Unit 05: Pharmacology

Question 1

what does the CNS include? what does it do?

Answer 1

cerebrum, diencephalon, cerebellum, brainstem and spinal chord

• relays and processes signals received from the PNS; processing results in responses that are formualted and related back to periphery
• responsible for perception (sensory, auditory and visual), wakefulness, language and consciousness

Question 2

how does communication occur in the CNS

Answer 2

• via neurons
• interneurons communicate within the same brain region and projection neurons have axons that project from one brain region to another
• neurons are organized into cirucits that allow for integration of information from interneurons and projection neurons
• nenurons relates neurotransmitters at synpase of target cells

Question 3

anatomic organization of the CNS

Answer 3

• CNS has 7 major regions
• cerebral hemispheres, diencephalon (thalamus), cerebellim, midbrain, pons, medulla and spinal chord
• cerebal hemispheres include cerbral cortex, underlying white matter and basal ganglia
• midbrain, pons and medulla makeup the brainstem
• spinal chord is divided into cervical, thoracic, lumbar and sacral segments

Question 4

what are the categoies of neurotransmitters used in the CNS

Answer 4

• amino acid neurotransmitters (glutemate and GABA)
• monomaine neurotramsitters (derived from decarboxylated aa: dopamine, norep/ep, serotonin)

Acetylcholine (nor aa or monoamine)

Question 5

what are the primary excitatory and inhibitory neurotransmitters in the CNS

Answer 5

amino acid neutrotransmitters

• acidic amino acid glutamate is primarily excitatory
• GABA is primarily inhibitory

-

Question 6

where is glutamate released from adn what does it act on?

Answer 6

• released from relay neurons throughout the CNS and acts on NMDA and non NMDA receptors

Question 7

what are NMDA receptors

Answer 7

sub type of glutamate receptor that are ion channels

-when activted permit the influx of Ca2+, Na+ and efflux of K+

*hallucinogenic drugs like pencyclidine (PCP) inhibit NMDA receptors

Question 8

where is GABA located and what does it act on

Answer 8

• located throughout the CNS and is associated with behaviour
• acts on postsynpatic GABA receptors such as GABAA - an ion channel that inc Cl- influx and GABAB - a G protein linked ion channel that inc efflux of K+
• GABAA receptor is the target for sedative hypnotics

Question 9

where deos norepinephrine act adn what deos it do there

Answer 9

• located thoguhout the CNS and is very important in awarenes, arousal and autonomic control
• if NE bind to adrenergic receptors α1 and β1, then the effects are excitatory
• fi binds to the α2 and β2 receptors, the effects are inhibitory.

Question 10

NE is synthesized from

Answer 10

dopamine

Question 11

what does dopamine do

Answer 11

affect complex processes like mood, attentiveness and empotion

• this neurotransmitter system is the therapeutic target for a number of important CNS disorders: parkinsons and schizophrenia

Question 12

what are dopamine receptors

Answer 12

• 5 subtypes - linked to G protein messanger system
• subtypes broken down into 2 families: D1 class which elads to increased cAMP and D2 class which leads to cAMP inhibition

Question 13

describe serotonin

Answer 13

• also called 5hydroxytryptamine
• another monoamine neurotransmitter
• found in nerve terminals of neurons that have their cell bodies in the midbrain and brain stem and axons projecting throughout the brain
• plays role in behaviour, control of sleep, temperature, appetite and various neuroendocrine functions

Question 14

how many different members are there in the 5-HT family, what types of receptors are they

Answer 14

• 7 members with diff subtypes
• all 5 HT receptors are linked to G-rptoein sceond messanger systems excpet for 5-HT3 which is ligand gated ion channel
• therea re more than 12 subtypes of 5-HT receptors that have both excitatory and inhibitory actions
  ex: MOA of 5-HT1A is inhibitory, decreasing cellular levels of cAMP while 5-HT2A is excitatroy, inc levels of DAG and IP3

Question 15

describe acetyl choline

Answer 15

In the CNS, acetylcholine acts as a diffuse system neurotransmitter.

Like the monoamines- its thought to regulate sleep and wakefulness. I

interneurons that release acetylcholine are associated with motor control

• projection neurons that release acetylcholine associated with learning, memory and cognition
• those are lost in Alzheimer disease which results in the symptoms observed.

Acetylcholine acts on many subtypes of muscarinic and nicotinic receptors.

Question 16

what are drugs of the CNS limited by

Answer 16

blood brain barrier

• consists of endothelial cells and astrocytes
• astrocytes support cells in the CNS and endothelial cells form tight junctions in the CNS blood vessels and are different fromt he endothelial cells of other vessels in the body
• some drugs cant pass thorugh or between the BBB
• transport occurs primarily via passive diffusion - diffusion dependent on drug lipid solubility and pKa

Question 19

what are neurodegenerative disorders

Answer 19

• progresive loss of a specific popualtion of neurons that lead to diff symptoms
• no cures available for these disorders but drugs can hep to alleviate symptoms
• with severe neuron loss, some drugs are no longer effective at treating symptoms
  ex: alzheimers and parkinsons

Question 20

what are the 2 types of alzheimers disease

Answer 20

familial easy onset - caused by genetic mutations and accounts for 5-10% of cases

• sporatic late osnet which has an unknown cause and accounts for 90-95%

Question 21

what is memory loss and cognitive ipmairment from alzheimers caused by

Answer 21

• cholinergic neurons, specifically degeneration of cholinergic input to the hippocampus (memory) and cortex (cognitive)
• in AD progressive loss of sholinergic neurons in the basal forebrain projecting to the hippocampus and cortex results in symptoms previously mentioned

Question 22

what anatomical cahnges occur in individuals with AD

Answer 22

• disease can be confirmed by neurofibrillary tangles and amyloid plaques present in hippocampus and cortex
• tangles represent intracellular accumulations of twisted fibers of phosphorylated tau protein
• plaques are extracellular deposits of beta-amyloid protein

Question 23

what to approved treatments for AD aim to do?

Answer 23

restore neuron communication and imporve symptoms

Question 24

what is Donepezil

Answer 24

acetylcholinesterase inhibtor used to treat AD

• easily enters the CNS and inhibts breakdown of acetylcholine
• effective tratment for mild to moderae AD when sufficient cholinergic neruons are still present

side effects: mainly autonomic and similar to AChE inhibitors

Question 25

what is parkinsonsism

Answer 25

• daignosed based on medical histroy and neurological examination - symptoms are caused by degenerative depaminergic neurons at basal ganglic
• neuron loss is irreversible

Question 26

what do therapeturic strategies aim to do for treatment of parkinsons

Answer 26

• aim to correct the imblanace of dopamine and acetylcholine activity in basal ganglia
• drugs that increase dopamine activity or decrease muscarinic receprot activation (or both) are desirable

Question 27

treatment for parkinsonism

Answer 27

depamine agonists: levodopa and repinrole

monoamine oxidase inhibitors: selegiline and deprenyl

antimuscarinic drugs: benztropine

Question 29

what are the two principal pathways in the basal ganglia that regualte movement and how does dopamine effect them

Answer 29

• two principle pathways = indirect pathway which inhibits morement and direct with enables movement
• dopamine inhibits indirect pathway and stimualtes direct pathway

*net bias allowing for purposeful movemnt

*excitatory pathway shown in blue and inhibitory in black

Question 30

what does the direct and indirect dopaminergic pathways signal

Answer 30

• direct pathway signals from the putamen to HPi to thalamus to the cortex
• indirect pathway signals from putamen to GPe to STN to GPt to thalamus to cortex

*GPi = internal segment of the globus pallidus

GPe = external segnemnt of the globus pallidus

SNc = substantia nigra pars compacta

SNr = substantia nigra pars reticulate

STN = subthalmis nucleus

Question 31

descibe onset of parkinsons

Answer 31

normally both direct and indirect pathways in putamen receive inputs from the nigrostriatal dopaminergic system (dotted blue arrow) and from cortical glutamatergic systems (solid blue arrow)

• inputs are processed in contect of local cholinergic influences and transmit GABAergic output
• Gegeneration of dopaminergic neurons in substantia bigra causes understimulation of the direct (movement enabling) pathway and underinhibtion of indirect (movement inhibiting pathway)

*net result = paucity of movement - dotted grey arrow indicated decreased activity caused by understimulation and thick black indicates increased activity caused by underinhibition