Renal Agents Flashcards
1
Q
ADH allows for:
A
Water permeability in the CCT
Alcohol inhibits this
2
Q
Osmotic Diuretics
A
Mannitol
Glucose in lumen
Promotes H2O retention in the tubular fluid
3
Q
Diuretics
A
Are natureitcs
- loop diuretics
- thiazides
Interfere with active or passive uptake of Na+
4
Q
Acetazolamide
A
Carbonic anhydrase inhibitor - inhibits carbonic anhydrase, excreted in PT
Acts on the PT after the glomerulus
Effectiveness decreases after several days because there is enhanced NaCl reabsoprtion at other sites due to bicarbonate depletion
5
Q
Acetazolamide
A
Blocks Na bicarbonate reabsorption -> decrease in NaCl reabsorption -> increase in water retention
Might result in:
- hypercloremia
- metabolic acidosis
6
Q
Mannitol
A
Osmotic agent
- expands the ECV
- inhibits renin release
Poorly absorbed, so must be given parents rally
Acts in the Thin Descending Limb
7
Q
Oral Mannitol
A
Eliminates toxic substances
To potential the effects of K+ binding resins
8
Q
Furosemide
A
Loop diuretic
Acts in the Thick Ascending Limb
Blocks the NKCC2 transporter
9
Q
Thiazides
A
Make the distal convoluted tubule impermeable to H20
Blocks the Na/Cl transporter = NCC
10
Q
Adenosine A1 Receptor Antagonists
Caffeine, Rolofyline
A
Enhances reabsorption of the Na+, counteracts diuresis
Activates tubuloglomerular feedback (TGF)
- stimulates afferent constriction
- decreases GFR
^inhibiting these mechanisms, increase diuretic responsiveness, maintain kidney function
11
Q
Dorzolamide
Briazolamide
A
Topical Carbonic Anhydrase Inhibitors
- used to correct for pts with metabolic alkalosis
12
Q
Adverse effects of carbonic anhydrase inhibitors
A
Parenthesis
Somnolence
Renal K+ wasting
Allergic Rxns to those sensitive to sulfonamides
13
Q
Contraindications of Carbonic Anhydrase Inhibitors
A
Hepatic cirrhosis
Decrease in NH4+ excretion might contribute to hepatic encephalopathy
14
Q
Osmotic diuretics
A
Increase H20 secretion in preference to Na+ excretion
- reduces intracranial/intraocular pressure
- removes renal toxins (e.g. post-radio contrast agents)
15
Q
Toxicity of Osmotic Diuretics (Mannitol)
A
ECV expansion causes hyponatremia
Headache/Nausea/vomiting
Dehydration
16
Q
Furosemide, Bumetanide, Torsemide, Ethacrynic Acid
A
Loop diuretics
2-6 hour until it takes effect
17
Q
Loop Diuretics
A
-mide
Blocks the NKCC cotransporter (Na+, K+, 2Cl)
Causes high Mg2+ and Ca2+ excretion!
Develop a positive lumen potential
Furosemide = less toxic, few GI problems, wider dose-response curve
18
Q
Loop Diuretics
A
Furosemide/bumetanide/torsemide
- block Tubuloglomerular feedback by inhibiting salt transport in macula densa
- induces synthesis of renal prostaglandins (FGE2) by increasing COX II
> increases blood flow and inhibits transport
NSAIDs ca interfere w/ loop diuretics by inhibiting COX
19
Q
Uses for loop diuretics
A
Acute pulmonary edema Edematous conditions Acute Hypercalcemia (Ca2+ wasting) Hyperkalemia Acute Renale Failure Anion OD (bromide, fluoride, iodide)
- not used to treat hypertension bc of short half lives
20
Q
Thiazides
A
Block the Na/Cl cotransporter
- increases Na/Ca exchange (enhances Ca reabsorption)
Like CA inhibitors, thiazides have unsubstituted sulfoamide group
21
Q
Hydrochlorothiazide
A
Thiazide
Increases Ca2+ absorption
Orally: less lipid like, must be given in high doses
- slowly absorbed, therefore longer duration of action
22
Q
Indications for thiazides
A
Hypertension
HF
Neprolitiasis (bc of hypercalciuria)
23
Q
Thiazides
A
Act on distal convoluted tubule
Some members retain significant carbonic anhydrase inhibitor activity.
Can be inhibited by NSAIDs.
24
Q
Thiazide toxicities:
A
Hypokalemia Metabolic Alkalosis
- Hyperuricemia: Similar to loop diuretics.
- Impaired Carbohydrate tolerance.
- Hyperlipidemia
- Hyponatremia
- Allergic reactions: Since thiazides are sulfonamides
25
Late Distal Tubule and Collecting Duct
Major site of K+ secretion (where virtually all diuretic-induced changes in K+ metabolism occur) and acidification of urine.
26
Loop Diuretics are used for..
Think Edema!
| - furosemide, torsemide, bumetanide
27
Action of Loop Diuretic
Blocks the co-transporter NKCC2 in thick, ascending limb
- prevents Na+ absorption
Must monitor the K+ levels = low K+ can cause arrhymias
28
Action of Loop Diuretic
Think edema, pulmonary congestion
1. Blocks the NKCC2 co-transporter
2. Induces prostaglandin and NO generation from endothelial cells
- reduces pulmonary congestion and mobilizes fluid out of lung
29
Furosemide
Most widely used
6 hr duration
Loop diuretic
30
Ethacrynic Acid
For pts allergic to sulfoamides
- can cause more otoxicity than furosemide
Decreases preload (as a loop diuretic)
31
Thiazides
Chlorothiazide, hydrocholorthiazide, chlorthalidone, metalazone, indapamide
32
Thiazide role
Blocks the Na/Cl - NCC cotransporter in the distal convoluted tubule
Used in combo with loop diuretics for those refractory to loops (furosemide)
33
Side effects of thiazides
```
Hyperkalemia
Metabolic alkalosis
Hyponatremia
Hyperuricema
Hyperglycemia
Hypercalcemia
```
- decreases afterload, therefore the BP is at level where easier pumping blood through
- decreases pulmonary congestion
34
K-Sparing Diuretics:
| Blockers of ENaC and Na+ channel
Trina Terence
| Amiloride
35
K-Sparing Diuretics:
| Aldosterone Antagonists
Spironolactone
| Eplernone
36
Direct aldosterone antagonists
- oppose aldosterone in late distal tubule and collecting duct
- prevents myocardial and. Vascular fibrosis
37
Aldosterone Antagonists: K+ sparing diuretic
Reduce cardiac remodeling
Prevention Na+ retention
Side effects: spironolactone
- gynecomastia
- hypocholremic metabolic acidosis
- hyperkalemia
Diuretic - decrease ECF
38
Gynecomastia
Endocrine abnormalities
Impotence, benign prostatic hyperplasia - reported with spironolactone
Use eplerenone instead
39
Side effects of K+ sparing diuretics:
Hypercholermic metabolic acidosis
They inhibit H+ secretion, therefore acidosis might occur
Hyperkalemia: oral K+ should be discontinued if aldosterone antagonists are administered
Gynecomastia - reported with spironolactone
40
ADH
Increase permeability of principal cells in late distal tubule to water
Increases up regulation of AQP2 channels
41
Contraindications of K+ sparing diuretics
1. chronic renal insufficiency
2. Liver disease -> dosing carefully adjusted
CYP34A inhibitors - increase the blood levels of eplerenone
42
ADH Receptor antagonists = VAPTANS
Treatment of euvolemic hyponatremia
43
Conivaptan
ADH receptor antagonist
44
Conivaptan
IV use
| ADH receptor antagonist at V1/V2 receptors
45
Lixivaptan/Tolvaptan
Selective ADH antagonist for V2 receptor
46
Li+ (demeclocyline)
No selective agent
Decreases production of cAMP
reduces cell responsiveness to ADH
Used to treat SIADH
47
Clinical Indications of ADH antagonists
1. SIADH
2. Elevated ADH
Complications associated with diuretic pt 2-3 wks
- initial Na+ loss
- gradually counteracted by antinatriuetric factors (decreasing Na excretion, like aldosterone)
48
ADH antagonist toxicity
Might cause:
- nephrogenic diabetes insipidus
- renal failure: Li+.demeclocycline causes renal failure
Li+ therapy:
- tremors
- mental obtundation
- cardiotoxicity
- thyroid dysfunction
49
Spironolactone/Eplerenone
Competitive aldosterone antagonist
K+ sparing diuretic
Eplerenone: more selective and less side effects
50
Triamtere/Amiloride
Blocks ENaC Na+ channel in apical cells of the collecting duct
K+ sparing diuretic
Spironolactone/Triamtere = dependent on prostaglandin secretion, therefore might be inhibited by NSAIDs
51
Blockers of ENaC Na+ channel
| K+ sparing diuretic
Used to treat hypertension in Liddle Syndrome (where there is an increase in ENaC activity)
52
Late distal tubule and CCT
Site of aldosterone
| Site of K+ secretion
53
What is aldosterone?
Increases Na+ reabsorption
| K+ and H+ secretion
54
K+ sparing diuretic
Useful in states of:
- mineralcorticoid excess
Primary hypersecretion- Conn Syndrome, ectopic ACTH production
Secondary Aldosteronism: HF, hepatic cirrhosis, nephrotic syndrome
55
Oral Androgens have...
Low oral bioavailability
- slow and continuously absorbed form
- chemically modified derivative that pay passes liver metabolism
56
Type A Oral Androgen
Esterification of the C17 hydroxyl group
- longer the chain=more prolonged the action
- more soluble / lipophillic
- must be hydrolysis back to become active
57
Type B Oral Androgen
Alkylation of C17 alpha
- inhibits hepatic catabolism (bypasses 1st metabolism)
- more suitable for oral
- can bind directly to the androgen receptor
Prolonged use = associated with liver toxicity (cholestasis, pelosis, hepatic cysts, neoplasms
58
Type C Oral Androgen
Modifications of A,B,C ring
- enhances androgenic potency
- usually occurs with C17 alpha methylation
- increases bioavailability of drug
- increases the half life
- does not make a stronger Kd
59
Stanozolol, Oxandrolone
Pure anabolic steroids
60
GnRH androgen synthesis blockers
```
Leuprolide
Gosenelin
Buserelin
Histrelin
“Chemical castration”
```
61
Estrogen Treatment - Androgen Synthesis Blocker
Estradiol
Diethylstilbestrol (DES)
Estradiol - negatively feedbacks to inhibit GnRH/LH “chemical castration”
62
1st generation androgen synthesis blocker
Ketoconazole
63
2nd generation androgen synthesis blocker
Abiratenone
64
Inhibitors of DHT biosynthesis
Finesteride
| Dutasteride
65
Side effects of Androgen Therapy
```
Increase in cholesterol
Increase in acne
Baldness
Liver damage
Polycythemia
Mood disorders
```
Increase in BP, fluid retention
66
Androgen Therapy Side Effects in Males
Decrease size of testes
Decrease sperm
Impotence
Gynecomastia
67
Androgen therapy side effects in Females
Infertility
Menstrual irregularities
Hisutism
Decrease in breast size
68
Anti-Androgens
Block the synthesis of androgen
Block the androgen receptor
Used for:
- prostate cancer (initially dependent on androgens for survival)
- benign prostate hyperplasia
- male pattern hair loss
- hirsutism (females)
69
Castration Levels cause..
<50ng/dL of testosterone
70
Ketoconazole
1st generation androgen synthesis blocker
- potent, non selective inhibitor of steroid biosynthesis
- inhibits 3/4 of enzymes involved in biosynthesis in Leydig cels
- inhibits CYP3A4
Binds to cytochrome 450 active site
Blocks cortisol/aldosterone synthesis too
71
Abiraterone
2nd generation
Selective inhibitor of CYP17 in testes and adrenal context
Does not inhibit CYP3A4
“Pyridine moiety”
72
Androgenic Precursors
DHEA
Androstenedione
Inactive from the adrenal cortex
73
Androgens
Mostly derived from testes
Testosterone - tests (potent in circulation)
DHT - androgen target cells/tissues (binds 5x more strongly than testosterone, the Kd is lower)
74
Leydig Cells
Produce testosterone into the blood stream
- express 17B HSD that allow conversion of DHEA and Andrestenedione -> testosterone
75
How does testosterone -> DHT?
5 alpha-reductase - found in androgen responsive tissues
76
What is CYP19?
Aromatase
- converts androstenedione/testosterone (the obligate precursors to estrogens) -> estrone
Estrone -> Estradiol (17HSD)
77
Pituitary gland releases...
LH - stimulates the Leydig Cells
| FSH - stimulates Sertoli cells
78
Androgens are responsible for...
Bone resorption by osteoclasts
Bone mass by osteroblasts
Increase in protein synthesis
Increase in muscle mass
Increase in sebum production in sebaceous glands
Increase in eryhtropoiten, maturation of erythrocytes
Increase in LDL
Decrease in HDL
79
Androgen therapy indicated for
```
Male hypogonadism
Andropause
Delayed Puberty
Improved Protein Balance
Osteoporosis
Anemia
Female Hypogonadism/Hypoadarenalism
```
80
Contraindications of androgen therapy
Prostate disorders
Cardiac/renal/liver disorders
Pregnant/lactating females
Infants/young children
Used as replacement in elderly men:
Mood, libido, bone density
81
Synthetic Progestogen
As a male contraceptive
Acne
Increased libido
Mood disorders
82
DHT synthesis inhibitors
Used to treat benign hyperplasia
Finastride
Dutasteride
83
Finasteride
| Dutasteride
Inhibit the 5alpha reductase, decreasing DHT
84
1st generation AR Antagonists
Glutamine
Bicalutamide
Nilutamide
85
2nd generation AR Antagonists
Enzalutamide: higher potency
| Apalutamide
86
1st generation AR antagonists
Flutamide, bicalutamide, nilutamide
- lower potency (higher Kd)
- imports into nucleus
- binds DNA
- recruits coactivators
87
Inflammation
```
Swelling
Heat
Redness
Red
Pain
```
88
Inflammation
SHARP
Vasodilation
Vascular permeability
Neutrophil leukocytes to the area
89
Neutrophils in Inflammation
1st WBC to the area
- remove damaged tissue through phagocytosis
- infiltrate injured tissue
90
Macrophages in inflammation
Phagocytosis debris
91
Mast Cells in inflammation
Mediate wound healing
Part of the immune system
Role in allergy/anaphalaxis
92
Role of Kinins in Inflammation
Cause vasodilation
Lowers blood pressure
Stimulates pain receptors
93
Role of prostaglandins in inflammation
Potentiate the action of bradykinin (vasodilation, lowering of BP, stimulate pain receptors)
Prostaglandins are a derivative of arachidonic acid.
Apart of the eicosanoid family
94
3 members of eicosanoid family
Prostaglandin
Thromboxanes
Leukotrienes
95
prostaglandins/thromboxanes
Grouped together as prostanoids
96
PGE2
Promotes gastric mucus secretion
Inhibits gastric acid secretion (protects the stomach lining)
Main prostanoid
Increases vascular permeability
97
What do mast cells and macrophages release into an area of inflammation?
PGE2
- promotes gastric mucus
- inhibits gastric acid
98
The expression of COX2 is induced by what?
It is induced by inflammation and causes an increase in PGE2 (increased vascular permeability, mucus secretion)
99
COX 1
More common than COX 2
| Produces prostaglandins involved in “house-keeping” functions
100
What is PGI2?
Prostacyclin
- inhibits platelet aggregation
- vasodilator
101
What is TXA2?
Thromboxane A2
- promotes platelet aggregation
- vasoconstrictor
Opposes PGI2
102
COX
Is responsible for converting arachidonic acid to Endoperoxides which are then converted to prostaglandins
103
NSAIDs
Analgesics (decrease pain)
Antipyretic (decrease fever)
Anti-inflammatory effects
Reduce PGE2 = attenuating inflammatory effects
- reduce edema/swelling
- attenuate. Bradykinin
- decrease in allodynia (tenderness of skin)
- decreases fever
104
NSAIDs
```
Aspirin
Ibuprofen
Naproxen
Indomethacin
Diclofenac
```
- inhibit the COX II enzyme, results obtained within a week
105
NSAIDs bind to
COX II
Might also bind to COX I (housekeeping functions)
- COX I offers protective effects that prevent stomach upset/bleeding caused by gastric acid, therefore might have GI discomfort
106
Contraindications of NSAIDs
Peptic ulcers
Hypersensitivity to aspirin
Coagulation defects
Severe HF
107
NSAID induced asthma
Arachidonic Acid -> Leukotrienes (LTC, LTD, LTE)
108
Aspirin
Prescribed for CAD pts at risk for thrombosis
- binds covalently to COX I and II in platelets
- inhibits TXA2 = reduces their ability to coagulate
Anti-platelet drug
109
COX I
Released by platelet cells
Which then releases TXA2
- vasoconstrictor
- pro-aggregator
110
COX II
Released from endothelial cells
- releases PGI2 and PGE2
Vasodilator
Anti-Aggregation
111
Celebrex
Selective COX II inhibitor
- inhibits pro-inflammatory prostaglandin (PGE2)
- slightly increases MI/stroke (bc they inhibit PGI2)
Leads to excess TXA2 - negative CV effects (vasoconstrictor, pro-aggregator)
112
Low Dose Aspirin is beneficial for..
CHD
- inhibits COX I and COX II
- small excess of PGI2, yielding positive CV effects
113
TXA2
Responsible for pro-aggregation
| Vasoconstrictor
114
PGI2
Vasodilator
| Anti-aggregator
115
Aspirin inhibits..
TXA2 - reducing ability to coagulate
| Binds covalently to COX I and II
116
Acetaminophen
Tylenol
Paracetamol
NOT an NSAID, as it does not have anti-inflammatory properties
117
Acetaminophen
Narrow therapeutic window
Anti-pyretic, Analgesic
Hepatotoxicity:
- 2-3x of the therapeutic dose
- creates NAPQI -> causes necrosis of the liver
118
What is N-acetylcysteine (NAC)?
Used to treat acetaminophen OD
- promotes metabolism/excretion of the drug
```
7.5g = min toxic dose
<4 = toxic dose for pts with severe liver injury
```
119
Cytochrome p450 is induced in alcoholics, therefore NAPQI is
Toxic
| Byproduct of acetaminophen -> NAPQI
120
Hydrocortisone
Steroidal - anti-inflammatory drugs (cortisol drugs)
121
Prednisolone
Steroidal - anti-inflammatory drugs (cortisol drugs)
122
Dexamethasone
Steroidal - anti-inflammatory drugs (cortisol drugs)
123
Betamethasone
Steroidal - anti-inflammatory drugs (cortisol drugs)
124
Steroid Anti-Inflammatory
Stress response/immune response
125
Steroidal Anti-inflammatory Drugs
Regulate inflammation
Metabolism carbs
Protein catabolism
Immune response/stress response
126
Steroidal Anti-Inflammatory Drugs (Cortisol)
Decrease in COX II -> Decrease in Prostaglandins
Decrease in the activity of immune cells, mast cells/macrophages
- reduces the production of histamine and inflammatory activity
127
Indications for Steroid Anti-Inflammatory Drugs
```
Asthma
Allergic Rxns
IBD
Arthritis
Bursitis
Edema
```
128
Side effects of Steroid Anti-Inflammatory
```
Muscle wasting
Osteoporosis
Suppression of response to infection
Cushingoid Face “moon face”
Iatrogenic Cushing Syndrome
```
129
Metabolic Complications of Steroidal AntiInflammatory Use
Carbs: hyperglycemia, diabetes, wt gain, insulin need
Lipids: increase in fat distribution, deposit of fat at selected anatomical locations - buffalo hump
Proteins: osteoporosis, muscle wasting
```
Poor wound healing
Peptic ulcers
Insomnia
Depression
Psychosis
Increased BP and Edema
```
130
In asthma aerosol delivery..
10-20% inhaled
80-90% swallowed
- under go first pass metabolism in the liver
131
To administer asthma drugs topically to lungs, increase the local concentrations and administer via:
Metered dose inhalers (MDI)
Nebulizers
Dry Powder Inhalers
132
Asthma:
| Anti-inflamm = used to?
Prevent symptoms
Whereas,
Bronchodilators = used to relieve acute symptoms
133
Bronchodilators
Used to relieve acute symptoms
134
Anti-inflammatory in asthma treatment
Used to prevent symptoms
135
B2AR Agonists
SABA
| LABA
136
SABA and LABA
Short acting/Long acting Beta Agonists
137
SABA
B2R Agonist
Lasts 3-4hrs
- bronchodilaton occurs in 15-30 min
- used for relief of acute symptoms/bronchospasm
138
LABAs
Lasts 12 hours
- administered MDI
- lacks anti-inflammatory action
- works well with corticosteroids
139
Terbutaline, Salbuterol, Albuterol, Fenoterol
SABAs
140
Formoterol, Salmeterol, Indacaterol
LABA
141
Adverse effects of B2AR Agonist
Tachycardia
Palpitations
Tremor
Do not use a B2AR agonist as monotherapy!
Black Box Warning
142
Methylxanthines
Relaxes bronchial smooth muscle
- reduces the release of inflammatory mediators/cytokines
- theophylline = effective
5-20mg = improved pulmonary functioning
>20 = anorexia
>40 =Seizures
Has a narrow therapeutic index.
143
Theophylline
Methylxanthines
CNS: increases alertness, cortical arousal
Weak diuretic
Secretes gastric acid
Improves contractility in COPD pts
144
Muscarinic Receptor Antagonists (SAMRA, LAMRA)
Methacholine, Acetylcholine binds to the M2R
Often combined with B2 agonists to enhance dilation
145
Leukotriene Modifiers for Asthma
Anti-inflammatory agent, anti-constrictor
Bronchoconstrictor associated in COPD/asthma with the following symptoms:
- mucus secretion
- increase in bronchial reactivity
- mucosal edema
146
Leukotriene Modifier = Zileuton
Anti-Leukotrienes
5-Lipooxygenase inhibitor (5-LOR)
147
Zarilukast, Montelukast
Blocks LTD4
| Anti-leukotriene
148
Zileuton
Anti-leukotriene
Inhibits multiple CYPs
- hepatitis
- dyespepsia
149
Zafirlukast
Anti-leukotriene
GI disturbances
Inhibits CYP2C9/3A4
150
Montelukast
Anti-leukotriene
| No CYP inhibition
151
Steroid action at the Nuclear Level
Dimerization of steroid-receptor complex at DNA level
| - leads to anti-inflammatory acativity
152
Corticosteroids for Asthma
Inhibits eosinophilia airway mucosal inflammation
- potentiates effects of B2 agonist
- oral steroids for ST treatment
153
Inhaled CS
Have very low bioavailability
Extensive first pass metabolism
Aerosol RX = most effective
154
Biologics for Asthma
Anti-IgE
Anti-IL5
Anti-IL5R
155
Omalizumab
Humanized antibody to IgE
- inhibits IgE binding to receptors
- lessens severity of asthma attacks
- given by subcutaneous injection
156
Reslizumab
Humanized ab to IL5
Decreases SABA use
Increases FEV1
157
Mepolizumab
Humanized ab to IL5
Decreases # of exacerbations
Little effect on FEV1
158
Benralizumab
Ab against IL5-receptor
159
Benralizumab
Ab again at IL5-R
Decreases number of exacerbations
Decreases oral glucocorticoid use
160
For mild-moderate asthma,
As needed SABA
Yet if:
Rescue therapy 2x/wk
Nocturnal symptoms 2x/mo
FEV <80% usual
...then add: ICS = budesonide or oral anti-leukotriene (monteleukast)
161
For refractory or severe asthma:
If poor response to an ICS (fluticasone or budesonide)
| -> add a LABA (salmeterol/formoterol)
162
Common combo-inhalers:
Advair, Symbicort
If don’t respond to combo inhaler, then might be a candidate for anti-IgE, IL-5
ICS+ LABA = safe
163
For pts with COPD, what is recommended as treatment?
Inhaled bronchodilator
Bronchodilator + steroid combo
(Fluticasone:steroid- Vilanterol:LABA)
164
Acute COPD
SABA (albuterol)
| SARA (ipratroprium) or a combo is effective
165
Chronic COPD
LABA
| LAMRA
166
Chronic COPD treatments
LABA
LAMBRA
Corticosteroid (Fluticasone) + LABA (vilanterol)= indicated
167
Statins are contraindicated for...
Pregnant women
168
Statins are approved for use in children who have...
Family of hypercholerestolemia
169
What drugs are for more severe Hypercholesterolemia?
Atorvastain
Rosuvastatin
They are more TG lowering
170
What are the toxic effects of statins?
Elevations of ALT (3x the normal)
Liver function enzymes should be measured initially and then clinically if recommended
Medication should be discontinued if:
- anorexia, malaise, decrease in LDL
171
What are adverse effects of statins?
Myopathy
- first in arms and legs, then the entire body
Fatigue
Effects are reversible when the drug is stopped
Rhabdomyolysis -> Myoglobinuria = can lead to renal failure
(Associated with pts with CK levels of 10x or higher)
172
What drugs can statins interact with?
When given with other drugs that are metabolized by CYP3A4
- grapefruit juice
- inhibitors of organic anion transport
173
Genetic variations in OATP1B1 (1B1) are associated with
Reduced hepatic uptake of simvastain acid
increase in simvastatin acid in plasma
Increase in risk of myopathy
174
Red Yeast Rice as a LDL lowering agent
Statin source
Contains 14 active compounds that inhibit hepatic cholesterol synthesis
Have 12 RYR products = gives variability in monacolin content
175
Monacolin K is also known as ...
Lovastatin
176
PCSK9 inhibitors
Monoclonal antibodies against the PCSK9 Protein
177
HMG CoA reductase inhibitors (statins) side effects
Decreases LDL and TG
| Increases HDL
178
HMG CoA Reductase Inhibitors
Statin
Side effects:
Myopathy
Increased liver enzymes
Contraindications:
Absolute: Active or chronic liver disease
Relative: Concomitant use of certain drugs
