Final Flashcards
1
Q
We get cholesterol from what 2 ways:
A
Diet or we make it ourselves
2
Q
Cholesterol 3 part synthesis in cells:
A
1) Mevalonate from Acetyl-CoA
2) Conversion of mevalonate to squalene
3) Cyclization of squalene to cholesterol
3
Q
Plaque formation
A
LDL becomes oxidized in the interstitium–>
Macrophages go into swallow up fatty build up–>
they become foam cells–>
foam cells crystalize, die then calcify –>
increased inflammation over time
4
Q
4 main Lipoproteins:
A
Chylomicrons
VLDL
LDL
HDL
5
Q
Chylomicrons:
A
Lipoproteins
- Formed in intestine (dietary)
- Carry triglycerides and cholesterol
- Degraded by cells, final in liver
- Transported to liver where they are converted to VLDL
- Should not be in blood. only lymphatic system.
6
Q
VLDL
A
Lipoprotein
- Secreted by liver
- Travel to peripheral tissues
- Converted to LDL
7
Q
LDL
A
Lipoprotein
- Main transport mechanism throughout body
- Transport to cells
- Uptake through LDL-R
- Excessive amounts will deposit into arteries
8
Q
HDL
A
Lipoprotein
- Takes extra cholesterol out from cells/lipoproteins, transports it to liver for degradation
- Decreased levels associated with atherosclerosis
9
Q
Total Cholesterol level
A
<200
10
Q
LDL level
A
<130
11
Q
HDL level
A
> 40-50
12
Q
Triglycerides level
A
<120
the number one fat in our body
13
Q
Cholesterol drug classes:
A
- Statins (HMG-CoA Reductase Inhibitors)
- Niacin
- Fibrates
- Binding Resins
- Absorption Inhibitors
- PCSK9 Inhibitors
14
Q
Statins: MOA
A
-Inhibits HMG-CoA Reductase which decreases cellular cholesterol synthesis
- Decreases LDL (-40%)
- Increases LDL-R
- Modest decreases in triglycerides
- increase in HDL (+10%)
15
Q
Statins: considerations
A
- Better at night
- Enhanced with food
- 10-80mg
- Restricted use in children, pregnant/lactating
16
Q
Statins: toxicity
A
- Elevated liver enzymes (asian descent)
- CK elevations (muscle pain/weakness)
17
Q
Niacin: MOA
A
- Blocks the production of VLDL
- Decreases VLDL, LDL (-20%)
- Increases HDL (+25%)
- Decrease Triglycerides
18
Q
Niacin: considerations/toxicity
A
2-6g daily
cutaneous vasodilation/flushing
19
Q
Fibrates: MOA
A
-PPAR mediated lipolysis
- Decrease VLDL
- Modest decrease in LDL (-10%)
- Increase HDL (+15%)
- Decrease triglycerides
- Increase lipolysis in liver
20
Q
Fibrates: Toxicity
A
Rare: GI upset arrhythmias elevated liver enzymes potentiation of coumarin myopathy
21
Q
Bile Acid Binding Resins: Drug names
A
Colestipol
Cholestyramine
22
Q
Bile Acid Binding Resins: MOA
A
- Surrounds dietary fat/biliary acids and prevents their reabsorption
- Decrease total cholesterol
- Isolated increases in LDL
- may increase VLDL
23
Q
Bile Acid Binding Resins:
considerations
A
- usually given with statins
- Granular preparation
- 5-30g per day
24
Q
Inhibitors of intestinal sterol absorption: Drug
A
Ezetimibe (Zetia)
25
Inhibitors of intestinal sterol absorption: MOA
Prevents reabsorption of dietary fat/biliary acids by inhibiting NPCT1
26
PCSK9
a protein that binds to LDL-R and will cause it to break down.
27
PCSK9 inhibitors: MOA
Monoclonal antibody binds to PCSK9 which prevents breakdown of LDL-R
28
PCSK9 inhibitors: considerations
New
Expensive
Injections 1-2x wk
29
autocoid groups
```
histamine
serotonin
bradykinin
prostoglandin
leukotrienes
```
30
Chronic inflammation mediators
```
Interleukins
GM-CSF
TNF
Interferons
PDGF
```
31
Cox-1
```
"good"
"housekeeping"
always on
Protects GI tract
Renal tract
Plt fx
```
32
Cox-2
"bad"
| induced during inflammation
33
NSAIDS: MOA
- Inhibition of COX (decreases inflammation)
- Decreases sensitivity of vessels to bradykinin/histamine (reverse vasodilation in brain to relieve HA)
- Inhibit plt aggregation (Cox-1)
34
NSAIDS: precautions
all can cause GI upset, nephrotoxicity, and heptotoxicity
35
ASA:
| MOA
Irreversible block of Cox.
| Cox1 > Cox2
36
Celecoxib:
MOA
use
SE
Cox2 selective
use: arthritis
black box warning for cardiac events, sulfa allergy
37
Ibuprofen:
MOA
SE
Cox1=Cox2
| less GI upset than ASA
38
Indomethacin:
MOA
Use
SE
Cox and Lox (may inhibit phospholipase A and C)
Use: arthritis, gout, patent ductus arteriosis
SE: GI upset 1/3 patients
39
Acetaminophen:
| MOA
Cox2
| no anti-inflammatory effect
40
Glucocorticoids:
| Acute action
Suppress inflammation
Mobilize energy stores
Improve cognitive fx
Salt and water retention
41
Glucocorticoids:
| Chronic use problems
Immunosuppression
DM, obesity, muscle wasting
depression
HTN
42
Glucocorticoids:
| MOA
Blocks transcription/translation:
- Suppresses pro-inflammation mediators.
- Up regulate anti-inflammatory mediators.
43
4 main proteins that are upregulated with glucocorticoids:
- Annexin-1 (lipocortin-1)
- Secretory leukoprotease inhibitor (SLPI)
- IL-10
- Inh-NFkB
44
Secretory leukoprotease inhibitor (SLPI)
decrease inflammation by blocking protease
45
IL-10
Immunosuppressive enzyme
46
Inh-NFkB
protein that directly inhibits the NFkB
47
Annexin-1 (lipocortin-1)
- suppresses phospholipase A2
| - Inhibits leukocyte response
48
Methotrexate:
non-biologic DMARD
| blocks adenosine production
49
Cyclophosphamide:
non-biologic DMARD
| B&T cell suppression
50
Cyclosporine:
non-biologic DMARD
| Inhibition of interleukins
51
Abatacept (Orencia)
Biologic DMARD
| Blocks Tcell activation
52
Rituximab (Rituxan)
Biologic DMARD
| Depletes B-lymphocytes
53
Adalimumab (humira)
Biologic DMARD
| Anti-TNF-alpha
54
Hierarchical system
stimulus travels down neuron, sends neurotransmitter, causes excitatory or inhibitory action
55
Diffuse system
Release Neurotransmitter throughout brian
56
A-beta fibers
touch and pressure
57
A Delta fibers
sharp fast pain/heat
58
C fibers
slow dull pain
| noxious chemical/ heath
59
Mu receptors
Most of the effects from this receptor
60
Delta and kappa receptors
less side effects but can cause dysphoric reactions
61
Full agonist of Mu receptors:
Morphine
| fentanyl
62
Partial agonist of Mu receptors:
codeine
| oxycodone
63
Morphine metabolism
More active after phase 2
64
Heroin metabolism
tissue esterases to morphine
65
2 main metabolic pathways for opioids:
CYP3A4
| CYP2D6
66
Opioids: MOA
- Reduce neurotransmitter release (glutamate, ACh, NE, serotonin, substance P)
- Hyperpolarize postsynaptic neurons
67
3 classes of opioids:
phenanthrenes
phenylheptylamines
phenylpiperidines
68
Strong agonist Phenanthrenes: drugs
Morphine
Dilaudid
Heroin
Codeine, oxycodone
69
Strong agonist Phenylheptylamines: drugs
Methadone:
(half life 25-50hrs, CYP3A4)
Propoxyphene (Darvon)
70
Strong agonist Phenylpiperidine: drugs
Fentanyl
Meperidine (demerol)
Loperamide (diarrhea)
71
Meperidine (demerol)
antimuscarinic effects (tachycardia)
(-) inotorpe
seizures
