Pharm Test Block 3 Week One

Front 1

aspirin

Back 1

antiplatelet

MOA: inhibits COX, platelets dont produce TXA2, cant activate eachother as well, and dont form the initial platelet plug. also, inhibits PGG2 and PGH2 formation. inhibits vasoconstriction?

USES:
1. prevent heart disease
2. acute MI - if pt has chest pain give them aspirin to prevent coagulation with ruptured plaque

NOTES:
inhibits circulating platelets for their lifetime (7-10 d)

Front 2

NSAIDs

Back 2

antiplatelet

Front 3

dipyridamole

Back 3

antiplatelet
dipyridamole [2 ways to prevent platelet activation]

USE: phrophylaxis of thromboembolic events

MOA: inhibits platelet activation by increasing platelet cAMP levels
2 methods:
a. blocking uptake of adenosine -> + A.C -> inc. cAMP
b. inhibits phosphodiesterase
inc'd cAMP inhibits platelet activation

Front 4

CLOPIDOGREL

Back 4

antiplatelet

MOA: blocks ADP receptor

USES: prevent thromboembolic events

similar: ticlopidine (clop)

Front 5

abciximab

Back 5

antiplatelet

MOA: blocks GP IIb/IIIa receptors (blocks activated receptors from binding fibrinogen)

USES: prevent thromboembolic events

Front 6

WARFARIN

Back 6

oral anticoagulant

MOA: inhibits epoxide reductase, preventing vitamin K from being converted to active form.
K+ is a necessary cofactor for the addition of a carboxyl group from glutamic acid to factors II, VII, IX, and X. w/o K+, inactive clotting factors are synthesized by liver

NOTES:
MUST BE MONITORED!!
-highly protein bound
-dose independent (highly ep on metabolism)
-green leafy veggies and cereals require extra warfarin. diets def. in vitamin K require less warfarin
-teratogenic - not for use in pregnancy (heparin better for pregnant women)
-antibiotics kill normal flora that make vitamin K and can lead to vitamin K deficiency and bleeding

actions are not immediate (vs. heparin). circulating factors are depleted enough in a week. can cause coagulation first b/c of depletion of protein C!!
monitor with INR=(PT/mean normal PT)^ISI. window b/t 2 and 3

risk factors for thromboembolic events: age, HTN, cerebrovascular and cardiovascular disease, DM, hyperlipidemia, smoking, drugs, INR < 2
risk factors for bleeding: age, hx of stroke or GI hemorrhage

Front 7

HEPARIN

Back 7

anticoagulant

used for prophylaxis AND after a thromboembolic event (works immediately)

MOA:
1. pentapeptide binds AT and increases accessibility to Active Site
2. binds Xa or IIa and inactivates it (like enoxaparin)
3. catalytic template - binds both AT and factor IIa, Xa, IXa, XIA, and XIIa. AT inactivates the factor, and heparin is ready to go again

NOTES:
antidote = protamine
monitor with PTT
MUST BE MONITORED
-binds many things
-liver failure will inc effects
-kidney failure will increase effects

S/E: HIT
heparin binds to platelet factor 4 and triggers immune response against these complexes. platelet FcR binds the complexes causing both thrombocytopenia and thrombosis. detect with platelet 4 antibody test.
Rx for HIT is DTI such as lepirudin or argatroban



drug of choice for pregnancy (doesnt cross placenta like warfarin)

Front 8

ENOXAPARIN

Back 8

LMWH (anticoagulant)

fragments of UFH
in contrast to heparin, it mainly inactivates Xa b/c the fragments are too short to bind Xa and AT
most frags donts have the pentapeptide to bind AT
most patients are not monitored, but you can monitor with anti-factor Xa test.

monitor: renal failure pts, large pts, small cachetic pts, women, those with tumors, pts with DIC, pts with bleeding or thrombi
may cross react with HIT antibody

Front 9

lepirudin

Back 9

direct thrombin inhibitor (from leeches)

use: heparin alternative, esp for HIT

no antidote
monitor with PTT (like heparin)

Front 10

argatroban

Back 10

direct thrombin inhibitor

ARGO LIKES LEACHES

monitor with PTT (like heparin)

Front 11

streptokinase

Back 11

plasminogen activator (fibrinolytic)

no intrinsic nzm activity. binds plasminogen and exposes active site. then SK-plasmin converts SK-plasminogen to more SK-plasmin.
USE:
1. acute MI

for strokes, use TPA (ALTEPASE) instead

Front 12

urokinase

Back 12

plasminogen activator (fibrinolytic)

directly converts plasminogen to plasmin - enzyme activity
(vs streptokinase-indirect)
USE:
1. acute MI

use TPA (altepase for strokes)

Front 13

eta-aminocaproic acid

Back 13

fibrinolysis inhibitor

USE: hemophiliacs (can make weak blood clot)

Front 14

tranexamic acid

Back 14

fibrinolysis inhibitor

USE: hemophiliacs (can make weak blood clot)

Front 15

ALTEPASE

Back 15

plasminogen activator (recombinant tPA)

fibrin selective - its activity is increased 100x when bound to fibrin, which decreases nonspecific fibrinolytic activity (it should just occur at the clot)
USE:
1. acute MI
2. pulmonary embolus, DVT, arterial thrombosis
3. acute nonhemorrhagic CVA (sometimes!)

Front 16

antihemophilic factor

Back 16

factor VIII

Front 17

phytonadione

Back 17

vitamin K

Front 18

fondaparinux

Back 18

fondaparinuX X X X
anticoagulant

Jane Fonda has hypercoagulation

pentasaccharide that binds factor Xa and inhibits it.

even smaller than lwmh

Front 19

folic acid

Back 19

needed to transfer methyl groups in purine and amino acid synthesis (folate cycle)
found in green leafy vegetables, liver, kidney, yeast

deficiency - megaloblastic anemia

measure levels with RBC-folate

prophylactic for pregnancy, alcoholism, dialysis, hemolytic anemia

drugs which inhibit folate abs: oral contraceptives, isoniazid, phenytoin

methotrexate and trimethorim block DHF reductase. these patients have "folate deficiency" but giving folate would be counterproductive.

Front 20

vitamin B12

Back 20

1. cofactor in methyl transfer from THF to methionine (eventually making SAM)

2. cofactor in isomerization of methyl-malonyl CoA to succinyl CoA (utilization of fatty acids)

found in meat, eggs, and dairy, stored in liver for YEARS

absorption: binds IF (from parietal cells) in stomach, absorbed in distal ileum

deficiency: there are NEUROLOGICAL SYMPTOMS!! (unlike folate) - paresthesias, weakness, ataxia. giving folate may mask!

Rx for def:
oral supplements if ileum and IF are intact
parenteral otherwise

labs to detect dficiency:
-vitamin B12 in serum
-MMA (will be HIGH!! in B12 deficiency)

Front 21

iron

Back 21

needed for hemoglobin (and cytochromes)

deficiency causes microcytic anemia with large RDW, low MCV, low MCHC

measure iron levels by plasma ferritin b/c it's in equilibrium with storage ferritin. transferrin is increased (increased TIBC)

oral supplements: give 325 mg Fe 3x/day (s/e - impractical)

S/E: constipation, nausea, black stool.

unable to tolerate: give parenterally. iron dextran (watch out for anaphylaxis)
S/E: pain at inj site, fever, H/A

Acute Iron toxicity:
-necrosis of gut!
Rx: bowel irrigation from both ends! also use activated charcoal and fe chelators

body has limited ability to excrete iron (intestinal cell sloughing?)

Front 22

epoietin alfa

Back 22

erythropoietin

USE: anemia

given SC or IV. given more often in dialysis pts. takes ~1 week to increase Hct

only give if epo is low... duh
to determine if bone marrow or kidney is problem, check the epo. if high, the marrow is the problem. must monitor Hb levels to prevent from getting too high. high Hb -> sludging -> clotting, htn, and seizures.

complications: seizures, clotting, hypertension

normal phys:
normally produced by peritubular system of kidney
acts on erythroid precursors in bone marrow

Front 23

G-CSF

Back 23

treat neutropenia

granulocyte CSF
stimulates neutrophil CFU
dose dep leukocytosis

use to treat CGD and others.
GM-CSF
granulocyte macrophage CSF
affects lots of CFU: macrophage, lymphocyte, RBC
dose dep leukocytosis

Front 24

PROPYLTHIOURACIL

Back 24

USE: hyperthyroidism
MOA (2):
1. blocks organification
2. blocks conversion of T4 to T3 (faster onset)
conjungation too?

notes: given 3x/day (vs methimazole 1/day)

Front 25

METHIMAZOLE

Back 25

USE: hyperthyroidism
MOA: blocks organification step

notes: give 1/day
slower onset of action b/c it blocks thyroids synthesis instead of conversion

Front 26

IODIDE

Back 26

low dose: hypothyroidism

high dose: hyperthyroidism

1. inhibits organification
2. inhibits endocytosis AND secretion
3. inhibits conversion of T4 to T3
great to use before surgery to shrink thyroid (also inhibits hyperplasia)

Front 27

propanolol

Back 27

use: thyroid storm
MOA:
1. blocks conversion of T4 to T3
2. blocks target organ effects of thyroxine (tachycardia, etc)

for thyroid storm, give corticosteroids, beta blockers, iodide and start slow onset antithyroid therapy such as methimazole

Front 28

steroids

Back 28

use: thyroid storm
blocks converstion of T4 to T3

Front 29

thiocyanate

Back 29

use: hyperthyroidism

moa: blocks iodide uptake

Front 30

perchlorate

Back 30

use: hyperthyroidism

moa: blocks iodide uptake (trapping)

Front 31

ipodate

Back 31

use: hyperthyroidism

those fucking ipods block t4 to t3

moa: blocks conv of T4 to T3

Front 32

LEVOTHYROXINE

Back 32

synthetic T4 for hypothyroidism

Front 33

liothyronine

Back 33

synthetic T3

preferred over T3 in myxedema coma b/c of its faster onset

Front 34

CALCITONIN

Back 34

dec bone ca reabs
inc kidney ca ecr

Front 35

PTH

Back 35

1. bone: inc. ca reabs
2. kidney: dec. ca excr. and inc. po4 excr.
3. inc 1,25-diOH-D3. inc ca and po4 abs in gut (ca-po4 cotransporter)

Front 36

VITAMIN D

Back 36

synthesis:
skin: calcitriol made
liver: -> 25-OH-D3
kidney: -> 1,25-diOH-D3
(kidney is last stop!)

vitamin D deficiency - give D3
in liver failure: give 25-OH D3
in kidney failure: give 1,25-di-OH D3

Front 37

BISPHOSPHONATE

Back 37

osteoporosis drug

moa: mimics pyrophosphate
incorporated into bone and stays there longer

S/E: take with lots of water b/c it can damage esophagus if it lodges there

Front 38

CYCLOSPORINE

Back 38

T cell blocker

uses: transplants, rheumatoid arthritis, psoriasis
MOA: suppresses lymphocyte proliferation
binds to cyclophilin, and cc complex inhibits calcineurin. NFAT cannot be dephosphorylated, and TCR signal does not trigger production of IL-2, IL-3, IL-4, and TNFalpha

S/E: narrow therapeutic index, hypertension and nephrotoxicity
drug interactions (CYP450)
must be monitored

forms: eyedrop, iv, oral
2 oral forms: sandimmune (soft gel) and neoral (microemulsion, better abs)

Front 39

TACROLIMUS

Back 39

T cell blocker

uses: transplants (liver and kidney)

moa: inhibits t cell proliferation. binds FK506, tacrolimus-FK506 complex inhibits calcineurin, NFAT cant be dephosphorylated, TCR signalling doesnt cause production of IL-2,3,4 and TNF alpha

s/e: nephrotoxicity, hypertension. neurotoxicity, diarrhea
drug interactions (CYP450)
must be monitored

Front 40

SIROLIMUS

Back 40

T cell blocker

moa: inhibits signalling pathway from IL-2 receptor to DNA synthesis
this means it inhibits prolif of t cells AND B CELLS* but not cytokine production (well?)

NOT CALCINEURIN INHIBITOR!

uses: acute rejection (with cylosporine and steroids)

s/e: leukopenia, thrombocytopenia, hypertriglyceridemia
less renal toxicity than cyclosporine and tacrolimus b/c of diff moa

Front 41

PREDNISONE

Back 41

corticosteroid

moa of immunosuppression:

1. blocks proliferation of activated T cells and B cells*
2. antiinflammatory - blocks production of inflammatory mediators
3. inhibits antibody production
4. increases neutrophils in blood (demargination-inhibits migration too)
5. decreaes lymphocytes in blood (movement out of vasculature)

use: organ transplantation and autoimmune disorders (combo therapy)

s/e: infections, growth deficiency, osteoporosis, diabetes, obesity, cushings

chronic use causes adrenal suppression. taper dose to prevent iatrogenic adrenal insufficiency. watch out during surgery.

IV form: METHYLPREDNISOLONE SODIUM SUCCINATE (give for liver failure pt)

Front 42

AZATHIOPRINE

Back 42

immunosuppressant
(cytotoxic drug)

moa: metabolized to 6MP (6-mercaptopurine) which antagonizes purine metabolism

prevents T cell proliferation (by preventing DNA synthesis)

notes: pharmacokinetic effect lasts minutes. pharmacodynamic effect lasts days

caution in renal and hepatic failure: hepatic dysfunction (will build up), renal problems (will build up) - decrease dose

drug interaction: allopurinol, which inhibits xanthine oxidase, which normally inactivates 6-MP. 6-MP stays active and has too much of an effect - pancytopenia

uses: PREVENTION of rejection in renal transplant
rheumatoid arthritis

s/e: bone marrow suppression and inc risk of neoplasia.
pancytopenia when given with allopurinol

Front 43

CYCLOPHOSPHAMIDE

Back 43

immunosuppressant
(cytotoxic)

moa: alkylating agent that interferes with DNA and RNA synthesis.

Uses: transplants

s/e: bone marrow suppression. GI, nausea, vomitting, cardiotoxicity, inc. risk of neoplasms, esp. bladder cancer

Front 44

MYCOPHENOLATE MOFETIL

Back 44

immunosuppressant
(cytotoxic drug)

prodrug of mycophenolic acid (MPA)
moa: inhibits inosine monophosphate dehydrogenase.
inhibits purine synthesis

decreases proliferation of T and B cells
decreasing B cell proliferation decreases antibody production

undergoes enterohepatic circulation, and inactive metabolites are converted back to MPA

use: transplants

s/e: (mild) GI and hematologic, inc. risk of infection

Front 45

leflunomide

Back 45

immunosuppressant
(cytotoxic drug)

moa: inhibits dihydroorotate DH, an enzyme in de novo PYRIMIDINE synthesis.

prevents T and B cell proliferation.

use: rheumatoid arthritis primarily (think LEFT knee)

s/e: mild. elevated liver function test, nausea, diarrhea, alopecia, and rash

Front 46

MUROMONAB-CD3 (OKT3)

Back 46

monoclonal antithymocyte antibody

purified monoclonal ab against CD3 antigen of T cells

use: reverse graft rejection by blocking function of t cells, which play a role in acute rejection
s/e: allergic reaction

Front 47

LYMPHOCYTE IMMUNE GLOBULIN
ANTITHYMOCYTE GLOBULIN

Back 47

immunosuppressant

moa: eliminates antigen reactive T cells in the blood or alters their function

purified, concentrated, POLYCLONAL sterile gamma globulin

administered IV only

use: transplantation (with azathioprine and corticosteroids in combo rx)

s/e: fever, chills, rash, itch (derm reactions)

Front 48

DACLIZUMAB

Back 48

immunosuppressant
humanized anti-CD25 antibody (anti - IL2 receptor) made from RECOMBINANT DNA

use: prophylaxis of acute rejection (with cyclosporine and corticosteroids)
moa: IL-2 mediates T cell activation. CD25 exp'd on activated T cells, and daclizumab inhibits IL-2 binding

s/e: GI effects, h/a, dizziness
similar: basiliximab

Front 49

basiliximab

Back 49

immunosuppressant

anti-CD25 antibody (an IL2 receptor) PRODUCED BY RECOMBINANT DNA

moa: IL-2 mediates T cell activation. CD25 exp'd on activated T cells, and daclizumab inhibits IL-2 binding

use: prophylaxis for rejection (with cyclosporine and corticosteroids)
similar: DACLIZUMAB

s/e: hypersensitivity

Front 50

ETNACERPT

Back 50

immunosuppressant
antibody that intercepts TNFalpha

prevent an eruption of rheumatoid arthritis by binding TNFalpha

monoclonal antibody from RECOMBINANT DNA against TNF-alpha, preventing it from binding TNF receptor.

normally, TNF causes induction of cytokines, leukocyte migration, neutrophil and eosinophil activation, induction of acute phase proteins in liver

use:
rheumatoid arhtritis (with methotrexate)

s/e: reactions at site of injection, upper resp infections, lupus-like syndrome

Front 51

infliximab

Back 51

similar to etnercept

monoclonal antibody from recombinant DNA

binds to TNF alpha

use: rheumatoid arthritis and crohn's disease

Front 52

TRASTUZUMAB

Back 52

breast cancer drug? wtf?

Front 53

INTERFERON BETA-1b

Back 53

immunostimulant:

use: reduce severity of multiple sclerosis attacks

Front 54

INTERFERON GAMMA-1b

Back 54

immunostimulant

use: prevent infections in chronic granulomatous disease

Front 55

IL-2

Back 55

immunostimulant:

moa: stimulate T helper and cytotoxic T cells

use: metastatic melanoma, renal cell carcinoma

s/e: highly toxic! severe hypertension, cardiotoxicity, pulmonary edema, renal toxicity

Front 56

levamisole

Back 56

levamisole (soul??)

synthetic immunostimulant - increases T cell mediated immunity. causes macrophages and T cells to secrete cytokines which suppress tumor growth.

use: hodgkin's disease, rheumatoid arthritis, colorectal cancer

moa: increase T cell mediated immunity