Chapter 2 - Basic Science Concepts Flashcards
Nervous system overview
- 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
NEUROTRANSMITTERS
- 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)
AUTONOMIC NERVOUS SYSTEM
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
Competitive inhibition
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.
Epinephrine function
Epinephrine normally increases heart rate and contractility when it binds to beta-I receptors.
Muscarinic and alpha-I receptors are targets for medications used to
- Reduce bladder contractions (oxybutynin)
- Relax the bladder (doxazosin)
Terbutaline is a
beta-2 agonist used in acute, severe asthma exacerbations
Isoproterenol is a mixed:
beta-I and beta-2 agonist; it is used for bradycardia and causes bronchodilation
Carvedilol moa
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.
Clonidine moa
is a centrally acting alpha-2 adrenergic agonist
Muscarinic
- acetylcholine
- agonist: Pilocarpine, bethanechol
– inc SLUDD* - antagonist: Atropine, oxybutynin
– dec SLUDD
Nicotinic
- acetylcholine
- agonist: Nicotine
– inc HR, BP - Neuromuscular blockers (rocuronium)
– Neuromuscular blockade
Alpha-1
(mainly peripheral)
- Epinephrine, norepinephrine
- Agonist: Phenylephrine, dopamine (dose- dependent)
– Smooth muscle vasoconstriction, inc BP - Antagonist: Alpha-1 blockers (doxazicin, carvedilol, phentolamine)
– Smooth muscle vasodilation, dec BP
Alpha-2 (mainly brain; central)
- Epinephrine, norepinephrine
- agonist: Clonidine, brimonidine (ophthalmic, for glaucoma)
– dec release of epinephrine and norepinephrine, dec BP,HR - Antagonist: Ergot alkaloids, yohimbine
– inc HR, BP
Beta-1 (mainly heart)
- 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
Beta-2 (mainly lungs)
- Epinephrine
- agon: Albuterol, terbutaline, isoproterenol
– Bronchodilation - antag: Non-selective beta-blockers
(e.g.,propranolol, carvedilol)
– Bronchoconstriction
Dopamine
- Levodopa, pramipexole
– Many including renal, cardiac and CNS effects - antag: First-generation antipsychotics (e.g., haloperidol), metoclopramide
– Many, including renal, cardiac and CNS effects
Serotonin
- 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
MAO function
An example enzyme is monoamine oxidase (MAO), which is responsible for breaking down catecholamines (dopamine, norepinephrine, epinephrine and serotonin}
Acetylcholinesterase
- Breaksdown acetylcholine
- Acetylcholinesterase Iinhibitors: donepezil, rivastigmine, galantamine
- Block acetylcholinesterase, resulting in
inc ACh levels; used to treat Alzheimer’s disease.
Angiotensin-converting enzyme (ace)
- 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.
Catechol-o- methyltransferase
(COMT)
- 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
Cyclooxygenase (COX)
- 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).
Monoamine oxidase
(MAO)
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
Phosphodiesterase (PDE)
- 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.
Vitamin K epoxide reductase
- 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.
Xanthine oxidase
- 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.
Additive effects with other drugs/foods that inc catecholamines and cause “catecholamine excess”
–> Hypertensive Crisis
bupropion, SNRls, TCAs, stimulants,
levodopa, linezolid, methylene blue, tyramine (from food)
Additive effects with other drugs that inc 5-HT
–> Serotonin Syndrome
SSRls, SNRls, TCAs, mirtazapine, trazodone, triptans, opioids, tramadol, buspirone, lithium, dextromethorphan, St. John’s wort
go over chemical structures from book
