CNS pharmacology Flashcards
describe the 3 types of receptors action a CNS drug can have
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
what effect may a CNS drug have on enzyme action ?
inhibition
what effect may a CNS drug have on ion channel action ?
Opener – enhances ionic flow through the target channel
Blocker – reduces ion flow
what is enteral drug administration route and what type of drug is required for it?
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
what is parenteral drug administration route? how may this be achieved?
drug is administered elsewhere int he body apart from mouth and GI tract.
Using intravenous for intramuscular route
what is a more invasive route of administration? describe it
intrathecal - when drug is injected into spinal canal/subarachnoid space so it reaches CSF
give 4 examples of use of intrathecal drug administration
intrathecal antibodies for meningitis
antispasmodics - muscle relaxers eg baclofen
chemotherapies
regional anaesthesia (epidural) - used in obstetric care and delivery
what largely restricts drug entry into the CNS?
Blood brain barrier
what is the function of the BBB?
- Maintain constant environment
- Protect brain from foreign substances
- Protect brain from peripheral transmitters
what are some disease of a compromised BBB?
- Hypertension
- Infection / Inflammation around blood vessels in brain
- Trauma (skull fracture)
what transporter transports glucose across the BBB and what happens if it gets disrupted?
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
list 6 main neurotransmitters in the CNS
GABA Glutamate Serotonin Acetyl Choline Dopamine Adrenaline (norepinephrine)
what type of NT is GABA and how does it function?
Inhibitory NT
it acts on the chloride ion channel and increases influx into cell which reduces its excitability and cell firing
what disorder require GABA to treat them?
anxiety and epilepsy
what type of NT is glutamate and how does it function?
principle excitatory NT
Activates Na and Ca channels with increases excitability of cells and promotes cell firing
when can glutamate act as a neurotoxin ?
if Oxygen levels decrease, the cell dies and becomes flooded with glutamate where it acts as a neurotoxin
what is the difference between an ionotropic and metabotropic receptor
ionotropic: membrane-bound receptor that respond to ligand binding by opening ion channel
metabotropic: works through a second messenger
list 3 types of glutamate receptors and briefly describe them
AMPA (only responds to Glutamate)
NMDA (responds to Glutamate and aspartate)
Kainate (does something different)
what is the main receptor that mediates rapid effects of glutamate?
AMPA
how many serotonin receptor subtypes are there and are they all the same in function and receptor type?
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
what conditions may serotonin be used as a drug for?
depression, anxiety, migraine
what are the 2 types of ACh receptors, what type of receptors are they?
Muscarinic receptors – G Protein
Nicotinic receptors – K+ and Na+
channels
what is the most important peripheral NT?
ACh (important at NM junction)
how do the roles/importance differ between muscarinic and nicotinic receptors ?
muscarinic - has metabolic effects, found around brain
nicotinic - most important peripherally (between peripheral nerves and muscles)
what conditions have disruption to muscarinic and nicotinic receptors ?
muscarinic = dementia, parkinson's nicotinic = myasthenia gravis
describe the 2 types of dopamine receptors
type 1 (D1 and D5) - inotropic causing either excitation or inhibition type 2 (D2, 3 ,4) - usually inhibitory action via G proteins
list some conditions caused by problems with dopamine
movement disorders thought disorder disrupted endocrine function addiction nausea and vomiting
what causes schizophrenia? list some symptoms
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
what drug treatments are recommend for schizophrenia?
D2 antagonists
- Typical (old) neuroleptics – chlorpromazine, haloperidol
- Atypical (newer) neuroleptics – clozapine, asenapine
describe the tuberinfundibular pathway
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
what effect does dopamine have on growth hormone?
increase in dopamine = increase in growth hormone
where is the chemoreceptor trigger zone and what is its function?
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.
what are the 2 types of receptors for adrenaline?
alpha and beta
what are 2 ways to influence brain function?
Affect Neurotransmitters
Affect Ion Channels
give examples of general anaesthetic agents which are administered intravenously or by inhalation
inhalation: halothane, isoflurane
intravenous: propofol
define anxiolytics/sedatives
drugs that cause sleep and reduce anxiety
give two examples of anxiolytics/sedatives
diazepam and pentobarbitone (antiepileptic)
give examples of atypical and typical antipsychotic/Antischizophrenia drugs
“typical” - e.g. chlorpromazine, haloperidol “atypical” - e.g. clozapine, olanzapine
give examples of antidepressant drugs, what is their usual therapeutic onset time?
monoamine oxidase inhibitors (phenelzine) tricyclic antidepressants (imipramine) SSRIs (selective-serotonin reuptake inhibitors) - fluoxetine
how does caffeine work?
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
what happens to neurotransmitter levels in alcohol withdrawal
there is unopposed, high levels of glutamate and low levels of GABA = anxiety, tremors
