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Pharmacology fall 2024 > Exam II > Flashcards

Exam II Flashcards

1
Q

What types of drugs are most relevant in relation to pharmacogenomics?

A

Antineoplastics.

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2
Q

What class of drug is 6MP? What is its mechanism of action?

A
  • 6-mercaptopurine is a Purine Analog.
  • Interference w/ nucleic acid synthesis.
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3
Q

What conditions/diseases do purine analogs treat?

A
  1. Lymphoblastic leukemia
  2. Autoimmune diseases
  3. IBS
  4. Post-Transplant
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4
Q

What limits the usage of Purine Analogs? Why?

A
  • Toxicity (poor Therapeutic index) and myelosuppression.
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5
Q

6-mercaptopurine is metabolized into 6-methyl-mercaptopurine by what enzyme?

A

TPMT (Thiopurine S-Methyl-Transferase)

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6
Q

What would a deficiency in TPMT (Thiopurine S-Methyl Transferase) cause?

A

Toxicity with Purine Analogs (specifically 6MP)

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7
Q

What is the pathway of Azathioprine?

A

Azathioprine → 6 Mercaptopurine → TPMT → 6-Methyl-Mercaptopurine

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8
Q

What therapy would be needed for someone with a TPMT deficiency who needed to receive 6MP to treat a lymphoblastic leukemia?

A
  1. A new drug would need to be found or…
  2. A much smaller dose of the 6MP would need to be given.
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9
Q

What drug ranks #1 in total mentions on death certificates for drug related deaths? What about emergency room visits?

A

Warfarin

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10
Q

What is the major bleeding side effect range for warfarin?

A

2-16% of patients

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11
Q

What does genetic analysis allow in regards to giving warfarin? How many bleeding events are avoided by genetic analysis? Is genetic testing for warfarin administration required by the FDA?

A
  • Allows for better therapeutic dose determination
  • 4500 - 22000 serious bleeding events?
  • No, it is recommended.
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12
Q

What are the two enzymes that metabolize warfarin?

A
  1. CYP2C9
  2. VKORC1
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13
Q

What do variant alleles of CYP2C9, such as CYP2C9*2 or CYP2C9*3, do to the metabolism of warfarin?

A

They inhibit metabolism leading to ⇡ warfarin concentrations.

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14
Q

60-70% of breast cancers express what receptors?

A
  • Estrogen Receptors (ERs)
  • Progesterone Receptors (PRs)
  • HER2
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15
Q

What breast cancer receptors indicated a less aggressive breast cancer?

A
  • Estrogen Receptors
  • Progesterone Receptors
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16
Q

Which breast cancer receptors indicate a more aggressive cancer?

A

HER-2 receptors.

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17
Q

What deprivation treatment is used for breast cancer?

A

Estrogen Deprivation

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18
Q

What drugs are used in Estrogen Receptor + tumors?

A
  • Tamoxifen
  • Aromatase Inhibitors
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19
Q

What happens to the number of HER-2 receptors in 15-25% of breast cancers? What is the result?

A
  • HER-2 is 2-20x more prevalent on the cell surface.
  • More receptors means greater cell proliferation.
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20
Q

What drug do HER2 cancers respond to? How does this drug work?

A
  • Herceptin (Trastuzumab)
  • Trastuzumab (a monoclonal antibody) binds to HER2 receptor and shuts it down.
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21
Q

Name 3 purine analogs?

A
  • Azathioprine
  • 6-Mercaptopurine
  • 6-Thioguanine
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22
Q

What are examples of solute carrier (SLC) proteins? What percentage of membrane proteins are SLC’s?

A
  1. Couple transporter, Exchanger, Passive transporter, etc.
  2. 15-30% of all membrane proteins are SLC’s
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23
Q

How were drug efflux transporters discovered? What are some characteristics of drug efflux pumps? Why do they exist?

A

Drug efflux transporters were found by researching people developing resistance to antineoplastics (anti-cancer drugs).

  • Broad substrate specificity ( Works on lots of different drugs)
  • Cellular survival mechanism
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24
Q

What is the most common family of Drug Efflux Transporters? Is there a lot of research in this area?

A
  • ATP-Binding Cassette (ABC) Transporters
  • Yes, very intense area of research.
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25
Q

What are the three major ABC family drug efflux transporters?

A
  • ABCB
  • ABCC
  • ABCG
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26
Q

What substrate specificity does ABCB1 have? Where are these transporters located? Maintenance of what critical system is enforced by ABCB1 transporters?

A
  • The broadest specificity ( everything from antineoplastics and antibiotics to opioids and HIV drugs)
  • GI, Kidney, Liver, Testes (They’re spread out in a lot of places)
  • Blood Brain Barrier.
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27
Q

Why are there no CNS effects when loperamide (an opioid) is given? What happens if Quinidine is given in conjunction with loperamide?

A
  • ABCB1 moves loperamide out of the system before it can be converted to morphine.
  • Quinidine is an ABCB1 inhibitor → Loperamide becomes systemic → CNS affected & respiratory depression.
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28
Q

What class of ABC transporters is the largest? What drugs does it efflux?

A

ABCC’s. These transporters efflux antineoplastics.

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29
Q

What led to the discovery of ABCG2? What drugs does the ABCG2 transporter efflux? What vitamin is influxxed by this transporter? Why?

A
  • ABCG2 was discovered for being a breast cancer antineoplastic resistant protein (but it does more than just work with breast cancer cells.)
  • Antineoplastics, toxins, and food borne carcinogens.
  • Folate is influxed by this transporter so that the cancer cell can grow.
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30
Q

What’s the most important non-ABC Drug Efflux Transporters? What is the important sub-type associated with this family?

A
  • SLC21 family which includes:
  • OATPs (organic anion transporter proteins)
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31
Q

What are the physical components of the blood brain barrier that prevent drugs from entering the brain tissue?

A
  1. Astrocytes
  2. Podocytes (effectively a macrophage)
  3. Tight junctions in the capillaries preventing leaking.
  4. Protein Efflux Barrier
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32
Q

Is the blood brain barrier weaker than the Spinal CSF barrier? Can drugs be administered into the CSF? What about antineoplastics in the CSF?

A

No, The Spinal CSF barrier has less effluxive proteins.

Yes, intrathecal drugs like bupivicaine.

No, Anti-cancer drugs administered in the CSF have been infeffective.

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33
Q

What is the most common transporter in the GI tract? Where are your GI tract transporters localized and how many things do they let in?

A
  • ABCG2
  • These transporters are in the microvilli and let most things in.
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34
Q

Which ABC transporter moves out glucuronidated drugs from hepatic metabolism? Give an example.

A

ABCC Transporters

Acetaminophen absorbed past ABCC → Glucuronidation → Glucuronide+Acetaminophen effluxed by ABCC.

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35
Q

What type of protein transports are found in the liver?

A
  • SLC Type OATPs
  • ABCs (all types)
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36
Q

Which ethnic group has ABCB1 polymorphisms affecting Fentanyl efflux?

A

Ethnic Koreans

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37
Q

What ABC Transporter has the broadest substrate specificity and what does this mean? What are other names for this specific ABC? Where is this ABC found?

A
  1. ABCB1, broad specificity means it works on a bunch of different things
  2. MDR1 and p-Glycoprotein
  3. Everywhere (GI, Kidney, liver, testes, etc.)
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38
Q

Which ABC Transporter is critical in maintaining the blood brain barrier?

A

ABCB1

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39
Q

What is the most important thing that separates brain vascular endothelial cells from other vascular endothelial cells? How?

A

Tight Junctions. These prevent the movement of things out of the vascular endothelium from between the endothelial cell space.

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40
Q

What transporter proteins are located in the liver? Where are effluxed drugs/toxins/etc dumped?

A
  • SLCs (essentially OATPs)
  • ABCs (all)

Effluxxed drugs/toxins/etc are dumped into the bile where they will be passed into the feces.

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41
Q

Muscarine is highly charged, this means that effects are seen where? Does Muscarine affect the ganglia?

A

Effects are seen at PNS rather than CNS (hydrophilicity prevents passage through BBB)

No, only the effector tissue.

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42
Q

Nicotine affects the __________ and the _______ rather than ________.

A

Autonomic Ganglia. - Skeletal Muscle NMJ. - Effector tissue.

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43
Q

What makes nicotine able to cross the BBB?

A

Lipophilicity

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44
Q

Which muscarinic receptors are stimulatory? Inhibitory?

A

Stimulatory = M 1,3,5

Inhibitory = M 2,4

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45
Q

What are the esters of choline? What is a major characteristic of these cholinomimetics?

A
  1. ACh
  2. Methacholine
  3. Carbachol
  4. Bethanechol

All Esters of Choline are charged and thus unable to cross the BBB.

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46
Q

What is ACh as a drug used for? Why is not used for anything else?

A

Pupillary Constriction

ACh is broken down too quickly by AChE.

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47
Q

What is the use of Methacholine?

A

Asthma Diagnosis by bronchoconstriction

If Forced Vital Capacity is decreased after methacholine is given then = asthma

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48
Q

What is Carbachol used for?

A

Decreasing Intraocular Pressure

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49
Q

What is Bethanechol used for?

A

Urinary retention

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50
Q

What is the order of Choline Ester metabolism from shortest excretion to longest excretion?

A
  1. ACh (rapid)
  2. Methacholine (fast)
  3. Carbachol/Bethanechol (slow)
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51
Q

What should be known about betel nuts?

A

Addictive nut to chew similar to nicotine.

leaves mouth red

parasympathetic agonist

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52
Q

Where are alkaloids excreted? What would enhance excretion?

A

Kidneys

Urine acidification (alkaloids are basic)

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53
Q

What are the two sub-groups of Direct-acting Cholinergic Drugs?

A
  1. Esters of Choline
  2. Alkaloids
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54
Q

What is an alkaloid in regards to cholinoceptor drugs? Which drugs should be known?

A

Alkaloids = Basic pH and plant-based

  1. Muscarine
  2. Nicotine
  3. Pilocarpine
  4. Lobeline
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55
Q

What are the effects of muscarinic agonists in regard to the eye? What is the result of this?

A

Myosis (pupillary constriction)

⇡ aqueous humor drainage

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56
Q

What are the cardiac effects of muscarinic agonists?

A

⇣ SVR with reflexive ⇡ HR

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57
Q

How many cases of glaucoma are open angle? How many are closed angle? What drug can never be given in closed angle glaucoma? Why?

A

90% open angle

10% closed angle

Atropine can never be given as it relaxes the ciliary muscle and blocks flow of aqueous humor out of the canal of Schlemm.

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58
Q

Will direct-acting cholinergics have CNS effects? What is the exception?

A

No, too charged to cross BBB.

Nictotine is exception due to lipophilicity.

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59
Q

What neurotransmitters does Nicotine release? What could large-toxic doses of nicotine cause?

A

Dopamine (thus addictiveness), Serotonin, GABA, and NE

Larger Doses = Ingestion = Tremor, emesis, convulsions, coma.

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60
Q

What Nicotinic Receptor Agonist causes paralysis? How? What is this drug’s structure?

A

Succinylcholine.

Immediate Muscular Depolarization that causes the muscle to “fasciculate”.

Two ACh molecules end to end.

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61
Q

What are the three Cholinomimetics in order of duration of action?

A
  1. Simple alcohols - 5-15 min
  2. Carbamic acid esters of alcohols - 0.5 - 6 hours
  3. Organophosphates - Days to weeks
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62
Q

What is the rapid-acting cholinomimetic? What is its use?

A

Edrophonium - used in diagnosis of myasthenia gravis

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63
Q

What are the 3 Cholinomimetics with an intermediate duration of action? What is the main use of these drugs?

A
  1. Neostigmine -
  2. Pyridostigmine
  3. Physostigmine

Reversal of paralysis from -curare derivatives.

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64
Q

What makes organophosphates duration of action so long? What are they used for?

A

Covalent bond forming at the active site.

As insecticides

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65
Q

Is there a reversal for organophosphate poisonings? What are considerations?

A

Yes, Pralidoxime (strong nucleophile)

Has to be given within the first 1-2 hours of poisoning to break bond.

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66
Q

What is “aging” in regards to organophosphates?

A

This concept refers to organophosphate bonding getting stronger over time.

Pralidoxime becomes ineffective after aging occurs.

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67
Q

What is the pathophysiology of myasthenia gravis? What are the symptoms? What is the treatment?

A

Progressive loss of ACh receptors.

Muscle weakness, worsens with exercise.

AChE inhibitors to produce more ACh at NMJ sites.

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68
Q

What drug is used as a diagnostic test for Myasthenia Gravis? How is this done?

A

Edrophonium

  1. Baseline muscle strength test
  2. Edrophonium is given.
  3. Muscle strength is reassessed, if improved then test is + for MG.
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69
Q

What two AChE inhibitors are given for reversal of paralytic ileus? Which one is generally avoided?

A

Neostigmine and Physostigmine

Physostigmine is generally avoided because of CNS effects.

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70
Q

What are the symptoms of parasympathetic toxicity? What is the antidote?

A

SLUDGE-M

  • Salivation
  • Lacrimation
  • Urination
  • Defecation
  • Gastroenteritis
  • Emesis
  • Myosis

Atropine is antidote

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71
Q

What are the signs of Cholinesterase inhibitor toxicity? What are the 3 steps in treating Cholinesterase inhibitor toxicity? What is the most common cause?

A

SLUDGE-M

  1. Vital sign maintenance
  2. Decontamination
  3. Atropine, then Pralidoxime (if organophosphate toxicity)

Insecticides

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72
Q

What two drugs are given as auto-injectors to military personnel for Sarin gas exposure?

A

Atropine and Pralidoxime

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73
Q

What is the most important anticholinergic drug? What is this drug derived from? How potent is this plant?

A

Atropine

Derived from Atropa Belladona (Nightshade)

Plant isomer is 100x more potent than racemic drug

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74
Q

What anticholinergic crosses the blood brain barrier? This makes it useful for what?

A

Scopolamine; useful for motion sickness.

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75
Q

What AChE inhibitor is useful for its bronchodilating effects?

A

Atrovent (Ipratropium Bromide)

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76
Q

What drug is used for pupillary dilation? What is its duration of action?

A

Tropicamide for Mydriasis (dilation of pupil)

Duration of action is 4 hours

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77
Q

What are contraindications to atropine use?

A

Closed Angle Glaucoma

Benign Prostatic Hyperplasia

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78
Q

What are the signs/symptoms of anticholinergic toxicity?

A

Hot, blind, dry, red and mad

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79
Q

What paralytic agent is characterized by continuous end-plate depolarization?
What are the indications for this drug?

Describe the two phases of this drug.

A

Succinylcholine

RSI and electroconvulsive therapy

Phase I = continuous depolarization causing relaxation

Phase 2 = repolarization occurs, ⇡ risk of ⇡K+ if more succ is given

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80
Q

What is the mechanism of action of -curare derivatives?

A

Competitive Antagonism of ACh at binding sites

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81
Q

Why would succinylcholine be given over the -curare derivates?

A

Very short duration of action. Essentially only to facilitate intubation

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82
Q

What drugs reverse Neuromuscular Blocking agents?

A

Neostigmine

Sugammadex (only for Vec and Roc, traps drugs like an ionophore)

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83
Q

Why would a drug be given that causes prolonged mydriasis?

A

To promote relaxation of ciliary muscle for healing.

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84
Q

Where is blood shunted away from in a sympathetic response?

A

Non-vital organs and systems (ex. endocrine, GI, and urogenital)

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85
Q

What is the scientific term for the “rest and digest” phenomenon of the parasympathetic nervous system?

A

Trophotropic

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86
Q

Long pre-ganglionic with short post-ganglionic nerve fibers is indicative of what branch of the ANS?

A

Parasympathetic Branch

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87
Q

Short pre-ganglionic with long post-ganglionic is indicative of which branch of the ANS?

A

Sympathetic Branch

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88
Q

Which two groupings of spinal nerves innervate the parasympathetic system? Which specific cranial nerve innervates 75% of the parasympathetic system?

A

Cervical and Sacral nerves.

Cranial nerve X (Vagus nerve)

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89
Q

Which two groupings of spinal cord nerves innervate the sympathetic system?

A

Thoracic and Lumbar

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90
Q

What is the primary feature of chain ganglia? Which portion of the ANS do these work with?

A

Chain Ganglia allow for rapid activation of multiple spinal nerves at once.

Sympathetic Nervous System

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91
Q

What nerve is responsible for 75% of all parasympathetic output?

A

Vagus Nerve (CN X)

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92
Q

What are the neurotransmitters of the GI tract?

A
  1. Serotonin
  2. Substance P
  3. Endorphins
93
Q

What organ system contains more serotonin that the CNS?

A

GI Tract

94
Q

Sympathetic input is _______ to the Enteric Nervous System?

A

Inhibitory

95
Q

Do we have drugs that target the enteric nervous system?

A

No

96
Q

What neurotransmitter(s) are released by the post-ganglionic fibers of the Autonomic Nervous System? What effects do the neurotransmitter(s) have? What is the effect dependent on?

A
  • ACh and NE
  • Effect can be inhibitory or stimulatory
  • Effect is dependent on receptor type
97
Q

What are some examples of direct-acting sympathomimetics? What makes these drugs “direct-acting”?

A
  • Epinephrine, Isoprotenerol, Albuterol, etc.
  • The drugs are direct-acting because they bind directly to the α and β receptors of the SNS.
98
Q

What drugs are examples of indirect sympathomimetics? What makes these drugs “indirect-acting” sympathomimetics?

A
  • Ephedrine, Amphetamines, Cocaine, etc.
  • These drugs do not bind directly to α or β sites directly.
99
Q

How do indirect-acting sympathomimetics cause an effect?

A

Release stored NE and/or Replace NE on NET → ⇡ circulating NE available at synapse.

100
Q

What are 4 common effects of direct and indirect-acting sympathomimetics?

A
  1. Vasoconstriction
  2. Inotropy and Chronotropy
  3. Bronchodilation
  4. Uterine relaxation. (suppress premature labor).
101
Q

How do sympatholytic drugs differ from sympathomimetic drugs?

A

Sympatholytic drugs inhibit the transmission of neurotransmitters in the SNS.

102
Q

What’s an example of an α-specific sympatholytic drug? What is the effect of giving this drug?

A

Phentolamine - peripheral vasodilation

103
Q

What’s an example of a β-specific sympatholytic drug? What is the effect of giving this drug?

A

Propanolol - suppressed inotropy and chronotropy.

104
Q

What enzyme breaks down ACh?

A

ACh esterase

105
Q

What are the two types of cholinergic receptors? What neurotransmitter binds to cholinergic receptors?

A
  1. Muscarinic
  2. Nicotinic

ACh binds to cholinergic receptors

106
Q

What are the 3 types of Adrenergic receptors?

A
  1. α - receptors
  2. β - receptors
  3. Dopamine - receptors
107
Q

How many Muscarinic receptors are there (that we need to know about)?

A

5 total (M1 - M5)

108
Q

How many Nicotinic receptors are there?

A

NM and NN

aka

Nicotinicmuscle & Nicotinicneuronal

109
Q

Where do we find NM receptors?

A

The Neuromuscular Junctions

110
Q

Where do -curare derivates work to produce paralytic effects? How? Where were these drugs derived from originally?

A

-curare derivates induce paralysis by blocking ACh at the Nn receptors, preventing skeletal muscle contraction.

Poison dart frogs.

111
Q

Where are α-1 receptors located primarily?

A

Peripheral Vasculature

112
Q

Where are α-2 receptors located primarily?

A

CNS

113
Q

Where are β-1 receptors located primarily?

A

Heart

114
Q

Where are β-2 receptors found?

A

Lungs

115
Q

Where are β-3 receptors found?

A

Adipose tissue.

116
Q

How many Dopamine receptors are there? Where are these primarily located?

A

5 Receptors (D1 - D5)

Brain and Renovascular capillary bed.

117
Q

What general type of receptor are all α and β receptors?

A

GPCRs

118
Q

What is the signal transduction pathway for α-1?

A

α-1 → GQ → PLC → IP3 and DAG

α-1 → GPCR α-subunit Q → phospholipase C → IP3 and DAG

119
Q

What is the signal transduction pathway for α-2 receptors?

A
  1. α-2 → GI (inhibitory)
  2. → Inhibition of adenylate cyclase, Ca++, and K+
  3. → ⇣ cAMP
120
Q

What is the signal transduction pathway for all β receptors?

A

β-1,2,3 → GS → stimulation of adenylate cyclase and Ca++ channels → ⇡cAMP

121
Q

What is the signal transduction pathway for M1 M3 and M5 receptors?

A

M1,3,5 → GQ → Phospholipase activation w/ DAG and IP3

122
Q

What is the signal transduction pathway for M2 and M4 receptors in a cardiac myocyte?

A

M2 → Gi → Inhibition of AC → ⇣cAMP = ⇣ Inotropy & Chronotropy

123
Q

What are NANC neurons? What neurotransmitters do these neurons use?

A
  • Non-adrenergic, non-cholinergic neurons.
  • NOS, Substance P, Somatostatin, etc. (there are lots)
124
Q

In α-1 receptors MLCP is _______, and MLCK is ______, Thereby causing _____.

A
  1. Inhibited
  2. Potentiated
  3. Vasoconstriction
125
Q

In a β-2 receptor of the lungs cAMP is released and ______ MLCK, producing ______.

A
  1. Inhibits
  2. Bronchodilation
126
Q

Myosin Light Chain Kinase (MLCK), in general, will cause _______.

A

Smooth Muscle Contraction

127
Q

Myosin Light Chain Phosphatase (MLCP), in general, wil cause ______.

A

Smooth muscle relaxation.

128
Q

What receptor is going to inhibit continued activation of β-1 and β-2 receptors by NE? Where is this receptor located?

A

α-2 will inhibit continued β stimulation through a negative feedback loop

the α-2 receptor is located on the sympathetic nerve that is delivering NE to the tissue site.

129
Q

What is the signal transduction pathway for β receptors in a cardiac myocyte?

A
  1. NE binds to β-receptor
  2. Gs → cAMP
  3. cAMP → PK (Protein Kinase)
  4. PK → ⇡Ca++ → Contraction
130
Q

What is the scientific term for our “Fight or Flight” response?

A

Ergotropic Response

131
Q

Where do baroreceptors send their signals?

A

Hypothalamus Vasomotor center

132
Q

What response would be elicited from activation of an M3 receptor on the Bronchiolar smooth muscle? What would be the purpose of this response?

A

Bronchiolar Contraction

This helps keep debris from getting deep into the lungs.

133
Q

Overstimulation of the M3 receptor would have what effect on the GI tract?

A

Increased secretions = Diarrhea.

134
Q

A β-1 receptor activation would have what response on the kidneys?

A

Renin release

135
Q

A β-2 receptor activation would have what response on the bladder?

A

Relaxation

136
Q

Activation of which receptor would cause decreased inotropy and chronotropy?

A

M2

137
Q

Activation of which receptor would cause smooth muscle in the peripheral vasculature to contract? How about dilate?

A

α1 = Contraction

M3 = Relaxation

138
Q

Activation of which receptor would cause contraction of the GI lining (stomach, intestines, etc.) ?

Which receptors, if activated, would have the opposite effect ?

A

M3 activation = GI contraction & food movement

α-2 , β-2 activation = GI relaxation & food stasis

139
Q

If GI muscle is contracted what happens to corresponding sphincters? Why?

A

Sphincters are relaxed, this is to allow for passage of food.

GI sphincter relaxation = PSNS

GI sphincter contraction = SNS

140
Q

Cholinomimetics will potentiate the _______.

A

Parasympathetic system

141
Q

Parasympatholytics (or Antimuscarinics) will inhibit the ________.

A

Parasympathetic system

142
Q

What is the defining characteristic of En Passant synapses? Where do we primarily find these?

A

En Passant synapses are synapses interacting with other neurons that occur along the length of the axon.

CNS

143
Q

What two organelles are often found at the terminal end of a neuron at the synapse?

A

Mitochondria for ATP

Endoplasmic Reticulum for neurotransmitter creation

144
Q

What are the 4 “fates” that end a neurotransmitter’s life?

A
  1. Diffusion away from synapse
  2. Enzyme degradation (ACh esterase)
  3. Re-uptake into pre-synaptic cell
  4. Uptake into target cell
145
Q

What are the 6 Neurotransmitter classes and what is an example of each?

A
  1. Esters (ACh)
  2. Monoamine (Epi, Dopamine, etc.)
  3. Amino Acids (GABA)
  4. Purines (Adenosine)
  5. Peptides (Substance P, Endorphins, etc.)
  6. Inorganic Gasses (Nitric Oxide)
146
Q

Which of the Amino Acid neurotransmitters is inhibitory? Excitatory?

A

GABA = Inhibitory

Glutamate = Excitatory

147
Q

NM receptors utilize what kind of membrane protein?

A

Ion channels

148
Q

NN utilize what kind of membrane channel?

A

GPCR’s

149
Q

What food is high in choline?

A

eggs

150
Q

What CNS effects are commonly associated with dopamine?

A

Reward and Pleasure

151
Q

Low levels of this transmitter are associated with depression. What is given to counteract the low levels?

A

Serotonin

SSRI’s

152
Q

What is the most important excitatory amino acid neurotransmitter in the brain? What brain functions is it necessary for? What are its receptor types and their corresponding transmembrane channel type?

A

Glutamate

Learning and Memory

  1. AMPA = Ion channel
  2. NMDA = Ion channel
  3. Metabotropic = GPCR + Ion channel
153
Q

Which inhibitory amino acid neurotransmitter is associated with strychnine poisoning? How?

A

Glycine

  1. Glycine is inhibitory to contraction
  2. Strychnine antagonizes Glycine
  3. Excessive contraction = Convulsions
154
Q

What is the most important inhibitory neurotransmitter? How does this relate to general anesthetics?

A

GABA

Many general anesthetics increase GABA activity

155
Q

What class of drug is given for a lack of NE in the CNS?

A

SNRI’s

(Serotonin/Norepinephrine Reuptake Inhibitors)

156
Q

What are the two neuropeptide pain signaling neurotransmitters?

A

Substance P and CGRP

157
Q

What endogenous neuropeptide is involved with pain control? What are the two subgroups?

A

Endogenous opioids

Endorphins and Enkephalins

158
Q

Excitatory neurotransmitters cause ________. What is the number 1 excitatory neurotransmitter of the CNS?

A

Depolarization

Glutamate

159
Q

Inhibitory neurotransmitters cause ________. What are the two most important inhibitory neurotransmitters?

A

Hyperpolarization

GABA and Glycine

160
Q

What are the two components of ACh? What enzyme combines these two?

A

Acetyl-CoA and Choline

ChAT (Choline Acetyl-transferase)

161
Q

How many molecules of ACh are present in each secretory vesicle present at a synapse?

A

1000 - 50,000 ACh molecules

162
Q

How does Acetylcholinesterase (AChE) split an ACh molecule? What are the two binding sites?

A
  1. Anionic Site - Ionic Bonding of the Nitrogen on the Choline.
  2. Esteric Site - H-Bonding of the ester group
163
Q

What transporter brings Choline into a pre-synaptic cell? What else is brought in? This makes it a what?

A

ChT (Choline Transporter)

Na+ and Choline

Symporter or Co-Transporter

164
Q

What transporter pulls ACh into the secretory vesicle?

A

VAT

165
Q

What are the 3 main steps of vesicular exocytosis of ACh? Summarize each step.

A
  1. Docking - getting ACh into vesicle
  2. Priming - SNAPs + VAMPs = Vesicular Anchoring
  3. Fusion - Action potential → Ca++ release → Exocytosis
166
Q

What are the two components that allow for fusion to occur between a secretory ACh vesicle and the presynaptic membrane?

A

Ca++ and Synaptotagmin?

Need to verify

167
Q

What happens if ACh is not broken down by AChE?

A

Flaccid paralysis

168
Q

What organelle is Acetyl-CoA found in?

A

Mitochondria

169
Q

What are the two primary SNARE proteins? What is the purpose of a SNARE protein?

A

Syntaxin and SNAP-25

Located on the presynaptic cell membrane and “anchor” the vesicle to the membrane.

170
Q

What protein, located on the secretory vesicle, interacts with the cell membrane to anchor the vesicle? What proteins does this specific protein bind to?

A

VAMP (Vesicular associated Membrane Protein)

SNAP’s

171
Q

What molecule binds to Ca++ and allows for rapid exocytosis of a secretory vesicle?

A

Synaptotagmin

172
Q

What does Vesamicol inhibit?

A

VAT (preventing ACh from entering secretory vesicle)

173
Q

What does Botulinum Toxin (Botox) inhibit?

A

SNAPs and VAMPs

174
Q

What is the lethal does of botulinum?

A

1 ng/kg

175
Q

What does Sarin (nerve gas) inhibit? What is the result of this?

A

AChE

Convulsions, flaccid paralysis, and eventual suffocation

176
Q

What drug class blocks CHT and is essentially only used for research purposes?

A

Hemicholiniums

177
Q

What is the pathophysiology of Myasthenia Gravis?

A
  1. Autoimmune disease destroys ACh receptors.
  2. Fewer receptors → muscle weakness → paralysis
178
Q

How is myasthenia gravis treated?

A

AChE inhibitors → more ACh available for the fewer receptors

179
Q

What amino acid is a precursor to almost all adrenergic neurotransmitters?

A

Tyrosine

180
Q

What is the largest difference between adrenergic and cholinergic transmission, in regards to how the neurotransmitter for each is broken down?

A

ACh broken down in synapse by AChE

NE broken down inside presynaptic cell by MAO

181
Q

What transporter pulls adrenergic neurotransmitters into their secretory vesicles?

A

VMAT (Vesicular MonoAmine Transporter)

182
Q

Which adrenergic inhibitors are no longer widely used?

A

Metyrosine - Inhibits tyrosine conversion

Reserpine - Inhibits VMAT

Bretylium / Guanethedine - Inhibits exocytosis

183
Q

What is the mechanism of action of cocaine and tricyclic antidepressants?

A

Inhibition of NET (and inhibit reuptake of serotonin too)

184
Q

How do indirect-acting adrenergic agonists elicit an effect?

A

By increasing NE at the synapse

185
Q

A Catecholamine’s organic chemistry structure is characterized by a benzene ring with hydroxyl groups at ___ and ___ as well as an ____ side chain.

A

3 position, 4 position, amine group

186
Q

What enzyme are catecholamines inactivated by? Where is this enzyme found that makes this route of administration essentially useless?

A

COMT (catechol-O-methyltransferase)

GI tract, catecholamines not given via PO because they are broken down too quickly in the gut.

187
Q

Does norepinephrine have a bronchodilating effect?

A

No, NE has no β-2 activity

188
Q

Agonist binding of an α-1 receptor elicits?

A
  1. Release of Ca++
  2. VasoConstriction
189
Q

β agonist binding produces what effect? How does this affect the Heart vs the Lungs?

A

β-agonist binding = ⇡ cAMP

increased cAMP = ⇡ Inotropy

increased cAMP = bronchodilation

190
Q

α-2 binding produces what effects?

A
  • ⇣cAMP
  • increased contraction (CNS effects drop BP past this)
  • decreased Inotropy
191
Q

What is the mechanism of action of methamphetamine?

A

Methamphetamine reverses reuptake of NE at the synapse increasing available NE.

(It also does the same with dopamine, 80% addicted on first dose)

192
Q

What is the mechanism of action of cocaine?

A

Cocaine blocks reuptake of NE at the synapse increasing available NE.

(20% addicted on first dose)

193
Q

What is the formula for cardiac output? What numbers are normally used?

A

CO (ml/min) = SV (70ml/beat) x HR (75beats/min)

194
Q

What effect do these drugs have on the eye?

  1. α-1 agonist
  2. β-agonist
  3. β-antagonist
A
  1. α-1 agonist = dilation
  2. β-agonist = little effect
  3. β-antagonist = decrease aqueous humor
195
Q

What are CNS effects of catecholamines?

A

Nervousness and feelings of doom ONLY in large doses

Little effect in lower doses.

196
Q

What makes dopamine triphasic?

A
  1. Low dose = Renal dilation and diuresis
  2. Moderate dose = Inotropy
  3. High dose = Vasostriction
197
Q

What is the main difference between norepinephrine and epinephrine?

A

Norepinephrine has no β-2 activity

198
Q

Which potent β-agonist has vasodilatory effects?

A

Isoproterenol

199
Q

Which β-1 agonist has indication for acute heart failure and cardiogenic shock?

A

Dobutamine

200
Q

What is phenylephrine and its mechanism of action?

A

Phenylephrine is a non-catecholamine pure α1-agonist.

201
Q

What is a “TET” spell?

What is a non-pharmacologic treatment?

What is the pharmacologic treatment?

A

Tetralogy of Fallot hypoxic episode.

“Squatting” forces blood back into RV

Phenylephrine

202
Q

What is midodrine and what is it’s indication?

A

α-1 receptor indirect-agonist (metabolite binds to α)

Utilized for orthostatic hypotension

203
Q

What is ephedrine? What is its mechanism of action? Does this drug cross the BBB?

A

Orally active non-catecholamine

  • Releases stored catecholamine and mimics epinephrine.
  • No.
204
Q

What class of sympathomimetics readily enters the CNS and has much greater CNS effects compared to PNS effects? What are general effects from these drugs when given in proper dosages?

A

Amphetamines

Improved focus, attention, and mood.

205
Q

What mild sympathomimetic has high concentrations in fermented foods? What metabolizes this compound? What drugs can increase BP significantly due to their interactions with this compound?

A
  • Tyramine
  • MonoAmine Oxidase (MAO)
  • MAOI’s can ⇡ BP if taken in conjuction with eating fermenteed foods.
206
Q

Which three organs are most dependent on consistent perfusion?

A

Brain, Heart, and Kidneys

207
Q

What α-2 agonist is useful for sedation?

A

Dexmedetomidine

208
Q

Which α-2 agonist is useful as a muscle relaxant?

A

Tizanidine

209
Q

Which α-2 agonist is useful for treating HTN, diarrhea, and hot flashes?

What use might this drug have during anesthesia?

A

Clonidine

Treats hemodynamic instability in anesthesia

210
Q

Which alpha antagonist is irreversible?

A

Phenoxybenzamine

211
Q

Which α-antagonists are reversible?

A
  • Phentolamine
  • Tolazoline
  • Prazosin
  • Labetalol
212
Q

What is a primary use for non-selective α-antagonists? What is a secondary use? What are the adverse effects of these drugs?

A
  • Decreasing BP in people with pheochromocytoma
  • Male erectile dysfunction and priapism.
  • Abdominal pain (↑ GI motility), N/V/D, cardiac stimulation
213
Q

Which α-antagonist drugs are useful for treating BPH?

A

-osin drugs (tamsulosin, prazosin, etc.)

214
Q

What are the two non-selective α-antagonist drugs? Which is irreversible?

A

Phentolamine
Phenoxybenzamine (irreversible)

215
Q

Which two α-2 selective drugs are marketed for penile blood flow but don’t really work?

A
  • Ergotamine
  • Yohimbine
216
Q

What would happen if epinephrine and phentolamine were given at the same time?

A

HR would ↑ and BP would ↓

217
Q

Which of the -osin drugs can be used for both HTN and BPH?

A

Prazosin

218
Q

Chronic use of β-blocker therapy usually indicates usage of what other class of drug? Why?

A

Statins
Chronic β-blocker use ↑ VLDL, and ↓ HDL

219
Q

What are the effects of β-blockers on asthma patients?

A

↑ bronchostriction = bad for asthma patients

220
Q

What are the effects of β-blockers on eyes?

A

↓ intraocular pressure

221
Q

What are the effects of β-blockers on metabolism?

A

Lipolysis inhibition (β3)
Glycogenolysis inhibition (↑ lipids)

222
Q

What are the two main things that should be known about Propanolol?

A
  • Non-selective β-blocker w/ long-acting form
  • Extensive 1st pass metabolism
223
Q

What should be known about metoprolol?

A

Cardio-selective β-blocker
Safer in COPD & Diabetes

224
Q

What should be known about nebivolol?

A

most cardio-selective β-blocker

225
Q

What should be known about Nadolol?

A

Long acting and non-selective

226
Q

What should be known about Labetolol?

A

α and β activity
racemic mixture

227
Q

What β-blocker is useful during surgery? Why? What does it treat?

A

Esmolol
- β-1 selective
- Ultra short acting
- Treats intraoperative SVT and tachycardia

228
Q

What β-blocker requires weaning when switching to a new medication?

A

Propanolol

Pharmacology fall 2024 (23 decks)

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