Immunology Block: Pharmacology : Drug List!

Front 1

Pharmacogenetics lecture:
Primaquine:

Back 1

primaquin is an antimalarial and antifungal. immediately think of G-6-phosphate dehydrogenase deficiency, present mostly in MEDITERANIEANS and ASIANS. Also Africans.. leads to hemolytic anemia.

Front 2

Isoniazid:

Back 2

Anti-mycobacterial. As in for TB.

Half of whites and blacks are "slow", and half are "fast" acetylators. If slow, drug sticks around too long.

Front 3

Succnylcholine:

Back 3

It's a muscle relaxant. If you have decreased cholinesterase activity, this can be bad. Could get apnea.

Front 4

imatinib?

Back 4

Gleevac! this is for CML, targets 9:22 Bcr-Abl protein. Attacks its tyrosine kinase activity.

Front 5

5-flouro-uracil:

Back 5

if you have DPD mutation, dramatically extend the half life. bad news. 1 to 3% of patients. genotype first.

Front 6

aspirin - also, quinidine.

Back 6

Know that it's acidic, so it's better excreted in alkaline urine

quinidine is a weak base, so it's excreted better by acidic urine.

Front 7

rifampin and st. john's wort

Back 7

induce hepatic P450 and induce intestinal PGP, both of which serve to inhibit the potency of other drugs.

know that these prevent the entry and promote the metabolism of other xenobiotics.

Front 8

what inhibits PGP and p450?

Back 8

cimetadine and grapefruit juice.

these incrase the absorption of other drugs and inhibits their excretion, making them more potent.

these can also increase the fraction of drug getting through the BBB.

Front 9

what drugs have serious first-pass effects?

Back 9

morphine - if you eat it, loose 85% instantly.

nitroglycerine

propranalol too.

Front 10

what's an example of drugs with really weird distributions?

Back 10

quinacrine ends in the liver and galbladder, giving it an exremely huge apparent Vd

thiopental is the classic one, ends up in fat, giving you a huge Vd as well.

Digoxin - same deal.

Front 11

give a list of potent inducers of cytocrome p450:

Back 11

rifampin, st. johns' wort, barbituates, ethanol in large quantitie. phenytoin.

Front 12

potent inhibitors of p450-?

Back 12

grapefruit juice, rifampin, erythromycin, cipro, and prozac.

Front 13

what are some important drugs metabolized by p450?

Back 13

warfarin

oral birth control

theophylline. 8

Front 14

erythromycin and ciproflaxin?

Back 14

like cimetadine, it's an inhibitor of P450 that makes drugs more intense.

Front 15

prozac

Back 15

also an inhibitor of p450, makes drugs more intense.

aka fluoxatine

Front 16

barbituates?

Back 16

activator of p450, inhibiting other drugs. same with ethanol.

Front 17

we know that warfarrin and oral contraceptives are metabolized by p450. what's another

Back 17

theophylline.

half of all drugs are.

Front 18

why can alcoholics get hyperglycemic?

Back 18

if they're taking tolbutamine - remember that ethanol over time can induce p450 to increase expression.

tolbutamine is for diabetics to keep their sugar down. if too much p450, not enough tolbutamine and too much sugar.

Front 19

what about phenobarbital?

Back 19

it's a barbituate, so we know it's an inducer of p450.

don't give phenobarbetol to people taking warfarin or phenytoin (dilantin), as these drugs won't work as well.

Front 20

what's disulfuram?

Back 20

it's antibuse. it inhibits acetl aldehyde dehydrogenase. makes boozers sick.

Front 21

phenytoin?

Back 21

dilantin - it's an anticonvulsant. note that taking it with phenobarbatol is bad, because inducing p450 will make people more likely to seize.

note that there are WIDE interpatient variability with drug dosing here.

also, at low dosing, it's "dose dependent" - meaning first order kinetics.

at high dosing, the system that metabolizes it is overwhelmed, so it becomes dose independent - add a little more and the dilantin levels go up way too high.

Front 22

aspirin?

Back 22

remember that it's better excreted in basic urine.

also, its half life goes up as the dose goes up. weird. "rate of metabolism is dose dependent"

so it has dose dependent kinetics, just like

Front 23

so to recap, which drugs exhibit a dose independent style?

Back 23

aspirin, penytoin (dilantin), and ethanol.

all of these saturate their respective metabolism pathways and become dose-independent. remember that for aspirin, the more you add, the higher the half life gets.

Front 24

give the classic list of things that induce P450:

Back 24

rifampin, phenobarbatol (barbituates), st. john's wort, ethanol, phenytoin, carbamezinepine

Front 25

classic things that inhibit P450:

Back 25

cimetatine, grapefruit juice, prozac (fluoxetine), erythromycin/ciproflaxin.

Front 26

what should g6p-dehydrogenase deficency make you think of?

Back 26

primaquin, sulfa drugs, chloremphenocol, aspirin, vitamin K analogues. without glucose six phosphate, have trouble keeping your levels of glutathione (GSH), and so the increased radicals blow up your RBC's.

Front 27

isoniazid?

Back 27

problems with slow acetylators, which half of whites and blacks are.

same thing with procanamide, sulfa drugs, and dapsone.

Front 28

succnylcholine:

Back 28

muscle relaxant.

people with plasma cholinesterase weirdness won't be able to metabolize it, and they'll end up in a coma if you give a full dose.

also, note that it can cause malignant hyperthermia.

Front 29

imatinib?

Back 29

same thing as gleevec

miracle drug against CML, fights the BCR/ABL fusion protein caused by the 9:22 c/some translocation.

Front 30

5 -flouro-uracil

Back 30

random SNP in 3% of cancer patients dramatically increases the halflife from 15 minutes to 160 minutes. high toxcisity. should genotype first.

Front 31

Cimetadine?

Back 31

H2 receptor blocker.

remember that it's an important inhibitor of p450. Specific isozymes include:
1A2, 2C9, 2d6, 3A4.

Front 32

prendisone?

Back 32

synthetic glucocorticoid, also called meticorten.

remember that glucocorticoids/corticosteroids increase the transcription of lots of GRE's. inhibit production of PAF, leukotrienes, prostiglandins, histamine, and bradykinin.

inhibit phospholipase A2, and downregulates expression of Cox2 (not cox1)

potent antiinflammatory effects of lots of organs. transplant rejection. stop future allergic reactions and treat autoimmune disease.

Front 33

cyclosporine?

Back 33

stops differentiation of T cells. Binds cyclophilin, stops calcinurin.

LOTS of toxcisities, including nephrotoxcisity. interacts with LOTS of drugs.

Front 34

tracolimus?

Back 34

also inhibits calcenurin.

Front 35

sirolimus?

Back 35

totally different mechanism from cyclosporine and tacrolimus.

targets the target of rapamycin (mTOR), which is required for cytokine-driven T-cell proliferation.

So cyclosporine, tacrolimus, and sirolimus all stop T-cell proliferation.

Front 36

azathrioprine?

Back 36

one of our cytotoxic drugs, targeting proliferating cells.

works by messing with purine metabolism, and it's cycotoxic and destroys stimulated lymphoid cells.

remember that aziothioprine, cyclophosphomide, and mycophenolate mofetil are examples of steroid sparing drugs - they're cytotoxic drugs used in organ transplant anti-rejection regiments, and they aren't steroids.

Front 37

cyclophosphamide?

Back 37

another cytotoxic drug. ALKYLATING AGENT, used with SLE.

Front 38

mycophenolate mofetil?

Back 38

renal and cardiac transplants. profylaxis of organ transplantation. prodrug.

Front 39

ATGAM?

Back 39

ATgam is anti thymocyte globulin. Uses cytotoxic antibodies to attack T cells, deplete lymphocytes, and block their function

Front 40

RhoGam?

Back 40

Also called Rho (D) Immune GLobulin.

Baby's red cells get cleared from the circulation before the mother can generate an immune response.

Front 41

Muromonab -CD3

Back 41

aka OKT3. another T cell targeting antibody, this time we're going after cytotoxic t cells and thier functions.

monoclonal murine.

looks like it stops CD4 cells.

Front 42

Dacluzimab?

Back 42

Zenapax - binds to the IL2 receptor, stopping T cell activation.

Front 43

Thalidomide?

Back 43

Anti TNF alpha. Bad news during pregnancy.

considered DMARD

Front 44

Etanercept?

Back 44

Recombinant form of the TNF alpha receptor, so it can bind it all up. Used in RA.

considered DMARD

disease modifying agents for rheumatoid arthritis.

Front 45

infliximab?

Back 45

should be up with dacluzamab - it's an antibody (humanized) that's anti-TNFalpha. Note that neutralizes TNF Alpha.

good for rheymatoid arthritis.

and chron's disease.

think that TNF alpha inflicts pain, as does chron's disease.

Front 46

Histamines and Anti-Histamines: where does histamine live, what are its receptors, how is it bound, etc. what causes the triple response of lewis?

in the stomach, what cells is it in?

Back 46

Uses H1 and H2 for our purposes, but there are more.

Cardiovascular system has H1 and H2. Gastric has H2. Bronchioles has h1.
Triple response of lewis mostly H1, some H2/3

tissue histamine bound in granules inside mast cells and basophils.

causes arteriolar vasodilation and leaky capillaries (venus constriction).

stimulates nerve endings to increase pain sensitivity).

in the stomach, it lives in enetrochromaffin-like cells in the fundus and bind H2 to turn on acid secretion.

Front 47

if histamine is our beta 1 agonist, what's our beta 2 agonist?

Back 47

betazol - not sure why you'd use this except to test stomach function...

Front 48

what are the first generation H1 blockers?

Back 48

Bromopheniramine

Chloropheniramine (chor-trimeton)

Diphenhydramine (benadryl)



Hydroxyzine (atarx, vistarl)

Front 49

Talk more about diphenhydramine:

Back 49

good for several things:

1. Antihistaminc

2. Motion sickness

3. Antiparkinsonism

4. Local anesthesia

5. Sedation.

Side effects: sedation, stimulation in children.

DIMENHYDRINATE - salt of diphenhyramine - is DRAMAMINE - good for treating motion sickness.

Front 50

what are our 2nd generation h1 blockers?

Back 50

Fexofenadine, Loratadine

Front 51

Fexofenadine

Back 51

this is allegra. It is selective for PERIPHERAL H-1 receptor antagonist.

note that it's a metabolite of TERFENADINE, which was taken off the market for causing some light heart attacks.

Front 52

Loratadine:

Back 52

Claratin! Long-acting.

Front 53

what are our degranulation inhibitors?

Back 53

Comolyn Sodium and Nedocromil.

Front 54

talk about cromolyn sodium:

Back 54

Thought to work by inhibiting delayed chloride channels in the membranes of mast cells and eosinophils. note that nedocromil works the same way.

aka NASAL-CROM.

Front 55

what are our H2 blockers?

Back 55

FC RN.

Famotadine

Cimetadine

Ranitidine

Nizatidine

Front 56

Famotadine:

Back 56

works like cimetadine, it's an H2 antagonist.

this is pepcid and pepcid AC.

sounds like family, families drink pepsi.

Front 57

Cimetadine

Back 57

tagamet.

lots of drug interactions, best not to take.

inhibits lots of forms of p450, including 1a2, p2c9, and p3a4.

also can inhibit PGP mediated secretion into the renal tubules.

ALSO, it stops dihydrotestosterone from binding its receptors and can cause bitch tits.

Front 58

Ranitidine

Back 58

Zantac and Zantac 75.

Front 59

Nizatidine

Back 59

Axid, Axid AR.

Front 60

Drug PBL: talk about cimetadine:

Back 60

potent inhibitor of most p450's, including 1a2, 2c9, 2d6, and 3a4.

Front 61

warfarin:

Back 61

lost of interactions:

pharmacokinetics - enzyme induction/inhibition, reduced plasma protein biding.

pharmacodynamics - synergysm (if hepatic disease = more bleeding), also see issues with vitamin K antagonism (stopping the effect of the drug). note also that people can have altared control lloops of fvitamin K synthesis, which makes people resistant to warfarin.

watch out for cimetadine and rifampin.

Front 62

rifampin

Back 62

potent inducer of most p450's. this increases the elimination of other drugs.

Front 63

nsaids! what's our selective cox inhibitor?

Back 63

celebrex

Front 64

what are our non-selective cox inhibitors?

Back 64

aspirin, ibuprofen, indomethacin, naproxen, nibumetone and diclofenac.

Front 65

aspirin?

Back 65

remember that its t1/2 goes way up as the dosing increases, and that it's better excreted by basic urine.

here, need to recall that it's an antiinflammatory, antypyretic, anelgesic, anti platelet, MI prophylaxis, TIA prophylaxis in men.

reye's syndrome in kids.

dose dependent side effects - theraputic dose side effects are GI (ulcers, gastric upset, etc).

high doses = salicisim = tinnits, vertigo, vomiting.

even higher = hyperpnea, metabolic acidosis, respiratory alkalosis,

toxic doses turns into respiratory depression and goucose intolerance.

Front 66

indomethacin?

Back 66

remember that this is the choice to close patent ductus arteriosis. given by IV.

note that high doses cause adverse effects in 30% of people.

Front 67

ibuprofen?

Back 67

analgesic, antipyretic, and antiinflammatory. note here that you can secrew up FUROSAMIDE (lasix) and thiazide diuretics, because PG's are important for keeping flow to the glomeruli - messing with that stops diuresis. Increase lithium plasma levels. Also, ace inhibitors may not work as well.


BIG ONE - if you take with aspirin, you can mess with the cardioprotective mechanisms of aspirin - note that aspirin is the only permanently binding COX inhibitor, and if you bind up all the spots with ibuprofen, it'll fall off later.

need to space out your dosing with ibuprofen and aspirin.

Front 68

nabumatone?

Back 68

AKA relafen. It's a PRO DRUG, and so its action is spaced out over 24 hours, making once daily dosing good.

Front 69

diclofenac?

Back 69

nsaid that tends to accumulate in the joints, making it good against arthritis.

Front 70

acetaminophen

Back 70

don't know how it works, NOT ANTIINFLAMMATORY.

heptatoxcisity - treat with N0acetylcystine.

Front 71

aspirin allergy?

Back 71

diversion of all that AA to leukotrieines.

Aspirin resistance = diminishing returns.

Front 72

while we're talking about COX inhibitors, why might you want to use a COX product theraputically?

Back 72

pg's can be given as therapy.

they tend to vasodilate and lower pressures.

so pulmonary hypertension can be dealt with using a PG.

also, peripheral vascular disease.

keeping the ductus arterioris OPEN so you can wait for surgery.

to abort or ripen a cervix and induce labor.

or erectile disfunction

or glaucoma.

Front 73

beclomethasone and dexamethasone:

Back 73

beclomethasone is an inhaled glucocorticoid - so it inhibits inflammation. dexamethasone is a powerful glucocorticoid.

Front 74

What are our DISEASE MODIFYING ANTI-RHEUMATICS (DMAR's)?

Back 74

Gold salts. azathrioprine. chloroquine. penicillamine. methotrexate, sulfasalazine.

GA-CPM

Front 75

gold salts

Back 75

have the word "auro" in them.

May take months for it to work. total body half life is 1 year.

Front 76

Azathioprine:

Back 76

Only in adults. NO USE WITH PREGGERS, as it's a purine antimetabolite. DNA synthesis screwed with, so no babies.

Allopurinol will decrease the metabolism of azathiorpine. Remember our two A drugs have a contraindication.

Front 77

Chloroquine -

Back 77

Restricted to adults. Makes RA better. 3-6 months to get effect. Occular toxcisity at high doses.

Front 78

Penicillamine -

Back 78

It's a chelator, so you can't use gold salts with it.

Front 79

Methotrexate -

Back 79

turns off dihydrofolic acid reductase, which inhibits DNA synthesis.

used in psoriasis, cancer, and RA.

DON'T USE PREGNANT (along with azathioprine). - cause death of flipper babies. Get blood and GI toxcisity (any fast growing cells). Careful with NSAIDS, as you may not excrete methotrexate as fast.

Leucovorin is what you use as antidote to methotrexate overdose.

Front 80

what are our TNF blocking agents?

Back 80

Adalimumab, Infliximab, and Etanercept.

Adilimumab - binds TNFalpha.

Infliximab - binds TNFalpha receptors

Etanercept - anti-TNFalpha binding drug.

note infliimab is given IV, the rest are SC.

Front 81

what do we use for gout?

Back 81

CAPPS:

cholcicine

allopurinol.

pegloticase

probenicid

sulfinpyrazone.

Front 82

cholcicine:

Back 82

cholchicine not sure how it works. reduces lactic acid production by leukocytes and reduces phagocytosis.

good for acute attacks AND as prophylacxis. Good for aborting an attack when FIRST SYMPTOMS SHOW UP.

Front 83

allopurinol:

Back 83

inhibits XANTHINE OXIDASE, so you don't get as much uric acid. Get some skin reactions which can be fatal. Stop if rash.

Contraindicated when given with PROBEECID and AZATHIOPRINE.

can cause ACUTE GOUTY FLARE UPS.

Front 84

Probenicid

Back 84

uricosuric. inhibits the transport sites that cause reabsorption of uric acid from the proximal tubule. so, pee more out.

this can cause renal stones.

note that because you're peeing out more acid, the pee acidity goes up (ph down), which causes acidic drugs to build up in the body.

see this with SULFONAMIDES.

note that aspirin can interfere with probenacid's uricosuric activity.

Front 85

Sulfinpyrazol

Back 85

same as probiniid

Front 86

pegolticase -

Back 86

recombinant uricase for breaking down uric acid. used for resistant gout.

Front 87

What are the glucocorticoids we should know?

Back 87

Prendisone, hydrocortisone, dexamethasone, triamcinalone, fludrocortisone, methylprendisone, mifeprestone, metyrapone.

Front 88

prednisone -

Back 88

also called METICORTIN.

stops lots of inflammatory mediators, it's a glucocorticoid. remember that it inhibits phospholipase A2.

Alsao, that it works in lots of organs.

used to prevent rejection. also to treat autoimmune disease.

it also has severe toxicities.

Front 89

hydrocortisone?

Back 89

this is cortisol. Called cortef, hydrotortone, solu-cortef.

used in addison's disease as a replacement for adrenocortical deficiencies.

also big time antiinflammatory..

side effects to know:
aseptic necrosis of femoral head! humoral too.

also can mimic cushing's - fluid retention, hyperglycemia, hypertension, ulcers, osteoporosis, mood disorders, impared wound healing.

Front 90

dexamethasone?

Back 90

glucocorticoid, also called decadron.

used in the dexamethasone suppression test. for diagnosing cushing's disease.

Front 91

triamcinolone -

Back 91

inhaled, for asthma. also called aristocort and kenacort.

also available as topical for treatment of dermatitis.

Front 92

fludrocortisone -

Back 92

only one of the list that also has mineralcorticoid activity. so, if you have addisons and need to replace your glucocorticoid AND mineralcorticoid levels, you can use fludrocortisone.

Front 93

methylprednisolone

Back 93

medium-acting glucocorticoid.

also called solumedrol, depo-medrol, and medrol.

Front 94

mifepristone -

Back 94

AKA Ru-486. Ends babies. If given with a prostiglandin, it's safe to kill babies up to 7 weeks.

Front 95

metyrapone -

Back 95

inhibits glucocaorticoid synthesis - so you can test pituitary function.