Basic Science

What does the central nervous system include

Brain and spinal cord

Function of CNS

Sending signals to the peripheral nervous system

2 systems of the PNS

Somatic and automatic

Function of somatic nervous system

Voluntary muscle movement

Function of the automatic nervous system

Involuntary bodily functions

What is a neurotransmitter (NT)

Chemical messengers released from the presynaptic neurons into the synaptic cleft then they travel to postsynaptic neurons or other parts of the body

Common NT

Acetylcholine (ACh)

Epinephrine (Epi)

Norepinephrine (NE)

Dopamine (DA)

Serotonin (5-HT)

Primary NT involved in the somatic nervous system

ACh

Function of ACh

Released in response to neuron signals and binds to nicotinic receptors in skeletal muscles to affect muscle movement

2 divisions of the autonomic nervous system

parasympathetic

symptathetic

Parasympathetic nervous system

rest and digest

How does the PSNS function

releases ACh which binds to muscarinic receptors causing SLUDD (salivation, lacrimation, urination, defecation, digestion)

Sympathetic nervous system

fight or fligh

How does the SNS work

releases Epi and NE which act on adrenergic receptors (alpha-1, beta-1, beta-2) in cardiovascular and respiratory system

What does activation of SNS cause

increased BP, HR, bronchodilation

Agonist

substance that binds to and activates a receptor to produce a reaction

antagonist

binds to receptor but does not produce effect, it blocks the agonist from binding and inhibits the subsequent reaction

Competitive inhibition

antagonist binds to the same active site of receptor as a substrate, preventing it from binding and causing a reaction

non-competitive inhibition

antagonist binds to the receptor at a site other than the active site (AKA allosteric site), this changes the shape of the active site and prevents the endogenous substrate from binding

Receptor targets of isoproterenol

beta-1

beta-2

to treat bradycardia and cause bronchodilation

receptor targets of carvedilol

alpha-1

beta-1

beta-2

to decrease BP (by causing peripheral vasodilation and decrease in HR) can cause bronchoconstriction

Epinephrine

A vasopressor that stimulates multiple receptors, such as alpha-1 and beta-1, leading to increased vasoconstriction, HR and BP.

Norepinephrine

A vasopressor that stimulates multiple receptors, such as alpha-1 and beta-1, leading to increased vasoconstriction, HR and BP.

Clonidine

A centrally-acting alpha-2 adrenergic agonist that decreases overall sympathetic output by binding to presynaptic alpha-2 receptors in the brain.

SLUDD

An acronym for salivation, lacrimation, urination, diarrhea/defecation, and digestion.

Pilocarpine

A muscarinic agonist that increases SLUDD.

Bethanechol

A muscarinic agonist that increases SLUDD.

Atropine

A muscarinic antagonist that decreases SLUDD.

Oxybutynin

A muscarinic antagonist that decreases SLUDD.

Nicotine

A nicotinic agonist that increases HR and BP.

Phenylephrine

An alpha-1 agonist that causes smooth muscle vasoconstriction and increases BP.

Rocuronium

A neuromuscular blocker that causes neuromuscular blockade.

Doxazosin

An alpha-1 blocker that decreases BP.

Phentolamine

An alpha-1 blocker that decreases BP.

Ergot alkaloids

Alpha-1 antagonists that affect vasoconstriction.

Yohimbine

An alpha-1 antagonist that affects vasoconstriction.

Dopamine

A beta-1 agonist that increases myocardial contractility, CO, and HR.

Dobutamine

A beta-1 agonist that increases myocardial contractility, CO, and HR.

Metoprolol

A beta-1 selective blocker.

Propranolol

A non-selective beta-blocker.

Albuterol

A beta-2 agonist that causes bronchodilation.

Terbutaline

A beta-2 agonist that causes bronchodilation.

Levodopa

A dopamine agonist with renal, cardiac, and CNS effects.

Pramipexole

A dopamine agonist with renal, cardiac, and CNS effects.

Serotonin

A neurotransmitter with many effects, including platelet aggregation and psychiatric effects.

Triptans

Drugs like sumatriptan that affect serotonin and have various effects.

Haloperidol

A first-generation antipsychotic with various effects.

Metoclopramide

A first-generation antipsychotic with various effects.

Ondansetron

A second-generation antipsychotic with various effects.

Quetiapine

A second-generation antipsychotic with various effects.

What does monoamine oxidase (MAO) break down

catecholamines

Acetylcholinesterase

Breaks down acetylcholine

What is the effect of Angiotensin-converting enzyme (ACE)?

Converts angiotensin I to angiotensin II (a vasoconstrictor)

Catechol-O-methyltransferase (COMT)

Breaks down levodopa

What does Cyclooxygenase (COX) do?

Converts arachidonic acid to prostaglandins (↑ inflammation) and thromboxane A2 (↑ platelet aggregation)

Monoamine oxidase (MAO)

Breaks down catecholamines (e.g., DA, NE, Epi, 5-HT)

What are some drug examples for Acetylcholinesterase inhibitors?

Donepezil, rivastigmine

What are ACE inhibitors?

Lisinopril, ramipril

What is a COMT inhibitor?

Entacapone

What are some examples of NSAIDs?

Aspirin, ibuprofen

What are MAO inhibitors?

Phenelzine, isocarboxazid, tranylcypromine, selegiline, rasagiline

What is the action of Acetylcholinesterase inhibitors?

Block acetylcholinesterase, resulting in ↑ ACh levels; used to treat Alzheimer's disease.

What is the action of ACE inhibitors?

Block angiotensin II production, resulting in vasoconstriction and aldosterone secretion; used to treat hypertension, heart failure and kidney disease.

What is the action of COMT inhibitors?

Blocks COMT enzyme to peripheral breakdown of levodopa, resulting in ↑ duration of levodopa; used to treat Parkinson disease.

What is the action of COX inhibitors?

Block COX enzymes to prostaglandins and thromboxane A2; used to treat pain/inflammation and platelet activation/aggregation (aspirin).

What is the action of MAO inhibitors?

Block MAO to ↑ catecholamine levels; used to treat depression.

What can excessive catecholamine ↑ cause?

Hypertensive crisis or serotonin syndrome (due to additive effects drugs or foods)

Phosphodiesterase (PDE)

Breaks down cyclic guanosine monophosphate (cGMP), a smooth muscle relaxant.

PDE-5 inhibitors

Examples include sildenafil and tadalafil.

PDE-5 inhibitors action

Competitively bind to the same active site as cGMP on the PDE-5 enzyme, ↓the breakdown of cGMP and prolonging smooth muscle relaxation (e.g., in the arteries of the penis); used to treat erectile dysfunction.

Vitamin K epoxide reductase

Blocks vitamin K epoxide reductase enzyme which production of clotting factors II, VII, IX, and X; used to treat or prevent blood clots.

Warfarin

Converts vitamin K to the active form required for production of select clotting factors.

Xanthine oxidase inhibitor

Breaks down hypoxanthine into uric acid.

Allopurinol

Blocks xanthine oxidase enzyme which decreases uric acid production; used to prevent gout attacks.

What can develop when catecholamines accumulate due to MAO being blocked by MAO inhibitor

hypertensive crisis or serotonin syndrome

Process of cause of hypertensive crisis

Multiple MAO inhibitors used at once caused blocking of MAO enzyme which blocks the breakdown of neurotransmitters increasing Epi and NE

Process of serotonin syndrome

Additive effect with drugs that increase serotonin by blocking the MAO enzyme which blocks the breakdown of serotonin and increased serotonin

Sulfonamide group

in celecoxib

Ester group

in procaine

Amide group

List neutral functional groups

Hydroxyl or alcohol

Ketone

Aldehyde

Amide

Nitrate

Nitro

Aromatic (benzene) ring

Urea

Carbonate

Carbamate

Ether

Thioether

List acidic functional groups

Carboxyl

Phenol

Imide

Sulfonamide

List basic functional groups

Amine (primary)

Amine (tertiary)

Imine

Amidine

Hydroxyl or alcohol group

Ketone group

Aldehyde group

Nitrate group

Nitro group

Aromatic (benzene) ring

Urea group

Carbonate group

Carbamate group

Ether group

Thioether group

Carboxyl group

Phenol group

Imide group

Amine primary group

Amine tertiary group

Imine group