Lecture 1: Introduction 23/05
Pharmacokinetics: how does a substance move through the body
Pharmacodynamics:
- To what receptors does the substance bind
- What effect does the substance have on the receptor
Interactions with neurotransmitters
Hypotheses are based on:
1. Basic knowledge
2. Clinical knowledge
Registration for medications is based on research into:
- Efficacy
- Administration routes
- Safety
Drug safety
Therapeutic index = relation between toxic dose and the effective dose (TD50 / EF50). Dose
at which 50% shows dangerous side effects (TD50) vs the dose at which 50% has the intented
effect (ED50).
TD50/ED50 should be really large number. This means that the toxic dose should be larger
than the effective dose.
Drug interactions at the level of the brain or metabolism can be helpful or harmful.
Toxicity (harmful effects): expected (often temporary and can cause desensitization) or
unexpected effects need to be written down.
Human drug research
Phase 1: is the substance safe?
Test whether the human subjects tolerate the substance. Mostly done on healthy volunteers. If
it’s safe, phase 2 starts. The costs/benefits should be considered here. How safe a compound
should be before moving forward depends on:
- Severity of the disease that may be cured or alleviated by the drug
- Whether there is already an alternative treatment
Phase 2: does it work?
1
,In phase 2, sick people take the drug. The aim is now to test evidence of whether the
substance really works against the disease. Most often this phase starts with a small number of
patients who take the new drug.
Phase 3: does it work and is it better than other existing drugs?
The drug is tested against other existing treatments, to find out if it’s better than the
alternative. After this point follows registration of the substance as an official medication.
The manufacturer will market the substance under a brand name.
What’s in a name?
- Chemical name/ formula
- Codename
- Generic name, easier to communicate
- Brand name (given from the manufacturer)
Phase 4: what are the effects in the long term?
Research continues after registering the drug. The focus is on side effects in the long term of
the optimal treatment duration. This phase is important because major side effects usually do
not come to light until this phase.
Optimalisation of the application:
- What is the optimal dose?
Clinical drug research is a long and costly process. Great disadvantage: medicines must
have enough market to be profitable for example antidepressants have a large market.
Tests of efficacy
- Randomised
- Placebo-controlled
- Double blind (person doesn’t know and researcher doesn’t know what substance is
received)
Placebo is a inert substance but can be quite effective for certain disorders. Especially in
disorders in which intensity of symptoms wax and wane regulary. Placebo-controlled research
is the golden standard.
Evidence based medicine
Meta analyses rather than relying on one study
2
,Answer to a number of clinical questions:
- What is the first choice treatment
- How long must this be maintained
- What to do if this treatment does not seem to work
3
, Lecture 2: Refresh neurotransmission 25/04
Psychoactive substances
• substances that influence behaviour
• if taken effectively
• dosage
• administration
• situation
• via brain
Everyone uses them
• recreationally
• medicinally
• addiction
Why psychopharmacology?
We want to understand the effect on our behaviour. Also we want to improve behaviour and
optimise the use of substances. Brain and neurotransmitters determine behaviour and
manipulate via psychoactive substances to understand behaviour. It concerns the effects of
psychoactive substances on behaviour and the brain.
Dose and dosage
Dose-Response Curve (DRC)
The effects of a drug depend on the dose. The response as function of a dose. It depends on
which response you look at.
What is a dose-response curve?
Simply it’s a graph with:
x-axis: increasing dose of a substance
y-axis: can be anything like a subjective report, objective observation of behaviour or a brain
process, concentration of another substance in the brain/body.
The DRC for a specific substance are not always the same. It can be different in each person.
4
Pharmacokinetics: how does a substance move through the body
Pharmacodynamics:
- To what receptors does the substance bind
- What effect does the substance have on the receptor
Interactions with neurotransmitters
Hypotheses are based on:
1. Basic knowledge
2. Clinical knowledge
Registration for medications is based on research into:
- Efficacy
- Administration routes
- Safety
Drug safety
Therapeutic index = relation between toxic dose and the effective dose (TD50 / EF50). Dose
at which 50% shows dangerous side effects (TD50) vs the dose at which 50% has the intented
effect (ED50).
TD50/ED50 should be really large number. This means that the toxic dose should be larger
than the effective dose.
Drug interactions at the level of the brain or metabolism can be helpful or harmful.
Toxicity (harmful effects): expected (often temporary and can cause desensitization) or
unexpected effects need to be written down.
Human drug research
Phase 1: is the substance safe?
Test whether the human subjects tolerate the substance. Mostly done on healthy volunteers. If
it’s safe, phase 2 starts. The costs/benefits should be considered here. How safe a compound
should be before moving forward depends on:
- Severity of the disease that may be cured or alleviated by the drug
- Whether there is already an alternative treatment
Phase 2: does it work?
1
,In phase 2, sick people take the drug. The aim is now to test evidence of whether the
substance really works against the disease. Most often this phase starts with a small number of
patients who take the new drug.
Phase 3: does it work and is it better than other existing drugs?
The drug is tested against other existing treatments, to find out if it’s better than the
alternative. After this point follows registration of the substance as an official medication.
The manufacturer will market the substance under a brand name.
What’s in a name?
- Chemical name/ formula
- Codename
- Generic name, easier to communicate
- Brand name (given from the manufacturer)
Phase 4: what are the effects in the long term?
Research continues after registering the drug. The focus is on side effects in the long term of
the optimal treatment duration. This phase is important because major side effects usually do
not come to light until this phase.
Optimalisation of the application:
- What is the optimal dose?
Clinical drug research is a long and costly process. Great disadvantage: medicines must
have enough market to be profitable for example antidepressants have a large market.
Tests of efficacy
- Randomised
- Placebo-controlled
- Double blind (person doesn’t know and researcher doesn’t know what substance is
received)
Placebo is a inert substance but can be quite effective for certain disorders. Especially in
disorders in which intensity of symptoms wax and wane regulary. Placebo-controlled research
is the golden standard.
Evidence based medicine
Meta analyses rather than relying on one study
2
,Answer to a number of clinical questions:
- What is the first choice treatment
- How long must this be maintained
- What to do if this treatment does not seem to work
3
, Lecture 2: Refresh neurotransmission 25/04
Psychoactive substances
• substances that influence behaviour
• if taken effectively
• dosage
• administration
• situation
• via brain
Everyone uses them
• recreationally
• medicinally
• addiction
Why psychopharmacology?
We want to understand the effect on our behaviour. Also we want to improve behaviour and
optimise the use of substances. Brain and neurotransmitters determine behaviour and
manipulate via psychoactive substances to understand behaviour. It concerns the effects of
psychoactive substances on behaviour and the brain.
Dose and dosage
Dose-Response Curve (DRC)
The effects of a drug depend on the dose. The response as function of a dose. It depends on
which response you look at.
What is a dose-response curve?
Simply it’s a graph with:
x-axis: increasing dose of a substance
y-axis: can be anything like a subjective report, objective observation of behaviour or a brain
process, concentration of another substance in the brain/body.
The DRC for a specific substance are not always the same. It can be different in each person.
4
