Intro to Pharma

Question 1

Pharmacokinetics

Answer 1

A study of the action of the body on administrated drug, how it is distrbutued and broken down, and how differently the body reacts when it gets drug in differnt ways (patch, vain, pill, inhale)

It refers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects.

Question 2

Pharmacokinetics

Answer 2

The study of the action of the body on administered drugs

The extent of drug absorption, metabolism and elimination from the body

Question 3

The agonist spectrum

Answer 3

One way to classify pharmacological agents, full agonist, partial agonist, antagonist or inverse agonist

Question 4

Full agonist

Answer 4

Full agonists are equal to naturally occuring neurotransmitters e.g. dopamine

As full agonist concentration increases the cell response increases, after some amount the is plato in response= the resonse is at 100% and cannot go higher

Question 5

Neutral antagonist

Answer 5

No change in signal transduction (also blocks an agonist if present)
As its concentration increases, it does not increase the response of the cell e.g. haloperidol

It will bind with receptors but it doesnt affect the response of the cell

If we are binding with the receptors it is BLOCKING access to the naturally occuring neurotransmitter decreasing its effect BUT the resposne of the cell is not changed

Question 6

Inverse agonist

Answer 6

Inverse agonist, as its concentration increases the activity of the cell decreases

They are not common in antipsychotics as they don’t fall in this category e.g. dyharonine (?)

Question 7

Partical agonists

Answer 7

As its concentration increases, the cell resposnes increases but it platos at ~50% of activity never reaching 100%.
○ Some antipsychotics fall into this category e.g. aripiprazole
○ They are still blocking access to naturally occuring neurtransmitter so some receptros have the drug allowing for partial response
○ Are useful becasue they often have other side effects

Question 8

Antipsychotic mechanisms of action on D2 for antagonists

Answer 8

(1) Antagonist action at D2 – we block the receptor and the cells response drops to a basal rate of firing.
Medicines like haloperidol or risperidone.

Question 9

Antipsychotic mechanisms of action on D2 for partial agonists

Answer 9

(2) Partial agonist (aripiprazole or cariprazine) have agonist properties so it causes stimulation of the cell output but it is not as strong as the full agonist or naturally occurring neurotransmitter. If this medicine is binding in the striatum in a synpase where there is an excess of dopamine associated with psychosis, it is stopping the excess dopamine from reaching the receptor and causing a full cell response. So it promotes a reduction in dopamine transmission to an intermediate level of output compared to someone taking placebo or someone with a full antagonist. This is important because it gives aripiprazole different properties – it does not tend to cause sedation, it is relatively weight neutral – people are less likely to have weight gain compared to medicines like olanzapine, quetiapine or clozapine.

Question 10

What is receptror binding affinity ?

Answer 10

It is the extent for a drug to bind strongly & preferencially with the receptor

Can be used to assess possible side effects- affinity graph shows other receptors a drug binds to (e.g. H1- histamine = increase in weight)

A bit more useful way of differenciating antipsychotics than ‘typica’ vs ‘atypical’

Question 11

Do FG antipyschotics have high D2 affinitiy?

Answer 11

Yes, they are the ‘typical antipsychoitcs’ and often have more side effects (or at least those related to tremours)

Question 12

What are Extra-pyramidal side effects (EPSEs) ?

Answer 12

Side effects, more common in 1st Gen anitpsychotics

- Dystonia (muscle stiffness, rigidity, spasms)
- Akathisia (restlessness, agitation, compulsion to move, inabilty to sit still assocaited with high levels of anxiety)
- Parkinsonism (shuffling gait, tremor, rigidity)

Question 13

What dopamine pathways are related to EPSEs?

Answer 13

Most likley Nigrostriatal and Tuberoinfundibular one

Nigrostriatal: Parkinsonism, Tremor, Rigidity

Tuberoinfundibular: relted to risen prolactin levels (hyperprolactinemia as EPSEs of antipsychotics)

Question 14

What signal transduction pathways are there? (4)

Answer 14

1. G-protein-linked
2. Ion-channel- linked
3. Hormone- linked
4. Neurotrophin- linked

Question 15

How does Neurotrophin- linked signal transduction pathway work?

Answer 15

Activates a series of kinase enzymes and is involved in functions such as synaptogenesis and neuronal survival

Question 16

How does Hormone- linked signal transduction pathway work?

Answer 16

Certain hormones can pass across the cell membrane before binding in a hormone nuclear receptor complex in the cytoplasm. This complex can then move into the cell nucleus and activate specific genes.

Question 17

How does Ion-channel- linked signal transduction pathway work?

Answer 17

e.g. nicotinic acetylcholine receptors.

Binding of the ligand (the neurotransmitter) allows ions or charged atoms to pass through the channel

Question 18

How does G-protein-linked signal transduction pathway work?

Answer 18

e.g. metabotropic glutamate receptors.

This cascade triggers the synthesis of cyclic AMP and it’s interaction with protein kinase A (PKA).

Question 19

Most antipsychotics target to which transduction pathways transportes? (5)

Answer 19

12-transmembrane transporter ~30%
G-protein linked transporter ~30%
Ligand-gated channels ~20%
Voltage-sensitive ion channels ~10%
Enzymes ~10%

Question 20

Pharmacodynamics

Answer 20

Study of the action of drug on a body