Midterm Flashcards

Pharmacology

1
Q

Kinectics of Statins

A

Extensive first-pass hepatic uptake (OATPIBI)-> (organic anion transporter protein 1B1)

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2
Q

Lovastatin

A

First statin
Metabolized by CYP3A4
DDI- CYP3A4 inhibitors increase risk of myopathy

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3
Q

Reductace inhibitors MOA

A

Competitive/reversible inhibitors
Increase in high-affinity LDL receptors (liver)-> decrease blood LDL levels
Mechanism is transcription
Reduces Rho and Rab proteins (leads to blood vessel relaxation)

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4
Q

Atorvastatin

A

Lipitor
With food AM or PM (better in evening)
Metabolism- CYP3A4
Half life 14 hrs
Monitor- Liver Function test (LFT) and Creatine Kinase (SCR)

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5
Q

AE and DDI of lipitor

A

AE- Myalgia
Discontinue if symptoms of renal failure or myopathy due to rhabdomyolysis develop
DDI- Gemfibrozil, Niacin-> myopathy

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6
Q

Simvastatin

A

Zocor
Very potent 5mg-40mg daily
Monitor- Liver function test (LFT) and signs of myopathy

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7
Q

Pravastatin

A

Pravachol
Should be given either 1 hr or more before or at least 4 hrs following resin
Not a prodrug

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8
Q

Rosuvastatin

A

Crestor
Use low doses with gemfibrozil and cyclosporine

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9
Q

AE and caution of crestor

A

AE - Myalgia
Caution- Renal failure may predispose to rhabdomyolysis, increase INR with concurrent warfarin (due to CYP2C9), heavy alcohol drinkers, Liver disease, proteinuria, Japanese/Chinese- predisposition to myopathy

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10
Q

Pitavastatin

A

Livalo
CI drugs- fibrates, cyclosporine
Does not affect warfarin’s effect (no increase in bleeding risk)

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11
Q

MOA of Bile acid binding resins

A

MoA
Oldest/safest because it does not get absorbed into blood
The bile acid sequestrants are highly positively charged and bind negatively charged bile acids Increases hepatic bile acid synthesis and hepatic triglyceride synthesis
Decreases LDL by stimulating the production of LDL receptors, similar to statins

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12
Q

AE of Bile acid binding resins

A

Chloride salts-> hyperchloremic acidosis, Severe hypertriglyceridemia is a CI (because they increase triglyceride levels), CI in diverticulitis, Malabsorption of vitamin K (clotting issues)
DDI with all anionic drugs

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13
Q

MOA of fibrates

A

PPAR- Alpha (agonist) activation induces fatty acid oxidation/ lipoprotein lipase
Have antithrombotic effects

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14
Q

PK of gemfribozil and fenofibrate

A

Gemfibrozil (does not undergo change), Fenofibrate (undergoes hydrolyzation-> has ester) Gemfibrozil- undergoes enterohepatic circulation, and eliminated through kidneys mostly unmodified
Fenofibrate- isopropyl ester prodrug that is hydrolyzed completely in the intestine

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15
Q

Thera of Fibrates

A

Useful for hypertriglyceridemia
Feno is more effective than gem at increasing HDL
Not much effect on LDL-C
Feno is the fibrate of choice for combo with a statin

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16
Q

AE of fibrates

A

Rashes, Myopathy (gem more than feno), Liver toxicity
Risk of Myopathy increases when given with statins
Avoid fibrates if pts have hepatic or renal dysfunction
Increase risk of cholithiasis (gallstones) when administered with ezetimibe Caution- coumarin anticoagulant

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17
Q

MOA of Ezetimibe

A

Allosteric Non-competitive inhibitor of NPC1L1
Inhibits intestinal absorption of phytosterols and cholesterol
Inhibits cholesterol uptake by inhibiting the transport protein NPC1L1

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18
Q

PK of Ezetimibe

A

Highly water insoluble
Glucuronidated in the intestinal epithelium
Excreted in the feces

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19
Q

Thera of Ezetimibe

A

Monotherapy- used in statin intolerant pts
Synergistic with statin for dyslipidemia
Useful for phytosterolemia

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20
Q

AE of Ezetimibe

A

Low chance for causing myopathy
Bile acid sequestrants inhibit absorption of ezetimibe and should not be administered together

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21
Q

What are the PCSK9 antibodies and their MOA

A

Proprotein convertase subtilisin/ kexin type 9 is a protease that binds to the LDL receptor on the surface of hepatocytes and enhances lysosomal degradation of the LDL receptor, resulting in higher plasma LDL concentrations which decreases LDL levels

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22
Q

Niacins 2 places of action and their MOA

A

Adipose tissue- inhibits the lipolysis of triglycerides by lipase and decreases hepatic triglyceride synthesis
Liver- reduces triglyceride synthesis by inhibiting synthesis and esterification of fatty acids This reduces hepatic VLDL production and LDL levels

23
Q

Omega 3 Fatty Acid / Fish Oil

A

Available OTC up to 1g daily, capsules
Acts on PPAR-alpha (same as fibrates)
Reduces VLDL, triglycerides
Prescription- if triglycerides higher than 1000, pancreatitis

24
Q

Agents decreasing O2 demand

A

(HR, Contractility, Preload, Afterload)- Beta blockers, Some CCB, Organic nitrates,

25
Q

Agents increasing O2 supply

A

(coronary blood flow, Regional myocardial blood flow)- Statins, vasodilators (esp. CCB), antithrombotics

26
Q

MOA of antianginals and its molecular mechanism

A

Decrease myocardial oxygen requirement. In some pts, the nitrates and CCB cause a redistribution of coronary flow which relieve spasm and increase oxygen delivery.
Increase cGMP, Decrease intracellular Ca++, and stabilizes vascular smooth muscle cell membrane

27
Q

What muscles do nitrates work on and do not work on

A

Effect mostly smooth muscles but not cardiac and skeletal muscles

28
Q

What are the effects of nitrates on smooth muscle

A

relaxation of veins with increased venous capacitance and decreased ventricular preload, heart size and output decreases, reflex responses: tachycardia and increased cardiac contractility. Redistribution of coronary flow from normal to ischemic regions

29
Q

MOA of nitrates

A

Release nitric oxide which activates soluble guanylate cyclase (sGC) causing an increase in cGMP activating PKG, which activates myosin phosphate resulting in blood vessel relaxation

30
Q

PK of nitrates

A

High first pass metabolism (oral bioavailability is low)
Excretion- glucuronide derivatives of the denitrated metabolites by the kidney
CAUTION (all nitrates)- don’t use with sildenafil

31
Q

AE of NTG

A

Throbbing headache, Hypotension, Tachycardia (reflex), Sublingual bruning, Contact dermatitis (patch-> that’s why you change patch location every time), Tolerance buildup

32
Q

Isosorbide Dinitrate

A

Longer SL coverage than NTG
Metabolized to active metabolites including the mononitrate (longer action) Sublingual dose rarely used because of high tolerance

33
Q

Isosorbide mononitrate

A

Bypasses first pass metabolism (low tolerance liability)
Metabolite of the dinitrate
Prophylactic: not used during periods of angina

34
Q

Extra info of NTG

A

Use Viagra before nitrates
SL NTG is used for acute attack and prevention only because time of action is low

35
Q

MOA of CCB

A

DHP- Bind alpha 1 and block from inside: open channels and inactivated channels
Organ system effects- CCB have more effect on arteries, DHP have greater vascular effect than cardiac, Verapamil and diltiazem (they have major effect on heart) are both similar so use one.

36
Q

Altepase (t-PA)

A

Low affinity for free plasminogen but a very high affinity for plasminogen bound to fibrin in a thrombus (fibrin-specific agent)
Half life- 5 mins (continuous IV)
Give within 3 hours of Acute ischemic stroke (acute MI or heart attack)
Reteplase and Tenecteplase- slightly modified proteins that have longer half lives

37
Q

AE and CI of Altepase

A

Hemorrhage (increased bleeding risk)
CI- Heparin, pregnancy, bleeding liability, metastatic cancer
Alternatives to Alteplase- mechanical reperfusion, mechanical thrombus extraction

38
Q

Aspirin MOA

A

Causes platelet aggregation and is a potent vasodilator
Irreversible Inhibition of COX-1
Action lasts for lifetime of the platelet (7 to 10 days)

39
Q

AE of Aspirin

A

GI bleeding, Occult bleeding (bleeding without cause), prolongation of bleeding time, iron deficiency anemia, thrombocytopenia, leukopenia, hemolytic anemia
CI- infants and small children (Reye’s syndrome), avoid in pregnancy
Decreased effect- NSAIDs, Antagonize probenecid
Increased effect- Methotrexate, Valproic acid, NSAI (GI bleed), Anticoagulants, Sulfonylurea hypoglycemics, Digoxin

40
Q

Which of the P2Y12 ADP receptor agonists are reversible and which are irreversible

A

Irreversible - Ticlopidine, Clodpiogrel, Prasgurel
Reversible - Ticagrelor and Cangrelor

41
Q

Clopidogrel MOA, thera, and AE

A

MoA:
P2Y12 receptor couples to Gi and is activated by ADP which inhibits adenylyl cyclase resulting in lower levels of intracellular cyclic AMP and platelet activation
in lower levels of intracellular cyclic AMP and platelet activation
Thera:
Commonly used with baby aspirin
AE:
Bleeding (risk is higher with aspirin and anticoagulant)
DDI- Inhibits CYP2C19

42
Q

Prasugrel

A

MoA same as clopidogrel
Efficacy is higher but toxicities (bleeding) also higher than Clopidogrel
Faster onset of action- 30 mins
Prodrug
AE- Bleeding
DDI- CYP3A4 inhibitors (protease inhibitors, statins, grapefruit)

43
Q

Ticlopidine

A

Same MOA as Clopidogrek
DDI - CYP3A4 inhibitors (PI, Statins, Grapefruit)

44
Q

Ticlopidine

A

Same MOA as clopidogrel
AE - 1% chance of Leukopenia

45
Q

Ticagrelor MOA, Thera, AE, DDI

A

Non-competitive allosteric inhibitor
Faster onset + offset of action than Clopidogrel
Thera- Coronary stent thrombosis
AE- Dyspnea (difficulty breathing~ 14%), bleeding
DDI- CYP3A inhibitor, increases statin conc.

46
Q

Cangrelor and AE

A

Used for precutaneous coronary intervention (PCI)
AE - bleeding (more than clopidogrel)

47
Q

What are the glycoprotein IIb/IIIa receptor blockers and their MOA

A

Abciximab, Eptifibatide, Tirofiban
MOA - Platelet activation and aggregation

48
Q

Info about Abciximab and its AE and CI

A

Fab fragment
Platelet-bound:18-24 hrs
AE- bleeding
CI- Bleeding, cranial hemorrhage, thrombocytopenia

49
Q

Eptifibatide

A

Ligand containing Arg-Gly-Asp (RGD) sequence
Cyclic peptide derived from rattlesnake venom containing a variation of RGD motif (KGD)
Renal elimination
Similar CI and AE to abciximab

50
Q

Tirofiban

A

RGD mimetic
can bind to bile sequestering agent via anion exchange mechanism

51
Q

Dipyridamole MOA

A

directly inhibits PDE5 which converts cyclic AMP to 3-5 AMP resulting in an increase in cAMP cascade platelets

52
Q

Extra info about Dipyridamole

A

Vasodilator and antithrombotic (prevents platelet aggregation)
Approved for secondary prevention of stroke when combined with aspirin
Its metabolite has no impact on bleeding time or platelet aggregation

53
Q

Cilostazol

A

Vasodilator
Inhibits phosphodiesterase
Treats intermittent claudication