pharm: PNS

Nueropharmacology

The study of drugs that alter processes controlled by the nervous system

• PNS and CNS

axonal conduction

electrical signal (axon potential) down the axon

synaptic transmission

neurotransmitter carried across the neuron gap and the post-synaptic cell(either neuron, muscle cell or cell in a secretory gland)

• most drugs interact here

Steps of synaptic transmission

1. transmitter synthesis

2. transmitter storage

3. transmitter release

4. receptor binding

5. termination of transmission

transmitter synthesis

making neurotransmitter

drugs can either: increase, decrease or cause the synthesis

transmitter storage

• when the transmitter is stored In vesicles in the axon terminal

• drugs can effect how they are stored and decrease receptor activation

transmitter release

• transmitter being released into the synaptic gap

• drugs can either promote or inhibit release

receptor binding

• neurotransmitter binding to post-synaptic cell

• drugs can either enhance (agonist) or block (antagonist)

termination of transmission

• when neurotransmitter “unsticks“ to receptors

• drugs can either block re-uptake (SSRIs or SNRIs)

• or they can inhibit transmitter degradation

when learning about PNS drugs what 3 pieces if information do we need

1. the type or types of receptor through which the drug acts '

2. normal response to the activation of those receptors

3. what the drug does to the receptor function

autonomic vs somatic nervous system

autonomic controls automatic Bodily functions, while somatic controls things in our consciences like movement

where are the pre-ganglionic and the ganglions the Parasympathetic Nervous System

• preganglionic - Cranial And sacral areas

• ganglions are always in or near the target organs

where are the pre-ganglionic and the ganglions the Sympathetic Nervous System

• preganglionic - thoracic and lumbar areas

• ganglions are not near the target organs

• adrenal medulla may also act as a ganglion

how does the adrenal medulla act as a ganglion

• doesn’t grow axons

• secreted epinephrine directly the bloodstream causing widespread effects

Somatic motor system

1 neuron directly to skeletal muscle

3 principal functions of the ANS

1. regulates heart

2. regulates secretory glands (salivary, gastric, sweat, and bronchial)

3. regulate smooth muscles (bronchi, blood vessels, GI and GU)

Functions of the Sympathetic NS 7

1. increases HR and cardiac output

2. vasoconstriction (raises BP)

3. piloerection (heat conservation)

4. brings blood to skeletal muscle and Brain

5. bronchodilation

6. mydraises

7. converts glycogen (storage form) to active glucose

what controls tone for the blood vessels

the parasympathetic nervous system controls the blood vessels, without innervation if the sympathetic

• baroreceptors - receptors for BP

Functions of the Parasympathetic NS (5)

1. slows HR

2. Increases gastric secretions

3. empties bladder and bowel

4. myosis

5. bronchioconstriction

what are the 3 neurotransmitter the PNS uses

acetylcholine, norepinephrine, and epinephrine

Acetylcholine is released by?

1. all preganglionic neurons of the parasympathetic and sympathetic NS

2. all post ganglionic nuerons of the parasympathetic NS

3. all motor nuerons to skeletal muscles

4. most post ganglionic nuerons of the sympathetic NS to sweat glands

Norephinephrine is released by

all other post ganglionic nuerons of the sympathetic NS (besides sweat glands)

Epinephrine is released by

the adrenal medulla

receptor subtypes

receptors that respond to the same transmitter but are differ slightly based on shape, and carry out different functions

receptor subtypes of cholinergic receptors

• all respond to AcH

• nicotinic N

• nictoninc M

• muscarinic

receptor subtypes of adrenergic receptors

• all respond to norepinephrine and/or epinephrine

• alpha 1

• alpah 2

• beta 1

• beta 2

• dopamine

when scientist added nicotine to skeletal and ciliary muscle ….

the skeletal muscle contracted and the ciliary did not

when scientist added muscarine to skeletal and ciliary muscle ….

the skeletal muscle did not contract but the ciliary did

d-tubocuranine does what

blocks cholinergic receptors responsive to nicotine (found in skeletal muscle)

atropine does what

blocks cholinergic receptors responsive to muscarine (found in ciliary muscle)

subtypes allow for more ?

selectivity

Nicotinic N: locations and what do they do?

• located in all ganglia of parasympathetic and sympathetic NS and adrenal medulla

• stimulates release of epi from adrenal medulla

Nicotinic M: locations and what do they do?

• located on skeletal muscle

• causes contraction of skeletal muscle

Muscarinic: locations and what do they do?

• on all parasympathetic target organs

• elicits appropriate response from the organ involved

alpha 1: locations and what do they do?

• blood vessels - vasoconstriction

• male sex organs - ejaculation

• eyes - mydriases

alpha 2: locations and what do they do?

• presynaptic neuron - inhibit release of nuerotransmitter

beta 1: locations and what do they do?

• heart - raise HR, force of contraction and conduction in AV node

• kidney - releases renin to raise BP

beta 2: locations and what do they do?

• lungs - bronchodilatotion

• uterus - relaxes uterine muscles

• blood vessels - vasodilation

• glycogenolysis (raises glucose )

dopamine receptors: locations and what do they do?

• kidney - dilates renal blood vessels to improve blood flow

what receptors do epinephrine activate

• all Alpha and beta receptors

• Not dopamine

what receptors do norepinephrine activate

• alpha 1, alpha 2, beta 1

• NOT beta 2 or dopamine

what receptors do dopamine activate

• alpha 1, beta 1 and dopamine

because epinephrine (adrenaline) is the only transmitter that acts on Beta 2 receptors…

beta 2 receptors will undergo significant activation in times of fight or flight

activation of beta 2 receptors will

produce full blown sympathetic response

Sympathomimetic drugs/ what are they used for

• mimics Sympathetic NS

• primarily used for hypertension, heart failure, angina and asthma

how is ACh terminated

• destroyed almost instantly by acetylcholinesterase (AChE)

• enzyme present on surface of post junctional cell

• degrades into acetate and choline

• choline is then reuptake for reuse

how is norepinephrine terminated

• reuptake back into the nerve terminal

• can either be reused or inactivated by MOA