
allostasis
homeostasis: internal equilibrium condition
allostasis: physiological changes to obtain homeostasis to adapt to severe environmental demands
- more permanent state with chronic illness or stress
cellular adaptation theory
cells adapt by changing the number of their receptors, not their sensitivity
upregulation to avoid toxicity
downregulation to increase sensitivity
opponent process theory:
B-processes (3)
problems (2)
B-processes:
- pharmacodynamic tolerance
- pharmacokinetic tolerance
- environmental tolerance
problems:
- doesn’t account for drug effects: zero-order elimination, tachyphylaxis, drugs not producing withdrawal
- compensatory response is not a response but a state
(allostasis, has separate mechanisms)
opioids (4)
dopamine (4)
opioids:
- inherent
- liking
- subjective feeling of pleasure
- cannot be conditioned
dopamine:
- learned
- wanting
- objective homeostatic response
- can be conditioned
dependence
addiction
dependence: reliance
- physiological requirement for homeostasis
addiction: compulsion
- psychological want/need (emotional impulse)
addictions:
physical
psychological
physical: continuation of use to avoid withdrawal
- negative reinforcement
psychological:
- use motivated by craving
- positive reinforcement
addictive personality? Keller’s law
impulsivity and addiction?
traits only appear to be assoicated with addiction bc publication bias for significant results
not much evidence for impulsivity in addiction (also bc developmental pattern of impulsivity is not constant)
addiction: interaction models
1) disposition (nature) x environmental stress (nurture), vulnerability x stress
2) protective factors (friends, resilience, exercise)
3) time/events (developmental trajectory, window of vulnerability)
diathesis-stress model
model of risk for addiction
- negative environmental factors
- individual vulnerability
- risk factors determine result
- addictions are cause -> effect
differential susceptibility model
model of risk for addiction
- positive and negative environmental factors
- individual susceptibility, individual plasticity
- result is plastic based on environment
- buffers for addiction not to develop
drug effects
primary: drug - effect at targeted s.o.a.
secondary: drug - effect at site other than targeted s.o.a.
side: metabolite - effect at other than intended s.o.a.
prodrug: metabolite - metabolite of prodrug acts at intended s.o.a.
additive/antagonistic for drugs/metabolites:
enzyme inhibition
enzyme induction
enzyme inhibition: drug B blocks, stops production of or decomposes enzymes for drug A
- additive for drug
- antagonistic for metabolites
enzyme induction: drug B activates or facilitates production of enzymes for drug B
- additive for metabolites
- antagonistic for drug
role of dopamine
relating problem to solution
motivation: dopamine depletion causes dishínhibition, facilitates action
guidance: dopamine released for correct actions (conditioning, memory, repeating response)
reinforcement: dopamine response to obtaining reward and to restoration fo homeostasis
hedonic homeostatic dysregulation
integrates physiology with psychological experience
within-system adaptation: opponent process and incentive salience -> withdrawal makes pleasure of drug use more rewarding by comparison
between-systems adaptation: allostasis -> chronic fluctuation enhances overall stress response, resulting in heightened preoccupation
=> at some point, drugs feel better because things generally feel worse
speed of absorption from parenteral administration
blood vessels > intraperitoneal > intramuscular > subcutaneous
pons: locus coeruleus and reticular formation
located in midbrain
locus coeruleus:
- reflexive processing of incoming sensory information
reticular formation:
- arousal, FFFS
- selective attention
- wakefulness (raphe nucleus: sleep, production of pertinent neurotransmitters)
reward circuitry: periaqueductal gray and ventral tegmental area
periaqueductal gray:
- pain as a sensation
- punishment (psychological) -> projects to PFC
ventral tegmental area:
- reward circuitry
- pleasure
what she includes in midbrain (5)
pons - locus coeruleus - reticular formation periaqueductal gray VTA hippocampus amygdala
insula
consciousness, self-awareness, imagination
Addiction in DSM-IV and DSM-5
DSM-IV:
- substance abuse (affects others)
- substance dependence (affects yourself)
DSM-5:
- substance use disorder (affects anyone)
protein binding
when drug molecules bind to large proteins
- permanent attachment, no crossing of membranes
- temporary attachment, slow release of molecules into blood
differences drugs and natural reinforcers (2)
1) natural reinforcers have satiation mechanism that terminates their reinforcing effect (drugs don’t)
2) drug reinforcement is much faster and more intense than natural reinforcers
what she includes in forebrain (4)
cerebral cortex
insula
thalamus
hypothalamus
medulla oblongata
autonomic:
- breathing, heart rate etc.
- vomiting!
