Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Block 2: Cardio, Renal, and Respiratory > Pharmacology (Melega) > Flashcards

Pharmacology (Melega) Flashcards

1
Q

Steps in neurochemical transmission

A

Synthesis

Storage

Release (Ca2+ triggers exocytosis)

Receptor interaction

Reuptake (into nerve terminal) or Inactivation (by metabolism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

NE synthesis/storage

A

Tyr gets into cytosol without regulation –> TH turning Tyr into L-DOPA is rate-limiting –> L-DOPA turned into DA by AAAD rapidly in cytosol –> DA into vesicles by vesicular monoamine transporter-2 (VMAT) –> DA turned into NE by dopamine beta hydroxylase (DBH) in vesicles and stored there

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Autoreceptors

A

Receptor on presynaptic membrane that binds NE after it’s been released into synaptic cleft

Ex: alpha2 autoreceptor on presyn membrane responding to NE

Provides feedback–inhibits NE release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Heteroreceptors

A

Receptor on presynaptic membrane that responds to input from another neuron (and different NT, ie Ach)

Ex: muscarinic receptor on adrenergic nerve terminal

Inhibitory–reduces NE release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Norepinephrine transporter (NET)

A

Reuptake of NE, located on presynaptic membrane

Called Uptake 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Catechol-O-methyltransferase (COMT)

A

Metabolizes NE –> normetanephrine

Metabolizes Epi –> metanephrine

(Metabolites have lower affinity for binding receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Monoamine oxidase (MAO)

A

MAO-A and MAO-B

Metabolizes NE by oxidizing it to aldehyde

(Then aldehyde further acted on by aldehyde reductase or aldehyde dehydrogenase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

MHPG and VMA

A

Terminal metabolites of NE metabolism

MHPG and sometimes VMA used as index of NE turnover when measured in CSF

Can be produced when MAO acts then COMT, or vice versa!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which receptors does NE bind?

A

Alpha1

Alpha2

Beta1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which receptors does Epi bind?

A

Alpha1

Alpha2

Beta1

Beta2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which receptors does isoproterenol bind?

A

Beta1

Beta2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Adrenal medulla

A

Located in central part of adrenal glands

Site of synthesis and storage of catecholamines

Responds to impulses from preganglionic sympathetic fibers that release Ach and bind nicotinic receptors

Secretes mostly 80% epi and 20% NE directly into circulation via chromaffin cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Synthesis of epinephrine

A

DA taken up into vesicles, converted to NE by DBH –> NE transported out of vesicles into cytosol –> NE converted to EPI by PNMT –> EPI transported back into vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Alpha1 adrenergic receptor signal transduction pathway

A

EPI/NE binds alpha1 receptor –> G-coupled protein activates PLC –> PLC creates DAG and IP3 –> IP3 binds to IP3-receptor gated Ca2+ channel to let Ca2+ into cytoplasm from SR –> Ca2+ binds calmodulin and activates MLCK –> MLCK activates myosin to bind actin and contract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Beta1 adrenergic receptor signal transduction pathway

A

EPI/NE binds beta1 receptor –> G-coupled protein activates adenylyl cyclase –> increased cAMP –> activation of PKA –> phosphorylation of L-type Ca2+ channels –> muscle CONTRACTION –> heart has increased contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Beta2 adrenergic receptor signal transduction pathway

A

EPI binds beta2 receptor –> G-coupled protein activates adenylyl cyclase –> increased cAMP –> activation of PKA –> phosphorylation of MLCK –> muscle RELAXATION

Note: same pathway for beta1 and beta2 but opposing effects because of LOCALIZED action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

EPI effects at low and high concentrations

A

Low [EPI]: stimulates beta2 > alpha1; vasodilation

High [EPI]: stimulates alpha1> beta2; vasoconstriction

Note: more alpha1 receptors overall, but have lower affinity for EPI. So when enough EPI to bind to alpha1, they bind to lots of alpha1’s and this effect overrides the few beta2 receptors that are occupied by EPI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

At physiological concentrations, what do NE and EPI do?

A

NE = vasoconstriction (via alpha1)

EPI = vasodilation (via beta2)

Both increase HR, contractility (beta1 (and beta2 for EPI))

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Direct mechanism of action

A

Drug binds adrenergic receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Indirect mechanism of action

A

Causes response by provoking release of NE from presynaptic terminal, or by interfering with NE reuptake

Do not have direct actions on postsynaptic receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mixed mechanism of action

A

Combination of direct and indirect mechanisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Reuptake inhibitor

A

Type of Indirectly Acting Sympathomimetic

Drug binds reversibly to uptake transporter (ex: NET), blocking access for NT to be re-uptaken back into presynaptic terminal

Get increase in extracellular NT

Ex: Cocaine

Other ex: methylphenidate (Ritalin for ADHD increase NE, DA), tricyclic antidepressants (increase NE, serotonin), SSRIs (increase serotonin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Neurotransmitter-releasing

A

Type of Indirectly Acting Sympathomimetic

Drug is taken up by presynaptic nerve terminals (through reuptake channel like NET) and enters vesicles, displacing NT from the vesicles, so NT gets into cytosol and is then pushed out of presyn membrane through channels (non-exocytosis exit)

Get increase in extracellular NT

Ex: Methamphetamine, Tyramine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Sympatholytic/Adrenolytic

A

Block NE effects

Direct Receptor Blocking Agents: Drug can be direct (competitive or irreversible) antagonist

Adrenergic Neuronal Blocking Agents: Drug can bind to vesicles and not allow DA in (so can’t be converted/synthesized to NE), or can not allow reuptake of NE into vesicle (so can’t be stored in vesicles and released into synaptic cleft), then DA and NE metabolized in cytosol by MAO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Pheochromocytoma
Rare catecholamine-secreting tumor derived from chromaffin cells of adrenal medulla that produces high NE and EPI, resulting in severe increase in BP Can use Phentolamine or Phenoxybenzamine (although that not used much anymore because it's irreversible) to treat hypertension caused by this
26
Reflex increase in heart rate
Happens when you block alpha1 and alpha2--get vasodilation then reflex increase in HR Alpha2 presynaptic receptors usually decrease NE release, so if they are blocked you get more NE released, and this NE can go to beta2 receptors and stimulate increased heart rate
27
What are beta blockers generally used for?
Manage ischemic heart disease by decreasing myocardial O2 demand Hypertension Congestive heart failure Abnormal heart rhythms Chest pain (angina) Sometimes in heart attack patients to prevent future heart attacks
28
Beta1 selective blockers
Metoprolol (penetrates BBB) Atenolol (doesn't penetrate BBB) Effects: decrease HR, decrease conduction velocity, decrease contractility, decrease lipolysis, decrease renin secretion
29
Non-selective beta blockers (beta1 and beta 2)
Propranolol Carvedilol (ALSO an alpha1 antagonist)
30
Things you need to think about before giving a patient a beta blocker
In diabetics: beta blockers can mask tachycardia they need to feel to know they're getting hypoglycemic In asthmatics: they need beta2 stimulation for bronchodilation, so be careful when giving nonselective beta blocker like propranolol or carvedilol
31
What are possible mechanisms for how beta blockers combat hypertension? (Even though we don't really understand this yet)
Lowered CO Inhibition of renin release Centrally mediated lowering of sypathetic activity
32
Does "selective" mean that it only binds to that one receptor?
NO! Selective beta1 blockers will bind and block beta2 at high doses!
33
Can beta blockers stimulate beta receptors?
YES! When **endogenous NE activity is low**, beta blockers can become a weak agonist and stimulate beta receptors like NE does. When endogenous NE activity is high, beta blockers block NE effects by competitively binding beta receptors. OVERALL: beta blockers have low efficacy for receptors, and to have agonist activity, a lot of receptors must be occupied
34
Effects of EPI
Act on beta receptors and alpha receptors **Vasodilation** from beta2 receptors on skeletal muscle causes decrease in resistance. Beta effects on heart cause **systolic to increase**, but since peripheral resistance decreased, your **diastolic goes down**! **Increase in HR** because of direct effect of epi on beta receptors, AND baroreceptor reflex responds to decreased stretch so also wants to increase HR.
35
Effects of NE
(PHARMACOLOGICALLY) Act on alpha1, alpha2, beta1. Increase peripheral resistance because alpha1 on vasculature causes **vasoconstriction**. THAT drives **increase in BP**. Beta1 should produce increase of HR, but **HR goes DOWN** because baroreceptor reflex overwhelms direct effect of NE.
36
Effects of ISO
Act on beta receptors **Vasodilation** by beta2 causes reduction in peripheral resistance. That causes **decreased diastolic** pressure. Causes **increased HR** directly and by baroreceptor reflex.
37
Where are cholinergic synapses located?
Presynaptic PNS and SNS (autonomic ganglia) Postsynaptic PNS (smooth muscle contraction, etc) Postsynaptic SNS sweat glands Brain Neuromuscular junction (voluntary contraction)
38
Acetylcholine synthesis
Choline transported into terminal with Na+ (rate-limiting step)--\> Choline + Acetyl CoA into ACh by choline acetyltransferase --\> ACh into vesicles by exchange with H+
39
Mechanisms to inhibit ACh release
1) Presynaptic autoreceptors (M2) 2) Heteroreceptors (NE on alpha2 receptors on cholinergic presyn terminal)
40
Nicotinic receptors
Ligand-gated ion channel; lets Na+ in (and K+ out) to depolarize membrane Location: CNS On postsynaptic PNS and SNS neurons On chromaffin cells Neuromuscular junction
41
Muscarinic receptors
M1, 3, 5: Activate phospholipase C, increase DAG then PKC and IP3 then Ca2+ intracellular storage and smooth muscle contraction = vasoconstriction M2, 4: Decrease cAMP for signal transduction and cell hyperpolarization and decreased HR Location: Blood vessel endothelium Sweat glands CNS Heart
42
How is ACh inactivated?
Hydrolysis by acetylcholinesterase in synaptic cleft
43
Effects of ACh
Decrease HR, decrease rate of conduction, decrease force of contraction Vasodilation (not nerves, but via NO, cGMP and PKG) Bronchoconstriction GI motility increase Urinary detrusor contraction and trigond/sphincter relaxation Neuromuscular contraction
44
Acetylcholinesterase inhibitors
AKA anticholinesterase drugs Cause increase in ACh Reversible inhibitors: derophonium, ambenonium, tacrine, donepezil (compete with ACh for AChE binding site) Slowly reversible inhibitors: physostigmine and neostigmine (carbamate esters which binds AChE and takes 20 minutes to inactivate it) Irreversible inhibitors: organophosphates (interact only with esteratic site)
45
Pralidoxime
Treats organophosphate inhibition of acetylcholinesterase (irreversible AChE inhibition) by reactivating AChE Interacts with anionic site of phosphorylated AChE. Must be used ASAP after exposure and before "aging of AChE"
46
NO-mediated relaxation
**ACh on muscarinic receptor** (and bradykinin, histamine, shear stress of blood flow) --\> **Ca2+** enters cell and triggers calmodulin to bind to membrane-bound endothelial NOS (e-NOS, aka **c-NOS**) --\> e-NOS makes NO --\> **NO diffuses into nearby smooth muscle cells** to cause cGMP and PKG (?)--\> decreased Ca2+, K+ channels cause hyperpolarization, activation of MLCP --\> Vasodilation (**relaxation**)
47
Muscarininc Agonists
AKA Cholinomimetics, parasympathomimetics Not used much other than to treat glaucoma, postop urinary retention and ileus because many side effects Bradycardia, vasodilation (so reflex tachycardia), bronchoconstriction, increased secretions of fluids, increased peristalsis, pupillary constriction/blurred vision
48
Muscarinic Antagonists (Atropinic Agents)
Competitive antagonist of ACh Atropine HR increase (but little effect on BP because no muscarinic on blood vessels ???)/contractility increase, AV conduction increase, reduced sweating/dry mouth, reduced bronchial mucous secretion, bronchodilation
49
Botulinum Toxin (BoTx)
Irreversibly blocks ACh release Results in flaccid paralysis of muscles Protease that cleaves specific proteins (SNAP25, synaptobrevin--SNARE proteins) involved in exocytosis Cosmetic to reduce wrinkles, excessive sweating, strabismus (lack of parallelism of eyes)
50
Injected NE (pharmacological) versus neuroeffector NE (natural/physiological)
Injected: Floating around bloodstream, acts on smooth muscle and causes **vasoconstriction** (alpha1), does NOT act on heart at all Neuroeffector: Released from synapse, acts on heart (SA node) to **increase HR**, contractility (beta1 and beta2). Also acts on smooth muscle to **vasoconstrict** (alpha1 and alpha2)
51
Which receptor does ACh bind more strongly?
Muscarinic
52
Why can't stimulation of vagus nerve cause vasodilation?
Vagus nerve does not innervate vascular smooth muscle (no connection to blood vessels!)
53
Alpha agonists
EPI (plus beta1, beta2) NE (plus beta1) Phenylephrine (alpha1) Midodrine (alpha1) Clonidine (alpha2, so basically "sympatholytic"--decreases NE release!) Oxymetazoline (partial alpha agonist) Tetrahydrozoline (partial alpha agonist) Naphazoline (partial alpha agonist)
54
Beta agonists
EPI (and alpha1, alpha2) NE (beta1, and alpha1, alpha2) ISO Dobutamine (beta1) Tertbutaline (beta2)
55
Alpha antagonists (alpha blockers)
Phenoxybenzamine (irreversible) Phentolamine (competitive) Prazosin (competitive alpha1) Terazosin (competitive alpha1) Doxazosin (competitive alpha1)
56
Beta antagonists (beta blockers)
Propranolol (beta1 and beta2) Carvedilol (alpha blocker too) Metoprolol (beta1)
57
Indirectly acting sympathomimetics
Cocaine d-Methamphetamine d-Amphetamine Ephedrine Pseudoephedrine (also alpha and beta blocker) Tyramine
58
Sympatholytics
Reserpine Alpha-Methyldopa
59
Cholinergic agonists
Nicotine (nicotinic receptors) Pilocarpine (muscarinic receptors)
60
Acetylcholinesterase inhibitors
Physostigmine Neostigmine Organophosphate inhibitors (irreversible)
61
Cholinergic antagonists (ACh blockers)
Atropine (muscarinic) Scopolamine (muscarinic) Tiotropium (muscarinic, only in periphery) Ipratropium (muscarinic, only in periphery)
62
Pseudocholinesterase
Hydrolyzes ACh in plasma, liver, glia (Like AChE, but different locations!)
63
Acetylcholinesterase (AChE)
Hydrolyzes ACh at postsynaptic membrane of synapse, and in RBCs

Block 2: Cardio, Renal, and Respiratory (36 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions