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Pharmacotherapy > An introduction to pharmacology and prescribing > Flashcards

An introduction to pharmacology and prescribing Flashcards

1
Q

What is meant by a biopsychosocial model?

A

Focus on biological first, then psychological and then social.

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2
Q

What are the issues with giving people medication?

A

Stigma
Feel disempowered
Potential sense of inadequacy and shame

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3
Q

What evidence shows we are over diagnosing

A

Three in four on antidepressants do not have depression

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4
Q

Is mental health an illness or a state?

A

It can be seen as similar to high blood pressure - that isn’t a disease but points to an issue in the future (heart attack)
arbitrary cut off point similar to DSM

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5
Q

Why doesn’t the myth of chemical imbalance mean medication is not worth prescribing?

A

It is similar to when you have pain, it is not a lack of paracetamol.
Clinical evidence shows it is theraputic for some to have more serotonin and noraprenefren at certain points.

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6
Q

What is the issue with most trials in terms of recruitment?

A

Majority of people would not be eligible.

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7
Q

How do antidepressants compare to wider medications?

A

Leucht et al showed similarly

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8
Q

What is pharmacokinetics (PK)?

A

Understanding what the body does to the drug

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9
Q

What is included in Pharmacokinetics (PK)?

A

Mathematical descriptions, prediction and understanding the time-course from administration to elimination

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10
Q

What is the (L)ADME acronym stand for?

A

Liberation
Absorption
Distribution
Metabolism
Excretion

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11
Q

What are the three types of modelling to understand in (PK)?

A

Empirical (Use of mathematical equations)
Physiological (predicting tools)
Kinetic (calculate time course as drug passes through the body)

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12
Q

Kinetic has a one, two and three compartment model. Explain the one compartment model.

A

One model - assumes the drug is distributed fully throughout the model.

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13
Q

Kinetic has a one, two and three compartment model. Explain the two compartment model.

A

A simple model of drug absorption and elimination

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14
Q

Kinetic has a one, two and three compartment model. Explain the three compartment model.

A

Represents organs/tissues and the organs/tissues scarcely perfused. includes the circulatory system

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15
Q

What is Absorption?

A

The process where drugs cross cell membranes on its way to the blood stream. The drug must
be in solution for this to happen.

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16
Q

Where does absorption take place after oral inception?

A

The small intestine - large surface area and good blood supply, drug permeability is high.

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17
Q

How long does it take for a drug to dissolve in the stomach?
What factors should be considered, therefore?

A

About 30 mins

Gastric emptying
Fat foods slow down absorption
Drugs (anticholenergics) slow gastric emptying

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18
Q

What part of the medication determines where it’s best absorbed?

A

The PH level of the medication

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19
Q

What is the PH partition hypothesis?

A

Weak acids: absorbed more easily in the stomach (PH1)
Codeine are more rapidly absorbed at (PH8) in the small intestine.

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20
Q

What is bioavailability?

A

The fraction of the administered dose that reaches the systemic circulation
Depends upon 1) properties of drug 2) route of administration

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21
Q

What are the 5 ways you can be given a drug?

A

Oral, skin, Inhaled, gum, vein

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22
Q

What factors affect absorption?

A

Ph
You need to put a weak acid in an acidic place. (An acidic environment = more protons)

A weak base - you need to decrease protons, need an alkaline base/

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23
Q

Which method means 100% of the drug passes to the vascular system?

A

Only IV. means 100%

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24
Q

How do we work out bioavailability fraction?

A

Area under curve
AUC oral / AUC IV

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25
Q

What 3 things affect bioavailability?

A

1) Solubility
More soluble more bioavailability
2) Instability
If drug breaks down less bioavailability
3) First pass effect
If oral, then goes through liver and not all reaches tissue

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26
Q

What does Distribution mean in relation to drugs taken?

A

How it gets to where it needs to be - from the blood stream to the different organs.

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27
Q

Certain organs get more blood flow, what are they? What gets less?

A

Brain, liver, kidney more

Skin,

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28
Q

What does above the line of maximum therapeutic range mean?

A

It will be toxic above this line.

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29
Q

What is absolute and relative bioavailability?

A

The comparison between absolute (IV) vs other way of entering the body.
Relative would be oral 1 vs oral 2 (so measuring against the same)

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30
Q

When is relative bioavailability used?

A

Only when no IV data available, or when comparing different formations.
(Quality control - Clinical trials - when a product comes of patent)

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31
Q

What is the extraction ratio?

A

Fraction of dose reaching the systemic circulation as intact drug

F = Fg x Fh

32
Q

What key forms of protein can bind to a drug?

A

Albumin
Alpha-1-acid Glycoprotein

33
Q

What occurs if Albumin decreased? Where do we see this?

A

Drug can have a toxic effect

34
Q

What occurs if alpha-1-acid is increased? Where do we see this?

A

It spits out the drug

35
Q

What are metabatropic drugs also called?

A

G-coupled protein receptors?

36
Q

Explain this chart briefly

A

Each neurotransmitter is either ionotropic or metabotropic or both.

37
Q

How many types of receptors are there? What are they?

A

1) Ligand gated (Ionotropic)

2) G-coupled receptors (metabotropic)

3) Kinase-linked receptors

4) Nuclear receptors

38
Q

Give an example of timescales that a drug would effect once attached to a receptor for each of the 4 types of receptors.

A
39
Q

What stage of synaptic transmission can drugs interfere with?

A

Almost all stages

Synthesis
Storage
Release
Receptor
Removal

40
Q

What happens, and given examples of drugs that interfere with synthesis

A

Remove or enhance synthesis

E.g. L-dopa enhances dopamine production in parkinsons disease

41
Q

How can drugs interfere with storage? give an example.

A

Lead to leakage of neurotransmitter into nerve terminals

e.g. amphetamine, causes release of dopamine and noradrenaline

42
Q

Give an example of how a drug can block a neurotransmitter release

A

Voltage operated calcium channes, open to release the vesicle. These can be blocked by a marine snail (Conotoxin) - experimentally used in pain releaf.

43
Q

How can drugs affect post-synaptic receptors?

A
44
Q

What are autoreceptors on a neuron? How do drugs effect these?

A

Found on the pre-synamptic neuron - part of self-regulating. It can be blocked to allow more neurotransmitter.

45
Q

What are heteroceptors? How can they effect drugs?

A

A different post-synaptic neuron that can block transmission
Drugs can block those allowing more neurotransmitter in.

46
Q

How can drugs affect the receptors themselves?
(4 different ways)

A

1) Agonists
Mimic effect of neurotransmitter by binding to its receptor and activating

2) Co-agonists cannot activate the receptor alone and act on separate sides on the receptor
protein on NMDA receptor both glutamate and glycine bind at the same time.

4) Competitive antagonists
Compete for the same sight as the neurotransmitter

5) Non-competitive antagonist
Act by another mechanism - eg blocking the channel

An example is PCP (angel dust, anasethetic - can cause halloucinations) which blocks the
channel of the NMDA receptor

47
Q

What is the GABA A receptor?
What does this image show.

A

GABA A has subunits

The BDZ site is the site of many drugs in the reward pathway.

It can be activated by GABA

BDZ potentiate GABA (ie increase it) such as benzodiazapine.

BDZ inverse agonists inhibit GABA

48
Q

How are neurotransmitters removed?

A

Enzymatic destruction
eg acetycholine (ACh) is broken down by acetylchloinestrase

Active uptake
eg dopamine uptake via transporter DAT

49
Q

Where the site of action occurs means a drug can either excite or inhibit. What does this mean?

A

The target cell could be at the end of a pathway or in the middle, or beginning. Depending this will impact the final outcome.

50
Q

Are changes with dopamine receptor drugs quick or slow?
Why?

A

Slow, because the change happens intracellularly - new receptors are placed on the membrane

51
Q

What happens with drug tolerance?

A

The effect of drugs gradually diminish with repeated use

52
Q

What are the characteristics of drug tolerance?

A

Once developed, it does not last indefinitely

You can have cross-tolerance between members of the same class of drug

It can be acute (short lasting)

It can be chronic (following prolonged exposure)
This can be pharmocodynamic (cellular level)
Pharmacokinetic (metabolic level)

53
Q

What neuronal activity is happening with chronic tolerance?

A

An adaptive response for example;

Receptor down regulation (decrease in receptor numbers)

Uncoupling of receptor and G protein

Decreased sensitivity of second messenger systems

Decreased production and release of the endogenous neurotransmitter

54
Q

What is meant by Cross tolerance?
Examples?

A

Individuals who are tolerant to one drug, can develop tolerance to related drugs.

55
Q

What are the 4 elements of physical dependance?

A
56
Q

What are 6 pharmacological principles to consider?

A

1) Consider pharmacodynamics, affinity at site of action
2) Drug concentration (ADME)
3) Biology of patient (age, disease, genetics)
4) Neuroadaptive processes (what adaptions are made from the drug)
5) Blood-brain barrier
6) Where drug acts in the brain

57
Q

What are special populations in pharmacological therapies?

A
58
Q

What is the standard pharmacological dose protocol based upon?

A

A 70Kg male

59
Q

What are the 3 key issues when prescribing to children? and a general principle.

A

Ethics for example Clinical - is anxiety the same in child as adult - why do we see more adhd in children?

Side effects - hard to see a child with side effects and encourage them to take meds

Long-term symptoms - more life to live, don’t want to cause harm. Also longer term use of
medication - brain still developing.

A general principle is Start low and go slow

60
Q

What are the depression rates in children?

6 - 12 yrs
13 - 18 yrs

A

Estimates
6 - 12 yr 2.8%
13 - 18 yr 5.6%

61
Q

What evidence base is there for using antidepressants in children?

A

Weak evidence (some because it’s hard to get)

A mega-analysis suggests a modest benefit but methodologically lacks strength.

TADS study has contradictory info, could cause suicidal thinking

62
Q

Are we over medicalising normal anxiety in children?

A

5 - 30% have problematic anxiety but doesn’t always need more than support.

There is an optimal level of anxiety for performance.

So perhaps yes we are.

63
Q

Does data support medication for ADHD?

A

Yes, but..

Very little-long term data
Medication can impact growth

64
Q

What % of children meet ADHD diagnosis criteria

A

5% in UK - stable

65
Q

What issues are there in prescribing to pregnant women?

A

● Changes in mothers physiology
● Direct toxicity to foetus
● Drug transfer during breastfeeding
● In general avoid medications
● Many pregnancies are unplaned (50%)
● Changing or stopping medication carries risks to mother and foetus
● The period of actual delivery is risky for development or recurrence of mental ill health

66
Q

What happens to plasma during pregnancy? What does this mean?

A

Typically women will gain about 1250mil of plasma (50% increase of normal)
- Greater dilution of medication

67
Q

When is the greatest time of vunerability for drugs, during pregnancy?

A

First trimester

68
Q

What are the considerations of using medication when breastfeeding?

A

Considerations with medication in breastfeeding
● Process of breastfeeding involves dopamine pathways (turboinfundibular)
● Breast milk is created from bodily fluids and will commonly contain medications
Risks of harm very low - but many women may stop either breastfeeding or pills
Positive effect from medication when breastfeeding
● Antidepressants during pregnancy - breastfeeding might help reduce withdrawal
symptoms (rare cases)
● Opiod addiction also help breastfeeding and weening off

69
Q

What are the rates of psychosis in pregnancy?

A

● 20 fold increase in background rates of psychosis in month following childbirth
● 50 - 80% chance of subsequent episode if woman has had past episode

70
Q

What are the risks of leaving psychosis untreated when pregnant?

A

● Poor self-care
● Deterioration of mothers mental state
● Deliberate harm
● Harm to baby
● Greater risk of foetal abnormalities

71
Q

What’s the information on using antipsychotics during pregnancy?

A

● Data supports use of older first-gen and newer second-generation
● First gen may lead to greater preterm birth, low weight and jitteryness
● Second gen may lead to neonatal diabetes
● Best practice - talk about risks
● Challenge emerges when a women is unwell but refuses to take meds

72
Q

What is the fraction for bioavailability?
What does it measure?

A

F = fg x fh
(Fg - fraction reaching mesenteric circulation in tact) fh - fraction left after ‘first pass’ hepatic extraction

It’s the fraction of dose reaching the systemic circulation as intact drug

73
Q

What is the equation for the extraction ratio (er) and what is it?

A

Er = Clh / q

Er= extraction ratio <1
Clh - hepatic clearance of drug
Q - blood flow to the organ

74
Q

What is elimination half life?

A

T(1/2)
Time taken for the concentration of a drug in blood/plasma to decrease by 50%

75
Q

If 100mg of a drug with a half life of 60mins is taken.
How much drug is left after 1 hour?
How much drug is left after 2 hours?
How much drug is left after 3 hours?

A

After 60 mins - 50mg remains
After 2 hours - 25mg remains
After 3 hours 12.5mg remains

Pharmacotherapy (1 decks)

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