Module 2: Intro to Autonomics, Cholinomimetics, Cholinesterase Inhibitors, Cholinoreceptor blocking drugs, Cancer Chemotherapy Flashcards
1
Q
What drug prevents the transport of Choline into the presynaptic cleft by CHT?
A
Hemicholiniums
2
Q
What drug inhibits the transport of Acetylcholine into the storage vesicle by VAT?
A
Vesamicol
3
Q
This drug preents the release of Acetylcholine from the terminal buoton
A
Botulinum toxin
4
Q
When is Acetylcholine released?
A
When Ca2+ channels in terminal membranes are opened
5
Q
What terminates ACh?
A
Acetylcholinesterase
6
Q
What prevents the conversion of Tyrosine to Dopamine?
A
Metyrosine
7
Q
What specific enzyme does Metyrosine inhibit?
A
Tyrosine Hydroxylase
8
Q
Dopamine gets transported into the vesicle via?
A
VMAT
9
Q
This drug inhibits the transport of Dopamine via VMAT
A
Reserpine
10
Q
This enzyme catalyzes the conversion of Dopamine to Norepinephrine
A
dopamine-beta-hydroxylase
11
Q
What drugs inhibit the release of Norepinephrine when calcium channels open
A
Bretylium & guanethidine
12
Q
After the release of norepinephrine, what transports it back to the cytoplasm?
A
NET
13
Q
What inhibits NET?
A
Cocaine, Tricyclic Antidepressants
14
Q
This ANS is tropotrophic, meaning its function is more on growth
A
Parasympathetic
15
Q
This ANS is ergotrophic meaning it involves energy expenditure
A
Sympathetic
16
Q
The sympathetic PREganglionic fibers are _____
and its POSTganglionic fibers are ____
A
PREganglionic SYMPATHETIC fibers are SHORT because they terminate at the ganglia in the PARAVERTEBRAL area.
POSTganglionic SYMPATHETIC fibers are LONG kasi nagsstart sya sa paravertebral area up to the end organ.
17
Q
What is the spinal cord origin of the sympathetic nervous system?
A
THORACOLUMBAR (T1-L2)
18
Q
What is the type of response exhibited by the sympathetic nervous system?
A
Diffused. It activates numerous receptors at the same time
19
Q
What is the origin of the parasympathetic nervous system?
A
CRANIOSACRAL (CN 3, 7, 9, 10 & S2-S4)
20
Q
Where do the preganglionic and post ganglionic fibers of the parasympathetic nervous system synapse?
A
Near the effector organ
21
Q
What is the length of preganglionic and postganglionic fibers of the parasympathetic nervous system?
A
PRE: long
POST: short
22
Q
this is a large and highly organized collection of neurons located in the walls of gastrointestinal system. This includes the Auerbach’s Plexus (myenteric plexus) and the Meissner’s Plexus (submucosal plexus).
A
Enteric Nervous System
23
Q
What do you call the fibers that synthesize and release acetylcholine? ALL preganglionic ANS fibers are of this type
A
CHOLINERGIC FIBERS
24
Q
What cells release a mixture of epinephrine and norepinephrine?
A
Adrenal Medullary cells. They are embryologically analogous to postganglionic sympathetic neurons
25
What are the key features of neurotransmitter function that are targets for pharmacologic therapy?
```
Synthesis
Storage
Release
Termination of Action
Receptor Effects
```
SSRRT
26
Acetylcholine is synthesized in the cytoplasm from acetyl-CoA and Choline via what enzyme?
Choline Acetyltransferase
27
This is dependent on extracellular calcium and occurs when an action potential reaches the terminal and triggers sufficient influx of calcium ions via N-type calcium channels
Physiologic release of transmitter
28
What is the rate limiting step in cathecholamine transmitter synthesis?
Tyrosine to L-dopa via Tyrosine Hydroxylase
29
What are the cotransmitters released in the snaptic cleft together with the primary transmitter norepinephrine?
ATP, Dopamine-beta-hydroxylase, peptide
30
What are the 2 processes involved in the termination of noradrenergic transmission?
a. ) Simple Diffusion
| b. ) reuptake into the nerve terminal by NET
31
These, in some cases, provide faster or slower action to supplement or modulate the effects of the primary transmitter. They also participate in feedback inhibition of the same and nearby nerve terminals
Cotransmitter
32
slowing of the heart and stimulation of digestive activity are typical actions of what ans?
Parasympathetic NS
33
Cardiac stimulation, increased blood sugar, cutaneous vasoconstriction are actions of what ans?
Sympathetic NS
34
What is the primary controlled variable in cardiovascular function?
Mean Arterial Pressure. Meaning, any changes in MAP evokes powerful homeostatic secondary responses to compensate for the directly evoked change.
35
The principle of negative feedback control is found at what level of autonomic function?
Presynaptic
36
These are presynaptic receptors that respond to the primary transmitter substance released by the nerve endings
Autoreceptors. They are usually INHIBITORY
37
Regulatory receptors that respond to many different substances are called
Heteroreceptors
38
This is an extreme form of up-regulation which occurs after DENERVATION of some tissues....
Denervation Supersensitivity
39
"Prolonged administration of large doses of reserpine, a norepinephrine depleter, can cause increased sensitivity of the smooth muscle and cardiac muscle effector cells served by the depleted sympathetic fibers."
This is an example of what type of up-regulation?
Denervation Supersensitivity
40
This Muscarinic receptor is found in the CNS, specificcally in the cerebral cortex, hippocampus and striatum
M1
41
This muscarinic receptor is found in the heart, nerves, smooth muscle, autonomic nerve termincals
M2
42
This muscarinic receptor is found in glands, smooth muscle, endothelium
M3
43
This muscarinic receptor is found in the forebrain
M4
44
this muscarinic recptor is found in the substancia nigra
M5
45
What are the muscarinic receptors found in the CNS
M1, M4, M5
46
Functional response of this receptor includes:
Inc Smooth muscle contraction (eg bladder)
Inc Glandular secretion (salivary)
Inhibits Dopamine release and NO synthesis
M3
47
Functional response of this receptor includes:
Inc cognitive fxn
Inc secretions, Inc depolarization of autonomic ganglia
Dec dopamine release and locomotion
M1
48
Functional response of this receptor includes:
Analgesia
Facilitation of Dopamine Release
M4
49
Functional response of this receptor includes:
Slowing of the HR via slowed spontaneous SA node depolarization
Smoth muscle contraction
Neural inhibition of tremors; hypothermia; analgesisa
M2
50
Functional response of this receptor includes:
Dilation of cerebral arteries and arterioles
Facilitates dopamine release
Augment drug seeking behavior
M5
51
Where are nicotinic receptors found?
Skeletal NMJ
Autonomic Ganglia
CNS
52
Stimulation of this nicotinic receptor causes skeletal muscle contraction
Nm
53
Stimulation of this nicotinic receptor causes depolarization and secretion of cathecholamines
Nn
54
What are DIRECT-acting cholinoreceptor agonists?
| These are lipid insoluble and do not cross the blood-brain barrier
Alkaloids or Choline esters
55
These are agonists that reversibly or irreversibly inhibits acetylcholinesterase or butyrylcholinesterases
Indirect-acting cholinoreceptor agonists
56
This acts on both nicotinic and muscarinic receptors and is rapidly metaboliozed by AChE and butyrylcholinesterases
Acetylcholine
57
This drug is resistant to AChE hydrolysis and has greater effect on muscarinic receptors though its potency is similar to ACh.
Metacholine
58
This drug has a longer duration of action than ACh and its effect on muscarinic receptors is greatest on the GIT and GUT. Least nicotinic effects in CVS.
This is used to constrict the pupils intraoperatively, preop and post op
Carbachol
59
This drug usually causes nausea/diarrhea after surgery
Carbachol. kasi greatest effect nya on GIT and GUT
60
What is the drug that is least susceptible to atropine?
Carbachol
61
What drug has the most nicotinic effect?
Carbachol
62
What drug has the least Gastrointestinal effect?
ACh and Methacholine
63
What drug has highes AChE susceptibility?
ACh
64
What drug has the least cardio effect?
Bethanecol
65
What drug do you give for a patient who has a bladder problem?
Carbachol, Bethanecol, Pilocarpine
66
These drugs are non-covalent inhibitors of the active site of AChE. These also target pseudocholinesterases
Competitive Anticholinesterases
67
These drugs binds and deactivates AChE
Non-competitive Anticholinesterases
68
Rivastigmine is given to patients with ______ to improve cognition
Alzheimers
69
Pyridostigmine is given to patients with ______ to increase the neurotransmitters leading to decrease in symptoms
Myasthenia Gravis
70
Neostigmine and Pyridostigmine are examples of...
Carbamate Esters
71
Diazinon and Parathion are examples of
Organophosphates
72
This is used as diagnostic test for Myasthenia Gravis (tensilon test)
Edrophonium
73
This drug is also used as treatment for Myasthenia Gravis. Also used for patients with Atonic Bladder
Neostigmine
74
This drug is also used as tx for Alzheimers
Physostigmine
75
This drug is used especially for patient with paralytic ileus
Pyridostigmine
76
This is a cholinesterase reactivator.
Pralidoxime
77
What is the MOA of Pralidoxime
regenerates cholinesterase via Pyridine-2-aldoxime methyl chloride (2PAM)
78
This results from overfiring/ excessive actions of cholines
Cholinergic Crisis
79
What drug do you give to patients suffering from Cholinergic crisis?
Atropine
80
Cholinergic drug interaction with aminoglycosides may result to...
Inc risk of neuromuscular blockage
81
Cholinergic drug interaction with depolarizing muscle relaxants may lead to...
prolongation of the block
82
Cholinergic drug interaction with non-depolarizing muscle relaxants may lead to...
antagonism of the muscle relaxant effect
83
These cholinergic antagonists block the effect of parasympa autonomic discharge at the receptor sites
Antimuscarinics
84
these cholinergic antagonists block the action of ACh at the autonomic gangla
Antinicotinic
85
Cholinergic antagonists may be used as preop medication for bronchoscopy because...
it decreases bronchial secretions
86
What anticholinergic drug is used as tx for parkinsonism because it has antimuscarinic properties that improves tremors and rigidity
Biperiden
87
What anticholinergic drugs are used for pupillary dilatation?
Atropine, Cyclopentolate, Tropicamide
88
What anticholinergic drug is used for asthma?
Ipatropium
89
What anticholinergic drug is used for diarrhea?
Lomotil
90
What are the effects of antinicotinic agents in the CNS?
Sedation, tremor, choreiform movts, mental abberations
91
What are the effects of antinicotinic agents in the Eyes?
Cycloplegia with loss of accomodation
92
What are the effects of antinicotinic agents in the CVS?
Hypotension, Dec inotropic
93
What are the effects of antinicotinic agents in the GIT?
motility inhibited, marked constipation
94
What are the effects of antinicotinic agents in the GUT?
Urinary retention
95
This hypothesis implies that a given dose kills a constant proportion of a cell population rather than a constant number of cells
Log-Kill Hypothesis
96
What property of the tumor cells allows them to become resistant to chemotherapy and radiotherapy?
Genetic Instability
97
What do you call the mammalian cellular genes that code for specific growth factors and their correspondin receptors. These are amplified and lead to constitutive overexpression in malignant cells
Oncogenes
98
This is a class of genes that may be deleted or mutated and may give rise to the neoplastic phenotype
Tumor Suppressor Genes
99
his is the best-established tumor supressor gene which plays an important rle in suppressing malignant transformation
p53
100
This is the type of chemotherapy given to patients who present with advanced cancer for which no alternative treatment exists
Primary Chemotherapyy
101
What are the goals of Primary Chemotherapy?
Relieve tumor related symptoms
Improve overall quality of life
Prolong time to tumor progression
102
This is the main approach in treating patients with advanced metastatic diseases
Primary Chemotherapy
103
This refers to the use of chemotherapy in patients who presents with localized cancer for which local therapies, such as surgey, exist but which are less than completely effective
Neoadjuvant chemotherapy
104
What is the goal of Neoadjuvant chemotherapy?
Reduce the size of the primary tumor (for easier surgical resection)
105
This is administered afer the surgery has been performed and its goal is to reduce the incidence of both local and systemic recurrence and improve overall survical of patients.
Adjuvant chemotherapy
106
True or False: Cell kill is proportional regardless of tumor burden.
True
107
True or false: The growth fraction of tumor increases exponentially with time.
False. Decreases
108
Single drugs at clinically tolerable doses have been unable to cure cancer except for 2 types... What are these?
Choriocarcinoma and Burkitt's Lymphoma
109
What are the 3 reasons why combination chemotherapy is important?
1) provides maximal cell kill
2) provides a broader range of interaction bet drugs and tumor cells
3) may prevent or slow subsequent devt of drug resistance
110
What are the 5 things to consider when choosing drugs for combination chemotherapy?
1) Efficacy
2) Toxicity
3) Optimum Scheduling
4) Mechanism of Interaction
5) Avoidance of Arbitrary Dose Changes
111
What is CISPLATIN's MOA? It is under what kind of drugs?
It is a Platinum Analogue
| MOA: forms intrastrand and interstrand DNA cross-links; binds to nuclear and cytoplasmic proteins
112
In general, Alkylating agents' adverse effects are...
Nausea and Vomiting
113
These drugs' mechanism of resistance is via increased capability to repair DNA lesion
Alkylating Agents and Cisplatin
114
These drugs' mechanism of resistance is via formation of trapping agents
Bleomycine, Cisplatin, Anthracyclines
115
These drug's mechanism of resistance is via changes in target enzymes
Methotrexate
116
What are the 6 mechanisms of resistance to anticancer drugs?
1. )Increased DNA repair
2. )Formation of trapping agents
3. )Changes in target enzymes
4. )Inactivation of anticancer drugs
5. )Decreased drug accumulation
6. )Decreased activation of prodrugs
117
Toxic effects of anticancer drugs can sometimes be alleviated by this strategy
Rescue therapy
118
After giving high doses of Methotexrate, this drug is given to rescue the normal cells. This drug bypasses the dihydrofolate reductase step in folic acid synthesis.
Rescue therapy for Methotexrate
Leucovorin
119
This drug traps acrolein released from cyclophosphamide and thus reduces the incidence of hemorrhagic
cystitis.
Rescue therapy for Cyclophosphamide
Mercaptoethane sulfonate (mesna)
120
This drug inhibits free radical formation and
| affords protection against the cardiac toxicity of anthracyclines
Dexrazoxane
121
These drugs lead to cross-linking
| of bases, abnormal base-pairing, and DNA strand breakage
Alkylating agents
122
These two drugs specifically alkylates guanine residues at N7
Cyclophosphamide & ifosfamide
123
This drug is used for leukemia, non-Hodgkin’s lymphoma, breast and ovarian cancers, and neuroblastoma. This is also used as an immunosuppressant for lupus nephritis and polyarteritis nodosa
Cyclophosphamide
124
This alkylating agent is used for testicular cancer
ifosfamide
125
These 2 drugs adverse effects are:
↑ risk of transitional cell bladder CA
Hemorrhagic cystitis
Cyclophosphamide & ifosfamide
126
What is the MOA of Mechlorethamine
spontaneously converts in the body to a reactive cytotoxic product
127
Mechlorethamine is used for what kinds of cancer
Hodgkin’s and non-Hodgkin’s lymphoma
128
What are the adverse effects of Mechlorethamine
Gastrointestinal distress
myelosuppression
Alopecia
sterility
129
These Platinum Analogs testicular is used for carcinoma
| cancers of the bladder, lung, and ovary
Carboplatin and Cisplatin
130
This Platinum Analog is used for advanced colon cancer
Oxaliplatin
131
What are the adverse effects of Cisplatin?
Neurotoxicity (peripheral neuritis + acoustic n damage)
| Nephrotoxicity (may be reduced by mannitol + forced hydration)
132
What are the adverse effects of Carboplatin?
myelosuppressant actions
133
What are the adverse effects of Oxaliplatin?
Neurotoxicity
134
This drug's MOA is: Formation of hydrogen peroxide
& generation of free radicals that cause DNA strand scission
This is also used for Hodgkin’s and non-Hodgkin’s lymphoma
Procarbazine
135
What are the adverse effects of Procarbazine?
Disulfiram-like reactions
| leukemogenic.
136
These are highly lipid soluble drugs used as adjuncts in the management of brain tumors
Nitrosureas: Carmustine and lomustine
137
What is the adverse effect of Carmustine and lomustine?
CNS toxicity (seizures, ataxia, dizziness)
138
This drug is sometimes used in chronic myelogenous leukemia (CML)
Its adverse effects are:
adrenal insufficiency, pulmonary fibrosis, and skin pigmentation
Busulfan
139
This drug is used in regimens for Hodgkin’s lymphoma
Adverse effects:
alopecia, skin rash, gastrointestinal distress, myelosuppression, phototoxicity, and a flu-like syndrome
Dacarbazine
140
These are structurally similar to endogenous compounds and have a dual effect: cytotoxic effects on neoplastic cells + immunosuppressant actions
ANTIMETABOLITES
141
What phase of the cell cycle do antimetabolites target?
S phase of the cell cycle
142
```
MOA of this drug:
inhibitor of dihydrofolate reductase
leads to a decrease in the synthesis of:
-Thymidylate
-purine nucleotides
-amino acids
interferes with nucleic acid and protein metabolism
```
Methotrexate
143
These drugs resist anti-cancer therapy by increasing DNA repair
Alkylating Agents and Cisplatin
144
These drugs resist anti-cancer therapy by forming trapping agents
bleomycin, cisplatin, and the anthracyclines
145
This drug resists anti-cancer therapy by changing its target enzymes
Methotrexate
146
Give examples of nitrogen mustards
chlorambucil, cyclophosphamide,
| mechlorethamine, ifosfamide
147
These drugs are activated to toxic nucleotides that inhibit several enzymes involved in purine metabolism and are used as tx for acute leukemias & chronic myelocytic leukemia
Mercaptopurine (6-MP) and Thioguanine (6-TG)
148
This inhibits thymidylate synthase via 5f-dUMP
5-Fluorouracil (5-FU)
149
This drug is an inhibitor of DNA polymerases and is
| most specific for the S phase of the cell cycle
CyTarabine (ARA-C)
150
This drug is converted into the active diphosphate and
triphosphate nucleotide form. It inhibits ribonucleotide reductase. It is clinically used for pancreatic cancer and non-small cell lung cancer
Gemcitabine
151
These drugs prevent the assembly of tubulin dimers into
| microtubules and specifically targets the M phase of the cell cycle
Vinblastine, Vincristine, Vinorelbine
152
These drugs induces DNA breakage through its inhibition of topoisomerase II and target late S phase and early G2 phases of the cell cycle
Etoposide and Teniposide
153
These drugs are used for small cell lung cancer, Prostate cancer, Testicular cancer via inhibition of topoisomerase II
Etoposide and Teniposide
154
These drugs damage DNA by inhibiting topoisomerase I
Toptecan and Irinotecan
155
This drug is used as second-line therapy for advanced ovarian cancer. It can also be used for :
small cell lung cancer
Cervical cancer
Topotecan
156
This drug is used for metastatic colorectal cancer
Irinotecan
157
These drugs prevent microtubule disassembly into tubulin monomers and targets the prophase stage of the cell cycle
"taxes stabilizes society"
Paclitaxel and Doclitaxel
Hyperstabilizes mitotic spindle
158
These drugs are used for breast, ovarian, lung, gastroesophageal, prostate, bladder, and head and neck cancers via hyperstabilizing mitotic spindles
Paclitaxel and Doclitaxel
159
These drugs are anthracyclines that lock the synthesis of RNA and DNA and cause
DNA strand scission by the ff mechanisms:
Intercalate between base pairs
inhibit topoisomerase II
Generate free radicals
Doxorubicin, Daunorubicin
160
This is an anthracycline used for Hodgkin’s and non- Hodgkin’s lymphoma, myelomas, sarcomas, and
breast, lung, ovarian, and thyroid cancers
Doxorubicin
161
This is an anthracycline used for acute leukemias
Daunorubicin
162
This drugs is used for Childhood Tumors:
Wilm’s Tumor
Ewing sarcoma
Rhabdomyosarcoma
Dactinomycin
163
Drug that targets the g2 phase
bleomycin
164
drugs that target the S phase
```
irinotecan
methotrexate
hydroxyurea
cytarabine
6-thioguanine
5-fluorouacil
etoposide
```
165
Drugs that target the M phase
vinblastine
vincristine
paclitaxel
166
These are non-cell-cycle-specific drugs
Alkylating Agents
Antitumor antibiotics
Nitrosoureas
