medical school pharmocology exam 4 wsu Flashcards

Terms Definitions
bile acid-binding resins used in the management of hyperlipidemia
cholestyramine, colestipol, colesevelam

(bind bile acids, preventing enterohepatic recycling, thus diverting hepatic efforts to renew bile acids, instead of producing plasma lipids)
inhibits the rate-limiting enzyme of cholesterol synthesis, HMG-CoA reductase, resulting in dramatically decrased LDL levels
Statins ( lovastatin, pravastatin, simvastatin, atorvastatin)

- may cause elevated liver enzymes, myositis, with increased creatin kinse from skeletal muscle and rarely rhabdomyolysis
cholesterol absorption blocker
ezetimibe

-dec LDL and has no effect on HDL or triglycerides

-rare se: inc in LFTs
lipid-lowering agent that causes cutaneous flusing, which can be avoided by admistering concurrently with aspirin
Nician

-directly reduces the secretion of VLDLs from liver and apolipoprotien synthesis by the liver, while increasing HDLs
agents that decrease triglycerides dramatically by stimulating lipoprotien lipase

-inhibits formation of ApoC III which is an inhibitor of Lipoprotien lipase
fibric acids

gemfibrozil
fenofibrate
clofibrate

-clofibrate has been associated with gallstones and hepatobiliary neoplasms
reduction of hepatic triglyceride production and increase in triglyceride clearance
omega-3 fish oils, omacor and other generics

-deep ocean fish are primary dietary source of omega-3 polyunsaturated fatty acids (PUFA)

SE: risk of hemorrhagic stroke inc
se of fibric acids (gemfibrazil and fenofibrate)
mild gi distress and myopathies
drugs categories used to tx elevated LDL - cholestrol
statins - primarily
bile acid-binding resins
niacin
ezetimbe - least used
drugs used to tx elevated VLDL - triglycerides
fibric acids: gemfibrozil or fenofibrate

moa: inhibit formation of ApoCIII which is an inhibitor of lipoprotien
lipid lab values requiring tx with statins
total cholestrol > 200
LDL-Chol > 130
HDL < 40
C-reative protien > 2.0
dec production of leukotirenes and prostaglandins by inhibiting phospolipase A2 and expression of cox - 2
glucocorticoids
-hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone

ae: introgenic cushings syndrome - buffalo hump, moon face, truncal obesity
glucocorticoid used for the tx of leukemias and lymphomas, as well as for RA and asthma
prednisone

-triggers apoptosis and can lead to hypercortisolism with cushing like symptoms. Drug must be tapered gradually to prevent life-threating adrenal insufficincy
commonly used analygesic and antipyretic, but unlike NSAIDS, has no anti-inflammatory properties
acetaminophen

-weaker inhibitor of COX, it inhibits prostaglandin synthesis in the cns, a related prodrug (phenacetin) is no longer available due to nephrotoxicity
NSAID with analgesic, antipyretic, antiplatelet and anti inflammatory properties that irreversibly inhibit COX
aspirin (acetylsalicylic acid)

-inhibits the formation of prostaglandin E (PGE)
-dec pain and fever
-dec syn of PGE in stomach, predisposing to acute gastritis
reversible inhibitors of COX widely used as over the counter (OTC) pain relevers
ibuprofen
naproxen
piroxicam

-these agents share many of the same effects as aspirin, but are more efficacious analgesics and anti-inflammatories

-they lack aspirin's long duration and antiplatelet effects
high potency NSAID used in tx of gout and arthritis, and for closure of patent ductus arteriosus
indomethacin

-conversely, prostaglandin E (PGE)can be used to maintain a patent ductus arteriosus in congenital cyanotic heart disease
newly avaiable NSAID, used in tx of RA and other chronic conditions, with dec risk of ulcer and other GI bleeds
celecoxib

-celecoxib and a similar drug, rofecoxib, selectively inhibit COX-2 present only in leukocytes

-these agents do not inhibit COX-1 that produces protective prostaglandins in the stomach, as sulfa drugs, they both can cause hypersensitivity in some patients
eicosanoid preparation used to prevent peptic ulcers in patients taking high doses of NSAIDs for conditions such as RA
misoprostol

moa: block histamine stimulated cAMP production

-this prostaglandin E (PGE) analog dec gastric acid production and inc mucus production, protecting the lining of the stomach

use: inflammatory GI disease esp when ulcer due to NSAID
used in the tx of RA and IBD (inflammatory bowel disease), a recombinate protien product that inhibits the effects of tumor necrosis factor alpha (TNF - a)
Etanercept

-adminstered iv, this drug is a fusion btwn the extracellular domain of TNF-a and the Fc portion of an antibody, a similar monoclonal antibody, infliximab, also binds and inhibits TNF-a
standard of care for disease modifying anti-rheumatic drugs (DMARD) therapy

-inhibits dihydrofolate reductase and consequent thymidine deficiency
Methotrexate

ae: gi, hematological and heptic effects, also teratogenic
txmt of malaria and ameba infestation

partitions into acidic vacuole of these organisms
hydroxychloroquine

-also reduces chemotaxis, phagocytosis and superoxide production in PMN, as a consequence of accumulation in lysosomes
a sulfonamide used to tx inflamamatory bowel disease
sulfazalazine

-drug is split into 5-aminosalicylic acid and sulfapyridine by enteric flora

-se: rash, dizziness, gi upset, photo senstivity
the estrogen partial agonist used to prevent osteoporosis in postmenopausal women
raloxifene

-in also inc serum high density lipoprotien (HDL), protecting against athrosclerosis and heart disease

-another selective estrogen receptor modulator (SERM), tamoxifen, it does not inc risk of endometrial cancer
these compounds reduce bone resorption and formation, and are used in the txmt of osteoprosis (postmenopausal, senile, or glucocorticoid-induces) and Paget disease
bisphosphonates
-alendronate, etidronate, pamidronate, risedronate

characterised by poor oral availability and can not bet taken with food, may cause esophageal ulcerations

-must be taken with large amounts of water and pts must be upright for at least 30 min afterward
used for tx of osteoporosis, this hormone produces by thyroid decreases bone breakdown, and dec serum calcium and phosphate levels
calcitonin

also used in txmt of acute hypercalcemia and paget disease

-salmon calcitonin is used because it is more potent and has longer half-life

adm intranasally or by injection
this form of insulin is given in the morning and in the evening, to maintain basal levels of insulin for 12 to 24 hrs
ultralente insulin

-supplemented throughout the day with insulin lispro, a moidifed version of human insulin, insulin glargine, has a even longer duration of action
oral hypoglycemic agents used to stimulate the release of endogenous insulin from B cells
sulfonylureas - glyburide and glipizide

-stimulate the closure of potassium channels, resulting in depolarization of B cells and the release of preformed insulin vessicles
oral hypoglycemic agent that does not require functional pancreatic islet cells and dec postprandial glucose levels with out resultant hypoglycemia or weight gain
metformin

-biguanide compound that functions by increasing peripheral glycolysis and therefore, hepatic gluconeogensis, resuling in dec in serum glucose levels
this ultra-rapid-acting human insulin is admistered immediately before meals
insulin lispro

-an altered form of insulin that enters the circulation more rapidly than crystalline zinc (regular) insulin
this insulin secretagogue has a rapid onset, but shorter duration of action than sulfonyluraeas
repaglinide

-belongs to a class of drugs known as meglitinides, which facilitate insulin relsease from pancreatic B cells by binding to potassium channels
these agents inc cell sensitivity to insulin, by stimulating the peroxisomal proliferator gamma (PPAR g) nuclear receptor
Thiazolidinediones (TZD) or "Glitazones" - rosiglitazone and pioglitazone

-PPARg regulates a number of genes involved in carbohydrate metabolism. The first member of this class, troglitazone, was removed from the market bc it caused hepatotoxicity
oral hypoglycemic agent that functions within the intestinal lumen, dec postprandial hyperglycemia, although there are not effects on fasting sugar
Acarbose and miglitol

-inhibits alpha-galactosidase, an enzyme required for rapid absorption of most dietary sugars
what reaction occurs between warfarin (anti-coag) and cimetidine (H2 blocker)?
bother are lipid soluble and metabolized by liver enzymes cyp P450

cimetidine must be dosed in large dose bc of low potency, inhibiting warfarin metabolism and inc prothrombin time

-use instead ranitidine bc cleared renally or proton pump inhibitor that dec stomach acid in pt on warfarin
what risk does a diabetic have when taking metoprolol?
Metoprolol is a B1 blocker and some B2 blocker, which blocks epi driven tachycardia, symptom which occurs when one is hypoglycemic, which is masked by B blockers. Best to give diabetics calcium channel blockers such as amlodipine to tx HTN
How does warfarin and St John wart interact with each other?
St John wart is a p450 inducer, since warfarin is metabolized by p450, there is low conc of warfarin and inc coagulation.
how does alendronate bisphosphonate, levofloxacin and Ca fortified orange juice interact with each other?
levofloxacin binds to calcium which causes it to not be absorbed. So dont drink the oj or any other calcium with the levofloxacin.
How does warfarin and acetaminophin react with each other?
both are metabolized by p450 enzyme in the liver. Acetaminophin is metabolized to a toxic metabolite NAPQI that inhibit Vit K carboxylase adn reductase accentuating warfarin effect and inc bleeding.

-best if pt on warfarin takes other analgesic like NSAID
what interaction occurs btwn methotrexate, cyclosporine and ketoconazole?
methotrexate
-inhibits dihydrofolate reductase and excreted renally

cyclosporine
-inhibit T cell activity and prevents nuclear localization of NFAT, excreted by liver p450 enzymes

Ketoconazole
-antifungal, inhibits fungal p450 involved in sterol synthesis

ketoconazole inhibits cyclosporin elimination leading to accumulation and renal toxicity with sx of pitting edma in ankles, azotemia , hyperuricema and hyperkalemia.
how does amiodarone, erythromycin and midazolam interact
the three together cause excessive sedation for days.

amiodarone is a a antiarrythmic and cyp3A4 inhibitor and p-glycoprotien pump inhibitor

erythromycin is a macrolide antibiotic and has the same actions as amiodarone.

midazolam is a iv sedative/anesthetic benzodiapine which is eliminated by cyp3A4

Midazalam along with amiodarone and erythomycin, inhibits midazalam elimination and inc conc of drug causing inc action of sedation
how does statins and grapefruit interact?
grapefruit consist of a compound called furanocoumarins which inhibits cyp3A4 lasting >24 hr. Pt should not EAT grapefruit when on statin because will cause inc conc of statin leading to rhabdomyolysis
drug with moa which inhibit efferent limb of immune system
anti-inflammatory effects of glucocorticoids such as cortisol
drug with following ae:

a. Cataracts (an early sign of intoxication)
b. Hyperglycemia and diabetes
c. Thinning of the skin
d. Edema
e. Peptic ulcer
f. Osteoporosis
g. Athersclerosis
h. Psychosis
i. Impaired wound healing
j. Susceptibility to infection
k.
adverse effects of glucocoritcoids
what COX? is found in the stomach, platelets and many other tissues?
COX1
What COX? is involved in inflammation (e.g. macrophages), the vascular
endothelium and the renal juxaglomerular apparatus
COX 2
What NSAID is NOT a good choice to tx gout and why?
Aspirin bc inc levels of uric acid
what drug has the following se?

central effects including tinnitus, vertigo and hyperventilation leading to respiratory alkalosis
Aspirin
Extensively metabolized in the liver, and in overdose, metabolites can cause irreversible and fatal hepatotoxicity and renal toxicity.

Prompt treatment with acetylcysteine reduces hepatotoxicity.
Acetaminophen (Tylenol)
drugs which have serious hematological (rarely agranulocytosis, aplastic anemia) and renal (more commonly acute renal failure, intersitial nephritis, nephrotic syndrome).
Ibuprofen (Advil), naproxen (Aleve), fenprofen, ketoprofen and others are
phenylpropionic acid derivatives
significantly lower incidence of gastric irritation than the non-selective drugs
celecoxcib
decrease the effectiveness of diuretics, beta-blockers and
ACE inhibitors and may increase the toxicity of methotrexate and lithium
NSAIDS
converted to 6-mercaptopurine, an inhibitor of several steps in purine interconversions that inhibits DNA synthesis
Azathioprine (Imuran)
anti-estrogen agent that undergoes hepatic metabolism to an active compound that inhibits dihydroorotate dehydrogenase

Diarrhea, hair loss and hepatic damage can occur
Leflunomide (Arava)
a fusion protein consisting of human TNF receptors and the Fc fragment of IgG.

effective forms of therapy against RA
Etanercept (Enbrel)
chimeric human-mouse monoclonal anti-TNF that
also reduces symptoms by inactivating TNF after intravenous injection

effective forms of therapy against RA
Imfliximab (Remicade)
effective therapy against RA

-used against a variety of other diseases ranging from anklosing spondylitis to psoriasis to ulcerative colitis.
Tumor Necrosis Factor alpha (TNF) Inhibitors

Etanercept (Enbrel)
Imfliximab (Remicade)
Adalimumab (Humira)
Opportunistic infections including tuberculosis may occur
Tumor Necrosis Factor alpha (TNF) Inhibitors

Etanercept (Enbrel)
Imfliximab (Remicade)
Adalimumab (Humira)
drug used in patients that have failed to respond to anti-TNF drugs in tx of RA
Abatacept (Orencia)
a chimeric monoclonal antibody that targets CD20 B-cell antigen.

approved for use with methotrexate against a variety of autoimmune diseases including rheumatoid arthritis that is resistant to anti-TNF agents
Rituximab (Rituxan)
an inhibitor of xanthine oxidase. It inhibits both steps in the synthesis
of urate.

-given chronically to prevent attacks and is of no value in relieving acute gouty attacks
Allopurinol
binds to tubulin in leukocytes and reduces both their mobility and ability to
undergo phagocytosis

->only used for short periods to control acute attacks
Colchicine
may precipitate acute gout when it is first administered (dissolution and reformation of urate crystals).
Allopurinol
inhibits both actively excreted and reaccumulated urate which results in a net loss of urate
Probenicid
can cause an increase in BMD - bone mass density

-associated with bloating, bleeding and breast tenderness as well as an increased risk for thromboembolism
Estrogen
None of these drugs is well absorbed by mouth, and their absorption is hindered by calcium supplements.

About half of the absorbed dose is bound to bone, and the remainder is lost unchanged in the urine.
Bisphosphonates

alendronate (Fosamax), ibandronate and risedronate
used against iatrogenic osteoporosis caused by glucocorticoids, male osteoporosis and in higher doses, against Paget’s disease
Alendronate
most frequent untoward effects are heartburn, esophageal irritation, diarrhea and GI effects.
orally administered bisphosphonates

To reduce damage to the esophagus, patients must take the drug with water in an upright position and maintain this position for an hour
the N-terminal 34 amino acids of PTH.

Like PTH it stimulates bone formation, and it has been approved for treatment of severe osteoporosis in both men and women
Teriparatide
insulin type?

solution of monomeric insulin -- rapid absorption.
Soluble or regular insulin
insulin type?

intermediate-acting – insulin mixed with protamine to slow
absorption.
NPH insulin
insulin type?

slow absorption – amorphous insulin zinc suspension
Lente insulin
insulin type?

very slow absorption -- insulin zinc suspension
Ultralente insulin
insulin type?

most soluble and most rapid-acting form -- mutations introduced into the human insulin B chain diminish insulin selfassociation.
Lispro and aspart insulin
finely powdered regular insulin self administered using bong-like inhaler device

Avoids insulin injections. Rapid onset, similar to sub-cutaneous injections of rapid-acting lis-pro insulin. Since there are no slow-acting forms of inhaled insulin, night-t
Inhaled insulin – EXUBERA (Pfizer)
traditional oral anti-diabetic – insulin secretagogues
Sulfonylureas

the first drugs used therapeutically include tolbutamide and
chlopropamide. Examples of the second generation which are approximately 100-fold more potent include glyburide (DIABETA) and glipizide (GLUCOTROL).
a biguanide – first-line drug of choice – lowers insulin resistance, particularly in the liver –reduces appetite.
Metformin
used for advanced T2DM patients with diminished β cell function
Insulin
lower insulin-resistance, potentiation of insulin action on peripheral tissue

primary site of action is agonistic binding to peroxisomal proliferator activator receptoer (PPAR)
Thiazolinediones – 'glitazones': rosiglitazone and pioglitazone
insulin secretagogues, act like sulfonylureas by inducing insulin secretion through closure of ATP-sensitive K channel, but have very rapid action and short duration
'Glitinides' - repaglinide and nateglinide
gila monster GLP-1 – insulin secretagogue – induces beneficial weight-loss.
Exenatide
agents bind to the ATP-sensitive K+ channel reducing its conductance. As a result, the β cell depolarizes and consequently induces all the
downstream events involved in the normal regulation of insulin secretion
Sulfonylureas

glyburide (DIABETA) and glipizide (GLUCOTROL).
T2DM drug with ae of anorexia, nausea, vomiting, abdominal discomfort, diarrhea, and lactic acidosis and contrindicated for pt with renal disorders
metformin (GLUCOPHAGE®),a BIGUANIDES
T2DM drug with Benefits of:
1. No hyploglycemia risk.
2. Associated anorexia may lead to weight loss.
metformin (GLUCOPHAGE®),a BIGUANIDES
insulin secretogogues, the risk of induced hypoglycemia is low
since, unlike the sulfonylureas, the GLP-1-induced insulin release also requires the presence of high blood glucose levels
Incretins
drug for T2DM

Actions:
1. Induces insulin releases
2. Depresses glucagon releases
Together, these first two actions blunt the post-prandial (following meals) glucose surge.
3. Delays gastric emptying – blunts appetite – associated with significant we
Exenatide (BYETTA)
adverse effects: Cancers & Cardiovascular diseases
Postmenopausal Hormone Replacement Therapy
Alternative therapies for managing menopausal symptoms
1. Phytoestrogens (e.g. isoflavones) in the natural products
2. Lifestyle Modifications:
Lower core body temperature, relaxation techniques, stop smoking, weight loss
increase the risk of endometrial and cervical cancer, this risk is reduced with the combination preparation.
Estrogen only contraceptive
Adverse reactions: cardiovascular and tumor

Cardiovascular effects: less than 35 years old, non-smoking women
Hormonal Contraception
(1) Combinations of Estrogens and Progestins (Oral)

(2) Progestin alone (oral or implanted)
These agents can induce the metabolism of oral contraceptives and
decrease their effectiveness
1. Antibiotics such as rifampin, penicillin, and tetracycline
2. Anti-HIV agents
3. Anti-epileptic drugs
4. Saint John’s Wort
Competitive Inhibitor, competing for Progestin receptors

Terminate early pregnancy when combine with prostaglandin
Mifepristone (RU486)

a Progesterone antagonist
a partial agonist Competitive inhibitor, Estrogen receptors, Breast cancer (palliative treatment)
Tamoxifen

a Estrogen antagonist
a partial agonist Competitive inhibitor, Stimulate ovulation (Infertility)
Clomiphene

a Estrogen antagonist
the gold standard of care for patients with estrogen-receptor-positive cancers (majority of breast cancer patients)
Tamoxifen
estrogen synthesis inhibitors that have recently been demonstrated for their effectiveness for replacing the clinical use of Tamoxifen in postmenopausal patients
anastrozole, letrozole, and exemestane

Aromatase inhibitors
Reverse protein loss after Trauma, Surgery, or Prolonged Immobilization (negative nitrogen balance was observed in these patients, anabolic activity of androgens can improve the nitrogen balance)
protein Anabolic Agents
used in the palliative treatment of prostate cancer since its action on the hypothalamus, can inhibit androgen secretion
Diethylstibestrol
In Women: masculinization, menstrual irregularity due to LH & FSH suppression, male pattern baldness during pregnancy, masculinization of female fetus
Adverse effects of Androgens
In Children: disturbances in growth and bone development
Adverse effects of Androgens
In Men: azoospermia due to the inhibition of gonadotropin secretion and the conversion of excess androgens to estrogens
Adverse effects of Androgens
a GnRH analog, as effective in the tx of prostate cancer and has fewer side effects (used in conjunction with antiandrogen).
leuprolide
These processes result in reduced transcription of the early cytokine gene Il-2 as well as Il-3, Il-4, TNF-a, interferon gamma, and GM-CSF.

These effects lead to a dose dependent inhibition of lymphokine production after the TcR-CD3 complex and other ce
cyclosporin A (Neoral®, Sandimmune) is a lipophilic cyclic decapeptide

tacrolimus (Prograf) is a macrolide antibiotic

Both drugs are fungal derived and bind with high affinity to a family of cytoplasmic proteins present in most mammalian cells.

Cyclosporine binds cyclophilins

tacrolimus binds FKBPs (FK binding proteins).
drugs are potent inhibitors of the prolactin gene that can act as an immunoactivator.
Cyclosporine and tacrolimus

CALCINEURIN-INHIBITING AGENTS
preferred in liver transplantation as cyclosporine is partially dependent on bile salts for absorption
Tacrolimus
HMG CoA reductase inhibitors can have elevated levels when used with ____?____ (a calcineruin - inhibiting agent) thus predisposing the user to rhabdomyolysis.
cyclosporine
most significant and common side effect limiting the
widespread use of cyclosporine and tacrolimus, both calcinurin - inhibiting agents
NEPHROTOXICITY
occurs within the first few weeks of cyclophilins and tacrolimus use and is mediated by the sodium retention and vasoconstriction caused by these agents.
HYPERTENSION
interferes with signal transduction of the second signals during the G1 phase delivered by Il-2, Il-4 or Il-6.
sirolimus

a non-calcinurin-inhibiting agent
major side effects of a non - calcinurine inhibiting agents are dyslipidemia and thrombocytopenia.
sirolimus
some concerns regarding a synergistic nephrotoxicity with cyclosporine or tacrolimus.
sirolimus
immunosuppressive agents which are eliminated by cyp3A4
sirolimus, cyclosporine and tacrolimus
decreasing intracellular purine synthesis, RNA production is decreased. This results in a decrease in B and T lymphocyte numbers, decreased immunoglobulin production and decreased Il-2 secretion.
azathioprine (Imuran®)
used as a maintenance immunosuppressive agent in organ transplantation and can be used in therapy of autoimmune disorders after a response has been established by more toxic agents (such as cyclophosphamide).
azathioprine (Imuran®)
immunosuppressive agent with major complications of myelosuppression, anemia, and alopecia
azathioprine (Imuran®)
potentially lethal interaction with allopurinol can lead to bone
marrow aplasia as allopurinol blocks the metabolism of ____?____ by xanthine oxidase
azathioprine (Imuran®)
structural analogue of folic acid that can competitively and irreversibly binds to the enzyme dihyfofolate reductase (DHFR) that reduces dihydrofolic acid (FH2) to the active intracellular
metabolite folinic acid (FH4).
Methotrexate
The common side effects of a immuosuppressive agent include gastrointestinal
upset, stomatitis, alopecia, macrocytosis, and CNS problems such as fatigue, headaches and loss of concentration.
methotrexate
immuosuppressive agent toxicity can be severe and even fatal
methotrexate
an antimetabolite derived from nitrogen mustard

widely used in the treatment of severe, life threatening autoimmune diseases and inflammatory diseases such as systemic lupus erythematosus, Wegener’s granulomatosis, vasculitis, and refractory rheumatoid
Cyclophosphamide
Barbiturates, alcohol, phenytoin, and rifampin may accelerate metabolism to the active forms and increase toxicity.

While drugs that inhibit microsomal enzymes such as corticosteroids, antimalarials, tricyclic antidepressants, and allopurinol may decrea
Cyclophosphamide
what drug interacts with succinylcholine possibly causing prolonged neuromuscular blockade?
Cyclophosphamide
Side effects include alopecia, nausea and vomiting, anaorexia, diarrhea, stomatitis and mucositis. It may cause sterility and gonadal suppression.

Congestive heart failure and pulmonary toxicity (pneumonitis and fibrosis) are potentially fatal complicati
cyclophosphamide
Lymphocyte proliferation and response to antigenic or mutagenic stimulation is thus depressed in the presence of
______?________.
Mycophenolate mofetil
(CellCept®)
Prodrug inhibitor of pyrimidine synthesis – rather than purine synthesis.
Drug is orally active. Currently approved for rheumatoid arthritis.
LEFLUNOMIDE
least likely to activate TB?

A. Abatacept (Orencia)
B. Etanercept (Enbrel)
C. Infliximab (Remicade)
D. Adalimumab (Humira)
E. Hydroxychloroquine
E. Hydroxychloroquine
Less gastric irritation is an advantage this drug has over nonselective NSAIDs
Celecoxib (Celebrex) is a selective COX 2 inhibitor
the best choice to reduce the level of urate in blood during first attack of
gouty arthritis
Probenicid
drugs causes human B-lymphocytes to die
Rutuximab (Rutuxin)
drug used to tx osteoporosis in man due to chronic use of corticosteriod
Alendronate (Fosamax)
used as the adjuvant treatment for male patients with estrogen receptor-positive breast cancer because inhibits the synthesis of estrogen in the patients.
Aromatase inhibitor (AI) such as anastrozole, letrozole, or exemestane
drug used for high risk estrogen receptor-positive breast cancer because of competitive antagonist acting at estrogen receptor
Tamoxifen
drug used along with methimazole to treat the cardiovascular effects of hyperthyroid patient
Propranolol
what drug combination in hyperthyroid pt would cause hypertensive crisis
Epinephrine and Propranolol
what drug combination would result in muscle aches along with the grossly elevated muscle enzyme levels in the serum and the dark urine are indicative of rhabdomyolysis
Simvastatin – amiodarone

bc both are metabolized by cyp3A4
- Time, amount, emesis, scenario
- Others ill?
- What other meds/products are possible?
- Reason for ingestion?
- Acute-on-chronic?
- Product identification
- Friends, family, EMS, police
- Search patient, retrieve containers
- PMH, social, medications, a
key historical points to be obtained from poisoned pt or witness
- ↑ pulse
- ↑ blood pressure
- ↑ respirations
- ↑ temperature
- ↓ bowel sounds
- Altered mental status (picking, Lilliputian speech)
- ↑ pupils
- Dry, hot, flushed skin
- Other: Urinary retention
Anticholinergic Toxidrome
- ↑ pulse
- ↑ blood pressure
- ↑ respirations
- ↑ temperature
- ↔ bowel sounds
- Altered mental status
- ↑ pupils
- Diaphoresis
- Other: bruxism
Sympathomimetic Toxidrome
- ↓ pulse
- ↔ blood pressure
- ↔ respirations
- ↓ temperature
- ↑ bowel sounds
- ↔ mental status
- ↓ pupils
- Diaphoresis
- Other: fasciculations, weakness, odors
- (diarrhea, urination, miosis, bronchorrhea, bronchospasm, emesis, lacrimatio
Cholinergic Toxidrome
- ↓ blood pressure
- ↓ pulse
- ↓ respirations
- ↓ temperature
- ↓ bowel sounds
- ↓ mental status
- ↓ pupils
- Diaphoresis
- Other: track marks
Opioid Toxidrome
- EKG
- Urinalysis
- Bedside tests:
- Methemoglobinemia
- Urine ferric chloride
- Wood’s lamp
Diagnostic Laboratory studies important in dx various poisoning
- Methanol / metformin
- Uremia
- Diabetic ketoacidosis / AKA
- Paraldehyde / phenformin / propylene glycol
- Isoniazid / iron
- Lactate
- Ethylene glycol
- Salicylates
these agents cause an inc in anion gap

Anion Gap = Na – (HCO3 + Cl)
- Salicylates
- Phenobarbital
- Toxic alcohols
- Lithium
compounds that can be removed with hemodialysis
- Ion trapping
- Hemodialysis
- Hemoperfusion
- Multi-dose charcoal
- Hyperbaric oxygen
- Antidotes
ways to enhance toxic elimination
antidote for digoxin
digibind
antidote for carbon monoxide
oxygen
antidote for cyanide
CAK

The Cyanide Antidote Package (also known as the Cyanide Antidote Kit (CAK), the Lilly Kit, the Pasadena Kit, and the Taylor Kit) is the only antidote currently available in the United States.

The CAK can be associated with
toxicities including Hypotension, which can Exacerbate shock, and methemoglobinemia, which reduces the oxygen-carrying capacity of the blood and can be particularly dangerous in oxygen-deprived victims of smoke-halation.
antidote for heroin
naloxone
antidote for Methemoglobinemia
Methylene Blue
- Skin / Eye decontamination
- Gut decontamination
- Activated Charcoal
- Cathartics
- Whole bowel irrigation
ways to reduce absorption of toxin

-reduce toxin load
- Binds material
- Interrupts enterohepatic recirculation
- Gut dialysis
- Initial dose 1 gram/kg
- Not all substances adsorb
actions of activated charcoal
- Corrosive injury to esophagus or GI tract
- Intestinal obstruction
- Ileus
activated charcoal contraindications
- Massive amount of toxin
- Metals
- Sustained release products
- Concretions
- Body packers
indications for whole bowel irrigations
- Inadequate airway protection
- Obstruction
- Ileus
- Perforation
whole bowel irrigation contraindications
- Unprotected airway
- Ingestion of corrosive substance
gastric lavage contraindications
- Life-threatening amount of toxic substance within 60-90 minutes of ingestion

- Altered mental status or critically ill patient within 60-120 minutes of ingestion

- Later, if concretions, delayed gastric emptying, or sustained-release
Gastric Lavage Indications
- Primary role is decontamination in home setting

- Max effectiveness only when within 60 minutes

- Only given upon advice of PCC or HCP
Ipecac Indications
- Age less than one year
- Absence of a gag reflex
- CNS depression
- Ingestion of CNS acting agent
- Corrosive agent
- Ingestion of cardiac depressant
Ipecac Contraindications
Increases the time to administration of charcoal once the patient is in the emergency department
Ipecac
- Aspiration
- Esophageal perforation/ spasm
- Hypothermia / electrolyte imbalance
- Epistaxis / GI bleeding
- Instillation of charcoal into the lungs
Gastric Lavage Complications
ae of rosiglitazone and pioglitazone, both thiazolidinediones
edema and potentially hepatotoxicity
ae seen in 79 yr old women with CAD present with nausea, vomitting and abd pain 3 days ago. Pt on warfarin, furosemide, digoxin, captopril, vit E and multivit.

what happened?
furoseminde is a loop dieurtic with ae of hypokalemia.

Hypokalemia produces digoxin toxicity manifested by gi sx
88 yr old male pt during last 1 mo deteriorating ability to perform daily activity and develop urinary incontinence

drugs:
terazosin, timolol eye drops, temazepan, tylenol, lisinopril and sleep aid (diphenhydramine) - otc

pe: mild bladder distention and
diphenhydramine anti-chol causes
1. perpherally, causes urinary retention and incontinence

2. centrally causes acute confusional state
102 yr old women with osteoarthritis started taking ibuprofen instead of tylenol and developed inc in BUN and creat
nsaids inc renal toxicity from reduction of renal prostaglandin formation

-> with inc age inc risk

drug-organ toxicity
88 yr old male pt during last 1 mo deteriorating ability to perform daily activity and develop urinary incontinence

drugs:
terazosin, timolol eye drops, temazepan, tylenol, lisinopril and sleep aid (diphenhydramine) - otc

pe: mild bladder distention and
diphenhydramine anti-chol causes
1. perpherally, causes urinary retention and incontinence

2. centrally causes acute confusional state
85 year old man with hx of demential and seizures disorder presents w/ inc confusion and inc fall

med: donepezil and phenytoin

pe: muscle wasting, MMSE = 17/30, ataxic gait

lab: low alb and normal phenytoin levels
total phytoin is both free and bound but the look at the free alone there is an increase in free phenytoin due dec albumin
86 yr old femail DM pt with also HTN, CAD, depression, OA, GERD, and glaucoma

hx & pe: CHF

med: insulin, enalapril, furoseminde, metoprolol, aldactone, digoxin, ranitidine, clecoxib, sertaline, asa, & various eye drops
pt cant afford her meds so her disease is beginning to be exacerbated, esp in this case CHF
Explain why celecoxib causes less gastric irritation than
aspirin. Why is aspirin a better thrombolytic agent?
less inhibition of Cox-1 with celecoxib(cox-2 inhibitor), asa accumulate in mucosa and does inhibit cox-1 and cox-2
What are imfliximab and rituximab, and what are their
mechanisms of action in chronic inflammatory diseases
like rheumatoid arthritis?
moa: scavenger of TNF-a

action by help regress disease

tx:
1. nsaids or celecoxib
2. methotrexate
3. remicade or entercept

if these dont work then use rituximab is an Antibody against CD 20

containdicated for latent TB
How do allopurinol and probenecid lower blood urate?
allopurinol acts by inhibit xanthine oxidase so less urate formed

probenecid acts by preventing the secretion of and reuptake of uric acid, at high doses

asa - acts like probenicid but only prevents secretion but at very high does inhibit reuptake, so that is why pt with gout should not take asa, does not block both actions at normal doses
A serious adverse effect that may occur with a single
therapeutic dose of one aspirin tablet is
(A) infertility
(B) hepatotoxicity
(C) nephrotoxicity
(D) bronchial asthma
(E) hemolytic anemia
A serious adverse effect that may occur with a single
therapeutic dose of one aspirin tablet is
(A) infertility
(B) hepatotoxicity
(C) nephrotoxicity
(D) bronchial asthma
(E) hemolytic anemia

D rare genetic condition in which inhibition of COX
shunts arachidonic acid through lipoxygenase to form
leukotrienes that provoke severe asthma
Which of the following agents used to prevent organ transplant rejection is
most likely to cause significant bone marrow suppression?
A. anti-lymphocyte globulin
B. cyclosporine (Sandimmune®)
C. prednisone
D. sirolimus (Rapamune®)
E. tacrolimus (Prograf
Which of the following agents used to prevent organ transplant rejection is
most likely to cause significant bone marrow suppression?
A. anti-lymphocyte globulin
B. cyclosporine (Sandimmune®)
C. prednisone
D. sirolimus (Rapamune®)
E. tacrolimus (Prograf®)

Answer:
D. sirolimus
Which of the following correctly matches an
immunosuppressant agent with its mechanism of action?
A. tacrolimus – inhibition of activation of T cell
transcription factors for cytokine expression
B. cyclosporine – prevention of clonal expansion of T an
Which of the following correctly matches an
immunosuppressant agent with its mechanism of action?
A. tacrolimus – inhibition of activation of T cell
transcription factors for cytokine expression
B. cyclosporine – prevention of clonal expansion of T and
B lymphocytes
C. cyclophosphamide - inhibition of antigen presentation
D. azathioprine – negative regulation of T cell expression
of lymphokines
E. prednisone – inhibition of IMP dehydrogenase

Answer:
A tacrolimus inhibits nuclear translocation of NFAT
Which of the following associates the correct mechanism of action with a
drug used in type 2 (non-insulin dependent) diabetes?
A. acarbose - reduction of insulin resistance
B. glipizide - inhibition of intestinal alpha-glucosidase
C. metaformin - inhibiti
Which of the following associates the correct mechanism of action with a
drug used in type 2 (non-insulin dependent) diabetes?
A. acarbose - reduction of insulin resistance
B. glipizide - inhibition of intestinal alpha-glucosidase
C. metaformin - inhibition of ATP-sensitive potassium channels
D. repaglinide - modulation of pancreatic insulin release
E. rosiglitazone - reduction in circulating glucagon levels

Answer:
D . repaglinide modulates pancreatic insulin release, binds like sulfonylureas but has a second binding site that may do other
functions.
correct answer for other choices:
a. acarbose - reduce intestial absorption of glucose
b. glipizide - stimulate insulin release from pancreas
c. metformin - lowers insulin resistance and reduces appetite
e. rosiglitazone - agonist binding to PPAR-gamma, reduce insulin resistance
Which of the following insulin regimens most closely mimics insulin
release from a normally functioning pancreas when used in a type 1
diabetic patient?
A. prebreakfast and predinner injections of lente insulin plus an injection
of regular insulin if bloo
Which of the following insulin regimens most closely mimics insulin
release from a normally functioning pancreas when used in a type 1
diabetic patient?
A. prebreakfast and predinner injections of lente insulin plus an injection
of regular insulin if blood glucose exceeds 150 mg/dl.
B. premeal injections of insulin lispro plus morning and evening
injections of lente insulin
C. premeal injections of neutral protamine hagedorn (NPH) insulin plus
an injection of insulin lispro at bedtime
D. postmeal injection of lente insulin plus a prebreakfast injection of
regular insulin
E. postmeal injections of insulin glargine

Answer:
B. The lente injections provide a baseline level of insulin and the premeal
injections of quick-acting lispro provide the insulin peaks needed to deal
with dietary intake of carbohydrates
inhibition of intestinal alpha-glucosidase
acarbose
Which of the following drugs reduces LDL-cholesterol by
reducing secretion of VLDL from the liver and also
reduces triglycerides?
A. atorvastatin
B. cholestyramine
C. ezetimibe
D. gemfibrozil
E. niacin
Which of the following drugs reduces LDL-cholesterol by
reducing secretion of VLDL from the liver and also
reduces triglycerides?
A. atorvastatin
B. cholestyramine
C. ezetimibe
D. gemfibrozil
E. niacin

Answer:
E. niacin reduces VLDL and LDL
Which of the following descriptions best describes the molecular
mechanism of action for the statins?
A. binding to PPAR-gamma receptor to activate lipoprotein lipase
B. increasing fecal excretion of bile acids to increase conversion of
cholesterol to bil
Which of the following descriptions best describes the molecular mechanism of action for the statins?

A. binding to PPAR-gamma receptor to activate lipoprotein lipase
B. increasing fecal excretion of bile acids to increase conversion of cholesterol to bile acid
C. inhibition of hepatic cholesterol biosynthesis to increase LDL receptor activity
D. inhibition of cholesterol uptake from the intestinal lumen
E. inhibition of cholesteryl ester transfer protein (CETP)

Answer:
C. Statins inhibit HMG-CoA reductase to block biosynthesis of
cholesterol in hepatocytes. Lowered intracellular cholesterol activates
transcription of the LDL receptor gene. After translation, the
increased LDL receptor activity allows greater uptake of LDL from the
circulation.
A 45-year-old woman who is being treated for hypertension
and hypercholesterolemia develops diffuse
muscle pain and weakness. Serum creatine kinase
activity is increased. Which of the following drugs is
most likely to have caused this clinical picture?
(A
A 45-year-old woman who is being treated for hypertension
and hypercholesterolemia develops diffuse
muscle pain and weakness. Serum creatine kinase
activity is increased. Which of the following drugs is
most likely to have caused this clinical picture?
(A) Captopril
(B) Hydrochlorothiazide
(C) Lovastatin
(D) Nicotinic acid
(E) Propranolol

Answer:
C
For lipid-soluble drugs, which of the following apply to
elderly patients as contrasted to younger adults? More
than one may be correct.
A. volume of distribution is larger
B. half-life is longer
C. % body fat is greater
D. liver is smaller
E. liver blood
For lipid-soluble drugs, which of the following apply to elderly patients as contrasted to younger adults? More than one may be correct.
A. volume of distribution is larger - true
B. half-life is longer - yes for lipid soluble drug
C. % body fat is greater - true, reason why vol of dist inc
D. liver is smaller - true, less capacity to metabolize drug in inc half life
E. liver blood flow is lower - not always true, can be imp if dec CO with CHF, esp for lipid soluble drug bc dec delivery drug to liver
F. Phase I metabolism activity is lower - (oxidation, conjugaion) yes
G. Phase II metabolism (glucoronidation, sulfonazation) is unchanged - true
f(D/T) = Css * Vd * (0.693/t1/2) -> as half life inc more likely to more effect and inc effect so steady state conc are going to be higher in elderly pt compared to younger pt
A 72-year old male is being treated for prostate cancer with leuprolide. Which of the following is the correct mechanism of action for leuprolide?

A. inhibitor of 5 alpha -reductase
B. competitive antagonist at androgen receptors
C. competitive inhibitor
A 72-year old male is being treated for prostate cancer with leuprolide. Which of the following is the correct mechanism of action for leuprolide?

A. inhibitor of 5 alpha -reductase
B. competitive antagonist at androgen receptors
C. competitive inhibitor of LH
D. synthetic analog of GnRH
E. agonist at estrogen receptors

Answer:
D. analog of GnRH - chronic treatment inhibits FSH and LH
release which shuts down testosterone synthesis
metabolism is saturated and elimination is zero order in overdose
aspirin
NSAID that causes severe gastric effect
indomethacin
inhibits both steps in SYNTHESIS of urate
allopurinol
partial agonist, COMPETITIVE INHIBITOR of estrogen receptors, stimulates ovulation
clomiphene
sediative drug which takes long to be metabolized in older pts due to inc lipid solubility of the drug and the inc in percent body fat in older pt
diazepam
/ 184
Term:
Definition:
Definition:

Leave a Comment ({[ getComments().length ]})

Comments ({[ getComments().length ]})

{[comment.username]}

{[ comment.comment ]}

View All {[ getComments().length ]} Comments
Ask a homework question - tutors are online