Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Unit 3 > Pharm > Flashcards

Pharm Flashcards

1
Q

Precursor molecule to dopamine?

A

Tyrosine

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

Where/how are dopamine molecules stored?

A

Stored in vesicles by VMAT2

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

Mechanism of dopamine synthesis and storage

A
  1. Tyrosine is taken up into dopamine nerve terminals via tryosine transporter
  2. Conversion into DOPA via tyrosine hydroxlyase (TOH)
  3. DOPA –> dopamine via DOPA decarboxylase (DDC)
  4. Dopamine is packaged into synaptic vesciles via vesicular monamine transporter (VMAT2)
  5. Stored until its release into the synapse during neurotransmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

DOPA decarboxylase (DDC)

A

Turns DOPA –> dopamine

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

tyrosine hydroxlyase (TOH)

A

converts tyrosine into DOPA

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

Mechanism of clearing dopamine once released from snaptic vesicles

A
  1. DAT (dopamine transporter) - reuptake transporter
  2. catechol-O-methyl-transferase (COMT) - breaks down dopamine extracellularly
  3. MAO-A or MAO-B (monoamine oxidase A/B) - present in mitochondria within the presynaptic neurons, breaks down dopamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

receptor responsible for reuptake of dopamine from the synaptic terminal

A

DAT (dopamine transporter)

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

responsible for the breakdown of dopamine extracellularly

A

catechol-O-methyl-transferase (COMT)

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

What breaks down dopamine intracellularly and where does it happen?

A

monoamine oxidase A/B - located within mitochondria of the presynaptic neuron

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

Where is the majority of the dopamine produced? (what area of the brain)

A

substantia nigra

Ventral tegmentum also produces a small amount but majority is in the substantia

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

What dopamine pathway controls movement?

A

Nigrostriatal (substantia nigra to striatum) pathway

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

Nigrostriatal (substantia nigra to striatum) pathway

A

controls motor function and movement

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

What happens if the nigrostriatal dopamine pathway is dying or inhibited/blocked?

A

Parkinson-like symptoms

This is the pathway that is insufficient in Parkinsons disease

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

mesolimbic dopamine pathway

A

Midbrain ventral tegmental area –> nucleus accumbens

Controls behaviors such as:

  • pleasurable sensations
  • the powerful euphoria of drugs of abuse
  • delusions and hallucinations of psychosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which dopamine pathway controls reward and perception?

A

mesolimbic dopamine pathway

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

Which pathway is associated with the mesolimbic dopamine pathway?

A

mesocortical dopamine pathway

Also projects from the midbrain ventral tegmental area, but sends axons to areas of the prefrontal cortex where they play roles in mediating symptoms of schizophrenia

  • cognitive symptoms (via the dorsolateral prefrontal cortex (DLPFC))
  • affective symptoms (via the ventromedial prefrontal cortex (VMPFC))
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

mesocortical dopamine pathway

A

Projects from the midbrain ventral tegmental area, but sends axons to areas of the prefrontal cortex where they play roles in mediating symptoms of schizophrenia

  • cognitive symptoms (via the dorsolateral prefrontal cortex (DLPFC))
  • affective symptoms (via the ventromedial prefrontal cortex (VMPFC))

Overall: controls executive function

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

Where does the mesocortical dopamine pathway project from and to?

A

From: ventral tegmental area

To:

dorsolateral prefrontal cortex – cognitive symptoms

ventromedial prefront cortex – affective symptoms

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

tuberoinfundibular dopamine pathway

A

projects from the hypothalamus to the anterior pituitary gland and controls prolactin secretion

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

Which dopamine pathway controls pituitary prolactin secretion?

A

tuberoinfundibular dopamine pathway

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

Major Dopamine pathways

A
  1. Nigrostriatal – controls movement
  2. Mesolimbic – controls reward and perception
  3. Mesocortical – controls executive function
  4. Tuberoinfundibular – controls pituitary prolactin function
  5. Thalamic – function unknown. arises from multiple sites projecting onto the thalamus.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What occurs if there is hypo/hyper functioning of the mesolimbic dopamine pathway?

A

Hypo – amotivation, apathy

Hyper – addiction, hallucinations

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

What occurs if there is hypo/hyper functioning of the mesocortical dopamine pathway?

A

Hypo – inattention

hyper – hypervigilance

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

What occurs if there is hypo/hyper functioning of the nigrostriatal dopamine pathway?

A

Hypo – dyskinetic movement, parkinsonism

hyper – dyskinetic movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What occurs if there is hypo/hyper functioning of the tuberoinfundibular dopamine pathway?

A

Hypo – hyperprolactinemia

hyper – hypoprolactinemia

Remember: dopamine naturally inhibits the secretion of prolactin, hence the negative correlation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Schizophrenia - what is occuring (in terms of brain activity) in the pre-frontal cortex?

A

DorsolateralPrefrontalCortext (DLPFC) is hypoactive.

VentromedialPrefrontalCortex (VMPFC) is hyperactive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What happens to dopamine levels in ADHD? Where does it mainly take place?

A

Loss of dopamine activity in anterior cingulates

28
Q

catechol-O-methyl-transferase (COMT)

A

responsible for the majority of the breakdown of dopamine extracellularly

29
Q

Dopamine enhancing drugs

A

Levodopa – precursor to dopamine (DA) and is freely able to cross the blood-brain barrier

Carbidopa – an agent often combined with levodopa to help reduce the side effects

30
Q

Levodopa

A

precursor to dopamine (DA) and is freely able to cross the blood-brain barrier

Side effect: – think of what happen when there is too much DA in your system

  • dyskinesias (choreic, quirky, quick, tic-like involuntary movements)
  • psychosis, mania
  • anxiety/agitation
  • fatigue
  • nausea

Therapeutics: Parkinson’s

31
Q

Levodopa side effects

A

Side effect: – think of what happen when there is too much DA in your system

  • dyskinesias (choreic, quirky, quick, tic-like involuntary movements)
  • psychosis, mania
  • anxiety/agitation
  • fatigue
  • nausea
32
Q

What drug is given to reduce the side effects of levodopa?

A

Carbidopa - inhibits DOPA Decarboxylase which converts DOPA into DA

Essentially stops the processing of the drug to completion

33
Q

Carbidopa

A

inhibits DOPA Decarboxylase which converts DOPA into DA

Used often in conjuction with levodopa to lessen the side effects

34
Q

role of methyl-THF and MTHFR

A

methyl-THF is associated with synthesis of methionine via methylation of homocysteine using the enzyem MTHFR.

MTHFR can also be used to syntehsize more tyrosine (precursor to DA) which can in turn result in increased DA. Need to double check this

35
Q

1 carbon cycle nutraceuticals

A
  • L-methylfolate – increase activity of MTHFR
  • s-adenosyl methionine – increase homocysteine (which in turn drives formation of L-methylfolate)

Both these drugs in the end drive the production of more tyrosine.

36
Q

Buproprion

A

Class: NDRI (norepinephrine-dopamine reuptake inhibitors)

Mech: blocks the dopamine transporter (DAT) – leaves more DA in the synapse to increase DA activity in the mesocortical pathway (can also lower depression symptoms)

Side effects:

  • DA SEs – insomnia, jitteriness/hypervigilance, seizures.
  • Also blocks NE reuptake –> increase sympathetic stimulation –> insomnia, anxiety, agitation, nausea, sweating, palptiations, mild increases in BP

Therapeutics: antidepressants

37
Q

Buproprion - side effects

A

Less severe than levodopa, but still get the same dyskinetic movements. In addition, patient also has increased NE in the synapse and will get increased stimulation of the sympathics

  • DA SEs – insomnia, jitteriness/hypervigilance, seizures.
  • NE SEs –> increased sympathetic stimulation –> insomnia, anxiety, agitation, nausea, sweating, palptiations, mild increases in BP
38
Q

amphetamines (drug)

A
  • dextroamphetamine
  • mixed amphetamine salts
  • lisdexamfetamine

Class: amphetamines – stimulants

Mech:

  1. blocks DAT like bupropion, and may even reverse it.
  2. increases vesicular monoamine transport (VMAT2) –> ejects more DA from nerve terminals

Therapeutics: ADHD

39
Q

What class of drugs is similar to amphetamines, but do not reverse the transporter?

A

Methylphenidate products

Blocks the DA transporter (DAT), but do not have any chance of reversing it. Less aggressive than amphetamines.

40
Q

Methylphenidate drugs

A

Blocks DAT (DA transporters) –> blocks reuptake of DA

Does not have any chance of reversing it.

Similar to amphematines but less aggressive –> less side effects

41
Q

Most useful metric for determining what type of headache a patient has?

A

Time course of the headache

42
Q

Migraine headache

A

Lasts 4-72 hours

occurs sporadically (but usually once or twice a month)

43
Q

Cluster headaches

A

Occur 15-180 minutes

may occur every other day to many (~8) times per day

These attacks occur in clusters with several months or years between the next bunch of attacks

44
Q

Tension headaches

A

Most common type of headache

sporadic, non-regular, and last minutes to days depending on underlying etiology

45
Q

First line treatment for headache

A

NSAIDs

46
Q

Sumatriptan

A

Class: Triptans

Mech:

  • selective 5HT1 agonists
  • constriction of extracerebral intracranial vessles
  • inhibition of trigeminovascular system

Therapeutics: acute Rx of cluster headaches

SE: flushing, tingling, dizziness, chest discomfort (noncardiac)

47
Q

Ergotamine

A

Class: Ergot alkaloid

Mech: vasoconstriction possibly; may also act as a 5HT agonist in the trigeminovascular pathway

Therapeutics: acute treatment of migranes

SE: Nausea, dizziness, paresthesia, chest pain, abdominal cramps

48
Q

Verapamil

A

Mech: calcium channel blocker

Therapeutics: migraine prevention (particularly for prolonged or disabling aura). Long term prevention of cluster headaches

SE: constipation, dizziness

49
Q

Natalizumab

A

mAb that binds α4 subunit of integrins (VLA-4) expressed on all leukocytes

inhibits the migration of leukocytes across BBB

Therapies: long term management of MS

SE: progressive multifocal leukoencephalopathy (PML), serious systemic hypersensitivity

2ndary treatment b/c of these seriously SEs

50
Q

Natalizumab - major side effect

A

mAb that binds α4 subunit of integrins (VLA-4) expressed on all leukocytes

inhibits the migration of leukocytes across BBB

SE: progressive multifocal leukoencephalopathy (PML), serious systemic hypersensitivity

2ndary treatment b/c of these seriously SEs

51
Q

Fingolimod

A

first oral medicine approved. much more effective than low dose IFN

Mech: agonist of the sphinosine-1 receptor (SIP1) –> induces internalization of receptors –> sequesters lymphocytes within lymph nodes

SE: cardiac abnormalities (ie bradycardia and heart block)

Therapeutics: Long term management of MS

52
Q

Fingolimod - SE

A

SIP1 inhibitor

Biggest issue is cardiac concerns ie bradycardia or heart block

53
Q

Teriflunomide

A

Selective hydro-orotate dehydrogenase inhibitor

blocks pyrimidine synthesis –> reduce T & B cell proliferation

SE:

  • decreased hair density
  • GI – diarrhea
  • liver enzyme (hepatotoxicity)
  • nausea
  • teratogenecity

Therapeutics: Long term MS management

54
Q

Dimethyl fumarate

A

Mech

  • Actives Nrf2 pathway and induces antioxiant production
  • protecting oligodendrocytes against free-radical induced cytotoxicity
  • also has anti-inflammatory effect (prevents migration)

SE:

  • GI pain, N&V – less symptoms if taken on a full stomach
  • flushing – controlled by aspirin

Therapeutics: Long term MS management

Used to treat psoariasis

55
Q

Alemtuzumab

A

humanized mAb to CD52 (CD52 function unknown)

primarily effects T&B cells - little effect on innate immunity

  • B cells return to normal in 6-9 months
  • T cells never return to normal but some recovery

SE:

  • infusion reactions
  • increased infections
  • autoimmunity (ITP, thyroid via both hypo/hyper)

Therapeutics: Long term MS management

56
Q

Treatment of acute attacks in MS

A

corticosterioids - antiinflammatory via suppression of both B and T cells. May also reduce cytokine release

alternatives: plasmaphoresis, ACTH (stimulates the production of endogenous steroids)

57
Q

mechanism of action of local anesthetics

A

bind reversibly to intracellular portion of sodium channel –> abolishing ability to generate an action potential

If the Na+ current is blocked over a critical length of the nerve, propagation across the nerve is no longer possible. May require 2-3 nodes of Ranvier

58
Q

how to tell the effect of local anesthetic is working

A

More sodium channels in the activated state than the resting or inactivated state

59
Q

differential blockade of local anesthetic

A
  • smaller nerves and myelinated nerves get blocked earlier than larger/unmyelinated ones
  • active fibers blocked more than inactive ones
  • fibers more proximal to injection site blocked earlier than distal ones
60
Q

Biotransformation of ester anesthetics

A
  • hydrolyzed by an enzyme in plasma: pseudocholinesterase –> rapid metabolism to water soluble metabolites
  • Makes esters relatively safe anesthetic because of its quick metabolism
  • CSF lack this enzyme. Esters injected intrathetcally are metabolized by absorption into blood
61
Q

Biotransformation of amide anesthetics

A
  • Transformed by hepatic carboxyl esterases and CYP450 enzymes –> slow metabolism
  • Liver disease may lead to accumulation –> toxicity
  • Low hepatic flow, CHF, vasopressor use prolong effects of these anesthetics
62
Q

local anesthetic toxicities

A

Associated with drugs such as Procaine and Mepivacaine

Cuases transient pain or dysesthesia linked to use of these drugs as spinal anesthesia

63
Q

Major toxicities associated with local anesthetics

A

CNS toxicity –> readily crosses BBB producing dose dependent effects

  • High risk for high potency agents
  • Factors that contribute to increasing risk
    • intrinsic: low protein binding, decreased clearance
    • extrinsic: metabolic acidosis (results in more in ionized form –> dissolves in blood –> moves to CNS more readidly), increased PCO2 by increased CBF and decreased plasma protein binding

Cardiac toxicity

  • much higher doses are required than for CNS toxicity
  • occurs via the cardiac Na channel blockade –> depression of myocardial contractility and reduced refractory period.
    • Since most local anesthetics are vaso-dilators (except cocaine and ropivacine) –> increased demand, but decreased output –> cardiac arrest
64
Q

Highest cardiac toxicity local anesthetic

A

Bupivacaine

R+ isomer blocks cardiac sodium channels fast and leaves channels slowly.

65
Q

Ester allergies - what is the allergen?

A

PABA - para aminobenzoic acid

66
Q

Ester allergies - what can you use instead?

A

Can use amides as long as the PABA is not used as a perservative

67
Q
A

Unit 3 (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions