CNS pharmacology

Question 1

describe the 3 types of receptors action a CNS drug can have

Answer 1

Agonist– activates a receptor, producing a functional response in the cell
Antagonist – binds to the receptor without activating it, blocking agonists
Partial agonist – partially activates a receptor, producing a smaller functional response in the cell

Question 2

what effect may a CNS drug have on enzyme action ?

Answer 2

inhibition

Question 3

what effect may a CNS drug have on ion channel action ?

Answer 3

Opener – enhances ionic flow through the target channel

Blocker – reduces ion flow

Question 4

what is enteral drug administration route and what type of drug is required for it?

Answer 4

drug is taken orally and passes through the GI tract, passes from gut to brain
Need lipophilic drug to reach the CNS and surpass blood brain barrier

Question 5

what is parenteral drug administration route? how may this be achieved?

Answer 5

drug is administered elsewhere int he body apart from mouth and GI tract.
Using intravenous for intramuscular route

Question 6

what is a more invasive route of administration? describe it

Answer 6

intrathecal - when drug is injected into spinal canal/subarachnoid space so it reaches CSF

Question 7

give 4 examples of use of intrathecal drug administration

Answer 7

intrathecal antibodies for meningitis
antispasmodics - muscle relaxers eg baclofen
chemotherapies
regional anaesthesia (epidural) - used in obstetric care and delivery

Question 8

what largely restricts drug entry into the CNS?

Answer 8

Blood brain barrier

Question 9

what is the function of the BBB?

Answer 9

• Maintain constant environment
• Protect brain from foreign substances
• Protect brain from peripheral transmitters

Question 10

what are some disease of a compromised BBB?

Answer 10

• Hypertension
• Infection / Inflammation around blood vessels in brain
• Trauma (skull fracture)

Question 11

what transporter transports glucose across the BBB and what happens if it gets disrupted?

Answer 11

GLUT-1
Patient should be put on a strict ketogenic diet (no glucose) which forces the body to make ketones and the brain feeds on this

Question 12

list 6 main neurotransmitters in the CNS

Answer 12

GABA
Glutamate
Serotonin
Acetyl Choline
Dopamine
Adrenaline (norepinephrine)

Question 13

what type of NT is GABA and how does it function?

Answer 13

Inhibitory NT

it acts on the chloride ion channel and increases influx into cell which reduces its excitability and cell firing

Question 14

what disorder require GABA to treat them?

Answer 14

anxiety and epilepsy

Question 15

what type of NT is glutamate and how does it function?

Answer 15

principle excitatory NT

Activates Na and Ca channels with increases excitability of cells and promotes cell firing

Question 16

when can glutamate act as a neurotoxin ?

Answer 16

if Oxygen levels decrease, the cell dies and becomes flooded with glutamate where it acts as a neurotoxin

Question 17

what is the difference between an ionotropic and metabotropic receptor

Answer 17

ionotropic: membrane-bound receptor that respond to ligand binding by opening ion channel
metabotropic: works through a second messenger

Question 18

list 3 types of glutamate receptors and briefly describe them

Answer 18

AMPA (only responds to Glutamate)
NMDA (responds to Glutamate and aspartate)
Kainate (does something different)

Question 19

what is the main receptor that mediates rapid effects of glutamate?

Answer 19

AMPA

Question 20

how many serotonin receptor subtypes are there and are they all the same in function and receptor type?

Answer 20

7 receptor sub-types
All except 5-HT 3 modulate intracellular activity
5HT3 – ligand gated ion channel : Ionotropic K and Na channels, whereas rest are GPCR

Question 21

what conditions may serotonin be used as a drug for?

Answer 21

depression, anxiety, migraine

Question 22

what are the 2 types of ACh receptors, what type of receptors are they?

Answer 22

Muscarinic receptors – G Protein
Nicotinic receptors – K+ and Na+
channels

Question 23

what is the most important peripheral NT?

Answer 23

ACh (important at NM junction)

Question 24

how do the roles/importance differ between muscarinic and nicotinic receptors ?

Answer 24

muscarinic - has metabolic effects, found around brain

nicotinic - most important peripherally (between peripheral nerves and muscles)

Question 25

what conditions have disruption to muscarinic and nicotinic receptors ?

Answer 25

muscarinic = dementia, parkinson's
nicotinic = myasthenia gravis

Question 26

describe the 2 types of dopamine receptors

Answer 26

type 1 (D1 and D5) - inotropic causing either excitation or inhibition 
type 2 (D2, 3 ,4) - usually inhibitory action via G proteins

Question 27

list some conditions caused by problems with dopamine

Answer 27

movement disorders
thought disorder
disrupted endocrine function 
addiction
nausea and vomiting

Question 28

what causes schizophrenia? list some symptoms

Answer 28

caused by too much dopamine action + a combination of genetic and environmental factors

Positive symptoms: (hyperactivation of mesolimbic pathway) hallucinations, delusions, disorder of logical thought, disorganised speech.

Negative symptoms (hypofunction of mesocorticol pahway): depression, inability to feel pleasure

Question 29

what drug treatments are recommend for schizophrenia?

Answer 29

D2 antagonists

1. Typical (old) neuroleptics – chlorpromazine, haloperidol
2. Atypical (newer) neuroleptics – clozapine, asenapine

Question 30

describe the tuberinfundibular pathway

Answer 30

dopamine cell bodies are in the arcuate nucleus of the hypothalamus and the neurons terminate in the median eminence. They secrete dopamine into the portal blood vessels leading to the anterior pituitary.

dopamine binds to D2 receptors on the prolactin secreting cells to inhibit prolactin secretion

Question 31

what effect does dopamine have on growth hormone?

Answer 31

increase in dopamine = increase in growth hormone

Question 32

where is the chemoreceptor trigger zone and what is its function?

Answer 32

in the area postrema in the medulla

It receives inputs from blood-borne drugs or hormones, and communicates with the vomiting centre to initiate vomiting.

Question 33

what are the 2 types of receptors for adrenaline?

Answer 33

alpha and beta

Question 34

what are 2 ways to influence brain function?

Answer 34

Affect Neurotransmitters

Affect Ion Channels

Question 35

give examples of general anaesthetic agents which are administered intravenously or by inhalation

Answer 35

inhalation: halothane, isoflurane
intravenous: propofol

Question 36

define anxiolytics/sedatives

Answer 36

drugs that cause sleep and reduce anxiety

Question 37

give two examples of anxiolytics/sedatives

Answer 37

diazepam and pentobarbitone (antiepileptic)

Question 38

give examples of atypical and typical antipsychotic/Antischizophrenia drugs

Answer 38

“typical” - e.g. chlorpromazine, haloperidol “atypical” - e.g. clozapine, olanzapine

Question 39

give examples of antidepressant drugs, what is their usual therapeutic onset time?

Answer 39

monoamine oxidase inhibitors (phenelzine)
tricyclic antidepressants (imipramine)
SSRIs (selective-serotonin reuptake inhibitors) - fluoxetine

Question 40

how does caffeine work?

Answer 40

Blocks adenosine receptors on serotonergic neurons, this causes a build up of adenosine = tiredness
it increases energy metabolism throughout the brain but decreases cerebral blood flow

Question 41

what happens to neurotransmitter levels in alcohol withdrawal

Answer 41

there is unopposed, high levels of glutamate and low levels of GABA = anxiety, tremors