Chapter 2 - Basic Science Concepts

Question 1

Nervous system overview

Answer 1

• CNS: brain & spinal cord.
  – Sends signals to PNS
• PNS: somatic and autonomic
  – Somatic nervous system (voluntary) controls muscle movement
  – Autonomic nervous system (involuntary) controls other bodily functions, such as digestion, cardiac output and BP
  –> Parasympathetic
  –> Sympathetic

Question 2

NEUROTRANSMITTERS

Answer 2

• Acetylcholine (ACh):
  – Primary NT involved in the somatic nervous system
  – It is released in response to neuron signals and binds to nicotinic receptors (Nn) in skeletal muscles to affect muscle movement.
• Epinephrine (Epi)
• Norepinephrine (NE)
• Dopamine (DA)
• Serotonin (5-HT)

Question 3

AUTONOMIC NERVOUS SYSTEM

Answer 3

1) Parasympathetic
- Rest and digest
- Release ACh, which binds to muscarinic receptors (GI tract, the bladder and the eyes)
- SLUDD (salivation, lacrimation, urination, defecation and digestion)
- Muscarinic Receptor: Stomach, Bladder

2) Sympathetic
- Fight or flight
- Release Ep and NE, which act on adrenergic receptors (alpha-I, beta-I & beta-2) in CV and respiratory systems
- Inc BP, HR & bronchodilation
- Stimulation of beta-2 receptors in the GI tract inc glucose production to provide muscles with oxygen & energy
- Digestion and urination are minimized

• Dec salivation, urination, peristalsis
• Inc pupil dilation, glucose production, bronchodilation, HR, BP
• Alpha-1 Receptor: Smooth Muscles, Including Blood Vessels
• Beta-1 Receptor: Heart
• Beta-2 Receptor: Lungs

Question 4

Competitive inhibition

Answer 4

Competitive inhibition
occurs when an antagonist binds to the same active site of a receptor as the endogenous substrate, preventing the activity. In non-competitive inhibition, the antagonist binds to the receptor at a site other than the active site (called the allosteric site), which changes the shape of the active site and prevents the endogenous substrate from binding.

Question 5

Epinephrine function

Answer 5

Epinephrine normally increases heart rate and contractility when it binds to beta-I receptors.

Question 6

Muscarinic and alpha-I receptors are targets for medications used to

Answer 6

• Reduce bladder contractions (oxybutynin)
• Relax the bladder (doxazosin)

Question 7

Terbutaline is a

Answer 7

beta-2 agonist used in acute, severe asthma exacerbations

Question 8

Isoproterenol is a mixed:

Answer 8

beta-I and beta-2 agonist; it is used for bradycardia and causes bronchodilation

Question 9

Carvedilol moa

Answer 9

inhibits alpha-I, beta-I and beta-2 receptors. It is used to decrease BP (by causing peripheral vasodilation and a decrease in HR), but it can cause bronchoconstriction.

Question 10

Clonidine moa

Answer 10

is a centrally acting alpha-2 adrenergic agonist

Question 11

Muscarinic

Answer 11

• acetylcholine
• agonist: Pilocarpine, bethanechol
  – inc SLUDD*
• antagonist: Atropine, oxybutynin
  – dec SLUDD

Question 12

Nicotinic

Answer 12

• acetylcholine
• agonist: Nicotine
  – inc HR, BP
• Neuromuscular blockers (rocuronium)
  – Neuromuscular blockade

Question 13

Alpha-1
(mainly peripheral)

Answer 13

• Epinephrine, norepinephrine
• Agonist: Phenylephrine, dopamine (dose- dependent)
  – Smooth muscle vasoconstriction, inc BP
• Antagonist: Alpha-1 blockers (doxazicin, carvedilol, phentolamine)
  – Smooth muscle vasodilation, dec BP

Question 14

Alpha-2 (mainly brain; central)

Answer 14

• Epinephrine, norepinephrine
• agonist: Clonidine, brimonidine (ophthalmic, for glaucoma)
  – dec release of epinephrine and norepinephrine, dec BP,HR
• Antagonist: Ergot alkaloids, yohimbine
  – inc HR, BP

Question 15

Beta-1 (mainly heart)

Answer 15

• Epinephrine, norepinephrine
• agonist: Dobutamine, isoproterenol, dopamine (dose- dependent)
  – inc myocardial contractility, CO, , HR
• antagonist: Beta-1 selective blockers (e.g.,metoprolol) and non-selective beta-blockers (Propranolol, carvedilol)
  – dec CO, HR

Question 16

Beta-2 (mainly lungs)

Answer 16

• Epinephrine
• agon: Albuterol, terbutaline, isoproterenol
  – Bronchodilation
• antag: Non-selective beta-blockers
  (e.g.,propranolol, carvedilol)
  – Bronchoconstriction

Question 17

Dopamine

Answer 17

• Levodopa, pramipexole
  – Many including renal, cardiac and CNS effects
• antag: First-generation antipsychotics (e.g., haloperidol), metoclopramide
  – Many, including renal, cardiac and CNS effects

Question 18

Serotonin

Answer 18

• Triptans (e.g., sumatriptan)
  – Many, including platelet, GI and psychiatric effects
• antag: Ondansetron, second- generation antipsychotics (e.g.,quetiapine)
  – Many, including Iplatelet, GI and
  psychiatric effects

Question 19

MAO function

Answer 19

An example enzyme is monoamine oxidase (MAO), which is responsible for breaking down catecholamines (dopamine, norepinephrine, epinephrine and serotonin}

Question 20

Acetylcholinesterase

Answer 20

• Breaksdown acetylcholine
• Acetylcholinesterase Iinhibitors: donepezil, rivastigmine, galantamine
• Block acetylcholinesterase, resulting in
  inc ACh levels; used to treat Alzheimer’s disease.

Question 21

Angiotensin-converting enzyme (ace)

Answer 21

• converts angiotensin I to II (potent vasoconstrictor)
• acei: ramipril
• Inhibit production of angiotensin II, resulting in dec vasoconstriction and dec aldosterone secretion; used to treat hypertension, heart failure and kidney disease.

Question 22

Catechol-o- methyltransferase
(COMT)

Answer 22

• Breaksdown levodopa
• COMT inhibitor: entacapone
• Blocks COMT enzyme to prevent peripheral breakdown of levodopa, resulting in inc duration of action of levodopa; used to treat Parkinson disease

Question 23

Cyclooxygenase (COX)

Answer 23

• Converts arachidonic acid to prostaglandins (cause inflammation) and thromboxane A2 (causes platelet aggregation)
• NSAIDs (e.g.,aspirin, ibuprofen)
• Block COX enzymes to dec prostaglandins and thromboxane A2; used to treat pain/inflammation and dec platelet activation/aggregation (aspirin).

Question 24

Monoamine oxidase
(MAO)

Answer 24

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

• MAO inhibitors: phenelzine, tranylcypromine, isocarboxazid, selegiline, rasagiline, methylene blue, linezolid
• Block MAO which inc catecholamine levels; used to treat depression.
  If catecholamines inc too much (due to additive effects with other drugs or foods), toxic effects can occur, such as hypertensive crisis or serotonin syndrome

Question 25

Phosphodiesterase (PDE)

Answer 25

• Breaksdown cyclic guanosine monophosphate (cGMP), a smooth muscle relaxant
• PDE-5 inhibitors (e.g., sildenafil, tadalafil)
• Competitively bind to the same active site as cGMP on the PDE-5 enzyme, preventing the breakdown of cGMP and prolonging smooth muscle relaxation (e.g., in the arteries of the penis); used to treat erectile dysfunction.

Question 26

Vitamin K epoxide reductase

Answer 26

• Converts vitamin K to the active form required for production of select clotting factors
• Warfarin
• Blocks vitamin K epoxide reductase enzyme which dec production of clotting factors I II, VII, IX and X; used to treat or prevent blood clots.

Question 27

Xanthine oxidase

Answer 27

• Breaks down hypoxanthine and xanthine into uric acid
• Xanthine oxidase inhibitor: allopurinol
• Blocks xanthine oxidase enzyme which decreases uric acid production; used to prevent gout attacks.

Question 28

Additive effects with other drugs/foods that inc catecholamines and cause “catecholamine excess”
–> Hypertensive Crisis

Answer 28

bupropion, SNRls, TCAs, stimulants,
levodopa, linezolid, methylene blue, tyramine (from food)

Question 29

Additive effects with other drugs that inc 5-HT
–> Serotonin Syndrome

Answer 29

SSRls, SNRls, TCAs, mirtazapine, trazodone, triptans, opioids, tramadol, buspirone, lithium, dextromethorphan, St. John’s wort

Question 30

go over chemical structures from book