06a: Anti-Inflammatories, Immunosuppressants Flashcards
1
Q
List the physiological roles of histamine.
A
- Allergic/inflammatory reactions
- Gastric acid secretion
- Neurotransmission
2
Q
List some CNS effects of His.
A
Arousal, neuroendocrine (ACTH, ADH), thermoregulation, hunger/satiety
3
Q
T/F: Distribution and storage of His found in nearly all tissues.
A
True
4
Q
His stored in (X) in mast cells and basophils. It’s in (active/inactive) form and (free/bound).
A
X = secretory granules
Inactive
Bound (to heparin and anionic protein)
5
Q
His release from (X) cells in GI tract is mediated by which NT/hormones?
A
X = ECC
ACh and gastrin
6
Q
T/F: Both His receptor subtypes H1 and H2 are RTK receptors.
A
False - both GPCR
7
Q
His H1 receptor utilized which 2nd messenger pathway?
A
Increase IP3/DAG (thus increase Ca)
8
Q
His H2 receptor utilized which 2nd messenger pathway?
A
Increase cAMP
9
Q
List the two important antagonists for the H1 receptor.
A
- Diphenhydramine (Benadryl)
2. Loratadine (Claritin)
10
Q
List the H1 receptor responses on vasculature.
A
- Vasodilation of arterioles/venules (via NO)
- Increase cap permeability
- Vasoconstriction of large a and v
11
Q
List the non-vascular H1 receptor responses.
A
- Bronchial smooth muscle constriction
- Stimulation of nerve endings (itch, flare, pain)
- CNS arousal
12
Q
List the H2 receptor responses. Star the responses only present if high His levels.
A
- Gastric acid secretion
- Vasodilation (smooth muscle relaxation)*
- Increased HR, contractility*
13
Q
Diphenhydramine, aka (X), is in what class of drugs?
A
X = benadryl
First generation anti-histamines
14
Q
Loratadine, aka (X), is in what class of drugs?
A
X = claritin
Second generation anti-histamines
15
Q
T/F: First generation anti-histamines have weak selectivity for H1 v H2 receptors.
A
False
16
Q
T/F: First generation anti-histamines have CNS access.
A
True
17
Q
First generation anti-histamines had which secondary effects, due to weak selectivity?
A
- Local anesthetic activity
- Muscarinic and alpha-adrenergic antagonism
- Sedation
18
Q
(First/second) generation anti-histamines helped develop other classes of drugs to treat (X).
A
First;
X = psychosis
19
Q
Weak selectivity of first generation anti-His results in side effects including: urinary (incontinence/retention), (hyper/hypo)-tension, (tachy/brady)-cardia.
A
Retention (anti-muscarinic), hypotension and reflex tachycardia (anti-alphaR)
20
Q
(First/second) generation anti-histamines used to treat Type 1 hypersensitivity reaction. And asthma?
A
Neither for neither!! Need Epi; anti-his are not bronchodilators
21
Q
(First/second) generation anti-histamines used to treat nausea/vomiting and motion sickness.
A
First - can access CNS
22
Q
T/F: First generation anti-histamines can be bought OTC for sleep aid.
A
True
23
Q
Toxicity of first gen anti-his presents similarly to toxicity by (X) drug.
A
X = Atropine (muscarinic antagonist)
24
Q
Compared to first gen, second generation anti-his have (extra/missing) (X) group that limits CNS access. This lowers incidence of which side effect?
A
Extra;
X = carboxylate
Sedation
25
Cases of sudden death due to ventricular arrhythmia (inhibited K channel) was seen in which class of drugs?
Older 2nd gen anti-his (taken off market)
26
Mechanism of NSAIDS primarily mediated by:
Ihibition of cyclooxygenase (COX)
27
NSAIDS and aspirin-like drugs used to treat (generally) which symptoms?
Pain, inflammation, fever
28
T/F: Second-gen anti-his help reduce watery eyes, rhinorrhea, and sneezing.
True
29
T/F: Second-gen anti-his help reduce nasal itching and congestion.
False - not nasal congestion
30
PGE2 (prostaglandin) causes (increase/decrease) body temp. Also (increase/decrease) pain and (X) in response to autocoids.
Increase;
Increase
X = edema
31
(PGE2/PGF2a) prostaglandins affect GI tract. In which way(s)?
Both;
1. Increase GI motility/secretion and cytoprotection
2. Decrease gastric secretions
32
Prostaglandins (PGE2/PGF2a) (increase/decrease) uterine contraction.
Both
| Increase
33
Prostacyclin is metabolite of (X), made in (Y) cells. What are its functions?
```
X = arachidonic acid (via COX pathway)
Y = endothelial
```
1. Inhibits platelet aggregation
2. Vasodilation
34
Thromboxane A2 (TXA2) is metabolite of (X), made in (Y) cells. What are its functions?
```
X = arachidonic acid (via COX pathway)
Y = platelet
```
1. Stimulates platelet aggregation
2. Vasoconstriction
35
COX (1/2) is constitutively expressed in (X) cells and is "good" for its effects on:
1;
X = all
Gastric cytoprotection, vascular homeostasis, platelet aggregation, kidney function
36
COX (1/2) is constitutively expressed in (X) cells and is also induced by (Y).
2
X = brain, kidney, bone, GI tissues
Y = cytokines, GFs, tumor promoters
37
COX-2 is associated with which physiological/pathological conditions?
Inflammation and cancer
38
"Traditional" non-selective NSAIDs, such as (X), inhibit COX (1/2). Is this optimal?
X = ibuprofen
Both;
No.. COX-1 inhibition, to some extent, mediates many adverse events
39
COX-2-selective agents, such as (X): preferred over traditional NSAIDs due to less adverse effects, especially on (Y) system.
```
X = Celecoxib
Y = GI
```
40
T/F: Acetaminophen is an NSAID.
False - not anti-inflammatory
41
Acetaminophen generally provides what kind of relief?
Antipyretic (reduce fever) and analgesic (reduce pain)
42
Acetaminophen acts by (reversibly/irreversibly)
| (stimulating/inhibiting) (X). Its effects are (stronger/weaker) than NSAIDs and salicylates.
Reversibly inhibiting;
X = COX (in CNS!!)
Weaker
43
Acetaminophen lacks (X) effect due to poor ability to inhibit COX in presence of (Y).
```
X = anti-inflammatory
Y = peroxides (at sites of inflammation)
```
44
(X) is the preferable antipyretic analgesic for patients with increased risk of NSAID toxicity.
X = acetaminophen
45
(NSAIDs/Acetaminophen/Aspirin) are problematic in excess due to buildup of (conjugated/non-conjugated) metabolite that causes centrilobular hepatic necrosis.
Acetaminophen;
| Non-conjugated
46
List conditions that increase risk of centrilobular hepatic necrosis via metabolite of (X) drug.
X = Acetaminophen
1. Inducers of CYP enzymes (CYP2E1, CYP3A4)
2. Alcohol (CYP induction, hepatotoxicity)
3. Glutathione depletion (less conjugation)
47
Drug of choice for children with viral infections is (NSAID/Acetaminophen/Aspirin).
Acetaminophen
48
List some "traditional" NSAIDs.
Ibuprofen, Aspirin, Non-acetylated salicylates
49
(X) drug irreversibly inactivates COX via (Y) modification.
```
X = aspirin
Y = acetylation
```
50
Aspirin has (short/long) half-life and is converted to (active/inactive) metabolite (X).
Short;
Active (antipyretic, analgesic, anti-inflamm)
X = sodium salicylate
51
NSAIDs: Antipyretic effects via (increase/decrease) in cutaneous blood flow and (increase/decrease) sweating.
Increase; increase
52
Avoid (X) drug class for children with viral infections due to association with (Y) Syndrome.
```
X = salicylates
Y = Reyes'
```
53
Primary mechanism of NSAIDs to relieve pain.
Inhibit PGE2 synthesis in periphery
54
List the mechanism of NSAIDs to reduce inflammation.
1. Inhibition of COX-2
| 2. Inhibit activation of TF (NF-kB)
55
The transcription factor NF-kB has key role in (X). (Stimulating/inhibiting) its activation is a role of which drugs?
X = cytokine and pro-inflammatory mediator production
Inhibiting;
NSAIDs
56
Baby aspiring taken daily provides some selective inhibition of (X) and stimulation of (Y). This makes it CV-protective.
```
X = thromboxane (in platelet)
Y = prostacyclin (in endothelial cell)
```
57
Role of NSAIDs in (stimulation/inhibition) of (X) synthesis makes (coagulation/bleeding) an adverse effect of the drugs.
Inhibition;
X = thromboxane
Bleeding
58
A single analgesic dose of (X) increases bleeding time by factor of (1/2/3/4/5) for how long?
X = aspirin (irreversibly inactivates COX-1 in platelets)
2;
Life of platelet (4-7 days)
59
T/F: Acetaminophen does not affect platelet function, so bleeding isn't adverse effect.
True
60
Aspirin requires relatively smallest dose for its (anti-inflamm/anti-platelet/analgesic) effect than (anti-inflamm/anti-platelet/analgesic) effects.
Anti-platelet (80 mg/day);
Analgesic (700-1000 mg/day)
Anti-inflamm (3 g/day)
61
Chronic use of (X) associated with "analgesic nephropathy", specifically which renal outcomes?
X = NSAIDs, acetaminophen
Papillary necrosis and interstitial nephritis
62
NSAIDs renal toxicity greater in patients with renal/CV diseases due to which side effects?
Na/water retention and edema
63
Most common side effect of NSAIDs involves (CNS/GI/Renal) toxicity, caused by (stimulation/inhibition) of (X) enzyme.
GI;
Inhibition
X = COX-1
64
List the GI toxicity effects of NSAIDs.
Bleeding, erosions, ulcers
65
Pt comes in with bronchospasm, rhinorrhea, and hives after taking aspirin. This is case of aspirin (allergy/intolerance). It's mediated by (X).
Intolerance (NOT allergy, no Ab)
| X = leukotrienes
66
T/F: Aspirin and acetaminophen intolerance will present similar to allergic reaction.
False - not acetaminophen
67
Aspirin intolerance more likely seen in (X) patient population due to (higher/lower) levels of and sensitivity to (Y).
X = asthmatics
Higher;
Y = leukotrienes
68
Rofecoxib, a(n) (X) drug, was taken off market for increasing risk of CV events (MI, stroke). Do other (X) drugs also have this risk?
X = COX-2 inhibitor
Yes (Celecoxib, for ex), but not any more toxic than traditional NSAIDs
69
Active center of COX(1/2) has larger side pocket. Thus, (ibuprofen/celecoxib) is bulkier.
COX-2;
| Celecoxib (selective)
70
T/F: Celecoxib, unlike Ibuprofen, has no GI or renal toxicity.
False - less GI toxicity, but still Na retention/edema (renal toxicity)
71
T/F: There's a CV (boxed) warning for all NSAIDs.
False - not aspirin
72
Glucocorticoids, such as (X), have which effects on immune system?
X = cortisol
Anti-inflammatory and immunosuppressant
73
T/F: Cortisol has equal affinity for glucocorticoid and mineralocorticoid receptors.
True
74
In (X) locations, cortisol converted to (Y) by 11-b-hydroxysteroid DH. (Y) is (active/inactive) and has which important characteristic?.
```
X = kidney, colon, salivary glands
Y = cortisone
```
Active;
selective to glucocorticoid receptors
75
Glucocorticoids (stimulate/inhibit) arachidonic acid pathway by (increasing/decreasing) transcription of:
Inhibit;
Increasing: Lipocortin (inhibits phospholipase A2)
Decreasing: COX-2 transcription
76
(X) drugs (increase/decrease) synthesis of IkB, which (stimulates/inhibits) NF-kB, thus (increasing/decreasing) its function of:
X = glucocorticoids
Increase;
Inhibits;
Decreasing
Transcription of pro-inflammatory proteins
77
(X) anti-inflammatory drugs decrease synthesis of adhesion factors affecting leukocyte localization.
X = glucocorticoids
78
List the advantages of anti-inflammatory synthetic steroids (over cortisol, for example).
1. Greater selectivity (glucocorticoid v mineralocorticoid receptors)
2. Longer half-life and duration of action
79
List examples of anti-inflammatory synthetic steroids, specific for glucocorticoid receptors.
1. Dexamethasone
| 2. Prednisone
80
List three therapeutic uses for glucocorticoids.
1. Adrenal disorders (replacement therapy)
2. Immunosuppressant effect (for autoimmune/transplants)
3. Anti-inflammatory (for RA, lupus)
81
Postural hypotension is symptom of glucocorticoid (toxicity/insufficiency) along with which other symptoms?.
Insufficiency;
Nausea/vomit, anorexia, joint/muscle pain, fever
82
T/F: Glucocorticoids used to treat severe allergic reactions.
True
83
T/F: Glucocorticoids are ineffective treatments for GI disorders.
False - used for UC and Crohn's
84
(X) anti-inflammatory drugs used to treat cerebral edema (from tumor).
X = glucocorticoids
85
(X) anti-inflammatory drugs used to neural inflammation (i.e. Bell's palsy).
X = glucocorticoids
86
T/F: Glucocorticoid toxicity could cause immune cell malignancies.
False - used to treat them (i.e. leukemia, lymphoma)
87
Prolonged treatment of glucocorticoids is not safe for which reasons?
1. Toxicity
2. Suppresses HPA axis
3. Abrupt termination is life-threatening
88
Upon cessation of long-term glucocorticoid administration, (X) gland is (hypertrophied/atrophied). Thus, you'll see a surge in (ACTH/Cortisol) and lag in (ACTH/Cortisol) levels.
X = adrenal cortex
Atrophied;
ACTH;
Cortisol
Over the time-course of months!
89
T/F: Glucocorticoids used to treat infection.
False - immunosuppressive (infection is consequence of GC long-term use)
90
Long-term GC use: (hyper/hypo)-tension, (hyper/hypo)-glycemia, and muscle (hyper/a)-trophy.
Hypertension, Hyperglycemia, and muscle atrophy (wasting)
91
(Local/systemic) administration of GC is preferred for which reason? Provide some examples of this admin method.
Local to reduce toxicity;
Nasal spray, topical admin, joint injection, slow-release capsule (high first pass effect)
92
Methotrexate used as (X) drug and functions to (stimulate/inhibit) (Y) process in high doses.
X = immunosuppressant
Inhibit;
Y = pyrimidine synthesis (arrest DNA replication/cell division)
93
Methotrexate used as (X) drug and functions to (stimulate/inhibit) (Y) process in low doses.
X = immunosuppressant
Inhibit;
Y = de novo purine synthesis
94
Infliximab is (low/high) MW drug that acts to:
High (Ab);
Block TNF-alpha (immunosuppressant)
95
Abatacept (increases/decreases) immune function by binding APC at (MHC/Co-stim ligand) and (stimulating/inhibiting) T-cell activation.
Decrease (immunosuppressant);
Co-stim ligand;
Inhibiting
