1
Q
It is the principal cholinergic neurotransmitter
A
acetylcholine
2
Q
acetylcholine acts on different sites in the peripheral nervous system, interacting with what receptors
A
muscarinic cholinergic receptors
nicotinic cholinergic receptors
3
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the HEART
A
depression of the sino-atrial node
decreased cardiac output
negative inotropic effect
depression of the atrio-ventricular node
increased automaticity of the ventricles which may lead to ventricular arrythmia
4
Q
increased automaticity of ventricles lead to
A
ventricular arrythmia
5
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the vascular smooth muscle
A
vasodilation
hypotension
6
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the gut
A
increased peristalsis
decreased sphincter tone
overall effect is to empty the bowel
7
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the urinary bladder
A
contraction
facilitates urination
8
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the bronchioles
A
bronchoconstriction
dyspnea
9
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the eyes
A
- pupillary constriction
- stimulation of the ciliary muscle causing spasm of accommodation (the lens are accommodated for near vision)
- opening of the canal of Schlemm to facilitate drainage of intra ocular fluid
10
Q
physiological effects of acetylcholine acting on muscarinic receptors
in the exocrine glands
A
increased secretion
11
Q
nicotinic effects are mediated at these 3
A
autonomic ganglia
adrenal medulla
motor end plate
12
Q
to demonstrate the nicotinic effect of acetylcholine on blood pressure, what are the 2 requirements must be satisfied
A
- blockade of the muscarinic nueroeffector sites with atropine in order to eliminate the influence of muscarinic effects of blood pressure
- administration of large dose of acetylcholine
13
Q
Acetylcholine produces this effect by acting on the sympathetic ganglia and at adrenal medulla
for what?
A
hypertensive effect (to discharge epinephrine and norepinephrine)
14
Q
norepinephrine and epinephrine can increase blood pressure by inducing?
A
inducing vasoconstriction and elevating cardiac output
15
Q
acetylcholine also acts on the nicotinic receptors at the motor end plate to cause?
A
muscle contraction, tremors, fasciculation
16
Q
sustained stimulation of nicotinic receptors at the motor end plate can cause
A
muscle fatigue and paralysis
17
Q
enzyme that terminates the activity of acetylcholine by hydrolysis into acetate and choline.
A
cholinesterase
18
Q
is taken back into the presynaptic neuron by active transport, and is used again in the synthesis of new acetylcholine molecule
A
choline
19
Q
2 types of cholinesterase
A
acetylcholinesterase / true cholinesterase
- substrate: acetylcholine
- location: neuro muscular junctions, CNS gray matter, erythrocytes, nerve terminals
butyrylcholinesterase / pseudocholinesterase
- substrate: acetylcholine, esters of choline, local anesthetics
- location: Plasma, CNS white matter
20
Q
Acetylcholine is not used in clinical therapeutics because of 2 reasons:
A
• (1) It causes too generalized but transient effects,
• (2) It is so readily hydrolyzed by plasma cholinesterases that it cannot be detected in the plasma a short time following absorption.
21
Q
if acetylcholine is not used in clinical therapeutics, what are used instead?
A
- more stable derivatives of acetylcholine
- analogue of acetylcholine
22
Q
mimic or potentiate the action of acetylcholine.
A
cholinergic stimulants
23
Q
3 categories of cholinergic stimulants
A
• (1) choline esters
• (2) natural alkaloids
• (3) cholinesterase inhibitors
24
Q
are derivatives of acetylcholine.
A
choline esters
25
choline esters bind directly to muscarinic receptors in?
glands, smooth muscle and cardiac muscle
26
enumerate 3 examples of choline esters
Methacholine (acetyl-beta-methylcholine)
Carbachol
Bethanechol
27
28
Resists degradation by cholinesterase and therefore has more prolonged action than acetylcholine
methacholine
29
T or F
Methacholine has action on nicotinic receptors;
False
30
methacholine produces typical muscarinic effects such as
increased glandular secretion, bradycardia, and
hypotension
31
It has an amine group instead of methyl in the esteratic end of the acetylcholine molecule, which makes it resistant to cholinesterase
carbachol
32
carbachol has most marked effect on?
smooth muscles of the urinary bladder and gut
33
•Carbachol has been used clinically in the treatment of
gut hypomotility and bladder paralysis; also for glaucoma as ophthalmic solution
34
It is almost totally resistant to cholinesterase with action lasting for several hours.
bethanechol
35
bethanechol is used clinically in such cases as
neurogenic urinary bladder paralysis and post-surgical treatment of esophageal achalasia
36
This group includes alkaloids of plant origin.
natural cholinergic alkaloids
37
is an active principle of poisonous
mushrooms including those belonging to the genera *Amanita and Clitocybe*
muscarine
38
t or f
natural cholinergic alkaloids is of toxicological importance only, and is not used in therapeutics.
true
39
The clinical signs of muscarine poisoning include
profuse salivation, lacrimation, dyspnea, colic,
diarrhea, and cardiovascular collapse
40
specific antidote for muscarine poisoning
atropine
41
muscarine belongs to what genera
*Amanita and Clitocybe*
42
Derived from the leaves of *Pilocarpus jaborandi*
pilocarpine
43
pilocarpine has most marked effects on ?
muscarinic receptors in the **eye and exocrine glands**
44
pilocarpine is derived from the leaves of
*Pilocarpus jaborandi*
45
pilocarpine causes
pupillary constriction (since its most marked effects is in the eye)
46
may be used alternately with a pupillary dilator (epinephrine or atropine) to prevent synechiae
pilocarpine
47
pilocarpine is used to prevent
synechiae (iris sticks to cornea (anterior) and to lens (posterior)
48
Because it opens the canal of Schlemm, it is used
in the treatment of glaucoma
pilocarpine
49
Used in the treatment of gut impaction in large
animals
pilocarpine
50
Arecholine is derived from the
fruit of *Areca catechu* (betel nut)
51
t or f
arecholine has both muscarinis and nicotinic effects
true
52
It may be used to eradicate tapeworms by its
purgative effect, but may cause toxic reaction in the host
arecholine
53
3 cholinesterase inhibitors:
acetylation
carbamylation
phosphorylation
54
• (with acetylcholine, at least for a very short time)
• is readily reversible (in seconds) and does not cause clinical problems
acetylation
55
• (with carbamates)
• Carbamylated enzyme takes longer time (hours) to restore activity, and may cause signs of poisoning in patients
carbamylation
56
• (with organophosphates) of the esteratic binding site of the enzyme
• generally causes irreversible inhibition of cholinesterase
phosphorylation
57
•In case of poisoning with these
cholinesterase inhibitors, what happens to the endogenous acetylcholine?
endogenous acetylcholine is spared from being
metabolized, and will accumulate in the
receptor sites
58
Prolonged stay of acetylcholine lead to
exaggerated or prolonged cholinergic response.
59
Since acetylcholine acts on both muscarinic and
nicotinic receptors, the clinical signs of cholinesterase inhibition, therefore, include?
exaggerated muscarinic and nicotinic signs
60
Drugs under this category inhibit cholinesterase for a few hours only, and some are used in the diagnosis and treatment of myasthenia
gravis
reversible cholinesterase inhibitor
61
enumerate 6 reversible cholinesterase inhibitors
physostigmine
neostigmine
edrophonium
ambemonium and pyridostigmine
carbamate insecticides
62
physostigmine is also known as
eserine
63
is a tertiary amine alkaloid derived from
Calabar bean or ordeal bean *Physostigma venenosum*
physostigmine
64
• It binds to the esteratic site of cholinesterase, inhibiting it for a few hours.
• The bond spontaneously breaks off to leave a fully active enzyme
physostigmine
65
The effects of physostigmine are mainly
muscarinic or nicotinic
muscarinic
66
what are the muscarinic effects of physostigmine?
increased gut motility, mild bradycardia, miosis, and stimulation of gravid uterus.
There is little inhibition of the enzyme at the nicotinic sites.
67
68
is almost exclusively used in ophthalmology to
relieve glaucoma
physostigmine
69
is used to reversed the effect of atropine in the eye
physostigmine
70
a synthetic quaternary amine analogue of physostigmine
neostigmine
71
neostigmine has dual action, what are those?
Inhibits cholinesterase and, at the same time, directly stimulates the cholinergic receptors.
72
the most marked effects of neostigmine is on the?
gut and urinary bladder (like carbachol)
73
has a potent anticurare action
neostigmine
74
75
a blocker of the nicotinic receptors in the neuromuscular junction
curare
76
4 clinical uses of neostigmine
treatment of:
gut hypomotility
urinary bladded paralysis
myasthenia gravis
counteract the effects of non-depolarizing muscle relaxants
77
78
is similar to neostigmine but with shorter duration of action.
edrophonium
79
It is used to differentiate between the muscle weakness **due to myasthenia gravis**, and the muscle weakness **caused by overstimulation of cholinergic receptors (fatigue)**
edrophonium
80
If the muscle weakness worsens with edrophonium, a diagnosis of
overstimulation or choligernic crisis
81
if the muscle weakness improves with edrophonium, what’s the diagnosis
it is due to myasthenia gravis
82
are similar to neostigmine but moderately longer-acting
ambenonium and pyridostigmine
83
are used to control external parasites of both large and small animals
carbamate insecticides
84
cause carbamylation of the esteratic site of the
cholinesterase and block its action on acetylcholine
carbamates
85
irreversible cholinesterase include?
organophosphate (OP) compounds
86
organophosphate compounds are used commonly as?
insecticides/acaricides, anthelmintics (dewormers), and agricultural pesticides to which domestic animals may be expose
87
examples of organophosphate compounds
malathion
parathion
ethion
fenthion
sarin
ronnel
ruelene
DFP
TOCP
disulfoton
88
t or f
Organophosphates are highly lipid-soluble, well absorbed and widely distributed.
true
89
OPs are so volatile that they can be absorbed through the
skin and lungs
90
OP compounds are extensively metabolized in the
liver
91
this process may lead to either activation
(lethal synthesis) or inactivation of the OP compounds
dealkylation or removal of the “leaving group X”
92
why is there selective toxicity to insects
because inhibition of the dealkylation reaction does not happen in insects.
93
CLASSIFICATION OF OPs based on their ability to undergo lethal synthesis
directly acting
indirectly acting
94
are those which can inhibit cholinesterase without prior metabolism
directly acting OPs
95
examples of directly acting OPs
Phosphonates (e.g. maloxon and paroxon)
96
97
need to be metabolized first to phosphonates before they can inhibit cholinesterase
indirectly acting OPs
98
they are essentially prodrugs
indirectly acting OPs
99
examples of indirectly acting OPs
phosphothionates (e.g. malathion and parathion)
100
Stages of cholinesterase inhibition by organophosphates
• Stage I: Phosphorylation of the enzyme
• Stage II: Spontaneous recovery
• Stage III. Aging
• State IV: Biosynthesis of new cholinesterase.
101
in this stage, there is a formation of strong covalent linkage between OP and cholinesterase
stage 1: phosphorylation of the enzyme
102
in this stage, it takes weeks or months to restore the normal level of cholinesterase in the body
stage 4: biosynthesis of new cholinesterase
103
in this stage, there is dephosphorylation of the enzyme cholinesterase
stage 2: spontaneous recovery
104
is the stage at which the enzyme cannot be reactivated. Spontaneous dealkylation occurs with increasing time elapsing from phosphorylation
stage 3: aging
105
Pharmacological effects of organophosphates
• Excessive stimulation of mostly muscarinic and some nicotinic cholinergic receptors by the uninhibited endogenous acetylcholine.
• The CNS effects include excitation and mania progressing to convulsion and coma.
• The usual cause of death in OP poisoning is respiratory failure (bronchoconstriction, dyspnea, excessive salivation and mucus secretion, and paralysis of the respiratory muscles
106
excitation and mania can progress to ?
convulsion and coma
107
usual cause of death in OP poisoning is?
respiratory failure
(bronchoconstriction, dyspnea, excessive salivation and mucus secretion, and paralysis of the respiratory muscles)
108
is the most important antidote to the effects of OP.
atropine
109
It blocks the muscarinic effects but not the nicotinic effects
atropine
110
atropine is given via __ to effect
IV
111
dosage of atropine for OP poisoning
0.2 - 2 mg/kg; give 1/4 of dose IV, the rest SC, IM
112
is clinically useful only during the early stages of poisoning.
pralidoxime (2-PAM)
113
It should not be used alone but always in combination with atropine therapy
pralidoxime
114
t or f
atropine is independent of pralidoxime
true
atropine is still useful even without pralidoxime
115
dosage of pralidoxime or 2-PAM for OP poisoning
10-50 mg/kg IM, IV every 12hrs
116
are **antagonists of acetylcholine** specifically at the muscarinic receptors
anticholinergics or parasympatholytics
(they have very little or no action on the nicotinic sites)
117
a racemic mixture of D- and L-hyocyamine
atropine
118
Atropine is well absorbed where
orally, parenterally, and from the eye
119
It distributes widely and crosses the blood-rain barrier and produces central nervous effect
atropine
120
what effects are produced by atropine
central nervous effects
121
are especially resistant to the effects
of atropine because of high concentration of
atropinase, an esterase that breaks down atropine
goats and rabbits
122
are also quite resistant to orally administered atropine, but may be responsive to parenteral administration.
horses and cattle
123
are sensitive to either oral or parenteral atropine
pigs, dogs, cats
124
enumerate 6 other atropine-like drugs
scopolamine
homatropine
eucatropine
hyocine
glycopyrrolate
propantheline
125
a natural congener of atropine, has more CNS effects than atropine
scopolamine
126
scopolamine has been used in women to produce this effect during childbirth
twilight sleep
127
t or f
scopolamine can be used in animals
false
128
has shorter duration of action than atropine and has only 10% of atropine’s potency
homatropine
129
has shorter duration of action than atropine and produces mydriasis with little cycloplegia
eucatropine
130
produces a greater CNS depression
hyocine
131
what is the effects of hyocine in dogs?
antiemetic effect (anti nausea, vomiting)
132
used as preanesthetic anticholinergic agent and is five times more potent than atropine
glycopyrrolate
133
t or f
glycopyrrolate lacks the initial decrease in heart rate
true
134
t or f
glycopyrrolate has greater CNS effects than atropine
false (less)
135
a synthetic atropine substitute; has a high ratio of ganglionic blocking to antimuscarinic
activity
propantheline
136
it is used as a gastrointestinal antispasmodic agent
propantheline
137
These agents block cholinergic receptors in the autonomic ganglia in both parasympathetic and sympathetic divisions
ganglionic blocking agents
138
have no intrinsic activity, compete with acetylcholine for receptor sites in the ganglia and adrenal medulla
non depolarizing ganglionic blocking agents
139
3 pharmacological effects of non depolarizing ganglionic blocking agents
• fall in blood pressure (blockade of sympathetic tone)
• decreased gut motility
• constipation
140
4 examples of non depolarizing ganglionic blocking agents
tetraethylammonium (TEA)
hexamethonium
pentolinium
mecamylamine
note: these are not commonly used clinically in animals
141
Cause powerful and persistent stimulation of cholinergic receptors leading to receptor blockade and fatigue
depolarizing ganglionic blocking agents
142
the effect of depolarizing ganglionic blocking agents is?
biphasic
143
what does biphasic effect means
initial stimulation and then inhibition
144
notable example of depolarizing ganglionic blocking agents
nicotine
145
uses of nicotine
Nicotine has been used as a wildlife capture
dog (very dangerous) and as an insecticide (as 40% nicotine sulfate).
146
this drug is absorbed from all routes of administration
nicotine
147
Poisoning with nicotine is characterized by
- hypertension and tachycardia
followed by hypotension and bradycardia
- salivation followed by drying of the mouth
- CNS stimulation followed by coma
- muscular hyperactivity followed by weakness and paralysis
Pharma
flashcards
Decks in class (6)
# Cards
