Pharmacology Chapter 7

Nervous system contains

10 billion neurons —> Thousands of synaptic connection —> Primitive reflexes to language, mood, and memory

Peripheral nervous system

• All nerves traveling between CNS and somatic and visceral sites

• Automatic nervous system (involuntary)

• Sensory and somatic nervous system (voluntary)

visceral sites

Visceral refers to the internal organs (such as the heart, lungs, stomach, intestines, liver, and bladder)

somatic sites

refers to the outer body structures (such as the skin, skeletal muscles, bones, joints, and connective tissues).

Central Nervous System

• Brain (Cerebrum,diencephalon, cerebelllum, brainstem) and spinal cord

• Relays info from PNS

• Perception including sensory, auditory, and visual processing, wakefulness, language, and consciousness

Common Involuntary responses

• Smooth Muscle and Glandular tissue

• Vasoconstriction, Heart rate, pupillary constriction, sweating, salivation, piloerection (goosies!), uterine contraction, GI motility, bladder function

Sympathetic Nervous System

fight flight or freeze

involuntary

Parasympathetic Nervous System

Rest and Digest

Involuntary

What is the two neuron pathway called?

Pre-Ganglionic and post-ganglionic

Pre-Ganglionic and post-ganglionic

Two neuron pathway

Pre-Ganglionic and post-ganglionic is part of which part of the nervous system?

In the autonomic nervous system, a preganglionic neuron of the CNS synapses with a postganglionic neuron of the PNS.

Peripheral motor and sensory nerves use which pathway

Fibers innervate their target directly instead of 2 neuron path in automatic nervous system

Peripheral motor and sensory nerves regulate

• Voluntary movement

• Neuromuscular junction

Cerebral Hemispheres

• High-level functioning

• Many drugs alter it —> Alcohol

• Does not fully develop until age 25

Diencephalon

• Thalamus and hypothalamus

• Temperature, hunger, and growth

Cerebellum

• Maintains balance, eye movement, hand eye coordination (video games!)

• alcohol interferes —> Alcohol balance reflex test

Brainstem

• Breathing, Heart rate, coughing, and vomiting

Peripheral nervous system only uses which neurotrasmitters

• norephinephrine

• Acetylcholine

CNS uses which Neurotransmitters

A wide variety of NT and neuroactive peptides

Amino Acid neurotransmitters

Acidic —> Glutamate and Aspartate —> excitatory

Neutral —> GABA and Glycine —> inhibitory

Amino Acid neurotransmitters are used where

• As the Primary excitatory and inhibitory NTs in the CNS

The more things a neurotransmitter does

The more side effects that result if we block it

Glutamate, aspartate and glycine are all used for

building blocks of proteins

Primary excitatiory NT in CNS

Glutamate —> Both Ionotropic and metabotropic receptors

Ionotropic receptor

Ligand gated ion channel

metabotropic receptor

Everything else —> G protein —> enzymatic

Excessive excitation of which neurotransmitter causes neuronal damage after a stroke?

Glutamate

What is the primary inhibitory neurotransmitter of CNS

GABA

Which drugs bind GABA receptor? via which mechanism

Barbiturates and benzodiazepines via allosteric mechanisms

How does the GABA receptor work?

It will open Cl^- channels —> Cl^- ions will flood into the cell causes the membrane potential to drop —> Hyper-polarization —> inhibits the neuron as it becomes less likely to fire an action potential.

Why is there a hyper polarization as a result of potassium leaving the cell?

Because those potassium channels are notoriously slow to close, too much potassium slips out, creating that brief "undershoot" or hyperpolarization phase

Biogenic Amine Neurotransmitters

Dopamine

Ephinephrine

Norephinephrine

Histamine

Serotonin

Biogenic Amine Neurotransmitters modulate

complex CNS function such as alertness and consciousness

Which biogenic amine does the PNS use

Norepinephrine —> released to effect sympathetic response

Adrenal medulla

Neuroendocrine tissue —> releases epinephrine in response to stress

All biogenic Amines are synthesized from

Amino Acids

Three categories of Biogenic Amines are based on

precursors

Three categories of Biogenic Amines

• Catecholamines —> Tyrosine

• Indolamines – Derived from the amino acid L-tryptophan

• Imidazoleamines (or sometimes classified under trace/heterocyclic amines) – Derived from the amino acid L-histidine

Why does benadryl cause sleepiness but Claritan does not?

Benadryl crosses BBB and blocks histamine

Clartian has Chloride conjugated to it so it cannot cross the BBB

Tyrosine is oxidized to form

L-DOPA

Can dopamine cross the BBB?

NO! —> must start as L-DOPA

Tyrosine Hydroxylase

Adds an OH to tyrosine to form L-DOPA

Aromatic L-amino acid decarboxylase

Converts L-DOPA into Dopamine via the release of CO2

Can L-DOPA cross the BBB?

YES! —> it will then be converted to Dopamine

Too little dopamine leads to

Parkinson’s Disease

Too much dopamine leads to

Psychosis and Schizophrenia

Dopamine is used as a treatment for

Parkinson’s Disease

Dopamine antagonists are used to treat

Schizophrenia

________ and ___________ activate brain reward pathways that depend on dopamineregic transmission

Cocaine and Amphetamines(ADHD meds)

Where is dopamine synthesized

Cytoplasm

Where is dopamine transported when it is made

Into a synaptic vesicle

In a dopaminergic neuron what happens to dopamine

Transported into synaptic vesicle and released as dopamine

In Adrenergic or Noradrenergic neurons what happens to dopamine

Converted into Norepinephrine

In adrenal medulla and a small number of neurons what happens to dopamine that got converted into norepinephrine

It gets converted into epinephrine

Agonist of Catecholamines are

bronchodilators —> treats asthma attacks by opening lungs better

vasopressors —> Epipen —> blood vessels constrict again so you can breathe —> increase blood pressure

Antagonist of Catecholamines

Antihypertensives —> lowers high blood pressure

Clonidine

Central adrenergic partial agonist —> Lower blood pressure and help children sleep

Alpha 1 vs alpha 2 receptors

Alpha-1 receptors act as an "accelerator" to stimulate the body's fight-or-flight response, while Alpha-2 receptors act as a "brake" to shut it down

Clonidine stimulates which receptor type

Alpha 2 - central adrenergic partial agonist —> which will lower blood pressure

how do Antidepressants work with norepinephrine

increase synaptic concentration of norepinephrine by blocking uptake and blocking breakdown

Antidepressants that block norepinephrine uptake

Tricyclic antidepressants, TCAs

Antidepressants that block norepinephrine breakdown

Monoamine oxidase inhibitors, MAOIs

TCAS block the uptake of

Norepinephrine and Serotonin

SSRIs

Selective serotonin reuptake inhibitors—> Block serotonin reuptake

Starting material for serotonin

Tryptophan

5-Hydroxytryptamine is also called

Serotonin

Histamine is the result of

decarboxylation of histidine

Peripheral H1 blockage treats ________ and may cause

inflammation , drowsiness

Why do we assume histamine causes wakefulness

Because anti-histamines cause drowsiness

Anti-histamines are used for

peripheral H1 blockage

H2 inhibition treats _________ and does not cause __________

peptic ulcers, drowsiness

peripheral H1 blockage anti-histamines tend to cause what side effect

antinausea effects

Which type of antihistamine causes drowsiness

H1 blockage

Which type of antihistamine does not cause drowsiness

H2 inhibition

Acetylcholine is used where

Peripheral neurotransmission and at the NMJ

autonomic nervous system is used by ALL preganglonic neurons

Preganglionic neurons release

Acetylcholine —> will effect both SNS and PSNS

Postganglionic neurons release

norepinephrine —> SNS

Ach —> PSNS

Which parts of the autonomic nervous system does Acetylcholine effect

BOTH the SNS and PSNS

Wide range Acetylcholine therapeutics

• Muscle paralytics

• Acetylcholinesterase inhibitors

• Receptor specific agonist and antagonists

Acetylcholine regulates

wakefulness

Donepezil

acetylcholinesterase inhibitor —> brightens people with dementia

Scopolamine

Blocks acetylcholine receptor to prevent nausea —> Drowsiness, amnesia, fatigue, and dreamless sleep

Pilocarpine

Ach agonist —> cortical arousal and alertness —> used for dementia

1st ever truth serum

Scopolamine —> forgot what you said

Purinergic neurotransmitters are derived from

adenosine and adenosine triphosphate

Purinergic neurotransmitters effect

CNS

Example of a Purinergic neurotransmitter competitive antagonist

Caffeine —> There are receptors on presynpatic NE neurons that inhibit the release of NE —> Caffeine inhibit these receptors —> cause release of NE —> mild stimulant

Nitric Oxide

Important for vasodilation

Used as a CNS NT

Where is nitrous oxide released?

The enzyme endothelial nitric oxide synthase (eNOS)—located in the inner lining of blood vessels called the endothelium releases it

Nitrous oxide messenger type

Retrograde —> Travels backwards to receptors within presynapic neurons

What part of nitrous oxide do therapies target

Vasodilatory effects

Neuropeptides

small chains of amino acids synthesized and secreted by neurons to act as chemical messengers, neuromodulators, or neurohormones in the central and peripheral nervous systems

Neuropeptide actions

Endocrine

autocrine

paracrine

Neuropeptide examples

Opioids, tachykinins, secretins, insulin, gastrins

Pituitary hormone

release and inhibiting factors

Opioid Family

enkephalins, dynorphins, endorphins —> runners high