Exam 2 sweep 1 Flashcards
(232 cards)
1
Q
Local anesthetics used in dental practice are ——— amines).
A
secondary or tertiary
2
Q
Local anesthetics cross the axon membrane and interact with the ——- forms of the Na+ channel, blocking Na+ conductance.
A
open and inactivated
3
Q
Local anesthetics are not effective ———.
A
outside the axon
4
Q
Because local anesthetics bind to the open form of the sodium channel, they produce a more rapid nerve block on axons with a more
A
rapid firing rate.
5
Q
Functions served by—– are more readily disrupted by local anesthetics than the motor functions served by ——–
A
B and C fibers
(larger) A fibers*
6
Q
- First on, last off.
A
The faster a fiber is blocked, the longer it takes to recover.
7
Q
Local anesthetic selectivity
Phenomenon: bupivacaine
A
produces sensory anesthesia at 1/3 the concentration required for motor blockade. Etidocaine shows no selectivity??
Although the mechanism is unclear, bupivacaine would be favored for epidural anesthesia during childbirth (maintain unterine muscle contractility).
8
Q
Inflammed tissue
Products released by cells in inflamed tissue ——– making it more difficult to get sufficient levels of anesthetic inside the axon.
A
lower pH,
9
Q
Anesthetic must be sufficiently ——– to diffuse to its site of action.
Once at site, the more ——— have a longer duration of action (increased protein binding, decreased clearance by local blood flow).
A
hydrophilic
lipid-soluble local anesthetics
10
Q
Most local anesthetics are prepared as a —— (pH of the solution around 6 or 7)
A
water soluble HCl salt
11
Q
If epinephrine is included, the pH is frequently lowered to —– to stabilize the epinephrine.
A
4 or 5
12
Q
Local anesthetics: in CNS
A
- Readily pass from the periphery to the CNS
2. CNS neurons are very sensitive to local anesthetics
13
Q
Local anesthetics Direct effects on the heart:
A
Block cardiac Na+ channels
Block cardiac Ca++ channels (much higher concentrations)
14
Q
Local anesthetics
Effects on the autonomic nervous system:
A
(inhibition of sympathetic responses)
Depress contractility Produce hypotension
15
Q
Bupivacaine is especially ——-
Binds tighter to Na+ channels and leaves slower
A
cardiotoxic
16
Q
Local anesthetics bind to ——-: (5%-95%, depends on hydrophobicity of the anesthetic)
A
plasma proteins
a1 glycoprotein albumin
17
Q
prilocaine
A
(secondary amine, dealkylation not required, extrahepatic metabolism)
18
Q
articaine
A
(inactivated in blood by esterase)
19
Q
Treatment of serious adverse events
Convulsions:
A
benzodiazepine, barbituate (thiopental), succinylcholine (treats symptoms only).
20
Q
Treatment of serious adverse events
Respiratory distress:
A
Ventilation, oxygen.
21
Q
Treatment of serious adverse events
Hypotension:
A
sympathomimetic agents (epinephrine)
22
Q
Treatment of serious adverse events
Cardiac function disrupted:
A
cardiopulmonary resuscitation
23
Q
2 week window in which to treat root canal after
A
root resection
24
Q
Antimuscarinics:
A
minimize salivation, laryngospasm (block vagal stimulation), reflex bradycardia
25
Various analgesics:
preoperative pain relief, sedation, amnesia
26
Nitrous oxide and/or opioids:
reduce anesthetic requirement, provide analgesia
27
Anti-nicotinics:
paralyze skeletal muscle
28
Antiemetics
no vomiting
29
Meyer-overton correlation
Solubility in olive oil related to anesthetic potency
30
Membrane lipid hypo
Anesthesia begins when the anesthetic reaches a critical concentration in membrane lipids.
31
Membrane Protein Based Theories of Anesthesia
Direct action of the anesthetic on proteins leads to alterations in protein function
The notion that anesthetics interact with hydrophobiic sites on proteins and affect their function is the more popular one these days
32
----- receptors are an attractive general anesthetic target
GABA - there is no one specific receptor though
33
Studies on the sympathetic nervous system indicate -------- generally more sensitive to anesthetics than action potentials
synaptic transmission
34
The ------------ appears to be important in consciousness
reticular activating formation
35
Many neuroscientists believe the -------- is essential to maintaining consciousness
thalamocortical loop
36
The -------- is involved in memory. Inhibition of this system is likely to be involved in anesthetic-induced amensia
limbic system
37
Pain pathways involve the --------
spinal cord
38
The blood gas partition coefficient
brain brain
| [blood]/[gas]
39
Lower blood gas partition coefficient
Faster induction and recovery
40
Higher blood gas partition coefficient
lower induction rate and slower recovery
41
Barbituates act as CNS depressants by potentiating the activity of the -------. Binding of GABA to its receptor activates ---------. The influx of the negatively charged chloride -------- the post synaptic membrane, thus providing an inhibitory influence on synaptic transmission.
GABA-A receptor
chloride channels
hyperpolarizes
42
Barbituates
Use of intravenous agents in anesthesia has become more popular: 1) Rapid distribution
Drug into vein
2) Reduced cardiac depression
rapidly gets to brain
3) No risk of malignant hyperthermia
4) Eliminate risk of occupational exposure to volatile anesthetics
43
Barbituates - major bad effect
respiratory depression
44
Barbituates used as
maintenance (total intravenous anesthesia).
45
Methoxhexital
Barbituates
Similar to thiopental but
2.5 x more potent, faster acting, shorter duration of action
Sleep time 5 -7 minutes
Cleared 3x faster than thiopental
Fast recovery renders it more favorable in dental outpatient procedures
46
Ketamine produces
Dissociative Anesthesia
47
Channels that let in ----- will hyper- polarize
Cl-
48
Channels that let in ------ will depolarize
Na+
49
Channels that let out------will hyper- polarize
K+
50
PREsynaptically: Hyperpolarization diminishes
Ca++ influx and neurotransmitter release
51
PREsynaptically: Depolarization enhances
Ca++ influx and neurotransmitter release
52
POSTsynaptically:
Hyperpolarization diminishes opening of Na+ channels and reinitiation of action potentials
53
POSTsynaptically:
Depolarization enhances opening of Na+ channels and reinitiation of action potentials
54
Opioid GPCRS
| They activate
Gai
55
Formed from processing of pro-opiomelanocortin (POMC)
| Made in the pituitary and hypothalamus
beta endorphin
56
is the natural agonist of the m-opioid receptor
b-endorphin
57
Dynorphin A, Dynorphin B, and a/b neo-endorphin agonists of
kappa opioid receptor
58
Opioid Receptors Activate
Gai and GbGg
59
Activation of Gi leads to an inhibition of -------, a diminution in ------ levels and a reduction in -------- activity. The reduction of ------ activity results in a reduction of
adenylate cyclase activity
cAMP
Protein Kinase A
PKA
Ca++ entry from voltage sensitive Ca++ channels.
60
Activation of opioid receptors will also lead to activation of a particular type of
potassium channel (via GbGg). This will hyperpolarize the cell.
61
Postsynaptically, hyperpolarization will diminish generation of an
action potential.
62
Presynaptically, ------ is required for transmitter release and inhibition of the voltage sensitive Ca++ channel and hyperpolarization will each diminish ------. Thus, opioids acting presynaptically will inhibit synaptic transmission by reducing
Ca++
Ca++ entry
transmitter release.
63
m receptors
| Three forms,
m1, m2, m3. m1 and m2 are physiologically important.
64
M receptors found in
Found in periaqueductal gray region, superficial dorsal horn of the spinal cord, nucleus accumbens, amygdala, cerebral cortex. Mainly, presynaptic.
Found in GI tract (inhibit peristaltic action, cause constipation).
65
Majority of analgesic drugs act primarily at
m receptors
66
3. Opioids inhibit the inhibitor, thus helping to activate the pathway that produces
CNS mediated inhibition of pain.
67
1. opioids inhibit ----- release
GABA
68
GABA activates a
Cl- channel, producing hyperpolarization
69
Opioids help reduce ------- system expression on pain
limbic (emotional)
70
All opioid analgesics produce:
analgesia, respiratory depression, constipation, gastrointestinal spasm, physical dependence
71
Constipation is a side effect of
morphine
72
Morphine is metabolized by ------- very quickly in the liver. -====== is the primary product ----- is the secondary product
UGT2B7
Morphine-3- glucuronide (M-3-G)
Morphine-6-glucuronide (M-6-G)
Reason why morphine isn't effective when taken orally.
73
Add methyl to ---- location to make opioids
3'
More effective
74
The difference in strength between morphine or heroin on one hand and fentanyl on the other hand arises from differences in their chemical structures. All three bind to the m opioid receptor in the brain, but two major factors contribute to fentanyl’s enhanced therapeutic activity. These two factors are also the major contributors to fentanyl’s enhanced toxicity. The two factors are:
(1) Fentanyl is more lipid soluble than morphine or heroin. (2) Fentanyl binds tighter to the m opioid receptor than morphine or heroin
75
therapeutic index is not the problem for
fentanyl
76
Fentanyl produces more prolonged ----- than other opioids
respiratory depression
77
m receptor antagonists. Used to treat
opioid toxicity. Naloxone is injected and works rapidly. Naltrexone is effective orally and lasts a long time Nalmefene is active orally and lasts even longer than naltrexone. (Could naltrexone or nalmefene be used as a treatment of opioid addiction??).
78
Since activation of all the opioid receptors produce analgesia, might it be possible to produce drugs that act on
k or d receptors and don’t have the major adverse effects (i.e. respiratory depression) and/or don’t produce dependence.
79
Injured cells release certain chemicals called
alarmins
80
The alarmin IL-33 can produce ‘-------’ of resident immune cells called mast cells
degranulation
81
---------- is one of the more important initial mediators of the inflammatory response released by mast cells
Histamine
82
--------- acts through a G protein coupled receptor to produce local --------- and render the capillaries ‘leaky’. This will allow more immune cells to enter the injury site and also produce edema.
Histamine
vasodilation
83
Histamine-H1 receptor activity on vascular endothelium increases
intracellular Ca++ - causes smooth muscle relaxation (endothelial cell pathway), causes MLCK mediated contraction of capillary endothelium
84
The anti-inflammatory properties and pain relief comes from attenuating the production of -----
prostaglandins
85
Prostaglandins are all derived from ----. The four principal ones are PGE2, PGD2, PGF2, and PGI2
arachidonic acid
86
The action of the enzymes ----- sends the arachidonic acid down the path leading to production of the prostaglandins
COX1 and COX2
87
Prostaglandins (via their G protein coupled receptors) act at ---------- to sensitize pain responses.
peripheral nerve endings
88
PGE2 mediated activation of ----- leads to increased activity of PKA. PKA mediated phosphorylation of the ------------ enhances its activity leading to a sensitized pain response.
Gas
TRP type nociceptor
89
Aspirin decreases
Pain
Fever
Inflammation
Thrombosis
90
ibuprofen and naproxen do the same as aspirin except
no decrease in thrombosis
91
acetamionphen lowers
pain, fever
92
Platelet aggregation is mediated in part through the --------- production of
autocrine
thromboxane (TXA2 in the picture).
93
COX enzymes inhibit -------- production
Thromboxane A2
94
Prostaglandins (made primarily from COX-1 activity) stimulate --------- that help comprise the ‘-------’ that protects the stomach from digesting itself
mucus and bicarbonate secretion
mucus gel
95
Adverse effects of NSAIDS
```
Increases in bleeding time (acetylsalicylic acid) Kidney problems (water, Na+ retention) Increased BP
Heart failure (rare)
```
96
Reye's Syndrome
Fatty change in liver and edematous encephalopy after aspirin use 3-5 days later. Preceded by upper respiratory tract infection.
97
Ulcer
| Acetylsicylic acid contraindication
Internal bleeding
98
Diabetes
| Acetylsicylic acid contraindication
Hyper or Hypo glycemia
99
Gout
| Acetylsicylic acid contraindication
Complex effects on plasma Urate levels
100
Hypocoagulation conditions
| Acetylsicylic acid contraindication
Bleeding
101
Anti-inflammatory - best
Ibuprofen or naproxen (not acetaminophen)
102
Risk of heart attack or stroke greater with
Greater with ibuprofen or naproxen
103
Liver toxicity most serious with
Most serious with high doses of acetaminophen
104
Lupus erythematosus is a name given to a collection of
autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues, including, but not limited to, the joints.
105
Psoriatic arthritis is a long- term inflammatory arthritis that occurs in people affected by the autoimmune disease
psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage- like appearance. Skin changes consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals.
106
Septic arthritis, also known as
joint infection or infectious arthritis, results from the invasion of a joint by an infectious agent, resulting in joint inflammation.
107
Osteoarthritis also involves the entire joint, including
subchondral bone and synovium
108
Chondrocytes of healthy cartilage:
Anabolic and catabolic activities are balanced. The extracellular matrix is maintained in a healthy state
109
Chondrocytes of inflammed cartilage:
Anabolic and catabolic activities are not balanced, the catabolic activities dominate. The extracellular matrix is not maintained in a healthy state.
One sees decreased production of collagen. Increased production of proteolytic enzymes such as matrix metalloproteases.
110
------- produce change in chondrocytes that shifts to osteoarthritis. ------- are particularly important
Inflammatory mediators
IL-1b and TNFa
111
```
Proinflammatory cytokines (e.g. IL- 1b, TNFa)
Reduced -----, increased ---------, increased expression of other proteases, increased --------
```
collagen expression
MMP expression
iNOS, COX-2, PEG-2
112
Then a pharmacological hierarchy for treating arthritis
If no inflammation: acetaminophen
| Acetaminophen fails or signs of inflammation NSAIDS Direct injection of corticosteroids into articular cartilage
113
Hyaline cartilage matrix is mostly made up of ---------, and ---------, both of which are also found in elastic cartilage. It also includes ---------
type II collagen
chondroitin sulphate
keratin sulphate
114
The -------- is the site of initial inflammatory process
synovium
115
Synovitis is characterized by proliferation of cells of the --------, increased vascularization, and infiltration by inflammatory cells (especially lymphocytes and macrophages).
synovial lining
116
Eventually, synovitis leads to extension of the inflammatory tissue mass to the articular cartilage. This overgrowth is called the -------.
pannus
117
Pannus is an abnormal layer of ------ or -------- tissue. Common sites for pannus formation include over the -------, over a -------- (as seen in rheumatoid arthritis), or on a ---------
fibrovascular tissue
granulation
cornea
joint surface
prosthetic heart valve.
118
The immune cells,
osteoclasts (cells responsible for bone resorption), and chondrocytes (cells involved in making and breaking down cartilage) make things and have activities that lead to the destruction of bone and cartilage.
MMP = matrix metaloproteases
Cathepsins = cysteine proteases
ROS = reactive oxygen species
119
What do we know about what causes Rheumatoid Arthritis?
Triggered by a----------- to an immunological trigger, such as an infectious agent.
People with certain alleles of ------ genes are predisposed
T cell-mediated response
MHC
120
The major histocompatibility complex (MHC) is a set of cell surface proteins essential for the
acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility.
121
The main function of MHC molecules is to bind to
antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.
122
T helper 17 cells (Th17) are heavily implicated in
autoimmune disorders such as RA
123
------ produce IL-17
Th17
124
Th17 cells play an important role in maintaining ------ and contributing to -----------, but they have also been implicated in ------------
mucosal barriers
pathogen clearance at mucosal surfaces
autoimmune and inflammatory disorders.
125
-------is a really, really, really important therapeutic target in auto immune disorders. - secreted by
(TNFa)
Th17
126
Some antibodies associated with RA
Anti-collagen antibodies
Anti-cardiolipin antibodies
Anti-keratin antibodies Anti-calpastatin antibodies
Antiperinuclear factor antibodies
127
Cardiolipin is a ------- that is an important component of the inner --------, where it constitutes about 20% of the total lipid composition.
phospholipid
mitochondrial membrane
128
Antiperinuclear factor antibodies
| ------- around nucleus of neutrophils
Stain
129
Calpastatin is an
endogenous calpain (calcium- dependent cysteine protease) inhibitor.
130
----------- is an antibody that is an important diagnostic marker of RA
Rheumatoid Factor (RF)
131
RF: antibody against the ---------.
Fc portion of IgG
132
RF and ------ join to form immune complexes that are likely to contribute to the disease process. Although predominantly encountered as -----, rheumatoid factor can be of any isotype of immunoglobulins, i.e. IgA, IgG, IgM, IgE, IgD.
IgG
IgM
133
Antibodies against --------- are frequent in patients with RA
citrullinated proteins
134
Citrullination of peptides catalyzed by
peptidyl arginine deaminase
135
Identification of antibodies directed against ----------** represent an important diagnostic test for RA and are liable to be causative factors in the disease
cyclic citrullinated peptide
136
---------- recognize a diverse set of proteins and are highly cross reactive
Anti-citrullinated Protein Antibodies (ACPA)
137
ACPAs bind and induce -------- by osteoclasts
bone resorption
138
Citrullinated fibrinogen and collagen are -------- in mouse models of arthritis
arthrogenic (impairment due to ongoing reflex)
139
Citrullinated fibrinogen activates --------
macrophages
140
DMARDS
2) Disease-Modifying Anti-Rheumatic Drugs (DMARDS)
141
DMARDS are
A category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is used to distinguish these drugs from nonsteroidal anti-inflammatory drugs (which refers to agents that treat the inflammation but not the underlying cause) and glucocorticoids (SAIDS?) (which blunt the immune response but do not slow down the progression of the disease).
142
Methotrexate:
Enzyme inhibitor of dihydrofolate reductase
| This interference with folate metabolism is the mechanism by which methotrexate acts as a chemotherapeutic agent
143
Potential mechanisms of action of low-dose methotrexate in rheumatoid arthritis
Possible (most likely?) bottom line, potentiation of adenosine signaling as an immune modulator
144
1. Reduction of cell proliferation
2. Enhanced apoptosis of T cells
3. Increased adenosine release
4. Altered expression of cellular adhesion molecules 5. Influences cytokine production
Some biological effects resulting from lower dose methotrexate
145
Bottom line: lower dose methotrexate treatment produces
immuno-suppressive and anti-inflammatory effects
146
leflunomide Inhibits
dihydroorotate dehydrogenase, thereby inhibiting pyrimidine biosynthesis
147
4) Cyclosporin (inhibitor of cytokine gene expression more frequently used to treat organ and graft rejection)
Cyclosporine forms a
complex with cyclophilin
The cyclosporin-cyclophilin complex inhibits a phosphatase called --------- that is activated by cell signaling. --------- of NF-AT (a transcription factor) by calcineurin results in activation of transcription of ----------- and boosting of the immune response. Thus, cyclosporin -------- the immune response
calcineurin
Dephosphorylation
cytokine gene expression
attenuates
148
Azathioprine
| a drug that inhibits
DNA replication
149
Tofacitinib – a
JAK
kinase inhibitor
It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), i.e. it interferes with the JAK-STAT signaling pathway.
150
7. Biologics that interfere with ------ signaling can be used to treat RA
TNFa
151
TNFa is a “-------------” that plays a major role in the immune/inflammatory response
pleotropic cytokine
152
Antibodies/biologicals directed against TNFa act as ------- in rheumatoid arthritis and have positive effects on a slew of autoimmune disorders
DMARDS
153
The ----- region recognizes antigens
Fab
154
Glutamate
| Sometimes glutamate acts as an ------ and sometimes it acts as ------- (activates a G protein coupled receptor)
excitatory neurotransmitter (opens a channel to let in Na+)
neuromodulator
155
GABA (g amino butyric acid) receptors activate ---- channels and produce ------
Cl-
hyperpolarization
156
Glycine receptors also activate ------- and
| produce hyperpolarization
Cl- channels
157
Schizophrenia positive symptoms
linked to excess dopamine
delusions, auditory hallucinations, disturbances in thought
158
Schizophrenia negative symptoms
linked to prefrontal pathology
Loss of affect, catatonia, immobility
159
-azine:
phenothiazine-like antipsychotics
160
Dopamine paths relevant to schizophrenia
mesolimbic path overactivity, mesocortical path disfunction.
161
Glutamate hypothesis
hypofunction of NMDA receptors
162
Schizophrenia drugs
Antagonism of D2 and D4 dopamine receptors,
5HT2A serotonin receptors,
H1 histamine receptors,
M1 muscarinic receptors
and a1 adrenergic receptors (Gq)
is thought to be important in producing the therapeutic and adverse effects of anti-pyschotics.
163
All G protein coupled receptors
Schizo drugs
164
Class of anti-psychotic drugs =
neuroleptic drugs
165
Atypical
5HT2, D4, weak D2 blockade.
166
Anti-psychotic drugs are known to be ------------ They are classified as typical (older, first generation) or atypical (newer second generation).
receptor antagonists (they might also be doing other things).
167
The ------ anti- pyschotics affect only the positive symptoms. The -------- anti-psychotics affect both the positive and negative symptoms
typical
atypical
168
Some atypical antipsychotics end in -
idone
169
Typical anti-psychotics generally are strong antagonists of the -------, have little activity on --------, and varying activities on ---------- receptors.
D2 dopamine receptor
D4 dopamine receptors
5-HT2 (serotonin), H1 (histamine), M1 (muscarinic AcCh), and a1 (adrenergic)
170
Atypical anti-psychotics generally have -------, are stronger on the------ receptor relative to the -------, and varying activities on
antagonistic activity on D4 dopamine receptors
5-HT2
D2 dopamine receptor
on H1 (histamine), M1 (muscarinic AcCh), and a1 (adrenergic) receptors.
171
Monoamine hypothesis
Depression due to lack of NE, serotonin, dopa
172
Most drugs that are used as anti-depressants act in one of three ways:
1. Block transmitter reuptake
2. Inhibit MAO
3. Inhibit presynaptic autoreceptors
173
Block transmitter reuptake
There are two types of drugs working here. The ------) are rather non-specific blockers of transmitter reuptake that are generally also muscarinic receptor antagonists. Both of these properties make for significant side effects.
The --------- are more specific for serotonergic systems and also have less anti-muscarinic activity.
tricyclic antidepressants (TCAs
Selective Serotonin Reuptake Inhibitors (SSRIs)
174
Normally, activation of -------- in the striatum affects acetylcholine and GABA release
dopamine D2 receptors(Gai) in
175
Difference between L dopa and dopa
L dopa crosses BBB
176
L-dopa treatment okay for
3-4 years - degenerate or too many adverse effects.
177
carbidopa, a
peripheral dopa decarboxylase inhibitor.
| Helps with vomiting, gets more to cross BBB
178
Dopamine receptor agonists benefits
1. Not as toxic as L-DOPA
| 2. Don’t require neuron from substantia nigra for delivery (function during more advanced stages of disease ???)
179
Phenytoin and other anti-seizure drugs block
high frequency firing of action potentials
180
anti-convulsants potentiate the effects of GABA to
dampen synaptic nerve impulses
GABA produces hyperpolarization by activating Cl- influx
This renders post- synaptic generation of an action potential more difficult
181
GABA transaminase is involved in metabolism of -----. Inhibition of the enzyme will potentiate the effects of GABA.
GABA
182
convulsing pts use
benzodiazepine
183
muscle spasm is the result of faulty coordination of the ------ mediating control of movement. There are different reasons why nerves might fire inappropriately (Electrolyte imbalance, faulty vertebrae, others).
spinal cord mediated reflex arc
184
The two major classes of drugs of the sedative-hypnotic and anti-anxiety type are
barbiturates and benzodiazapines.
185
barbiturates and benzodiazapines.
| Both of these types of drugs increase ---- conductance via action at ----- receptors but they do it slightly differently
Cl-
GABA-A
186
The GABA A receptor is a -----. The GABA B receptor is a ----. GABA is the ligand for both types of receptor. Activation of either receptor results in hyperpolarization
ligand gated ion channel
G protein coupled receptor
187
GABA B hyperpolarize by activating --------. They also diminish ----- entry into cells
K channels via GbGg
Ca++
188
Barbiturates increase the
duration and frequency of GABA -mediated channel opening
189
Benzodiazapines Anti-anxiety effects at doses that don’t produce
ataxia or somnolence. Barbiturates tend to knock-out everything.
190
Sedative-hypnotic drugs
Barbiturates
191
Drugs to treat anxiety/retrograde amnesia
Benzodiazepines in conjunction with local anesthetics
192
Drugs to treat anesthetic-induced seizures
Benzodiazepines
193
COPD:
chronic bronchitis and emphysema, a pair of two commonly co-existing diseases of the lungs in which the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath.
194
T effector cells are critical mediators of
asthma
195
----- determine the course of an inflammatory asthma response
Th cells
196
Th2 cells mediate an inflammatory response in (eosinophilic) asthma leading to eosinophil infiltration of the lung by
cytokines
197
Cytokines also regulate the balance between
Th1 and Th2
198
Th1
Cell mediated immunity
Intracellular pathogens
Yeast, viruses, intracellular bacteria, cancer
199
Th2
Humoral or antibody mediated immunity
Extracellular pathogens
Parasites, normal bacteria, toxins, allergens
200
Atopy: Predisposition to
Th2 responses (frequently linked to asthma
201
Eosinophilic Asthma
Eosinophils, basement membrane thickening
ICS* first line of defense
*Inhalational Corticosteroids
202
Non-eosinophilic Asthma
No eosinophils, no basement membrane thickening
New treatment regimens needed - usually refractory to tx with ICS
203
Eosinophilic asthma is glucocorticoid
responsive Th2
204
Neutrophilic asthma is glucocorticoid
resistant - Th17
205
-------- (1000x more potent than histamine in the airway)
Leukotrienes
206
Goals of asthma treatment
1) Relieve or prevent bronchoconstriction
| 2) Inhibit airway inflammation (reduce mucus production) 3) Prevent airway remodeling
207
Goals of COPD treatment
Relieve bronchoconstriction
Improve exercise tolerance (keep patient active) Prevent and treat complications
Slow progress of the disease
208
In asthma Brochoconstriction part of ------ response, while in COPD Broconconstriction results from change in -----
allergic
vagal tone
209
In COPD, -------- are involved while in Asthma -------- are involved
Neutrophils
Eosinophils
210
Tools currently in the toolbox to treat Asthma/COPD
b2 adrenergic receptor agonists
| corticosteroids leukotriene modifiers anticholinergics anti-IgE
211
Agents stimulating ---- will act as bronchodilators
PKA (activates K+ channels)
- blocks MLCK
212
Agents increasing ------------ will act as bronchoconstrictors
Ca++ in the smooth muscle cell
213
Activation of b2AR leads to ----- activation
PKA
214
SABAs have a
rapid onset of action and are used as rescue
| medication - Short acting B2 agonists
215
LABAs have a
long duration of action and are used as a component of maintenance therapy
Long acting beta 2 agonists
216
Short-acting b agonists (SABA)
Administered by ---------
Provide acute relief, or used as prophylactic for exercise induced asthma, rescue mediation
Effective within -----
inhalation
minutes, effects last 4-6 hrs
217
Long acting b agonists (LABA)
| Control -----------
persistent asthma, maintenance therapy COPD
218
Long acting b agonists (LABA)
Not for ----- treatment
acute
219
Long acting b agonists (LABA)
Sometimes combined with -----------
Sometimes combined with ----------
corticosteroids
anticholinergics
220
Long acting b agonists (LABA)
| Relatively ---------
hydrophobic
221
```
LABA
Lipophilic (Salmeterol > Formoterol)
• Initial accumulation in -------
• Membrane translocation to aqueous layer
• Bind to the receptor
```
lipid bilayer
222
Hypothalamic-pituitary axis (HPA)
```
• Cortisol is produced on demand
• Cortisol levels follow ACTH levels
• Production is regulated by:
1) Negative Feedback 2) Stress response
3) Diurnal rhythm:
```
223
Cortisol
```
Carbohydrate & protein metabolism:
• Support glucose-dependent organs
• Stimulate gluconeogenesis (liver)
• Stimulate protein and fat catabolismgglucose
• Decrease glucose utilization by cells
• Increase blood glucose levels
```
224
-In mast cells, ------------ produces tonic inhibitory influence on reactivity (i.e. mast cell degranulation)
-Annexin-A1 attenuates the -------------
decrease leukocyte adhesion
decrease leukocyte transmigration (crossing endothelial barrier) increase leukocyte apoptosis
-Annexin-A1 attenuates -------------
annexin-A1
innate immune response
eicosanoid production
225
-In mast cells, ------------ produces tonic inhibitory influence on reactivity (i.e. mast cell degranulation)
-Annexin-A1 attenuates the -------------
decrease leukocyte adhesion
decrease leukocyte transmigration (crossing endothelial barrier) increase leukocyte apoptosis
-Annexin-A1 attenuates -------------
annexin-A1
innate immune response
eicosanoid production
226
The transcription factor ------- regulates genes responsible for both the innate and acquired immune responses
NF kB
227
Gluccorticoids induce transcription of ----
IkB
228
Gluccorticoids block NFkB mediated transcription by ---------
chromatin remodeling
229
Corticosteroids (glucocorticoids) 1)Acute treatment (--------)
2)Long-term management (------------)
systemic
inhaled
230
Adverse effects of inhaled corticosteroids
• Dysphonia
• Oropharyngeal candidiasis
• Adrenal suppression (usually at high doses, systemic absorption)
• Others
-osteoporosis -growth suppression -thinning of skin -easy bruising -cataracts
• Systemic absorption in asthma patients normal?
• Rinse mouth after inhalation
• Benefits normally outweigh risks, particularly in children
231
ICS treatment not effective for
non eosinophilic asthma, pts with Glucocorticoid resistance
232
An increase in ------- contributes mightily to broncho-constriction in COPD
vagal tone
