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PDSA > Block 5 > Flashcards

Block 5 Flashcards

1
Q

The therapeutic index =

A

LD50/ED50

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2
Q

The categories of chemical exposure in relation to duration are

A

Acute (<24 hours, usually 1 exposure)
Subacute (typically 28 d, repeated exposure)
Subchronic (typically 90 d, repeated doses)
Chronic (>12 mo, repeated doses)

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3
Q

During toxicity studies, which study level requires both rodent and non-rodent species and 6 months or longer of study

A

chronic

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4
Q

What is the Ames test?

A

A test that will often detect mutagens

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5
Q

What are different types of cancer risk factors?

A

Lifestyle/Social
Dietary
Other (infection)

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6
Q

What is TCDD?

A

A teratogen

  • contaminant of herbicides
  • causes chloracne and a wide range of birth defects, carcinogenicity, neuropathy, etc.
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7
Q

Define teratogenesis

A

Relates to the production of structural malformations during fetal development

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8
Q

Chromaffin cells of the adrenal medulla secrete ___% epinephrine and ____% norepinephrine into circulation.

A

80

20

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9
Q

Most of the blood vessels, and sweat glands, are innervated exclusively by

A

sympathetic nerves

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10
Q

Pre-ganglionic neurons of the _____ nervous system are shorter, with longer post ganglionic neurons.

A

Sympathetic

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11
Q

Small ganglia of the _________ are present near the target organs or within the target organs.

A

parasympathetic nervous system

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12
Q

True or False: all pre-ganglionic neurons secrete epinephrine.

A

False

they secrete acetylcholine

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13
Q

Describe the sympathetic and parasympathetic effects on blood vessels

A

Sympathetic - vasoconstriction (vascular tone)

Parasympathetic - little to no effect

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14
Q

Describe the sympathetic and parasympathetic effects on the heart

A

Sympathetic - increase HR

Para - decrease HR

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15
Q

Describe the sympathetic and parasympathetic effects on the lungs

A

Sympathetic - bronchodilation

Para - bronchoconstriction

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16
Q

Describe the sympathetic and parasympathetic effects on the gut lumen

A

Sympathetic - decreases peristalsis

Para - increases peristalsis

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17
Q

Describe the sympathetic and parasympathetic effects on the eye pupil

A

Sympathetic - dilates

Para - constricts

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18
Q

Describe the sympathetic and parasympathetic effects on basal metabolism

A

Sympathetic - increases up to 100%

Para - none

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19
Q

The post ganglionic NT for the sympathetic system is _____ and the parasympathetic is _____.

A

NE

ACh

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20
Q

The neuron supplied to the adrenal medulla secreted ____ as its NT

A

Acetylcholine

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21
Q

Glutamate and Aspartate are both _________ NTs.

A

Excitatory

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22
Q

GABA (gamma amino butyric acid) and glycine are both ______ NTs.

A

Inhibitory

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23
Q

Acetylcholine, norepinephrine, and epinephrine are ____ NTs.

A

Mixed (either excitatory or inhibitory)

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24
Q

MAO stands for

A

monoamine oxidase

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25
Q

Acetylcholine is synthesized by ______ in the ______. It is made up of _____________________.

A

Cholineacetyltransferase in the cytoplasm

It is made up of acetyl-CoA and choline

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26
Q

Choline uptake transporter (CHT) is responsible for… and can be blocked by…

A

Reuptake of acetylcholine into the presynaptic terminal

Inhibited by Hemicholinium

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27
Q

VAT (acetylcholine vesicle associated transporter) is responsible for

A

moving acetylcholine into its storage vesicle.

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28
Q

Vesamicol blocks

A

Acetylcholine vesicle uptake transporter

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29
Q

VAMP is… and is responsible for…

A

Vesicle associated membrane protein

Associating with SNAPs (synaptosomal nerve-associated proteins) to release ACh into the synapse

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30
Q

Botulinum toxin blocks

A

release of acetylcholine into the synapse by cleave SNAP and VAMP
- the result is a loss of muscle contraction

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31
Q

Acetylcholine esterase…

A

breaks down acetylcholine

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32
Q

Give two examples of AChE inhibitors

A

Neostigmine and Physostigmine

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33
Q

Why is type A botulinum toxin used for cosmetic applications?

A

It has a delayed onset of action and a longer duration of action, as well as causes less pain at the injection site.

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34
Q

A chain of gangila is present in which type of cell?

A

Somatic and Sympathetic

35
Q

What are the muscarinic receptor subtypes? Which G protein do they each use?

A

M1, M3, and M5 all use Gq (so excitation, smooth muscle contraction, and increased secretion)

M2 and M4 are Gi (so inhibition, decreased CV function)

36
Q

M2 receptors are found at ________ and its effects are…

A

SA node and AV node

Cause a decrease in heart rate with no effects on the ventricular muscles

37
Q

Describe the responses to M3 stimulation on the:

  • lungs
  • GIT
  • eye
  • exocrine glands
  • BV
  • urinary bladder and sphincter
A
  • lungs = increased bronchial secretion and constrictions
  • GIT = diarrhea and peristalsis
  • eye = contraction of pupil (miosis), increased tear drainage, and decreased intraocular pressure
  • exocrine glands = increased secretion
  • BV = vasodilation via NO (not direct innervation)
    Bladder/sphincter = bladder contraction and sphincter relaxation = pee
38
Q

Blood vessels are exclusively innervated by ______________, so Nn receptor stimulation at autonomic ganglia exerts ________.

A

sympathetic NS

vasoconstriction

39
Q

What is occurring (intracellularly) when M1 and M3 are stimulated?

A

increased PLC activity –> hydrolyzed PI –> DAG and IP3

IP3 –> increased calcium –> increased smooth muscle contraction and glandular secretion

40
Q

M2 stimulation leads to

A

decreased adenyl cyclase activity, decreased cAMP levels, increased K+ and Ca2+, hyperpolarization, and decreased cardiac function

41
Q

The two alkaloid muscarinic agonists are

A

Muscarine and Pilocarpine

42
Q

Choline esters include

A

Methacholine

Carbachol

Bethanechol

43
Q

What is the clinical use of bethanechol?

A

activates smooth muscle of bladder and bowel

acts on M receptors; resistant to AChE

Used to treat urinary retention

44
Q

What is the clinical use of carbachol?

A

Miosis, increased tear drainage, decreased intraocular pressure

resistant to AChE; targets both N and M

used for antiglaucoma and mitotic effects

45
Q

Methacholine’s specificity is

A

M&raquo_space; N

46
Q

What is the clinical use of methacholine?

A

+M receptors in lungs when inhaled

used to test for asthma

47
Q

What is the clinical use of pilocarpine?

A

contracts ciliary muscle of eye, increases tear drainage, and decreases intraocular pressure

is a potent stimulator of the salivary gland

resistant to AChE

used for antiglaucoma, dry mouth due to radiation, and damage of the salivary glands

48
Q

Give an example of an irreversible, long acting indirect acting cholinomimetic.

A

Organophosphates such as malathion, parathion, nerve gas (sarin), and ecothiophate

49
Q

Why can’t neostigmine and edrophonium cross the BBB?

A

They have positive charges, so they concentrate in the NMJ instead.

50
Q

Which indirect acting cholinomimetic has a tertiary amine, is lipophilic, and has no charge?

A

Physostigmine

51
Q

Why would you not use physostigmine to treat myasthenia gravis?

A

because it can cross the BBB and would not be useful at the neuromusclar junction

52
Q

What is the clinical use of physostigmine?

A

antidote to atropine overdose/poisoning

53
Q

What is the clinical use of neostigmine/pyridostigmine?

A

treatment of myasthenia gravis, reversal of neuromusclar blockade after surgery

54
Q

What are donepezil, rivastigmine, and galantamine used for?

Why?

A

treatment of Alzheimer disease

are lipophilic so have CNS penetration

55
Q

Ecothiophate is used for

A

antiglaucoma; miotic

56
Q

What happens with organophosphate (OPC) poisoning (acute toxicity)?

A 
DUMBELS
D - diarrhea
U - urination
M - miosis
B - bronchoconstriction
E - excitation
L - lacrimation
S - salivation
57
Q

Atropine is an

A

anti muscarinic agent

58
Q

List the pharmacological effects of atropine

A 
eye - dilation
lung - decreased secretion
exocrine glands - decreased secretion and hyperthermia
gut - decreased motility (constipation)
heart - tachycardia
bladder - urinary retention
59
Q

What muscarinic antagonists are used to treat COPD and asthma? Why?

A

Ipratropium and Tiotropium

they’re bronchodilators
- quaternary amine with (+) charge; typically concentrate in the lungs and prevents constriction/secretion

60
Q

What is the clinical use of oxybutinin?

A

overactive bladder and bladder spasms (no pee)

61
Q

What is the clinical use of hyoscine/dicycloverine?

A

treat smooth muscle spasms

62
Q

What is the clinical use of benztropine?

A

Parkinson’s disease (given as an adjunct therapy)

63
Q

competitive antagonists of ACh at Nm receptors are used for

A

muscle relaxation

64
Q

Curonium, Mivacurium, Pancuronium, Rocuronium, and Vecuronium are all

A

muscle relaxants

65
Q

Muscle function recovery (after using a muscle relaxant) depends on

A

renal and hepatic elimination of the drug

66
Q

The only non competitive depolarizing blocker (Nm agonist) is

A

Succinylcholine

67
Q

Which phase (I or II) block can be reversed with an acetylcholinesterase inhibitor?

A

Phase II

68
Q

ANS Ganglionic Receptors are

A

nicotinic

69
Q

What is the effect of ganglionic stimulation on blood vessels?

A

vasoconstriction

70
Q

M3 stimulation in the lungs causes

A

bronchoconstriction

71
Q

What drug is an alkaloid muscarinic antagonist that is resistant to AChE?

A

Pilocarpine

72
Q

Which of the following drugs is used to inhibit AChE in the treatment of alzheimer’s?

  • neostigmine
  • edrophonium
  • organophosphates
  • donepezil
A

Donepezil

73
Q

The metabolic precursor of NE and E, that is also a neuromodulator in the CNS

A

dopamine

74
Q

synthetic derivative of NE, not present in the body

A

isoprenaline

75
Q

All catecholamines contain

A
  • benzene ring
  • hydroxyl group
  • ethylamine side chai

aka they’re a catechol nucleus with an ethylamine side chain

76
Q

Describe the process by which tyrosine is converted to norepinephrine

A

1 - tyrosine is converted to L-DOPA by tyrosine hydroxylase
2 - L-DOPA is converted to dopamine by L-amino acid decarboxylase
3 - Dopamine is brought inside a storage vesicle via VMAT
4 - once inside, dopamine is converted to norepinephrine by dopamine beta-hydroxylase

77
Q

what extra step in catecholamine synthesis only occurs in the kidney?

A

the norepinephrine will be converted to epinephrine by phenylethanolamine-N-methyltransferase

78
Q

what three cofactors are required during the synthesis of epinephrine?

A

1 - vitamin B (for the conversion of L-DOPA to dopamine)
2 - vitamin C (for the conversion of dopamine to norepinephrine)
3 - SAM (S-adenosylmethionine for the conversion of NE to epinephrine)

79
Q

where in the kidney is epinephrine produced?

A

the adrenal medulla

80
Q

norepinephrine release is controlled by

A

auto-inhibitory feedback mediated by alpha-2 receptors

81
Q

about ____% of released NE is retaken by _____ in the ________.

A

70-80%
norepinephrine transporter (NET)
presynaptic neuron

82
Q

where is the remaining NE captured?

A

the remaining NE that is not taken up by NET is captured by non-neuronal cells in the vicinity by OCT

83
Q

circulating epinephrine uptake is more dependent upon ______.

A

OCT

84
Q

isoprenaline is removed by

A

OCT transporters

PDSA (6 decks)

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