Test 1 PSYC 345A Flashcards

Question

Drug Classification Problems and Issues

Answer 1

- not easily classified by site of action .... never restricted to only one functional or anatomical division of brain. Alch effects cerebral cortex, pons... - not easily classified according to NT interactions - many interfere w one another - not easily class by behavioral effects

Answer 2

1. Alcohol - ethyl alcohol 2. Barbiturates - 4 types 3. Non- barbiturate hypnotics

Answer 3

1. Long acting - phenobarbital - 6 hrs, sleeping pill, long flight anxiety ... 2. intermediate acting - amobarbital - 4 hrs 3. short acting - secobarbital - 1-1.5 hrs, sleep onset, bad news ... 4. ultra short acting - thiopental - 15-30 mins, must be constantly administered

Answer 4

- genetic variability - ppl see Benzo as safer ... an overdose on barbituates will more likely cause LOC that benzo. easier to overdose on barbituates (since the barbituates interacts with GABA) benzo has an extra step and has to get through the GABA pathway... someone w suicidal ideation may be safer with benzo equally effective in TREATING deprression

Answer 5

for anx and sleep long acting, diasapam intermediate - lorazapam short- triasolam

Answer 6

amhetamines, cocaine, nicotine, caffiene

Answer 7

haloperidal

Answer 8

sometimes in stimulant category? - elevate and stabilize mood older ones are tri and MAO 1. Tricyclic antidepressants - imipramine 2. Monoamine oxidase (MAO) inibitors; tranylcypromine 3. Selective Serotonin Reuptake Inhibitors (SRRIs): fluoxeti 4. Second Generation Aytpical Antidepressants: buproprio (when treatment resistant, go back to tricyclin) 5. Dual Action: Serzan ** will not give high to someone without depression

Answer 9

6. Anti-manics - Lithium some prophylactic effects, can prevent future issues. old and cheap... now is used to augment effects of antidepressants

Answer 10

1. Anticholinergic psychedelics: atropine 2. Norepinephrine psychedelics: mescaline C.  3. Serotonin Psychedelics: LSD 4. Psychedelic anesthetics: PCP 5. THC (for some ppl, can cause hallucinations) sometime categorized according to NT that they effect the levels of ... many psychedelics often effect serotonin

Answer 11

reduces pain 1. Opiates: morphine, heroin, Demerol 2. Inhalants: ether 3. Psychedelic anesthetics 4. THC

Answer 12

antiepileptic drugs - dilantin

Answer 13

- non addictive Narcotic means SLEEP PRODUCING ...and DEPENDENCY PRODUCING ... potential for abuse

Answer 14

Not easily classified according to site of action - action of drug not restricted to one functional or anatomical division of brain * Not easily classified according to NT interactions - many drugs interfere with more than one NT and NT have more than one effect themselves * Not easily classified according to behavioral effects - different responses seen as function of different doses

Answer 15

- Reflect abuse potential of the drugs (could they be addictive?) - Reflect the degree of control exercised over storage and dispensing of the drugs - Schedule 1-5 - 1-2, high potential to become dependent schedule 1 are more strictly controlled (dispensing and storage) - 6-8 for plants as well - schedule 9 regulated the equipment used to make drugs.

Answer 16

Schedule 1 - in US heroin. not widely accepted. ppl are given morphine instead.... in Canada, cocaine and meth. stored in vaults. - opiates are often schedule 1 drugs (tramadol) - schedule 1 is highly controlled, harder to get prescriptions. Schedule 2 in US - morphine, methadone, cannabis Schedule 3 - accepted medical use, less danger. moderate control. prescription reg is not as strict. long acting barbituates, amphetamines, riddalen, - can be harmful if ppl step outside of regular use Schedule 4 - can get renewals without needing to go back to doctor... Schedule 5 - cough prescription medications

Answer 17

controls precursors, plants, how much plant one can purchase. you can only purchase so much sage! schedule 9 is about controlling devices used to make medications

Answer 18

* Schedule N – Narcotic Drugs - high potential to become dependent - BUT have accepted medical use with strict limitations * Schedule J – Considered illegal (j for jail) - not widespread accepted medical use (marijuana, used to be a J) - LSD and mushrooms are schedule J * Schedule G – Controlled drugs - some regulations over prescriptions - pharmacists have close records - amphetamines, barbituates * Schedule F – Drugs treating wide variety of illnesses requiring physician supervision - can call in for a renewal, does not need to see person - antidepressants, antihypertensives...

Answer 19

- drugs only work at specific sites of actions - ex, if you throw up, or swallow drug thats meant to be administered a different way .

Answer 20

– whether it gets to site of action – how fast it gets to site of action – how much gets to site of action

Answer 21

mouth, swallow or consume... most common. - any pills tabs capsules - some absorbed thru lining of stomach -> bloodstream - best way is thru small intestine - best absorption cross concentration gradient, enters bloodstream - technically includes chewing tobacco, absorbed thru buccal membrane of mouth. - intrarectal admin - suppositories in the rectum * stomach contents IF full stomach, drug can get stuck there w food... stuck in intestine. slowly absorbed on full stomach. * drug form drugs in pill or tab form take longer to be absorbed to bloodstream ... gel or liquid gets to bloodstream faster. - longer drugs stay in stomach, less likely they are in active form once they get to intestines. stomach enzymes and acid biodegrade the drug. * lipid solubility of drug how readily drug dissolved to fatty tissue - cell walls are made of large protein molecules. increased lipid solubility means they can move thru more easily ... other rely on portal or holes. more lip sol, more rapid absorb *** heroin is more potent than morphine because heroin is more lipid soluble. more drugs gets to site of action most efficient absorption in intestines... taking a drug with a meal slows its absorption ... intestinal walls lined with capillaries - lipid bilayers - olive oil test to see lipid solubility or drugs (vs H2o)

Answer 22

* Advantages: – generally safest, cheapest, and most convenient "safe" because we can get the drug OUT of system - induce vomiting or pumping system. prevent too much from getting to site of action * Disadvantages: 1. slow absorption - like reversing the effects of another drug... (thing naloxone) 2. delayed feedback - ppl have expectation of when they'll "feel it" - wait and not feel effect yet, then they take more. accidental overdose. - common with PCP - angel dust. ppl use the same way as theyd use LSD. is it NOT as potent at LSD ... so theyll take more, and it created toxic side effects. doing PCP as sniff or smoke is more popular. 3. variability of absorption - gut health stuff? not feeling well when they take it? 4. irritating substances - fillers can be irritating to stomach, get nausea with pill.

Answer 23

* through skin or membrane into bloodstream * positioning drug against skin, inserting into rectum, snorting it into nasal cavity, placing under tongue or against cheek - drugs found in plans may be chewed on and release liquid that absorbed in mucus membranes of mouth. - patch - nitroglycerine - under the tongue - cocaine, rub on gums - snuff tobacco

Answer 24

* Advantages include: 1. Useful alternative to oral route - helpful when unconscious and cannot swallow - if frequent vomiting * Disadvantages include: 1. Irritation of skin or membranes - 2. Variable absorption - need to hold in mouth for a while rectal suppositories? may not stay in proper position

Answer 25

* by breathing (rich capillary density in lungs) * absorption occurs in lungs * Two types 1. smoking dried material - with smoking, other substances come with ... tary, hydrocarbons, other chemicals from burning process. carbon monoxide... toxic bc it blocks O2 carrying ability. 2. vaporous inhalation VAPROUS - nitrous oxide.. used as anisthetic and in dentistry (as well as recreationally) - rags soaked in solvent - sniffing paint thinner? sniffing solvent Huffing or bagging from container smoking CRACK not cocaine

Answer 26

contact of gas with moist surface of lungs, dissolve and diffuse into blood. diff between smoke and gases is that the drug in the smoke particles will not re-vaporize after it is dissolved in the blood and cannot be exhaled. * Advantages: 1. Extremely fast absorption - to bloodstream bc straight to lungs (many capillaries) - can be controlled with precision - reason used for anesthesia * Disadvantages: 1. Effect c/be limited to time drug being inhaled 2. Lung and throat irritation with chronic use 3. Risk of brain damage with chronic use, with accompanying cognitive impairments (in abusive/ rec fashion) - most common is attention and memory difficulties ** depends on individual susceptibility!! ** hard to eliminate substance once its administered Sniffing gasoline can cause immediate death from someone who is genetically susceptible

Answer 27

- could be used recreationally - case of dentist who chronically used NO, personality changes (became inappropriate, manic...) ** temporary! ** with legit dental procedures, its given 50/50 with O2

Answer 28

* by injection (hypodermic syringe) * drug is dissolved or suspended in a liquid (normally saline, water, or vinegar) - the liquid is called the vehicle - THC requires oil as vehicle - lipid soluble drug in oil wehicle slows rate of absorption three (4) types * intravenous (vein) * intramuscular (butt, thigh) * subcutaneous (into fatty tissue under skin) * intraperitoneal

Answer 29

may be called subQ Advantages: 1. easiest of all injection techniques - with venous, can be hard to find vein or too much scarring usually under skin of arm or thigh, sometimes hand or wrist used for self administer rec drugs (heroin), skin popping Disadvantages: 1. slower absorption than IM or IV 2. risk of skin irritation or deterioration - unclean needle? skin unclean? with routine injection of drugs youll see notable skin abscesses and lesions. - risk of blood borne diseases ** skin lesions are a major injury treated by street docs

Answer 30

inserted into muscle, bolus left there. most common in deltoid, glute max... absorb thru capillaries within hour * Advantages: 1. quicker to do than IV (dont have to find vein) 2. faster absorption than SC * Disadvantages: 1. slower absorption than IV (15s for IV drug to get into site of action in vein) 2. risk of piercing vein by accident - tear vein, OR cause it to get to site of action VERY quick (too quick...) - this could be a problem bc IM drugs are meant to be administered this way

Answer 31

into vein, direct to bloodstream. "mainlining" - must find a vein close to surface (usually inside of elbow). opposite of blood test procedure. * Advantages: 1. faster absorption than SC or IM (person administering can be quite sure it gives patient effects right away. 2. immediacy of effects (15 sec) 3. allows for accurate dosages * Disadvantages: 1. immediacy of effects c/be lethal (NO WAY for drug to be recalled) 2. drugs cannot be recalled 3. requires sterile conditions; unsterile conditions seen with street use leading to development and spread of infectious diseases - when done too freq, vein can collapse *** the needle can often take up a little blood and spread to the other person would probably be helpful for EMS to have naloxone in lower dose to give IV .. faster act

Answer 32

* Opened in 2003 @ DTES vancouver... , first in North America (lots of controversy...) * Hours of Operation: 7 days/week, 18 hrs/day * Staff: 2 registered nurses, on-site manager, counselor, doctor on call * Provides: – 12 seat injection room – “Chill Room” – Clean injecting equipment – Medical attention in case of overdose – Access to, or referral to other health care services (some treatment of skin lesions here) - some sites do drug testing too $$$ to run - approx $500,000/year http://www.vch.ca/locations-services/result?res_id=964 * also safe inhalation sites now too.

Answer 33

- the cost of bringing ambulances to respond to OD and dealing with long term health issues and jails is LOTS more $ than safe injection sites. - separate the users from dealer - "the user is sick, the dealer is evil" says mayor. https://www.canadawildproductions.com/film/fix/ they use frankfurt as a model of somewhere safe injection sites have worked. - safe injection sites offer a pathway into methadone programs, medical help, other counselling programs ... - shows protests against a safe injection site in chinatown... does not want it in city. "force them to abstain" ... opposing protests. - Ann Livingston - didn't use VANDU money, but created a drop in centre to support the problem. creates her own safe injection site with her own $. https://www.abundantcommunity.com/author/annlivingston/ - some sites offer drug checking - at this time, lot of the controversy abt supporting the mayors plan , plan for task force. ( reluctant...) voted in favor, after months of demonstrations, they are going through the programs for drug users dean gets through 8 days of detox

Answer 34

* Decrease public injection drug use – Up to 1000 injections per day (many less injection on the street!) ** early 2020 state 3000 per day * Decrease unsafe disposal of syringes in public spaces – CMJ: decreased drug litter on street (this worked!) * Decrease overdoses – Overdoses common, but no deaths (in Insite) * Decrease Infectious Disease Risk – 70% reported less syringe sharing (The Lancet; Marshall et al, 2007)) – 2009 Stats showed 8% reported needle sharing in Vancouver vs 29% in Victoria (CARBC research study) - Vic didnt have site at this time) – Incidence of HIV/AIDS dropped by over half (BC Centre for Excellence HIV/AIDS – Estimated 20-30 new cases of HIV/AIDS prevented yearly (Des Jarlais et al, 2008) * Improve Access to Healthcare Services – # of abcess treatments = 3, 130 (Vancouver Coastal Health, 2009) – 1 in 5 accessed detox centers – Onsite: 30 bed detox facility - more ppl accessing this ** money saving studies! treating HIV aids

Answer 35

>35,000 Canadians accessing. - 66% male, 33% female, 1% not specified. -25% age 25-31

Answer 36

– Cell membranes – Capillary walls – Blood-brain barrier – Placenta

Answer 37

Cell Membrane: a bi-lipid layer embedded with large protein molecules - fat soluble drugs absorb quite well in the body BUT Large amounts of highly lipid soluble drugs tend to accumulate outside CNS. as drug moves thru bloodstream, the fatty tissue acts as a sponge and takes up the drug. - for ex, cocaine, can get reverse tolerance. w repeated use, the regular dose might cause convulsions. the pH of intestinal lining is 50 % ionization, at ph5 meets acid curve. most bases like morphine are poorly absorbed when taken orally, but absorption depends on pKa (for ex, caffeine is a base with a pKa of 0.5, ionization curve drops off quick at very low pH - therefore is almost entirely non-ionised at pHs in digestive system ... therefore is well absorbed orally.

Answer 38

https://www.ted.com/talks/guy_felicella_i_died_six_times_let_s_stop_the_stigma_of_harm_reduction

Answer 39

Tiny Blood Vessels with walls formed by a single layer of tightly packed cells - drug molecules can fit thru the capillary pores. BUT if the drug bonds to a protein molecule, it becomes too big to move through the capillary and it gets excreted. - * Exiting of drug molecules also affected by rate of blood flow

Answer 40

a feature of the physical structure of the brain capillaries. much smaller pores than other capillaries in the body. - FEWER pores in brain capillaries as well often a fatty sheath (lipid layer) surrounding this as well. - not much of a barrier for highly lipid soluble drugs - some drugs may be actively transported across

Answer 41

* Network of blood vessels and pools of maternal blood into which fetal capillaries protrude - active transport of nutrients, can get rid of waste. can bring drugs to the embryo/fetus * Drug concentration can reach 75-100% of mothers within 5 min of admin * Some drugs can have harmful effects on developing fetus - similar to blood brain barrier. highly lipid soluble substances cross more easily - ** drug concentration in the blood of fetus usually reached 75-100% of that o mother within 5 mins - offers little protection to fetus

Answer 42

* Small amounts of some drugs will be eliminated through body secretions i.e., sweat, saliva, breast milk (non-metabolized methamphetamine in sweat ) * Some drugs may be excreted in feces and bile * Some drugs will be eliminated through the lungs (sometimes unchanged, alchohol eliminated in breath) * Most drugs leave the body in the urine - excretion organs: the liver and kidneys work together to elininate drugs (dynamic duo!)

Answer 43

kidneys and liver

Answer 44

located right under diaphragm contains many enzymes - includes alcohol dehydrogenase - removes H from a molecule of alcohol and makes it acetaldehyde enzyme biodegrade drugs, change structure, make less lipid soluble, more water soluble. if more water soluble, when it reaches the kidneys, it will not be reabsorbed, will be eliminated cytochrome 350 enzymes make them "drug metabolites" water soluble and excreteable ** chloral hydrate, psilocybin and THC are all more active after metabolism than original drugs - metabolites are more likley to ionize - important w kidneys bc ionized molecules cannot be reabsorbed into blood

Answer 45

Kidneys remove drug molecules/drug metabolites from blood and by products of metabolism by liver enzymes ... and send to ureter filtering system physically removes certain substances from blood... each kidney has millions of nephrons ** works by filtering everything out of blood then selectively reabsorbing what is required. - nephron is long tube, one end us cup, Bowmans capsule, with a clump of capillaries inside called the glomerulus... other end empties into collecting tubules, to urinary bladder. - of note: lots of capillarization of the glomerulus within nephron - these capillaries have porse for fluid in blood to flow through - glomerulus filters fluid out of the blood into the nephron and capillary bed to reabsorb -

Answer 46

* In addition to being less lipid soluble, drug metabolites are generally less active than parent molecule - usually biodegraded and biotransformed - Heroin get metabolized into morphine - THC becomes more active after being metabolized. * Some drug molecules are as active or more active than parent molecule * Some drug molecules will not be metabolized by liver; will be excreted intact * Rate of drug metabolization affected by the number of enzymes in the liver * The number of enzymes in liver c/be significantly increased with continuous use of drug (homeostatic relationship) * Enzymatic action of liver responsible for drug (metabolic) tolerance (metabolized quicker, excreted quicker.... ppl need to increase their intake to make up for this)

Answer 47

oral drugs are absorbed by digestive system and that blood does to the kidneys and liver before returning to the heart and then the brain. ... therefore, a drug absorbed in digestive system will pass thru liver before going anywhere else in the body and will have some metabolism by liver enzyme... this is first pass metabolism - blood levels are much lower at the site of action * “First pass” metabolism accounts for lower blood levels of orally administered drug - nasal, mouth or rectal administation does not have this and may lead to higher blood levels in body. - alcohol is a good example bc it has some metabolism before its absorbed

Answer 48

* Elimination rate of drugs will be described in terms of a drug’s “half life” nicotine half life = 30 minutes at 30 minutes, 50% of the nicotine has been eliminated. 60 minutes after cigarette, 75% of the nicotine has been eliminated. 90 minutes after cigarette, 87.5% will be eliminated. - every 30 minutes, half more is degraded (goes from 50% left, to 25% left to 12.5% left... - different half lifes depending on drugs Half-life will also vary from person to person due to genetic (insufficient enzyme, hepatic liver/death) make-up or age or disease related states of kidney or liver functioning absorption and elimination are happening at the same time normally takes 5-6 half lifes to eliminate 98% of the drug absorbed EXCEPTION: alcohol is metabolized in a linear fashion - avg person will eliminate within 1-1.5 hrs. higher concentration at beginning, faster it gets eliminated. - excretion curve for alcohol is linear (about 15mg alcohol/100mL blood / hour

Answer 49

DRUG TESTING * Commonly involves blood or urine analysis * Drug detected in blood suggests recent use * Drug detected in urine indicates recent or past use * Detection times substantially longer if drug metabolites can be measured by testing method (some highly lipid soluble drugs will continue to move around in bloodstream for a while ... high enough levels in the urine) Detection time ranges generally shorter than elimination time ranges, thus – Positive results cannot provide precise info re: when drug used – Negative results may not be 100% confirmation of non-use - maybe not enough concentration (ppl can fake it!) * Methods used to get false negatives: * Substitution * Adulteration - substances that will interfere * Dilution

Answer 50

* Different drugs will have different detection time ranges (cocaine will be excreted more quickly that THC) * Detection rates will also vary as a function of: * Length of drug use * Individual differences in how drug handled by body * Less common drug testing methods: * Hair analysis * Oral fluid testing (absorbent collection pad in cheek)

Answer 51

sensory, interneurons, motor neurons

Answer 52

cell body axon myeline sheath nodes of ranvier synaptic end bulb (NT) dendrites

Answer 53

Structure within reticular formation Raphe Nucleus - plays a role in sleep

Answer 54

Structure within reticular formation Substantia nigra - role in motor movement. also releases significant amount of dopaminein brain (referred to as dopaminergic) Parkinsons disease is damage to dopamindegic neurons in substantia nigra.

Answer 55

Structure within reticular formation plays a role in pain sensation and defensive behavior contains a "punishment system" - when this area is stimulated, theres an unpleasant sensation... research with animals. - opiates work in this area to releive pain - has connections to Raphe nuclei stimulates spinal cord to block pain pain blocked in the brain and in the spinal cord - part of lower brain area pain signals never reach, so we do not experience pain if issue here

Answer 56

Structure within reticular formation refers to roof or ceiling of midbrain (closer to front of body) - plays a role in reward related behaviuor, motivation and addiction feels good, feels pleasure ... animals will engage in activities to get stimulated in this area - sends to areas that will release dopamine in thalamus, hypothalamus, NUMERUS drugs effect functioning of VTA

Answer 57

medulla pons cerebellum reticular activating system raphe nucleus substantia nigra periaquaductal gray area ventral tegmental area

Answer 58

Inferior and Superior Colliculi Ventral Tegmental Area

Answer 59

Inferior and Superior Colliculi – Relay and process (at basic level) auditory and visual infor respectively

Answer 60

Ventral Tegmental Area – Contains cell bodies involved in drug dependency

Answer 61

- in FOREBRAIN – Referred to as “relay center” or “traffic officer” * directs all sensory info – Sends sensory information to cerebellum and cerebral cortex – Sends motor commands to muscle groups in connection with RAS, regulates general arousal and excitability of the cerebral cortex psychedelics have big impact here

Answer 62

within forebrain – In connection with pituitary gland regulates physiologically based drives master hormonal gland controls hunger, thirst, sex drive, "munchies" with THC is due to how THC effects hypothalamus - low sex drive w optiates is due to effects on hypothalamus (opposite with cocaine and meth)

Answer 63

within forebrain Plays a role in learning and memory; formation of new memories - may play a role in drug dependency behaviours, memory of having done a drug in a place can cause a conditioned response - barbiturates have effect - alcohol can impact

Answer 64

thalamus hypothalamus hippocampus basal ganglia cerebral cortex

Answer 65

Reinforcement/Pleasure/Reward Centers – Include : * Mesolimbic Dopamine System (across the limbic system) impacts dopamine * Nucleus Accumbens * Pre-frontal Cortex – Play a role in intense euphoric effects of some drugs and addiction (e.g., amphetamine, cocaine, heroin) begins in ventral tegmental area when active, when a lot of dopamine.... experience a lot of pleasure (tiny spot in ventral area of brain?)

Answer 66

part of forebrain Basal Ganglia - collection of structures ◦ Plays a role in  integrating voluntary motor movements - conjunction w cerebellum for motor control  Maintaining posture and muscle tone  Learning/forming automatic stimulus response S-R behaviors i.e., habits this is important, big role w parkinsons. some antipsychotic drugs causes a parkinsons like response (regards to movement)

Answer 67

Medulla – Site of “life-maintaining” centres – Contains “vomiting centre” - for proper function of the autonomic NS - contains descending reticular formation - controls HR BP breathing, muscle, couch swallow ....reflexes. death from OD is usually due to suffocation bc respiration centre is deprssd

Answer 68

* Pons - bridge – Contains nerve pathways relaying sensory info to thalamus, cerebral cortex, cerebellum * bridges and refines motor commands – Plays a role in body movement, sleep, dreaming - Contains locus coeruleus, involved in SNS activation

Answer 69

Reticular Activating System – Plays a role in ANS reactions; readying one to act – Controls wakefulness/neurological alertness

Answer 70

- first part of nervous system to response to potentially threatening stimuli info from sensory reaches this within 5ms, this reacts and illicits fear stress related behavior.

Answer 71

- higher mental processes Responsible for higher mental processes e.g., language, reasoning, decision making, problem solving Has four divisions, referred to as lobes - differ in what they do * Frontal *Parietal *Occipital *Temporal frontal lobe is most complex Brocas area, auditory association cortex recognition - visual association cortex with the temporal lobe

Answer 72

judgement (cerebral cortex, frontal lobe) visual - occipital balance - cerebellum

Answer 73

inside of neuron is MORE NEGATIVE - at rest? the neuron is at -60mV larger neg charged = chloride pos charge = potassium ions hyper-polarization - when the resting potential increases, meaning more negative. depolarization - becomes less negative (goes -60 to -50) - closer to zero action potentials "hop" - wave, as if in a stadium ** outside of membrane is considered zero - nerve conduction - non-gated ion channels - always open for K+ and Cl- to pass thru. - there are also sodium potassium pumps if neuron is depolarized to -55, this is threshold and resting potential breaks down - breakdown due to stim of voltage gated channels "all or none rule"

Answer 74

-NTs bind to receptors on ion channels when a NT molecule bonds to ionotropic receptor, the channel opens or closes, altering the flow of ions "fast acting" - the neurotransmitters fit into and activate the receptor site - channel opens inside neuron (inside G protein) allow ions to flow in only lasts ms

Answer 75

slow acting - when a NT binds to a metabotropic receptor causes a signal protein to change the signal in signal protein - not binding directly to ion channel, but on extracellular portion of long protein - a subunit of the G protein breaks off into neuron and binds/stimulates a message

Answer 76

- There are both post-synaptic and pre-synaptic neurons Autoreceptors - Located on pre-synaptic neuron - Respond to neurotransmitters in synaptic cleft - if NT levels too high, autoreceptors cause/ provide feedback for reduction in synthesis and release of neurotranmitters - negative feedback loop? antidepressant drugs may not work bc of this - autoreceptors are trying to reduce production due to increase inNT Heteroreceptors - Retrograde signalling - Located on pre-synaptic neuron - Respond to chemicals released by post-synaptic neuron (called retrograde signalling) - Will decrease synthesis and release of neurotranmitters by pre-synaptic neuron Depolarization-induced suppression of excitation or inhibition - not responding to amount in symapptic cleft, but responding to the amount in the postsynaptic cell

Answer 77

(1) Action potential traveling along pre-synaptic neuron to terminal button (2) Release of neurotransmitters into synaptic gap (3) Diffusion of neurotransmitters into synaptic gap (4) Binding of neurotransmitter to post-synaptic receptor and possible activation (5) Integration of IPSPs and EPSPs in post-synaptic neuron, leading to possible action potential in postsynaptic neuron (6) Released neurotransmitters bind to autoreceptors blocking release of more neurotransmitters (7) Termination of neurotransmitter effects - biodegradation of neurotransmitter - reabsorption of neurotransmitter - diffusion of neurotransmitter

Answer 78

- depending what they bind to determines the effect that they have -elevated norephinephrine - better feelings, more alertness COMP enzyme biodegrades this

Answer 79

limbic areas - emotional processing

Answer 80

nothing additional

Answer 81

plentiful, cell bodies are everywhere!

Answer 82

blocking NT site -

Answer 83

* In addition to showing ED50 and LD50, DRCs illustrate four other characteristics of a drug – Dose that produces max effect – Potency of drug – Intenseness of response to dose increases – Drug interactions asprin, many physiological effects (less pain, inflammation, fever....but also slows bloods ability to clot) - this reduced likelyhood of strokes (taking prophylacticaly)

Answer 84

TYPES OF DRUG INTERACTIONS (1) ANTAGONISM (a) Pharmacological antagonism - at site of receptors – Competitive vs. noncompetitive *** naloxone is a competitive antagonist of opiates*** often have a higher affinity for the receptor site (b) Physiological antagonism - offsetting effect between drugs (often happens when ppl are on lots of drugs) -ppl take one drug to deal w sde effects of another (opiate for chronic pain, then take laxitaves for constipation assocaited w )

Answer 85

TYPES OF DRUG INTERACTIONS (2) SYNERGISM (a)Additive effects - combining a drug with one drink of beer, makes it seem as it youve had 2 beers (b) Superadditive effects - drug + 1 beer = effects of 10 beers when is it additive effect vs superadditive effect? - 2 combined drugs causing potentiation: IF usually one drug alone has NO effect - but when combined, causes increase in overall effectiveness of drug or increase in potencey.

Answer 86

TOLERANCE * Occurs as a result of repeated use/administrations of drug - tolerance to opiates develops QUICKLY! will prob only be nauseous the first time * State of decreased effectiveness and/or need to increase dosage for same level of effect * Varies as a function of drug effects * Eventually dissipates - ** tolerance to euphoria is the first to adapt

Answer 87

MECHANISMS OF TOLERANCE Pharmacokinetic Tolerance * Aka Metabolic Tolerance * Increase in number of drug metabolizing enzymes (e.g., cytochrome P450) in liver * Aka Physiological Tolerance * Homeostatic adjustments to continued presence of drug through processes of * Type of adjustment made will vary as function of drug effect - adjustments of body to deal with the continual presence of a drug - to maintain homeostasis when drug is given repeatedly, it may induce of increase the action of the enzyme used to destroy it - creates cross tolerance w drugs that may be metabolized by the same enzyme

Answer 88

MECHANISMS OF TOLERANCE Cross Tolerance * Repeated use of one drug, diminishes effect of other drug not used * Partly function of non-specificity of drug metabolizing enzymes in liver - has to do with production of metabolizing enyzmes on liver - production increased by repeated use of drug using particular barbituate but switch to benzodiazapine - theyhave some tolerance to this although theyve never used it shown between all classes of opiates some cross tolerance between alchohol and opiates

Answer 89

MECHANISMS OF TOLERANCE Reverse Tolerance * State of increased sensitivity to drug effects * Hypothesized factors behind phenomenon: – Lipid solubility of drug – Subjective expectations need less of a drug for particular effect to be realized for a seizure to occur with cocaine ... need to take >90mg ...BUT w repeated use, (5-10mg) could cause a seizure - sensitizes the body, "kindling effect"

Answer 90

MECHANISMS OF TOLERANCE Acute Tolerance * Aka tachyphylaxis - RAPIDLY DEVELOPING TOLERANCE * - means one may not need repeated use in order to develop tolerance. can become tolerant after single exposure. * Rapid developing tolerance Psychedelics such as LSD-25 and psilocybin-containing mushrooms demonstrate very rapid tachyphylaxis. pupils - we never really develop tolerance to this!

Answer 91

MECHANISMS OF TOLERANCE Behavioral Tolerance *learn - Due to habituation and conditioning * Involves body’s physiological atttempt to resist conditioned response to drug we develop competsetory strategies to offset the effects the drug has on us. - we could learn to turn off a high - varies based on the drug - THC for example ,can distort our sense of time .... BUT ppl can be taught to not get the "high" feeling, but they still have the perception of time Unconditioned stimulus --> Unconcitioned response unconditioned drug --> euphoria neutral stimulus (a NEEDLE) --> conditioned response --> euphoria conditioned stimulus (NEEDLE) --> euphoria

Answer 92

Dependance vs addiction... DEPENDENCE * Compulsive use of drugs despite adverse consequences - using despite consequences ... ** the more immediate the reward the stronger association - the immediate euphoria is more important * Types include: – Physiological dependence – Psychological dependence – Cross dependence

Answer 93

* Experiencing a cluster of unpleasant physical and psychological effects upon termination of drug use i.e., presence of withdrawal symptoms/abstinence syndrome - when withdrawl happens depends on the method of admin,...noted below * The effects experienced opposite of drug effects * Severity, length, timing of withdrawal influenced by dose, moa, and rate of elimination longer half life, longer for withdrawl symptons shorter half life, sooner withdrawl symtoms will appear ** if quick intense symptoms, they are not as bad!

Answer 94

can be primary and secondary PRIMARY - strong desire / CRAVING for the drug - the euphoria, or the relief from anxiety. the calming effect SECONDARY - desire to eliminate withdrawal symptoms - dean in the viewo, wants to feel normal means theyve been in withdrawl before

Answer 95

* Phenomenon in which use of a drug (typically from same class) stops withdrawal symptoms -

Answer 96

* Addiction – Characterized by tolerance, psychological, and physical dependency, and organ changes * 3 C’s – Compulsion – Loss of Control – Continued use despite adverse consequences

Answer 97

* Diagnostic Criteria * Tolerance * Craving or strong desire to use drug * Withdrawal * Great deal of time is spent in activities necessary to obtain drug, use drug or recover from its effects * Continued use having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the drug * Continued use despite having a persistent or recurrent physical or psychological problem that is likely to have bee caused or exacerbated by the drug * Persistent desire or unsuccessful efforts to cut down or control drug use * Important social, occupational, or recreational activities are given up or reduced because of drug use * Recurrent drug use resulting in failure to fulfill major role obligations at work, school, or home

Answer 98

Selling of drug * Exposure to Drugs * Religion

Answer 99

* Low self-esteem * Anxiety/depression * Personality - Sensation seeking, Impulsivity, narcissism, harm avoidant temerment

Answer 100

* Several hundred family, twin, adoption studies provided evidence of genetically related variability in individuals’ sensitivity to and bodys’ handling of drugs

Answer 101

It is also sometimes abbreviated as the ED50, meaning "effective dose for 50% of the population". The ED50 is commonly used as a measure of the reasonable expectancy of a drug effect, but does not necessarily represent the dose that a clinician might use. This depends on the need for the effect, and also the toxicity. median effective dose

Answer 102

The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity. - for ex, botulinum toxin is 1nanogram per kg for a human -The most accurate estimate of the LD50 of caffeine orally to rats is 367mg/kg. median lethal dose

Answer 103

naloxone is a competitive antagonist (within pharmacological antagonism), this has higher affinity and competes for receptor, blocks the opiate. compete for same receptor site.

Answer 104

- not the same receptor sites - can interfere with the antagonistic action - allosteric site - NCA binds to an allosteric site, then impacts the shape/structure and ability of the receptor.

Answer 105

if there is constant stimulation? it might downregulate, move receptors ... make adjustments that vary as function of drugs effect

Answer 106

- talks about the intensity and pervasiveness of addictions - ppl comments that he is not scared of becoming dependent again - ppl comment that they feel neutral - not ecstatic, just getting through ... something caged up that needs more? - blonde haired women said she was surprised that she was dependent ... does to take kid to school... to do dishes /// - John says he needs to go look for heroin every 4-6 hrs - girl in taxi, she was in school and used all of student loans for drugs (borrowing lots of money), did a ton of lying to get $ for heroin. gets fired...constantly calling/texting @ work to arrange hookups. * highlights the diversity of ppl who use heroin, the dependency does not discriminate - - dependency - timing of reward... from feeling like I am dying, to the BEST feeling the poetry gives sense for how intense the withdrawl symptoms are - ppls really want to stop using, but the body reacts... teens vs adults - teens usually have external factor ... theres no internal motivation to stop using drugs - they dont recognize issues guy who flagged blood in washroom...they want to pass out and have someone take him to treament ... to get a hospital morphine drip. does not want to do the work himself. lots of ppl looking for relief from self loathing / anxiety using drugs - there is often a community of drug users which provides an identity, support, a place to fit in... they want to stop the drugs, but realize with this will have to withdraw from this community. importance of ppl leading the treatment centres have previously been addicted

Answer 107

cell membranes, capillary walls, blood brain barrier, placenta

Answer 108

a bi-lipid layer embedded with large protein molecules - lipid solubility? large amounts of highly lipid soluble drugs accumulate outside the CNS - -highlt lipid soluble drugs will accumulate in body fat outside of CNS. but - drug dissolved in BF has no effect on body (is inactive) - body fat is a sponge for lipid soluble drug, preventing it from reaching site of action

Answer 109

important for elimintion - has proximal convoluted tubule, distal convoluted tubule, glomerulus and cortical collecting duct - The nephrons work through a two-step process: the glomerulus filters your blood, and the tubule returns needed substances to your blood and removes wastes. Each nephron has a glomerulus to filter your blood and a tubule that returns needed substances to your blood and pulls out additional wastes

Answer 110

* Kidneys remove drug molecules/drug metabolites from blood and send to ureter, and enzymes in the liver metabolize drug molecules into excretable drug metabolites * Excretable drug metabolites are more water soluble, less lipid soluble

Answer 111

* Cholinergic neurons project to cortex, hippocampus, and down spinal cord * Binds to two types of receptors: – Nicotinic - ionotropic... allow influx of Na+ ... depolarize --> EPSP ** Nicotine stimulates these receptors – Muscarinic - open channels to hyperpolarize the cell - IPSP * Plays a role in: – Motor movement/contraction of muscles – Memory and learning * Actions terminated via Acetylcholine Esterase alzheimers diseases is marked by loss of ACh NT ** Botox blocks release of ACh at NMJ, preventing muscles from contracting

Answer 112

Noradrenergic neurons project to entire CNS * Binds to four main receptors – Alpha 1, Alpha 2, Beta 1, Beta 2 adrenergic receptors * Plays a role in: – Attention, neurological alertness, and information processing, mood states * Actions terminated via uptake or Monoamine Oxidase or Catechol – O- Methyl – Transferase

Answer 113

Dopaminergic neurons project to basal ganglia, cortex, and limbic areas * Three major pathways: – Nigrostriatal pathway – Mesocortical pathway – Mesolimbic pathway * Binds to five types of receptors (D1-5) * Plays a role in: – Motor movement, mood, and memory, impulse control * Dopaminergic activity greatly modulated by neurons projecting to VTA * Actions terminated via uptake or Monoamine Oxidase Cocaine blocks reuptake - agonist. Amphetamine reverses reuptate - agonist

Answer 114

* Serotonergic neurons project to entire CNS * Binds to 15 receptors (Type 1A-F, Type 2A-C, Type 3- 7) * Plays a role in regulation of mood, sleep-wake cycle, eating, and sexual and aggressive behaviors * Actions terminated via uptake or MAO fluoxetine - SSRI - agonist LSD - stimulates 5-HT receptors - agonist

Answer 115

* GABAnergic neurons project to entire CNS * “Binds to two types of receptors : – GABA A – GABA B * “Major Inhibitory Neurotransmitter” * Actions terminated via uptake alchohol stimulates GABA receptors - agonist

Answer 116

* Glutaminergic neurons project to entire CNS * Binds to metatrobic and ionotropic receptors – Complex NMDA (N-methyl-D-aspartate) receptor “Major Excitatory Neurotransmitter” * Plays a role in general cognition and brain plasticity * Actions terminated via uptake AMPA - stimulates AMPA receptors - agonist

Answer 117

* Neurons releasing peptides project to entire CNS * Consist of enkephalins, endorphins, dynorphins, endomorphines * Bind to three types of receptors : – Mu – Kappa – Delta * Mediate processing of painful sensations and regulate mood morphine - stimulates mu recpetors agonist methadone - stimulates mu agoinist naloxone - blocks mu - antagonist

Answer 118

- within brainstem / hindbrain controls fine motor mvmt, motor coordination, postural adjustments - role in cognitive tasks

Answer 119

within brainstem/hindbrain – Ascending and Descending Pathways – Plays a role in ANS reactions; readying one to act – Controls wakefulness/neurological alertness – Also part of the midbrain

Answer 120

within brainstem/hindbrain – Ascending and Descending Pathways – Plays a role in ANS reactions; readying one to act – Controls wakefulness/neurological alertness – Also part of the midbrain

Answer 121

1: Na+ channels open, NA+ begins to enter cell (membrane potential at -60mV) 2: K+ channels open, K+ begins to leave the cell (becomes less negative...) 3: Na+ channels become refractory, no more Na+ enters the cell. (peak!) 4: K+ continues to leave the cell - causes membrane potential to return to the resting level. 5: K+ channels close, Na+ channels reset. 6: drop below ... Extra K+ outside cell diffuses away

Answer 122

when a neuron experiences several post synaptic potentials on a neuronal dendrite or cell body. (when 2 EPSPs elicited in rapid succession sum to form a larger EPSP)

Answer 123

when two or more post synaptic potentials occur in close proximity on a neuon (2 simultaneous ESPSs sum to create a greater EPSP)

Answer 124

EPSP stands for the Excitatory Postsynaptic Potential and IPSP stands for the Inhibitory Postsynaptic Potential. - EPSP is a temporary depolarization that is caused by the flow of positively-charged Na+ ions into the postsynaptic cell ...the resting potential moves closer to AP threshold. many ESPS may deporarize the cell for AP - IPSP is a hyperpolarization caused by the flow of negatively-charged ions into the postsynaptic cell. OR as K+ rushes out - resting potential increases, hyperpolarization, harder to reach AP The main difference between EPSP and IPSP is that EPSP facilitates the firing of an action potential on the postsynaptic membrane whereas IPSP lowers the firing of the action potential.

Answer 125

* Small lipid molecules that act as neuromodulators – Anadamide – AG (2-arachidonoyl glycerol * Bind to two types of receptors: CB1 and CB2 * CB1 receptors in frontal cortex, anterior cingulate cortex, hypothalamus, hippocampus, basal ganglia, and cerebellum and found on neurons that release Ach, DA, NE, 5-HT, glutamate and GABA * Are involved in retrograde signalling Endocannabinoids * Play a role in sedation, analgesia, appetite, concentration, memory, mood

Answer 126

(1) Agonistic (2) Antagonistic (3) Disruption of re-uptake mechanism (4) Disruption of synthesis or degradation of neurotransmitters (5) Leakage (6) Interfere with 2nd messengers and/or ion channels

Answer 127

- the drug increases synthesist of NT (increases amount of the precursor) - drug increases the # of NT molecules by DESTROYING degrading enzymes - drug increases release of NT from terminal buttons - drug binds to autoreceptors and blocks their inhibtory effect on NT release - drug binds to postsynaptic receptor and either activates them or increases effect of receptor on NT - drug blocks the deactivation of NT molecules by blocking the degredation or reuptake.

Answer 128

- drug blocks the synthesis of NT molecules (destroying the synthesizing enzyme) - drug causes the NT molecules to leak out of vesicles and be destroyed by degrading enzymes - drug blocks the release of NT molecules from terminal bottons - drug activates autoreceptors and inhibits NT release - drug is a receptor blocker - binds to postsynaptic receptors and blocks effects of NT

Answer 129

* Diagnostic Criteria * Tolerance * Craving or strong desire to use drug * Withdrawal * Great deal of time is spent in activities necessary to obtain drug, use drug or recover from its effects * Continued use having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the drug * Continued use despite having a persistent or recurrent physical or psychological problem that is likely to have bee caused or exacerbated by the drug * Persistent desire or unsuccessful efforts to cut down or control drug use * Important social, occupational, or recreational activities are given up or reduced because of drug use * Recurrent drug use resulting in failure to fulfill major role obligations at work, school, or home

Answer 130

Social Learning – e.g., peer pressure, “fitting in”/connecting

Answer 131

Self-medicating – e.g., treat depression, anger, anxiety, attention problems

Answer 132

* Several hundred family, twin, adoption studies provided evidence of genetically related variability in individuals’ sensitivity to and bodys’ handling of drugs

Answer 133

* Drugs as Reinforcers – Positive – Negative – Stress and Reinforcement – Immediate vs Delayed Consequences * Drugs Alter Functioning of the Motivation Control System and hence behavior

Answer 134

* Stimuli that activate the MLDS ( Mesolimbic Dopamine System) have incentive salience – Stimulus is easily noticed – Motivates behavior toward it * Drugs activiate the MLDS, so thus have incentive value and so presence of drug or stimuli associated with drug will lead to drug use behavior

Answer 135

* A dysfunction in information processing and integration amongst multiple brain regions * Circuits that – regulate “reward/saliency” (e.g., nucleus accumbens and ventral tegmental area) – “motivation/drive” (e.g., orbitofrontal cortex and motor cortex) – “memory/conditioning” (e.g., amygdala and hippocampus) – “inhibitory control/executive function” (e.g., dorsolateral prefrontal cortex and anterior cingulate gyrus)

Answer 136

* 13 Principles of Effective Treatment Program * Treatment Programs – Detoxification and medically managed withdrawal. – Outpatient treatment programs. – Short-term residential treatment. – Long-term residential treatment. * Treatment Approaches – Behavioral treatments – Pharmacological treatments

Answer 137

how drugs get from their place of administration to where they act

Answer 138

- heat and exercise can have effects - faster absorption if exercised and or heated. slow absorp if chilled. - drug must pass thru capillariy wall to enter bloodstream and be absorbed - capillary is single layer of cells - small openings or pores. RBC and large protein cannot leave. - areas w many capillaries absorb drugs faster than areas w few capillaries - muscles have more capillaries than skin. - absorption thru capillaries is not a factor for IV injections bc the drug goes directly into blood stream

Answer 139

the pKa of a rug can effect where the drug ends up in body - weak bases tend to ionize in acidic solutions, and weak acids ionize in basic solutions. - ionized molecules are not lipid soluble, the pKa of drug can change speed of absorption or excretion.

Answer 140

there are large protein transport molecules within membranes - in passive transport, large protein molecule may create a channel large enough for pass thru. - carrier protein - specilized molecule allows molecule to diffuse and release to other side - high to low concentration as if it were lipid soluble (no expenditure of energy active transport requires ATP - includes ion pumps, Na K transporter protein - blood brain barrier has some of these systems - the BBB actively removes selective product, toxic waste, some AA ... -

Answer 141

some drugs attach to large protein molecules so strongly that theyre attached until metbolized. - and never reach site of action...

Answer 142

usually enough enzymes, all of drug metabolized at once. low concentration, slower metabolism. - metabolism slows as drug levels fall ** curve shows how the level of drug in blood overtime slows to an asymptote with excretion... trailing off and level of excretion is half life Factors that alter metabolism... - levels of a specific enzyme can be increased by previous exposure to drug that uses that enzyme .... known as enzyme induction , allow development of metabolic tolerance. example of this is the increase level of alcohol dehydrogenase in the livers of heavy drinkers - heavy drinkers can metabolize alcohol faster than non-drinkers, more resistant to its effects. St Johns wort example - reduces effectiveness of other drugs bc it induces production of the enzyme that destroys them... reduces effeciencey of oral contracetives

Answer 143

EXCEPTION: alcohol is metabolized in a linear fashion - avg person will eliminate within 1-1.5 hrs. higher concentration at beginning, faster it gets eliminated. - excretion curve for alcohol is linear (about 15mg alcohol/100mL blood / hour)

Answer 144

- certain drugs can block the enzyme systems of other pathways ... drug that blocks aldehydra dehydrogenzae causes buildup of metabolites from alcohol ... makes ppl feel sick same w grapefruit - shown to block an intestinal enzyme - takine grapefruit guice can increase blood levels of drug (could od due to blocking of the excretory/metabolic pathway)

Answer 145

time course graph ...drug on y axis. 3 curves - there is time of absorption from administration - hypothetical curve assuming the liver and kidneys are not slowing down as it goes. - elimination curve - hypothetical elim assuming instantaneous absorption - resultant - shows that there is an ascending phase that works faster than elimination, then later, elimination is happening more than absorption. half life remains constant, absorption rate may change by method of admin which may change rate of curve IV drugs have very steep absorption phase ex. naloxone, need quick and short Oral drugs have small absorption curve and last longer in body. for ex, antibiotics you want slow constant blood levels.

Answer 146

needing blood level of drug to be effective, but not so high it causes unwanted side effects. - taking drug at regular intervals - for drugs that are absorbed and excreted rapidly, this is extra important. - Lithium carbonate for ppl with bipolar - narrow theraputic window. this is improved w lithium in a slowly dissolving pill. may need to change individuals therapeutic window ... tolerance builds quickly for opioids

Answer 147

- depolariazation in cell body referred to as graded or postsynaptic potentials - PSPs arise from same type of ion flow, intensity is proportional

Answer 148

caffeine blocks the A2 receptors - works as an antagonist to adenosine - low levels of adenosine correspond with alertness and wakefulness - levels slowly rise dueing wakefulness and heightened neural activity, fall during sleep