NAPLEX PRACTICE NOTES
PHARMACY FOUNDATIONS PART 1 (42-113)
Chapter 2: Basic Science concepts (42-52)
Substrate (or ligand): substance that creates signal/effect by binding to a receptor, enzyme
or transporter
Endogenous: substance produced by the body
(natural) Exogenous: substance produced outside body
(drug/chem)
Agonist: substance that combines with receptor to initiate a reaction (endo/exo) (mimics
endo sub)
Induction: when a substance increases the activity of an enzyme
INhibition: when a substance decreases or blocks the activity of an
enzyme
Nervous system overview
CNS: brain + spinal cord, controls rest of body by sending signals to the
PNS PNS:
- Somatic (voluntary): muscle movement
- Autonomic (involuntary): digestion, CO, BP, etc.
NTs (Neurotransmitters): are what send messages between PNS and CNS
(substrates/ligands)
- Common: Ach, Epi, NE, DA, 5-HT
NTs in somatic: Ach: released in response to neuron signals and binds to nicotinic (Nn)
in skeletal muscles
NTs in Autonomic
1. Parasympathetic (rest and digest)
a. Releases Ach - binds to muscarinic receptors (GI, bladder, eyes) →
SLUDD (salivation, lacrimation, urination, defecation, digestion)
2. Sympathetic (fight or flight)
a. Releases EPI and NE → binds to adrenergic receptors (A1, B1, B2) in CV
and respiratory systems → increases BP, HR, bronchodilation. Stimulation
of B2 receptors in GI increases glucose production to provide muscles with
oxygen and energy. When sympathetic activated para is paused.
Parasymp
- Increase SLUDD
- Ach → muscarinic receptors (stomach and
bladder) Symp
- Decrease SLUDD, increase glucose, bronchodilation, HR, BP
- NE and Epi
- A1 - smooth muscles, blood vessels
- B1 - heart
- B2 - Lungs
,Receptors and substrates
- NTs acta as substrates/ligands by binding with cells to communicate and send
signals
- Substrate binds to receptors on receptor cell to cause signal or change
- Can be endo/exo. Once bound, receptor substrates complex causes
some change that results in biological effect
- Substrates that bind to receptors can be agonists/antagonists
- Agonist: binds to and activates a receptor (producing response)
- Antagonist: blocker/inhibitor, binds to a receptor but doesn’t produce a
reaction
→ it blocks the agonist from binding and inhibits that subsequent reaction
- Can be competitive or non-competitive
- Competitive: antagonist binds to same active site (prevent binding)
- Non-Competitive: antagonist binds to site other than active site
(allosteric), will change shape of active site and prevent
endogenous substrate from binding
Drug Receptor Interactions
- Drug = exogenous agonist/antagonist
- Ex: albuterol = B2 agonist (similar to epi) = bronchial smooth muscle
relaxation
- Ex: B1 blockers = prevent adrenergic NTs (Epi) from binding to B1
receptors, by blocking this they decrease HR and contractility
- Common drug receptor targets
- A1: increase or decrease bladder contractions and muscarinic
- Terbutaline: B2 agonist for severe asthma
- Multiple receptors
- Isoproterenol: mixed B1/2 agonist, used for bradycardia and
causes bronchodilation
- Carvedilol: inhibits A1, B1/2 receptors, used to decrease BP
(vasodilation and HR), can cause bronchoconstriction
- Vasopressor (Epi and NE): stimulate multiple receptors A1, B1
and increase vasoconstriction, HR and BP
- CNS to affect amount NT released to PNS
- Clonidine CNS acting A2 adrenergic agonist, when presynaptic A2
receptors in brain are stimulated, a decrease in overall sympathetic
output and decreased release and availability of NE and Epi to bind →
vasodilation (decrease BP and HR)
Common Receptors, substrates and drug examples
- Muscarinic: endo sub = Ach: agonist action increase SLUDD (pilocarpine,
bethanechol): antagonist action decrease SLUDD ( atropine, oxybutynin)
- Nicotinic: endo sub = Ach: agonist action increases HR and BP (nicotine):
antagonist action neuromuscular blockade (rocuronium)
- Alpha 1 (peripheral): endo sub = NE and Epi: agonist action smooth muscle
constriction and increase BP (phenylephrine, dopamine): antagonist action
smooth muscle vasodilation decrease BP (A1 blockers, doxazosin, carvedilol)
, - Alpha 2 (brain): endo sub = NE and Epi: agonist action decrease release of Epi
and NE, decrease BP and HR (clonidine, brimonidine): antagonist action increase
BP and HR (ergot alkaloids, yohimbe)
- Beta 1 (heart): endo sub= NE and Epi: agonist action increase myocardial
contraction CO and HR (dobutamine, isoproterenol, dopamine): antagonist
action decreases CO and HR (BB1 selective (metoprolol), BB nonselective
(carvedilol, propranolol))
- Beta 2 (lungs): endo sub = NE and Epi: agonist action bronchodilation
(albuterol, terbutaline, isoproterenol): antagonist action bronchoconstriction
(nonselective BBs, propranolol, carvedilol)
- Dopamine: endo sub = dopamine: agonist action (many renal, cardiac
CNS)(levodopa, pramipexole): antagonist action (many renal, cardiac CNS) (1st
gen antipsychotics, haloperidol, metoclopramide)
- Serotonin: endo sub = serotonin: agonist action (many PLT, GI, psychiatric)
(triptans): antagonist action (many PLT, GI, psychiatric) (ondansetron, 2nd gen
antipsychotics (quetiapine)
Enzymes
- Speed up (catalyze) a reaction
- Can be agonistic or antagonistic, competitive or non competitive
- Ex: MOA (monoamine oxidase), breaks down catecholamines
(dopamine, NE, Epi, 5-HT)
Common Enzyme targets for meds
ENZYME ENDO EFFECT DRUG EX: DRUG ACTION
Ach Breaks down Ach Acetylcholinesterase Blocks
inhibitors: donepezil, acetylcholinesteras
rivastigmine, e to increase Ach
galantamine levels (Alzheimers)
Catechol-O-Methyltra Breaks COMT Blocks enzyme to
nsferase (COMT) down inhibitors prevent breakdown
levodopa (entacapone) of levodopa →
increases action
duration
(parkinsons)
ACE Angiotensin 1→2 (a ACEIs (-prils) Inhibit production
potent of angio II resulting
vasoconstrictor) in decreased
vasoconstriction,
aldosterone
secretion (HTN, HF,
CKD)
Cyclooxygenase Converts NSAIDs Blocks COX enzymes
(COX) arachidonic acid to to decrease
prostaglandins(infla prostaglandins and
m
, mation) and thromboxane A@
thromboxane A2 (for pain and
(PLT aggregation) inflammation) and
decrease PLT
aggregation
Monoamine Breaks down MAOIs (phenelzine, Blocks MAI
oxidase (MOA) catecholamines tranylcypromine, increases
isocarboxazid, catecholamines, if
selegiline, too many
rasagiline, catecholamines
methylene blue, toxic effects
linezolid) (hypertensive crisis,
sero syndrome)
Phosphodiesterase Breaks down cyclic PDE-5 inhibitors Competitively bind to
(PDE) guanosine (sildenafil, same active site as
monophosphate tadalafil) cGMP on PDE-5
(cGMP), a smooth enzyme preventing
muscle relaxant the breakdown of
cGMP and
prolonging smooth
muscle relaxation
(ED)
Vitamin K epoxide Converts vit K to warfarin Blocks k epoxide
reductase active form reductase enzyme
required for which decreases
production of production of
select blood clotting factors 2, 8,
clotting factors 9, 10
Xanthine oxidase Breaks down Xanthine oxidase Blocks xanthine
hypoxanthine and inhibitor oxidase enzyme
xanthine into uric (allopurinol) which decreases
acid uric acid
production
(treat/prevent gout)
MAOIs, hypertensive crisis and serotonin syndrome
- Due to additive effects, build up of catecholamines, but too many can
accumulate and result in hypertensive crisis and sero syndrome
- Hypertensive crisis drugs: bupropion, SNRIs, TCAs, stimulants, levodopa,
linezolid, methylene blue, tyramine
- Serotonin syndrome drugs: SSRIs, SNRIs, TCAs, mirtazapine, trazodone,
triptans, opioids, tramadol, buspirone, lithium, dextromethorphan, St. J wort
Chemical Structures
- Expected effects of a drug can be predicted from MOA and chemical structure
this is called structure activity relationship (ex: sulfonamide group on
celecoxib)
- (Look in naplex pic folder or notes for drawings)
PHARMACY FOUNDATIONS PART 1 (42-113)
Chapter 2: Basic Science concepts (42-52)
Substrate (or ligand): substance that creates signal/effect by binding to a receptor, enzyme
or transporter
Endogenous: substance produced by the body
(natural) Exogenous: substance produced outside body
(drug/chem)
Agonist: substance that combines with receptor to initiate a reaction (endo/exo) (mimics
endo sub)
Induction: when a substance increases the activity of an enzyme
INhibition: when a substance decreases or blocks the activity of an
enzyme
Nervous system overview
CNS: brain + spinal cord, controls rest of body by sending signals to the
PNS PNS:
- Somatic (voluntary): muscle movement
- Autonomic (involuntary): digestion, CO, BP, etc.
NTs (Neurotransmitters): are what send messages between PNS and CNS
(substrates/ligands)
- Common: Ach, Epi, NE, DA, 5-HT
NTs in somatic: Ach: released in response to neuron signals and binds to nicotinic (Nn)
in skeletal muscles
NTs in Autonomic
1. Parasympathetic (rest and digest)
a. Releases Ach - binds to muscarinic receptors (GI, bladder, eyes) →
SLUDD (salivation, lacrimation, urination, defecation, digestion)
2. Sympathetic (fight or flight)
a. Releases EPI and NE → binds to adrenergic receptors (A1, B1, B2) in CV
and respiratory systems → increases BP, HR, bronchodilation. Stimulation
of B2 receptors in GI increases glucose production to provide muscles with
oxygen and energy. When sympathetic activated para is paused.
Parasymp
- Increase SLUDD
- Ach → muscarinic receptors (stomach and
bladder) Symp
- Decrease SLUDD, increase glucose, bronchodilation, HR, BP
- NE and Epi
- A1 - smooth muscles, blood vessels
- B1 - heart
- B2 - Lungs
,Receptors and substrates
- NTs acta as substrates/ligands by binding with cells to communicate and send
signals
- Substrate binds to receptors on receptor cell to cause signal or change
- Can be endo/exo. Once bound, receptor substrates complex causes
some change that results in biological effect
- Substrates that bind to receptors can be agonists/antagonists
- Agonist: binds to and activates a receptor (producing response)
- Antagonist: blocker/inhibitor, binds to a receptor but doesn’t produce a
reaction
→ it blocks the agonist from binding and inhibits that subsequent reaction
- Can be competitive or non-competitive
- Competitive: antagonist binds to same active site (prevent binding)
- Non-Competitive: antagonist binds to site other than active site
(allosteric), will change shape of active site and prevent
endogenous substrate from binding
Drug Receptor Interactions
- Drug = exogenous agonist/antagonist
- Ex: albuterol = B2 agonist (similar to epi) = bronchial smooth muscle
relaxation
- Ex: B1 blockers = prevent adrenergic NTs (Epi) from binding to B1
receptors, by blocking this they decrease HR and contractility
- Common drug receptor targets
- A1: increase or decrease bladder contractions and muscarinic
- Terbutaline: B2 agonist for severe asthma
- Multiple receptors
- Isoproterenol: mixed B1/2 agonist, used for bradycardia and
causes bronchodilation
- Carvedilol: inhibits A1, B1/2 receptors, used to decrease BP
(vasodilation and HR), can cause bronchoconstriction
- Vasopressor (Epi and NE): stimulate multiple receptors A1, B1
and increase vasoconstriction, HR and BP
- CNS to affect amount NT released to PNS
- Clonidine CNS acting A2 adrenergic agonist, when presynaptic A2
receptors in brain are stimulated, a decrease in overall sympathetic
output and decreased release and availability of NE and Epi to bind →
vasodilation (decrease BP and HR)
Common Receptors, substrates and drug examples
- Muscarinic: endo sub = Ach: agonist action increase SLUDD (pilocarpine,
bethanechol): antagonist action decrease SLUDD ( atropine, oxybutynin)
- Nicotinic: endo sub = Ach: agonist action increases HR and BP (nicotine):
antagonist action neuromuscular blockade (rocuronium)
- Alpha 1 (peripheral): endo sub = NE and Epi: agonist action smooth muscle
constriction and increase BP (phenylephrine, dopamine): antagonist action
smooth muscle vasodilation decrease BP (A1 blockers, doxazosin, carvedilol)
, - Alpha 2 (brain): endo sub = NE and Epi: agonist action decrease release of Epi
and NE, decrease BP and HR (clonidine, brimonidine): antagonist action increase
BP and HR (ergot alkaloids, yohimbe)
- Beta 1 (heart): endo sub= NE and Epi: agonist action increase myocardial
contraction CO and HR (dobutamine, isoproterenol, dopamine): antagonist
action decreases CO and HR (BB1 selective (metoprolol), BB nonselective
(carvedilol, propranolol))
- Beta 2 (lungs): endo sub = NE and Epi: agonist action bronchodilation
(albuterol, terbutaline, isoproterenol): antagonist action bronchoconstriction
(nonselective BBs, propranolol, carvedilol)
- Dopamine: endo sub = dopamine: agonist action (many renal, cardiac
CNS)(levodopa, pramipexole): antagonist action (many renal, cardiac CNS) (1st
gen antipsychotics, haloperidol, metoclopramide)
- Serotonin: endo sub = serotonin: agonist action (many PLT, GI, psychiatric)
(triptans): antagonist action (many PLT, GI, psychiatric) (ondansetron, 2nd gen
antipsychotics (quetiapine)
Enzymes
- Speed up (catalyze) a reaction
- Can be agonistic or antagonistic, competitive or non competitive
- Ex: MOA (monoamine oxidase), breaks down catecholamines
(dopamine, NE, Epi, 5-HT)
Common Enzyme targets for meds
ENZYME ENDO EFFECT DRUG EX: DRUG ACTION
Ach Breaks down Ach Acetylcholinesterase Blocks
inhibitors: donepezil, acetylcholinesteras
rivastigmine, e to increase Ach
galantamine levels (Alzheimers)
Catechol-O-Methyltra Breaks COMT Blocks enzyme to
nsferase (COMT) down inhibitors prevent breakdown
levodopa (entacapone) of levodopa →
increases action
duration
(parkinsons)
ACE Angiotensin 1→2 (a ACEIs (-prils) Inhibit production
potent of angio II resulting
vasoconstrictor) in decreased
vasoconstriction,
aldosterone
secretion (HTN, HF,
CKD)
Cyclooxygenase Converts NSAIDs Blocks COX enzymes
(COX) arachidonic acid to to decrease
prostaglandins(infla prostaglandins and
m
, mation) and thromboxane A@
thromboxane A2 (for pain and
(PLT aggregation) inflammation) and
decrease PLT
aggregation
Monoamine Breaks down MAOIs (phenelzine, Blocks MAI
oxidase (MOA) catecholamines tranylcypromine, increases
isocarboxazid, catecholamines, if
selegiline, too many
rasagiline, catecholamines
methylene blue, toxic effects
linezolid) (hypertensive crisis,
sero syndrome)
Phosphodiesterase Breaks down cyclic PDE-5 inhibitors Competitively bind to
(PDE) guanosine (sildenafil, same active site as
monophosphate tadalafil) cGMP on PDE-5
(cGMP), a smooth enzyme preventing
muscle relaxant the breakdown of
cGMP and
prolonging smooth
muscle relaxation
(ED)
Vitamin K epoxide Converts vit K to warfarin Blocks k epoxide
reductase active form reductase enzyme
required for which decreases
production of production of
select blood clotting factors 2, 8,
clotting factors 9, 10
Xanthine oxidase Breaks down Xanthine oxidase Blocks xanthine
hypoxanthine and inhibitor oxidase enzyme
xanthine into uric (allopurinol) which decreases
acid uric acid
production
(treat/prevent gout)
MAOIs, hypertensive crisis and serotonin syndrome
- Due to additive effects, build up of catecholamines, but too many can
accumulate and result in hypertensive crisis and sero syndrome
- Hypertensive crisis drugs: bupropion, SNRIs, TCAs, stimulants, levodopa,
linezolid, methylene blue, tyramine
- Serotonin syndrome drugs: SSRIs, SNRIs, TCAs, mirtazapine, trazodone,
triptans, opioids, tramadol, buspirone, lithium, dextromethorphan, St. J wort
Chemical Structures
- Expected effects of a drug can be predicted from MOA and chemical structure
this is called structure activity relationship (ex: sulfonamide group on
celecoxib)
- (Look in naplex pic folder or notes for drawings)
