Pharm Exam Study Guide Exam 4

Front 1

Know theTNF-alfainhibitors and the indications and precautions for administration

Back 1

Inhibits TNF-alpha, which is a cytokine central to manyaspects of inflammatory response; stimulates macrophages to produce cytotoxicmetabolites, thereby increasing phagocytic killing activity; stimulatesproduction of acute-phase proteins, has pyrogenic effects, and fosters localcontainment of inflammatory response

Front 2

Know theTNF-alfa inhibitors and the indications and precautions for administration

Back 2

Etanercept (juvenileRA) , infliximab (Crohn’sdisease, ulcerative colitis) , adalimumab, certolizumab, golimumab

Prescreen for TB, would need aggressive abx therapy ifdevelop infection

Rheumatoid arthritis, psoriasis, and Crohn’s diseaseare three disorders in which inhibition of TNF-alpha has demonstratedtherapeutic efficacy

Front 3

TNF-alfa inhibitors

Back 3

do not cure diseases just improve them on symptoms

Etanercept, infliximab and adalimumab are proteins andmust be administered parenterally

Front 4

GVHD – Graft Vs HostDisease

Back 4

Whendonor lymphocytes attack recipient tissues

prevent by Remove T-cellsfrom donor before transplant

benefit in chemo by When transplantedT cells attack tumor cells left over from chemo tx - LEUKEMIA

Front 5

Self tolerance

Back 5

Ptsown immune system attacks its own tissue – own antigen as invader

Central on own t-cells and cells (mostly bone marrow/thymus)

Peripheral - on t-cells

Front 6

Hyperacute Rejection

Back 6

mediatedby pre-formed recipient antibodies against donor antigen Occurs very quickly

transplantedorgan becomes: cyanotic, mottled, flaccid

Usually related to mistyped blood or between species such as a pig valve

Front 7

Acuterejection

Back 7

Cellular andhumoral

cellular usually months after tx you get cytotoxic t-cells

Humoral - B-cells become sensitized to donor cells. antibodies develop antigens within 7-10days. occurs weeks to years after tx.

Tx with immunosuppression

Front 8

Chronic Rejection

Back 8

Occurs months toyears after transplant - irreversible organ damage

No currentsuppression tx – looking for ways to develop tolerance

Front 9

Stool softeners

Back 9

Docusate sodium (Colace)

Not absorbed –acts as a surfactant to increase mixing of aqueous and fatty materials à water penetrates to soften stool

Used mainly toprevent constipation (after surgery, heart attack; where straining should beavoided)

Front 10

Lubricants

Back 10

Mineral Oil

coats stool to make easier passage

inhibits colonic absorption - decrease transit time.

Side effects : absorbed systemically - causes immune reaction, avoid in bedridden patients, decreased fat soluble vitamins, watch for leaking out of sphincter.

Front 11

Osmotic laxatives

Back 11

Lactulose and sorbitol

Poorly absorbed,draw additional fluid into the GI tract

Lactulose(disaccharide): costly, no more effective than milk of magnesium, useful inelderly

suppositories work in 30 minutes

Front 12

Explain the differencesbetween 1st And 2nd generation antihistamines, includingthe side effects and molecular makeup.

Back 12

Used mainly torelieve the symptoms of allergies, but many have other uses due to theiranticholinergic activity

First generationagents are more sedating (non-selective) than the second generation lesssedating (peripherally selective decreased CNS) agents

Front 13

What are the advantages ofICSs over other drug delivery routes? What are their side effects andparticular concerns in the younger and older populations?

Back 13

Anti-inflammatoryto decrease hyper-responsiveness to triggers

PO for ACUTEsymptoms in exacerbation

Aerosolsteroids DO HAVE systemic bioavailability via lungs +/- GI tract, but stillless than PO and IV;

Front 14

ICS adverse side effects

Back 14

Decreased bonemineral density, esp elderly, post-menopausal women

Cataracts,increase ocular pressure, esp in elderly

Can stunt growth

Adrenal axissuppression – magnified by PO steroids chronically

Front 15

What is the mechanism ofaction of cromolyn (Intal) and what is its indicated use?

Back 15

Inhibit mast cell degranulation to block release ofinflammatory compounds, ? other effects

Pre-allergen orpre-exercise -not for acute

Mild chronicpersistent asthma only

Front 16

What is the mechanism ofaction of tiotropium (Spiriva) and why is it good for chronic conditions likeCOPD?

Back 16

Competitiveinhibitors of cholinergic receptors

Avoid innarrow-angle glaucoma, prostatic hyperplasia, bladder obstruction

Tiotropium (Spiriva) - long acting 5-6 days. Moreeffective than ipratropium

Front 17

tx acute asthma attack

Back 17

epi, albuterol, O2

Front 18

What is the mechanism ofaction of Leukotriene antagonists and what is their role in AR and Asthmatherapy?

Back 18

Leukotrienes aresome of the most potent bronchoconstrictors known

Zafirlukast(Accolate), Montelukast (Singulaire) (QD, Peds), Zileuton

]“Controller”in mild persistent asthma

Front 19

What are the side effects ofB2 agonists and why do they occur?

Back 19

Constitutional”– tremor, jitters, nausea, headache

“Tolerance”but not when PRN or in acute asthma episodes - due to down regulation of receptors.

arrhythmias,reflex tachycardia hyperglycemia,hypokalemia

Front 20

Explain acetaminophen(Tylenol) toxicity and how it is treated

Back 20

Overdose of acetaminophen can overwhelm glutathionestores, leading to cellular and oxidative damage and, in severe cases hepaticnecrosis

tx overdose: Acetylcysteine – Mucomyst - Protects livercells from damage in acetaminophen toxicity (give within 8-10 hours ofacetaminophen) it normalizes hepatic glutathione levels and binds with the reactivemetabolite of acetaminophen

Front 21

Mucomyst precautions

Back 21

Pts withrespiratory compromise

Caution in asthmapts

Severe hepaticdisease (these pts already have increased acetylcysteine)

Pregnancy category B

Front 22

other tx for tylenol overdose

Back 22

Activatedcharcoal – soaks up acetaminophen, makes you vomit

Gastric lavage –“stomach pumping”

Emetics

Front 23

What is the mechanism of ondansetron (Zofran) and whatdrugs work by the same mechanism?

Back 23

Block serotonin receptors (5-HT3 receptors, involvedchemotherapy response, post-op N/V) in area of CTZ and serotonin receptors onvagal afferents in GI tract

Front 24

What are the factors thataffect drug delivery in an aerosol form?

Back 24

Small particlesize increase drug deposition

Nebulizers –most expensive, somewhat portable, equal efficacy to MDIs for chronic use§ Use in young(<6 years), those with poor inspiratory effort, esp. in acute diseaseexacerbation

Front 25

DPI AND MDI

Back 25

Dry powder inhalers – not all drugs available as powder, not all techniques are the same

Metered-dose inhalers (MDI) – cost-effective (vs nebs), convenient,technique/cooperation may require “spacers” for children, uncoordinated,elderly

Front 26

CFC to HFA change

Back 26

Same amountalbuterol base (90 mcg

Different tasteand feel but greater drug deposition in lung

Efficacy, safetycomparable between HFA and CFC

Increased costsas replacing generic form

Products maycontain alcohol; need priming

Front 27

What is the mechanism ofaction of Dextromethorphan and it’s precautions/contraindications?

Back 27

Suppresses the cough reflex

Contraindications and precautions: Chronic coughfrom emphysema asthma, Use with cautionin patients with extensive hepatic impairment, Pregnancycategory C

Front 28

drug interactions with dextromethorphan

Back 28

May increasesedation when used with other CNS depressants

MAOIs – possibleserotonin syndrome

Fluoxetine – possiblehallucinations

Grapefruit and orangejuices

Front 29

What is the mechanism ofaction of PSE and it’s precautions/contraindications?

Back 29

Mimics sympathetic stimulation

inhibits catecholamine storage- u get a short term increase but long term decrease

Urinary alkalinizers increase [PSE]- increase tubular reabsorption

Front 30

1. What is 1st linetreatment for Peptic ulcer due to H. Pylori?

Back 30

Four drug therapy: Bismuth subsalicylate + 2antibiotics of different mechanisms + an H2 antagonist (healingdose) or a PPI (eradic`ation dose)

Front 31

1st line tx of GERD

Back 31

Life style changes (elevate HOB, avoid foods thatinitiate attack – citrus juice, tomato products, coffee – and foods thatdecrease LES tone – chocolate, mints, alcohol, fatty foods-

Antacids and/or OTC H2 blockers or PPIs

Front 32

What are the side effects andcontraindications for Bismuth salicylates?

Back 32

Colloidalbismuth – salt that combines withmucous glycoproteins to form a barrier that protects an ulcer from furtherdamage by HCL and pepsin

ADE of black stool and tongue discoloration

Front 33

What is the mechanism of action of sucralfate

Back 33

Forms a viscous gel in the acidic environment of thestomach

Protects the lumen surface from HCL and pepsin

does not work systemically

Front 34

What is the mechanism ofaction of PPIs? Are they well tolerated?

Back 34

PPIsblock the parietal cell H+/K+ ATPase pump

Single dose can effectively inhibit 100% of acidsecretion

thisbinding is irreversible, to start producing HCL again the cell must synthesizenew pumps which requires 18 hours

Front 35

What is the mechanism ofaction of H2s? Do they differ in efficacy? Potency? Are they well tolerated?

Back 35

H2 antagonists differ in potency, but areequally efficacious

Cimetidine: inhibits metabolism many drugs, crossesplacental barrier, antiandrogenic effects

Front 36

What are the potential side effects andtoxicities of antacids

Back 36

NaHCO3(sodium bicarbonate) – Absorption of HCO3à systemic metabolic alkalosis and Absorption ofNaCl salt à fluid retention (CHF,HTN)

CaCO3(calcium carbonate) – Tums - Some absorptionof Caand à hypercalcemia à rebound acid release

Front 37

What are the potential side effects and toxicities of antacids

Back 37

Al(OH)3(aluminum hydroxide) – Amphajel,Alterna Gel

Binds(high doses) with phosphate in gut, decrease phosphate, bone issues.

side effect may causeconstipation, obstruction

Front 38

Mg(OH)2(magnesium hydroxide) –Milk of magnesia

Back 38

MgCl2– insoluble salt à osmotic diarrhea, maycause dehydration

Front 39

dosing with antacids

Back 39

Stagger dosing of antacids 2 hours before or 2 hoursafter other medications (bind with other drugs)

Ca, Mg, and Al can accumulate with renal insufficiencyà toxicities

Front 40

Explain the differences inthe mechanisms of action between H2s and PPIs and what that means in terms ofacid suppression.

Back 40

PPIs are superior to H2 antagonists forsuppressing HCL and promoting peptic ulcer healing .. PPI 100% suppression, bind irreversibly

Front 41

Situationsthat may favor H2 antagonists over PPIs

Back 41

Adverse effectshave been better studied and in use longer than PPIs, therefore with theexception of cimetidine (Tagamet), they have been proven safe in pregnancy,where PPIs are unproven and avoided if at all possible

Cimetidine(Tagamet) – H2 blocker à Inhibits CYP 450 enzymes

Front 42

What is the differencebetween GER and GERD?

Back 42

GER: movement of gastric contents from the stomach intothe esophagus through the lower esophageal sphincter (LES)

GERD: frequent episodes of GER – heartburn andregurgitation 2 or more days/week chronically

Front 43

Do H2s and PPIs meettreatments goals for ulcers? Why or why not?

Back 43

PPIs do- contribute to H. pylori eradication by inhibitinggrowth and helps to heal

Front 44

Explain where Pepsin comes from and how it contributesto damage of the epithelial lining of the stomach

Back 44

Pepsinogen is secreted by the gastric chief cells

Then activated by HCL to convert to pepsin, aproteolytic enzyme that can damage epithelial

Front 45

Explain PGs role inprotection of the stomach lining and the consequences of inhibiting theirproduction. What drug can be given to replace inhibited PGs to regainprotection and what is its mechanism of action and its contraindications?

Back 45

Prostaglandinds stimulate mucus secretions

Misoprostol – prostaglandin analog used to prevent NSAID inducedulcers- can't use with pregnancy

Front 46

Explain thepathway and receptor for histamine in the role of stomach acid production.

Back 46

Histamine is released by ECL cells and mast cells

Histamine binds to H2 receptors on parietalcells

The binding stimulates adenylyl cyclase and increasescAMP, which activates protein kinases, which phosphorylates H+/K+ATPase pump, which results in the release of H+ into the gastriclumen from the parietal cell

Front 47

Explain the mechanism ofaction of the NSAIDs and the differences between the types of NSAIDs. (How theydiffer in selectivity and enzymes they inhibit etc.)

Back 47

NSAIDs are important because of their combinedanti-inflammatory, antipyretic, and analgesic properties

Ultimate goal of most NSAID therapies: inhibit theCOX-mediated generation of proinflammatory eicosanoids and to limit the extentof inflammation, fever, and pain

Front 48

Because of COX-1 inhibition, long-term NSAID therapyhas many adverse effects:

Back 48

Cytoprotectiveroles of the COX-1 eicosanoid products are eliminated à NSAID induced gastropathy including dyspepsia,gastrotoxicity, subepithelial damage and hemorrhage, gastric mucosal erosion,ulceration, and gastric mucosal necrosis

Can cause renal issues - decrease GFR.

Front 49

Aspirin

Back 49

Except for aspirin, all NSAIDs act as reversible,competitive inhibitors of cyclooxygenaseo TraditionalNSAIDs inhibit both COX-1 and COX-2 to different degrees

Front 50

Salicylates

Propionic acid derivatives

Back 50

Aspirin

ibuprofen,naproxen, ketoprofen, flurbiprofen

Front 51

Fenamate derivatives

Ketones

Back 51

Mefanamate,meclofenamate

Nabumetone

Front 52

COX-2 selective inhibitors

Oxicam derivatives

Back 52

Celecoxib,meloxicam

Piroxicam

Front 53

Acetaminophen

Back 53

Technically NOTan NSAID

Front 54

Acetic acid derivatives

Back 54

Indole aceticacids – Indomethacin (PDA open), sulindac, etodolac

Phenylaceticacids – diclofenac (renal stones), ketorolac