Medchem Exam 1

Front 1

Ginko biloba
a.) MOA

Back 1

Inhibits PAF, platelet activating factor (role in platelet aggregation). Ginko biloba is an antiplatelet agent

Front 2

Feverfew
a.) MOA (2)

Back 2

Inhibits arachadonic acid release (prostaglandin precursor). Also inhibits platelets binding to collagen in the extrinsic pathway

Front 3

Ginger
a.) MOA

Back 3

Inhibits platelet cyclooxygenase products = inhibit platelet aggregation

Front 4

Garlic
a.) MOA (2)

Back 4

Allicin gets broken down to ajoene, which has fibrolytic properties as well as inhibits platelet aggregation

Front 5

Pynogenol

Back 5

This pine bark extract prevent platelet aggregation

Front 6

What stimulates Nitric oxide? (4)

Back 6

Stress on vessels, hypoxia, neurochemicals (bradykinin, histamine, acetylcholine), drugs (ACE where the bradykinin causes NO release, CCB causes NO release from endothelium, statins which stabalize eNOS for more NO production)

Front 7

Biosynthesis of nitric oxide
a.) precursor
b.) reaction
c.) enzyme
d.) product

Back 7

Biosynthesis of nitric oxide
a.) L-arginine
b.) gets oxidized to Ng-hydroxy-L-arginine
c.) eNOS (endothelial nitric oxide synthase)
d.) citruline and nitric oxide

Front 8

Why is nitric oxide so short lived? (2)

Back 8

Super oxide anion has high affinity for NO. It reacts with heme or guanylate cyclase

Front 9

MOA of NO
a.) receptor based MOA
b) enzyme based MOA

Back 9

MOA of NO
a.) NO binds to nitrate and causes oxidation of sulfhydryl groups on the receptor, leading to vascular relaxation and increase O2 supply
b.) NO activates guanylate cyclase, which catalyzes GTP to cGMP. An increase in cGMP means that it will phosphorylate myosin light chain kinase. This means it can't be activated by calmodulin-Ca complex, which means that myosin can't get phosphorylated. It won't bind with actin to cause a contraction. Thus vasodilation and increased O2 supply will occur.

Front 10

How does nitrate tolerance occur?

Back 10

Nitrate esters react with thiols to make [nitrosothiol] -> nitric oxide. There are only a finite amount of thiols in the liver and endothelium. When they are all consumed, the nitrate can't be converted to nitric oxide, thus nitrate tolerance occurs.

Front 11

What nitrate ester is involved in treating cyanide poisoning?

Back 11

Amyl nitrite

Front 12

a.) What does PDE5 do?
b.) what does a PDE5 inhibitor do?
c.) structural feature of PDE5 inhbitor
d.) drug

Back 12

a.) PDE5 catalyzes the degradation of cGMP to GMP
b.) thus a PDE5 inhibitor prevents cGMP breakdown, leading to an increase in cGMP, which will phosphorylate myosin light chain kinase instead of it getting activated by calmodulin-Ca complex, thus no myosin phosphorylation, which can't bind to actin to cause a contraction, thus vasodilation occurs
c.) guanidine
d.) sildenafil

Front 13

a.) What does PDE3 do
b.) what does PDE3 inhibitors do? DEPENDS ON LOCATION
c.) indication (2)
d.) drugs (2)

Back 13

a.) PDE3 catalyzes the degradation of cAMP to AMP.
b.) IN HEART TISSUES PDE3 inhibitors inhibit cAMP degradation, leading to increased cAMP levels, causing increased intracellular Ca2+ levels in the myocardial tissue, leading to troponin C-Calcium complex, leading actin to be free to bind with myosin-P to cause cardial contraction. IN PLATELET AGGREGATION, cAMP activates protein kinase, which phosphorylates proteins, causing protein-phosphorylation complex, chelates with calcium, decreased mobilzatoin so no platelet shape change, no receptor revealed, no arachadonic acid and txa2 synthesis, no platelet aggregation.
c.) since PDE3 inhibitors increase the force of contraction, they are used for CHF management, not angina. Also decreases platelet aggregation

Front 14

a.) How do potassium/ K channels fit into decreased vasocontriction?
b.) drugs

Back 14

There is a ATP-sensitive postassium channel opener. When opened, there is a rapid efflux of K, resulting in decreased intracellular K, leading to calcium channels to close in the vascular smooth muslces. This causes a decrease in intracellular calcium, leading to no calmodulin-Ca complex which can't activate myosin light chain kinase, can't phosphorylate myosin, can't bind to actin = no vasoconstriction.
b.) minoxidil, hydralazine

Front 15

Dipyridole
a.) MOA (2)

Back 15

Dipyridole
a.) Decreases platelet aggregation by increases cAMP in hemestasis. Also is a adenosine deaminase inhibitor, increasing the levels of adenosine, a coronary vasodilator.

Front 16

Why do you want to block late Na current?

Back 16

In increase in Late Na entry is seen in heart failure and ischemia. Increase in Late Na means increase in total intracellular Na, leading to increased Calcium via the reverse mode of Na-Ca exchanger. Increase in intracellular calcium means calcium overload, leading to ischemic damage, increase myocardial oxygen consumption, and increase vascular space constriction which decreases coronary blood flow.

Front 17

Ranolazine

Back 17

Late Na inhibitor. Want to inhibit late Na entry because increased Na intracellularly = increased Ca via reverse mode of Na-Ca exchanger. Calcium overload = ischemia damage, decreased coronary flow, increased myocardial oxygen consumption. Inhibit this to decrease ischemia and heart failure.

Caution drinking grapefruit juice bc metabolized via 3A4 and 2D6

Front 18

Grapefruit juice
a.) interactions

Back 18

Grapefruit juice
a.) CYP450 inhibitor. Change in AUC in CCB, ranolazine (late Na inhibitor)

Front 19

guanylate cyclase (2)

Back 19

Nitric oxide, nesiritide

Front 20

Nesiritide

Back 20

Binds to guanylate cyclase to increase cGMP levels, a second messenger for vascular smooth muscle relaxation, dilation of veins and arteries, and increased fluid excretion by the kidneys.

Front 21

Hydralazine MOA (2)

Back 21

K channel opener and NO maker.

1.) Hydralazine activates the ATP-modulated postassium channel, causing an efflux of potassium. This leads to decreased intracellular K. Decreased intracellular K means calcium channels stay closed, resulting in decreased intracellular calcium, no calcium-calmodulin complex to activate MLCK, no myosin-p + actin = no contraction in vasculature

2.) Stimulates formation of nitric oxide via the endothelium, which activates guanylate cyclase to make cGMP. Increase in cGMP = phosphorylation of MLCK (not activated), no myosin-P + actin = no contraction

Front 22

Nitrate esters
a.) MOA

Back 22

a.) nitroglycerin reacts with endogenous liver/ endothelium esters to make nitrosothiol, undergoes enzyme to yield nitric oxide, which will then react to nitrate receptor or guanylate cyclase to cause vasodilation

Front 23

Voltage gated ion channels (2)

Back 23

Sodium, calcium

Front 24

Mushroom
a.) drug class
b.) SAR

Back 24

a.) Sodium channel blockers. Physical occlusion.
b.) hydrophobic bulk (cap), spacer, ionizable 2/3 amine (stalk)

Front 25

Sodium/ Na channel blockers
a.) SAR
b.) how are they classified?
c.) how is their MOA determined?
d.) indication

Back 25

Na channel blockers
a.) hydrophobic bulk (cap), spacer, ionizable 2/3 amine (stalk)
b.) via dissociation rate. Fast = weak IB, intermediate= IA, slow = potent Na blocker, IC
c.) if they have hydrolyzable bulk, they work within the membrane. Ionizable amine = extracellular & intracellular
d.) antiarrhythmic

Front 26

Class IA Na blockers
a.) dissociation rate
b.) drugs (3)

Back 26

Class IA Na blockers
a.) intermediate
b.) quinidine, procainamide, disopyramide

Front 27

Procainamide
a.) side-effect
b.) class
c.) MOA (3)

Back 27

Procainamide
a.) drug-induced lupus because of the aniline. Usually in patients that are slow acetylators
b.) class IA intermediate Na blocker
c.) blocks Na channel, decreases rate of phase 0 depolarization, blocks K channel (like quinidine)

Front 28

Quinidine
a.) class
b.) major MOA (2)
c.) minor MOA

Back 28

Quinidine
a.) IA Na blocker
b.) blocks Na channel & decreases rate of phase 0 depolarization
c.) blocks K channel (like procainamide)

Front 29

Disopyramide
a.) class

Back 29

Disopyramide
a.) IA Intermediate blocker

Front 30

Class IB Na blockers
a.) MOA
b.) dissociation rate

Back 30

Class IB Na blockers
a.) shortens phase III repolarization, little effect on phase 0 depolarization (class IA & IC)
b.) fast dissociation, low potency

Front 31

Lidocaine
a.) class
b.) unique characteristics (3)

Back 31

Lidocaine
a.) IB-fast dissociation Na blocker
b.) reversible amine for stability/limits hydrolysis but still occurs, no aniline = no drug induced lupus or K blockage (like IB procainamide)

Front 32

Orthostatic hyptension

Back 32

The S isomer of propafenone (1C Na blocker)

Front 33

What class are Beta1 blockers?

Back 33

Class II

Front 34

Potassium/ K channel blockers
a.) class
b.) MOA (2)

Back 34

K channel blockers
a.) class III
b.) blocks K efflux, increases repolarization time

Front 35

Benzofuran

Back 35

Seen in class III K blockers (amiodarone, dronedarone)

Front 36

What class are calcium channel blockers?
a.) MOA

Back 36

Class IV
a.) decreases rate of repolarization via blockade of calcium influx

Front 37

IP3

Back 37

Second messenger when ETa receptors get activated via ET-1. Increased IP3 causes calcium to be released from the SR to cause vascular contraction (via calmodulin-ca complex that activates MLCK which phosphorylates myosin P + actin = contraction)

Front 38

Activation of ETa receptor causes

Back 38

vasoconstriction

Front 39

Activation of ETb receptor causes

Back 39

vasodilation or vasoconstriction

Front 40

MOA of prostacyclin agonists

Back 40

These Gs-coupled protein receptors stimulate adenylate cyclase, causing an increase in cAMP, which causes the opening of Calcium activated K channels. Increase in K conductance causes calcium channels to close, which decreases contractions.

Front 41

What drugs treat PAH?
a.) major (3)
b.) alternatives (3)

Back 41

a.) Endothelin antagonists, prostacyclin agonists, serotinin 5-HT2b antagonists
b.) CCB, nitrates, PDE5 inhibitors

Front 42

MOA of endothelin receptors

Back 42

These Gq proteins form the second messenger IP3. Increases IP3 causes release of calcium from the sarcoplasmic reticulum. Increased intracellular calcium = contraction

Front 43

How does cAMP increase and decrease contraction?

Back 43

Increase contraction via PDE3 inhibitor, which inhibits degradation of cAMP, which increase intracellular calcium, which binds to troponin-C to free actin to bind to Myosin-P to cause contraction
b.) decrease contraction in prostacyclin agonists, which stimulates adenylate cyclase to make cAMP which opens calcium-mediated K channels. Increase K causes calcium channels to close, decreasing contraction.

Front 44

High cGMP

Back 44

results in phosphorylation of MLCK = no contraction. Seen in PDE5 inhibitors

Front 45

Serotinin antagonists
a.) indication
b.) receptor
c.) MOA

Back 45

Serotinin antagonists
a.) PAH
b.) 5-HT2b
c.) block this receptor, stops serotonin-mediated growth and proliferation

Front 46

Fibrolytic phase: Explain the cascade

Back 46

Plasminogen gets catalyzed to plasmin via t-PA, then plasmin is the enzyme that degrades fibrin to fibrin degradation products.

Front 47

Problems with streptokinase (3)

Back 47

Streptokinase, a fibrin degrader, has a short half-life (possible so short that it can't lyse clots), it causes hypersensitivity reactions, and the antibodies to strep infections also affect streptokinase

Front 48

tPA MOA
a.) main SAR
b.) affinity

Back 48

tPA MOA is to catalyze plasminogen to plasmin.
a.) serine protease
b.) low affinity to free plasminogen, high affinity to plasminogen bound to fibrin

Front 49

Lysine antagonists
a.) indication
b.) MOA

Back 49

Lysine antagonists (amicar/ aminocaproic acid)
a.) bleeding too much and need clots
b.) there are lysine receptors in plasminogen and plasmin (agents that degrade fibrin). By blocking these receptors, there is a decrease in plasmin and a decrease in fibrin breakdown.

Front 50

Serine protease inhibitor
a.) indication
b.)

Back 50

Serine protease inhibitor
a.) prevents blood loss
b.) serine protease is the main SAR in t-PA, the agent that activates plasminogen to plasmin. Thus inhibiting serine protease inhibits plasmin and thus fibrin degradation.

Front 51

Inhibits cyclooxygenase products

Back 51

Ginger

Front 52

Inhibits arachadonic cascade

Back 52

Feverfew

Front 53

Inhibits PAF

Back 53

Ginko biloba

Front 54

Broken down to allicin, which is broken down to ajoene, which has fibrolytic properties and also inhibits platelet aggregation

Back 54

Garlic

Front 55

Pine bark extract that inhibits platelet aggregation

Back 55

Pynogenol

Front 56

Formation of atherosclerotic plaque
1.) how does it start
2.) location and action
3.) player involved and action
4.) action of product
5.) second action of product and player
6.) action, location, product
7.) end results

Back 56

Atherosclerosis formation:
1.) Starts with high LDL
2.) In the arteria intima, LDL gets oxidized
3.) macrophage digests LDL and frees the cholesterol
4.) cholesterol gets re-esterified by ACAT
5.) high esterified cholesterol = foam cells in the presence of macrophages
6.) foam cells accumulate in the arteria intima and become fat streaks
7. fat streaks become plaque = atherosclerosis

Front 57

MOA of BIle Acid sequestrants
a.) Endogenous pathway
b.) Exogenous pathway

Back 57

MOA of BA sequestrants
a.) BA sequestrants will bind to bile acids and increase their fecal elimination. This causes a decrease in bile acid levels, so hepatic cholesterol gets used up to make more bile acid. This decreases cholesterol levels. However, a negative effect is that a decrease in cholesterol means an increase in LDL receptors and stimulation of HMG CoA reductase, leading to an increase in cholesterol, although it is not significant.
b.) BA sequestrants decrease the absorption of dietary fats and cholesterol

Front 58

Niacin MOA (2)

Back 58

Niacin MOA
1.) niacin receptor agonist: inhibition of lipolysis = decreased free fatty acid, decreased biosynthesis of triglycerides and VLDL
2.) stimulation of lipoprotein lipase: increases the degradation of VLDL and thus LDL decreases

Front 59

Flushing MOA
a.) Which Niacin form?
b.) which niacin product causes this?
c.) MOA

Back 59

Flushing MOA
a.) happens in the IR form of niacin
b.) nicotinuric acid
c.) IR niacin quickly saturates the nicatinamide pathway, so the glycin conjugation pathway starts and the nicotinuric acid product causes flushing

Front 60

Hepatotoxicity in niacin
a.) which niacin form?
b.) which niacin product?
c.) MOA

Back 60

Hepatoxicity in niacin
a.) controlled release
b.) nicotinamide
c.) Since you get a steady release of drug over time, the nicotinamide pathway doesn't get saturated enough to start the glycine conjugation pathway and make nicotinuric acid, the product responsible for flushing. Instead, you get more nicotinamide product, which is responsible for hepatotoxicity.

Front 61

Statins
a.) Main SAR (2)

Back 61

Statins
a.) 3,5 dihydroxy acid (open lactone = active, closed lactone = prodrug), lipophilic planar anchor (make sure it has double bond)

Front 62

Rosuvastatin metabolism

Back 62

N-dealkylation

Front 63

Fluvastatin metabolism

Back 63

ONDealkylation, aromatic hydroxylation

Front 64

Simvastatin

Back 64

Elimination and addition of H20 across double bond

Front 65

Lovastatin

Back 65

Elimination and addition of H20 across double bond

Front 66

Pravastatin

Back 66

Epimerization of alcohol

Front 67

PPAR alpha receptor
a.) MOA
b.) drug

Back 67

PPAR alpha receptor
a.) increases gene expression to increase HDL
b.) fibrates

Front 68

Lipoprotein lipase stimulation
a.) seen in (2)
b.) MOA

Back 68

Lipoprotein lipase stimulation
a.) niacin, fibrates
b.) decrease TG

Front 69

MOA of fibrates
3

Back 69

1.) Stimulates lipoprotein lipase to degrade TG (like niacin)
2.) PPAR alpha agonist increases gene expression of HDL
3.) Increase LDL affinity to receptor to have it removed from circulation quickly and decrease its amount

Front 70

Fibrates
a.) SAR
b.) what increases half-life?

Back 70

a.) Ar-X-Spacer-Isobutyric acid
b.) chloro group on the Ar

Front 71

Ezetimibe
a.) MOA (3)
b.) SAR (3)

Back 71

Ezetimibe
a.) inhibit cholesterol absorption on the small intestine brush border, increase plasma cholesterol clearance, and decrease hepatic cholesterol stores
b.) b-lactam ring for activity, OH for targeting, para-fluro on Ar to decrease metabolism

Front 72

1.) Carbonic acid SAR
2.) Loop SAR
3.) Thiazide SAR
4.) Thiazide-like SAR
5.) Aldosterone SAR
6.) Na/K exchange

Back 72

1.) thiadiazole core + sulfamoyl
2.) alpha, beta unsaturated + phenoxy acetic acid or 2 or 3 aminobenzoic acid
3.) 1,2,4 benzothiadiazine 1,1 dioxide
4.) amide
5.) steroid, 3-keto-4-ene
6.) pteridine analog, closed lactone

Front 73

ACE Inhibitors MOA (2)

Back 73

1.) ACE converts ang I to ang II, a potent vasoconstriction. Thus it inhibits vasoconstriction
2.) ACE degrades bradykinin. Thus inhibiting its degradation increases bradykinin levels, which stimulate the biosynthesis of PGI2 and NO (vasodilators) which contribute to the persistent cough

Front 74

1.) ACE SAR
2.) ARB SAR

Back 74

1.) zinc + carboxylic anion binding
2.) Biphenly + acidic ortho, imidazole, linear hydrophobic

Front 75

Renin
a.) type of enzyme (2)
b.) specific sequence
c.) inhibitor types (2)

Back 75

Renin
a.) aspartyl protease, endopeptidase
b.) amine, side-chain, carbonyl
c.) reduced amide (carbonyl to CH2); hydroxyethylene (carbonyl to OH). point is to make it non-hydrolyzable

Front 76

Vascular phase
a.) Major events (3)

Back 76

Vascular phase
a.) Vasoconstriction, release of ADP and PGI2, plasma clotting factors exposed to collagen and endothelial basement membrane

Front 77

Platelet phase
a.) Role of platelets
b.) explain roles

Back 77

Platelet phase
a.) Hemostatic phase, thromboplastic phase
b.) In the hemostatic phase, ADP causes platelets to adhere. Then there is a mobilization of calcium that causes platelets to change shape and reveal the fibrinogen receptor; fibrinogen binds to the receptor and starts the arachidonic acid cascade, leading to the synthesis of PGI2 and TXA2

Front 78

cAMP in platelet aggregation
a.) explain role and its MOA

Back 78

a.) cAMP works to decrease platelet aggregation by decreasing Ca mobilization. cAMP activates protein kinase, which phosphorylates proteins to cause a protein-phosphate complex. This complex chelates with calcium, causing calcium unable to be mobilized to change platelet shape, reveal fibrinogen receptor, no fibrin bound, no arachonic acid cascade and no TXA2 synthesis so no platelet aggregation

Front 79

adenosine deaminase inhibitor
a.) MOA
b.) indication

Back 79

Adenosine deaminase inhibitor
a.) adenosine deaminase catalyzes adenosine to inosine. So inhibitor causes increased adenosine, increased cAMP, decreased calcium, no platelet aggregation

Front 80

Fibrinogen receptor antagonists
a.) SAR

Back 80

Fibrinogen receptor antagonists
a.) RGD (arginine, glycine, aspartic acid) OR Need to have a positive and a negative end

Front 81

ADP receptor antagonists
a.) SAR
b.) indication
c.) caution

Back 81

ADP receptor antagonists
a.) thienopyridine (open form is active)
b.) inhibit platelet aggregation
c.) metabolized by cyp3A4 and cyp2C19, so caution cyp inhibitor meds

Front 82

Thienopyridine

Back 82

ADR receptor antagonists

Front 83

Lactone notes
a.) open for activation
b.) closed for activation

Back 83

Lactone
a.) statins, ADP antagonists
b.) aldosterone blockers

Front 84

Aspirin
MOA

Back 84

Aspirin
a.) Inhibits ADP release. Also irreversibly acetylates cyclo-oxygenase, inhibiting the arachadonic acid cascade, so no TXA2 or PGI2

Front 85

Calcium's role in the coagulation cascade

Back 85

Dicarboxylic acid chelates with calcium. It is chelated to glutamic acid residues, causing prothrombin to change shape and be active with factor Xa to make thrombin, which can be used to change fibrinogen to fibrin

Front 86

Vitamin K deficiency

Back 86

No vitamin K means that vitamin K can't be oxidize to carboxylate prothrombin. No glutamic acid carboxylation of prothrombin means that prothrombin can't chelate with calcium and thus it has a defective shape and cant be in its active conformer to yield thrombin, thus no fibrin

Front 87

Warfarin MOA (2)

Back 87

Inhibits vitamin K epoxide reductase and vitamin K reductase. These are enzymes that recycle oxidized K to reduced K. No reduced K means it can't be use for the glutamic acid carboxylation of prothrombin (with calcium), thus no thrombin, thus no fibrin

Front 88

Why doesn't warfarin need a loading dose?

Back 88

Warfarin only has effect on newly biosynthesized vitamin K, not present vitamin K in the circulation. So using a loading dose will overshoot the necessary amount once the half-life of the factors are up

Front 89

Ginseng

Back 89

decrease warfarin effectiveness

Front 90

Cranberry products

Back 90

flavanoids that inhibits CYP450 isozymes (2C) which affect warfarin metabolism

Front 91

Glucosamine

Back 91

decreases warfarin action

Front 92

Vitamin E

Back 92

inhibits platelet aggregation and antagonizes vitamin K dependent factors

Front 93

Coenzyme Q10

Back 93

decrease warfarin effects bc similar to menaquinone

Front 94

Fish Oil

Back 94

antithrombic effects; inhibit coagulation if >3g/day

Front 95

Red Clover (2)

Back 95

has coumarins, which are anticoagulants; also inhibits 3A4 and cyp2c9 (warfarin

Front 96

pomegranate juice

Back 96

inhibits cyp2c9 (warfarin)

Front 97

What is the role of anti-thrombin III (AT-III) with factor Xa?

Back 97

AT-III, in the presence of heparin, will change its shape so that factor Xa will bind and can't be used to change prothrombin to thrombin, thus no fibrin.

Front 98

Heparin
a.) MOA
b.) SAR

Back 98

Heparin
a.) Heparin increases the complexation of AT-III to factor Xa, causing the inhibition of prothrombin activation and thus no fibrin
b.) pentasaccharide sequence (with negative charge)

Front 99

1.) How to correct heparin overdose
2.) How to correct warfarin overdose

Back 99

1.) protamine sulfate, a positevly charged protein that neutralizes heparin and prevents it from binding to AT-III
2.) vitamin K

Front 100

Direct factor Xa inhibitors

Back 100

oxazolidinone

Front 101

oxazolidinone

Back 101

direct factor Xa inhibitor

Front 102

D-phe-Pro-Arg

Back 102

Thrombin inhibitor (mimics the substrate of fibrinogen)

Front 103

Thrombin inhibitor
a.) SAR

Back 103

Thrombin inhibitor
a.) d-Phe-Pro-Arg

Front 104

LMW Heparin

Back 104

Binds to AT-III to cause shape change for factor Xa (no prothrombin to thrombin). Does not interact with thrombin (so can still catalyze fibrinogen to fibrin)

Front 105

Regular length heparin

Back 105

Binds to AT-III to cause shape change for factor Xa binding (no prothrombin to thrombin). Also binds to thrombin for inhibition. (so can't catalyze fibrinogen to fibrin)