Psychobiology: Psychopharmacology, WEEK 6 Flashcards
(47 cards)
1
Q
What is Psychopharmacology?
A
- Studying interaction between psychoactive drugs and the body
2
Q
What do psychoactive (psychotropic) drugs do?
A
- Alter neurotransmission
- Affect mood or behaviour
- Effective in managing psychological problems
- Aren’t naturally in the body, come from plants or synthesised from labs
3
Q
Why do we study psychopharmacology?
A
- Tells us something about how the brain works;
1. Role of specific transmitters and receptors in psychological processes > e.g: if we know a drug alters serotonin neurotransmission, we can see the effect of the drug on behaviour + infer role of serotonin in the behaviour
2. Causes of psychiatric illness > changes in brain functions which underlie psychiatric disorder > could develop better treatment - Helps us understand and deal with problematic drug use > wider social implications: concerns with health consequences of drugs + controversy over drug usage in psychiatry
- Education allows responsible assessment of costs/benefits of drug use in society > are certain drugs more helpful to our health or less.
4
Q
What does pharmacokinetics look at?
A
- Route of administration> how drugs get into the body
- Absorption/distribution> how drugs move through the body
- Metabolism > how drugs are transformed by the body
- Elimination/excretion > how drugs are removed from the body
5
Q
Routes of administration
A
- Drugs need to get into the bloodstream to have impact
- Oral/Ingestion
- Rectal
- Other mucous membranes : sublingual, buccal + nasal
- Transdermal
- Inhalation
- Injection (Intravenous, Intramuscular and subcutaneous)
6
Q
Routes of administration: Oral
Advantage + Disadvantage
A
- Oral/Ingestion: Most commonly used, comes in form of tablet or capsules > dissolves in stomach, passes into intestines where it gets to bloodstream via intestinal membrane
- Adv: It is convenient (can take it at any place without needing extra instruments) + Cheap and easy access
- Dis: Absorption is slow so shouldn’t be used in emergencies + could cause gastric irritation
7
Q
Routes of administration: Rectal
Advantage + Disadvantage
A
Rectal: Drugs in solid forms such as suppositories or in liquid forms are given by this route (mainly used on old patients) > some drugs can’t be ingested as it induces vomiting or get dissolved by acids in stomach so can’t reach bloodstream > use suppository like laxatives
- Adv: This route is preferred in unconscious or uncooperative patients + avoids nausea or vomiting
- Dis: Usually not accepted by patients + is invasive
8
Q
Routes of administration: Other mucous membrane
Advantage + Disadvantage
A
- Sublingual = under tongue, Buccal = cheek + nasal = nose>drug can get into bloodstream via other membranes
- E.G: sublingual: tablets placed under the tongue or between cheeks. The drug has to be lipid soluble and small
- Adv: Rapid absorption of drug + enters stream directly
- Dis: Might irritate mucous membrane
9
Q
Routes of administration: Transdermal
Advantage + Disadvantage
A
- Enters bloodstream via skin using patches containing drugs > drug gets released slowly over a period of time > e.g nicotine patch
- Adv: Steady intakes, avoids overdose
- Dis: shouldn’t be used in emergencies
10
Q
Routes of administration: Inhalation
Advantage + Disadvantage
A
- Inhaling via smoking + which takes drugs in quickly to the lungs > lungs have rich blood supply so drugs enter stream quickly > e.g: tobacco
- Adv: Effects are felt quickly as they absorb fast
- Dis: can irritate airways + damage lungs
11
Q
Routes of administration: Injection
Advantage + Disadvantage
A
- Intravenous: direct administration into vein + lacks precise amount of drug inserted (D) > e.g anaesthetic
- Intramuscular: drugs injected directly to muscles (e.g: vaccines)
- Subcutaneous: drugs injected under skin (e.g: insulin)
- Intrav: + Very fast rate of absorption - is invasive
- Intram: + Can hold large amounts of the medication -can cause side effects such as pain, numbness
- Subc: + Slow absorption -limited in volume of drug administered + retention at the injection site can lead to side effects.
12
Q
Absorption
A
- How the drug gains access to the blood plasma
- Unless drug is directly put into the vein, the membrane acts as a barrier which drug has to pass > some drugs will pass easier than others
- Diffusion of drugs across lipid membranes is affected by various factors: lipid-soluble and small molecules drugs diffuse best + Un-ionized drug molecules are more lipid soluble
13
Q
Journey of the drug
A
- Drugs have no sense of direction + have access to receptors all over the body
- Drugs circulate throughout body in plasma then enter tissue sites
- Encounter receptors for which they have affinity > bind to them
- Pharmacological response
14
Q
Distribution
A
- Target for psychoactive drugs is the usually brain > but in blood plasma a drug will reach all parts of the body
- Some side effects of psychoactive drugs are due to binding at receptors outside the brain > these side effects can be both desirable + undesirable
- Some drugs are temporarily inactivated by being stored in fat or attached to blood plasma proteins
- blood brain barrier acts as a selective barrier to drug distribution > only allows some drugs to pass
- Brain capillaries are different to normal ones, they are surrounded by glial cells which blocks drug molecules entering > lipid soluble molecules can’t pass easily
15
Q
Metabolism
A
- Converts the drug chemically into another compound
Can be inert (inactive) or can be active or even more active - Mainly takes place in the liver as it contains enzymes that help metabolism
- Sometimes essential for the drug to be eliminated > if it is a fat soluble drugs, it needs to metabolise to a water molecule to be eliminated via urine
16
Q
Elimination
A
- Can be eliminated in many ways
1. Urine: via the Kidneys, Only possible for water-soluble compounds > Fat-soluble drugs may be metabolised to make them water-soluble
2. Breath: eliminated by breathing via lungs E.g. certain amount of alcohol gets eliminated by breathing out, releasing the drug
3. Sweat + hair: Often un-metabolised + can be eliminated via sweat in skin + could get reincorporated through hair > is why hair-analysis can be used for drug testing (e.g: cocaine)
17
Q
Time-course of drug
A
- Amount of effect of drug increases by absorption, delay effect at the start.
- Process of metabolism + elimination reduces drug concentration + effect wears off as drug concentration isn’t enough to maintain activity
18
Q
Drug half life
A
- Half life quantifies duration of action of a drug
Half life of drug is time taken for amount of drug in plasma to fall by 50% - Impacts how frequently a drug has to be taken
- If half life for a drug is short it will be taken more frequently as effect wears off too quick > if half life is long it wont be taken as frequently.
19
Q
Pharmacodynamics
A
- How do drugs bring about their effects
20
Q
Types of drug action
A
- Most drugs that affect behaviour alter chemical neurotransmission
- Drugs either enhance the effects of a neurotransmitter, an agonist
- Or dampen or block the effects of a neurotransmitter. an antagonist
21
Q
Agonist drugs
A
- Either mimics the effects of a particular neurotransmitter by binding to postsynaptic receptors in a similar way and producing a similar response in the postsynaptic neuron (= direct agonist)
- or enhances the action of a natural neurotransmitter
(= indirect agonist) - e.g: drug enhances release of neurotransmitter, increasing amount of neurotransmitter available to bind
- could also block re-uptake of neurotransmitter so there is more to interact
22
Q
Full and partial agonists
A
- Direct agonists can be classed as full or partial > depends how far they mimic effect of endogenous neurotransmitter
- Full agonist > fully reproduce effect
- Partial agonist won’t get the maximum effect of neurotransmitter
23
Q
Antagonist drug
A
- Binds to a receptor but has NO physiological effect at that receptor.
- Antagonist binds to a receptor, blocking other neurotransmitters from binding, thus the effect of the neurotransmitter is dampened or blocked as the antagonist has no effect on it’s own but stops the neurotransmitter having an effect
24
Q
Agonist efficacy
A
- How effective the drug is as bringing about an effect
- An antagonist will have 0% agonist efficacy as it = no effect
- A partial agonist will have 50% agonist efficacy as it brings partial effect
- A full agonist has 100% agonist efficacy as it fully mimics an effect and reproduces it. > > >
25
Inverse agonist drug
- Produces the opposite physiological changes to an agonist.
- Binds to a receptor and has an effect but this effect is the opposite physiological change to the agonist
- Can be partial and full inverse agonists too (same concept) > partial = 50% agonist efficacy > full = 100% agonist efficacy but in the opposite direct. < <
26
Allosteric modulator
- method of changing neurotransmission
- A chemical (modulator) binds to a different part of the receptor than the neurotransmitter and by doing so it alters the receptor’s response to the neurotransmitter.
- The modulator binds on the same receptor site but at a different part of it, this binding changes the shape of the receptor site > this change enhances effect brought when neurotransmitter binds = bigger effect.
27
Quantifying drug effects
- The extent of a drug-receptor effect depends on its concentration at the target site and the affinity of the drug for the receptor site
- This can be quantified by a dose-response curve
- Plotting the relationship between drug dose and response under identical conditions allows comparison of pharmacological profile of drugs
28
Dose-response curve
- Compare 2 drugs + give different doses until the extent or level of effect is the same
- e.g: drug 1 may show a low dose has a sufficient effect but drug 2 may need a higher dose to get the same sufficient amount of effect
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Therapeutic index
- 2 different effects of the same drug > measures safety
- Shows a smaller dose = therapeutic effect (desirable)
High dose = toxic effect (undesirable)
- The gap between both effects show a safety margin called therapeutic index > this gap needs to be wide to avoid accidentally taking too high of a dose > distinct doses that aren't similar
30
Action of psychoactive drugs: Alcohol
- Ingested (i.e. by drinking)
Alcohol can produce behavioural stimulation (low dose) or depression (high dose), depending on dose
- But alcohol is usually categorised as a depressant drug
- Higher the dose the more inhibitory effects begin
- Low dose = no effect to giddyness while high doses can = sleep, unconscious + even death (inhibitory eff)
31
Effect of alcohol on the brain: GABA + allosteric modulation
- Primary effect of alcohol is to enhance inhibitory neurotransmission in brain = inhibitory eff
- Enhances GABA transmission (inhibitory neurotransmitter) by binding to the GABA A receptor (acting as allosteric modulator)
- Alcohol binds to GABA A rec > increases the flow of Cl– ions through the ion channel > this enhances effect of GABA = more inhibitory effects
32
Effect of alcohol on the brain: other forms
- Alcohol inhibits excitatory neurotransmission via NMDA glutamate receptors > less excitatory eff + more inhibitory
- Indirectly affects neurotransmission in serotonin, opioid and dopamine systems > Alcohol can increase mesolimbic dopamine transmission via action at cannabinoid receptors
33
Long-term effects of chronic alcohol consumption
- General health issues: Liver cirrhosis (scarring of liver), greater likeliness of cancer, foetal alcohol syndrome limits growth of foetus if mother drinks
- Brain effects: Korsakoff syndrome > people having excessive amounts of alc + have poor diet become deficient in vitamins like thiamine > causes damage to brain which can cause memory problems
- Brain adapts to having lots of alcohol so when this stops abruptly, they experience rebound of hyper-excitability due to withdrawal > characterised by anxiety, tremors + seizures
34
Action of psychoactive drugs: cocaine
- One of the stimulant class of drugs > increases activity in CNS + body
- Stimulant effects include increases temp, pupils dilate, increased blood pressure, increased heart rate etc..
- Extracted from the leaves of the Coca plant
Route of administration: Nasal (snorted)> absorbed by nasal mucous membrane or inhaled (smoking of crack cocaine)
35
Effect of cocaine on the brain
- Blocks dopamine transporter which is meant to take dopamine away from the synapse back to the pre-synaptic neuron > is a re-uptake inhibitor
- Means more dopamine is in the synapse
- Prolongs the duration that dopamine remains in the synapse > enhances effect of dopamine indirectly > indirect agonist
36
Long-term effects of cocaine
- effect of cocaine depends on route of administration >
Smoking: lung congestion while Snorting: damaged nasal membranes
- Cardiovascular damage
- Psychosis > some may experience drug induced psychosis > one experience of psychosis could be formication (feeling of insects crawling under their skin)
37
Amphetamines origins
- Stimulant drug w/ similar effect to cocaine
| - Developed in 1927 > synthetic drug (made in lab)
38
Action of psychoactive drugs: Amphetamines
- Synthetic stimulants
- Types of amphetamines include: d-amphetamine +
methamphetamine
- Route of administration: Swallowed, snorted or injected, or smoked (crystal meth)
-Absorption: Methamphetamine is more lipid-soluble than d-amphetamine so it crosses membranes more easily meaning it also enters the brain more quickly
May explain the higher use of “ICE” (Methamphetamine) > effects felt more quickly
39
Initial psychological effects of amphetamines
- Initially feelings of euphoria, feeling of well-being + decreased tiredness
- Followed by irritability, paranoia, tremor.
- Long term use = Psychosis, depending on route of administration can lead to damage too (e.g smoking affects lungs)
40
Effect of amphetamines on the brain
- Blocks dopamine and noradrenaline reuptake > amphetamines are a dopamine + noradrenaline re-uptake inhibitor > means more dopamine + noradrenaline is left in the synapse
- But also stimulates the release of dopamine and noradrenaline > means it doubly increases dopamine (and noradrenaline) neurotransmission > twice the amount is left
41
Nicotine
- Stimulant drug + effect
- primary mechanism is to act as a direct agonist at acetylcholine receptor > nicotinic acetylcholine is where nicotine binds
- This agonist action increases release of neurotransmitters like dopamine + seratonin> effect of nicotine is to enhance dopamine neurotransmission too
- Present in tobacco products + in patch + gum for those giving up smoking.
42
Action of psychoactive drugs: Caffeine
- most widely consumed drug w/ stimulant eff when taken acutely
- acute effects include: alertness, less fatigue, better motor coordination but can trigger panic attacks in those who suffer from them
- Certain genetic differences underlie sensitivity to caffeine which means experiences differ from this drug
43
Effect of caffeine on the brain
- Direct antagonist acting at adenosine receptor > reduces effect of adenosine
- Adenosine receptors inhibit the activation of dopamine receptors > Caffeine reduces this inhibition
- Thus increasing dopamine signalling
So, caffeine is a stimulant through being an antagonist increasing dopamine neurotransmission
44
Action of psychoactive drugs: Opiates
- Opioids can be natural or synthesised in labs > morphine is present in the brain already but heroin is synthesised.
- Opiates are related to metabolism > e.g: heroin has to metabolise to have it's effects.
- Heroin crosses the blood-brain barrier more easily than morphine (distribution) > In the brain, heroin is metabolised into morphine > It is morphine that has the biological effect in the brain
45
Effect of opiates on the brain: Mu receptor
- Opioids like morphine act at certain opioid receptors in the brain
- Mu receptor is believed to be where behavioural effects result > behavioural effects we are interested in are mediated by Mu rec (morphine + heroine act via these rec)
- Action at Mu rec brings about pain relieving effects of opioid drugs + mainly account for dependence inducing effects
- Administered opioid drugs bind to the same receptors which natural opiates like beta endorphins bind to
46
Effect of opiates on the brain: increasing dopamine
- Dopamine neurons in VTA project to nucleus accumbens (NA) so when dopamine neurons are stimulated they release DA to NA
- GABA neurons are in VTA too + have inhibitory effects on dopamine neuron as it is an interneuron so when GABA binds to DA, it inhibits release of DA so not too much dopamine is released.
- When we have opioid drugs, the opioid neuron in the VTA releases opioids which bind to GABA, when opioids bind, they inhibit the release of GABA > this means when GABA is released, it is a reduced amount due to the inhibition of GABA by opioids, this means more DA is released as there is less inhibition from GABA as there is less GABA to inhibit DA
- This is process of disinhibition
47
Cannabis
- from cannabis Sativa plant + contains dozens of chemicals
- Main active ingredient is cannabinoid Delta 9-THC
- THC enhances cannabinoid neurotransmission + can also increase dopamine release
- Elimination: THC is metabolised and then eliminated in urine. THC is lipid-soluble so the metabolism is necessary for elimination > needs to become water sol
- Slow elimination as THC is very lipid soluble + is stored in fat > because it's not in circulation to bind to sites, it starts being slowly released by fat stores = means relatively prolonged action of cannabis
