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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
Acetylcholine is synthesized by ______ in the ______. It is made up of _____________________.
Cholineacetyltransferase in the cytoplasm It is made up of acetyl-CoA and choline
26
Choline uptake transporter (CHT) is responsible for... and can be blocked by...
Reuptake of acetylcholine into the presynaptic terminal Inhibited by Hemicholinium
27
VAT (acetylcholine vesicle associated transporter) is responsible for
moving acetylcholine into its storage vesicle.
28
Vesamicol blocks
Acetylcholine vesicle uptake transporter
29
VAMP is... and is responsible for...
Vesicle associated membrane protein | Associating with SNAPs (synaptosomal nerve-associated proteins) to release ACh into the synapse
30
Botulinum toxin blocks
release of acetylcholine into the synapse by cleave SNAP and VAMP - the result is a loss of muscle contraction
31
Acetylcholine esterase...
breaks down acetylcholine
32
Give two examples of AChE inhibitors
Neostigmine and Physostigmine
33
Why is type A botulinum toxin used for cosmetic applications?
It has a delayed onset of action and a longer duration of action, as well as causes less pain at the injection site.
34
A chain of gangila is present in which type of cell?
Somatic and Sympathetic
35
What are the muscarinic receptor subtypes? Which G protein do they each use?
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
M2 receptors are found at ________ and its effects are...
SA node and AV node Cause a decrease in heart rate with no effects on the ventricular muscles
37
Describe the responses to M3 stimulation on the: - lungs - GIT - eye - exocrine glands - BV - urinary bladder and sphincter
- 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
Blood vessels are exclusively innervated by ______________, so Nn receptor stimulation at autonomic ganglia exerts ________.
sympathetic NS vasoconstriction
39
What is occurring (intracellularly) when M1 and M3 are stimulated?
increased PLC activity --> hydrolyzed PI --> DAG and IP3 IP3 --> increased calcium --> increased smooth muscle contraction and glandular secretion
40
M2 stimulation leads to
decreased adenyl cyclase activity, decreased cAMP levels, increased K+ and Ca2+, hyperpolarization, and decreased cardiac function
41
The two alkaloid muscarinic agonists are
Muscarine and Pilocarpine
42
Choline esters include
Methacholine Carbachol Bethanechol
43
What is the clinical use of bethanechol?
activates smooth muscle of bladder and bowel acts on M receptors; resistant to AChE Used to treat urinary retention
44
What is the clinical use of carbachol?
Miosis, increased tear drainage, decreased intraocular pressure resistant to AChE; targets both N and M used for antiglaucoma and mitotic effects
45
Methacholine's specificity is
M >> N
46
What is the clinical use of methacholine?
+M receptors in lungs when inhaled used to test for asthma
47
What is the clinical use of pilocarpine?
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
Give an example of an irreversible, long acting indirect acting cholinomimetic.
Organophosphates such as malathion, parathion, nerve gas (sarin), and ecothiophate
49
Why can't neostigmine and edrophonium cross the BBB?
They have positive charges, so they concentrate in the NMJ instead.
50
Which indirect acting cholinomimetic has a tertiary amine, is lipophilic, and has no charge?
Physostigmine
51
Why would you not use physostigmine to treat myasthenia gravis?
because it can cross the BBB and would not be useful at the neuromusclar junction
52
What is the clinical use of physostigmine?
antidote to atropine overdose/poisoning
53
What is the clinical use of neostigmine/pyridostigmine?
treatment of myasthenia gravis, reversal of neuromusclar blockade after surgery
54
What are donepezil, rivastigmine, and galantamine used for? | Why?
treatment of Alzheimer disease are lipophilic so have CNS penetration
55
Ecothiophate is used for
antiglaucoma; miotic
56
What happens with organophosphate (OPC) poisoning (acute toxicity)?
``` DUMBELS D - diarrhea U - urination M - miosis B - bronchoconstriction E - excitation L - lacrimation S - salivation ```
57
Atropine is an
anti muscarinic agent
58
List the pharmacological effects of atropine
``` eye - dilation lung - decreased secretion exocrine glands - decreased secretion and hyperthermia gut - decreased motility (constipation) heart - tachycardia bladder - urinary retention ```
59
What muscarinic antagonists are used to treat COPD and asthma? Why?
Ipratropium and Tiotropium they're bronchodilators - quaternary amine with (+) charge; typically concentrate in the lungs and prevents constriction/secretion
60
What is the clinical use of oxybutinin?
overactive bladder and bladder spasms (no pee)
61
What is the clinical use of hyoscine/dicycloverine?
treat smooth muscle spasms
62
What is the clinical use of benztropine?
Parkinson's disease (given as an adjunct therapy)
63
competitive antagonists of ACh at Nm receptors are used for
muscle relaxation
64
Curonium, Mivacurium, Pancuronium, Rocuronium, and Vecuronium are all
muscle relaxants
65
Muscle function recovery (after using a muscle relaxant) depends on
renal and hepatic elimination of the drug
66
The only non competitive depolarizing blocker (Nm agonist) is
Succinylcholine
67
Which phase (I or II) block can be reversed with an acetylcholinesterase inhibitor?
Phase II
68
ANS Ganglionic Receptors are
nicotinic
69
What is the effect of ganglionic stimulation on blood vessels?
vasoconstriction
70
M3 stimulation in the lungs causes
bronchoconstriction
71
What drug is an alkaloid muscarinic antagonist that is resistant to AChE?
Pilocarpine
72
Which of the following drugs is used to inhibit AChE in the treatment of alzheimer's? - neostigmine - edrophonium - organophosphates - donepezil
Donepezil
73
The metabolic precursor of NE and E, that is also a neuromodulator in the CNS
dopamine
74
synthetic derivative of NE, not present in the body
isoprenaline
75
All catecholamines contain
- benzene ring - hydroxyl group - ethylamine side chai aka they're a catechol nucleus with an ethylamine side chain
76
Describe the process by which tyrosine is converted to norepinephrine
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
what extra step in catecholamine synthesis only occurs in the kidney?
the norepinephrine will be converted to epinephrine by phenylethanolamine-N-methyltransferase
78
what three cofactors are required during the synthesis of epinephrine?
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
where in the kidney is epinephrine produced?
the adrenal medulla
80
norepinephrine release is controlled by
auto-inhibitory feedback mediated by alpha-2 receptors
81
about ____% of released NE is retaken by _____ in the ________.
70-80% norepinephrine transporter (NET) presynaptic neuron
82
where is the remaining NE captured?
the remaining NE that is not taken up by NET is captured by non-neuronal cells in the vicinity by OCT
83
circulating epinephrine uptake is more dependent upon ______.
OCT
84
isoprenaline is removed by
OCT transporters

PDSA (6 decks)

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