Pharm2Exam2

Question 1

Toxicokinetics

Answer 1

Absorption, distribution, metabolism, and excretion of toxins, toxic doses of therapeutic agents, and/or their metabolites.

Question 2

Toxicodynamics

Answer 2

Describes the harmful effects of the toxins or toxic doses to vital organ functions. (what the drug does at the receptor level)

Question 3

DEFG of toxicology

Answer 3

Decontamination
Targeted Elimination
Focused Therapy
“Get toxicologist’s help”

Question 4

Anticholinergic Toxicity

Answer 4

Decreased PANS
myadriasis, blurred vision, fever, flushed dry skin, AMS, seizures, urine retention/constipation, hypertension, tachycardia

Question 5

Anticholinergics

Answer 5

Antihistamine (diphenhydramine)
Anticholinergic (atropine)
Antipsychotic (haloperidol)
Antidepressants (TCAs)
Environmental (Jimson Weed, Gyromitra)

Question 6

Physostigmine

Answer 6

Treatment for anticholinergic toxicity
Reversible AChE antagonist
Increases cleavage of ACh at the neuromuscular junction
Used IF: no co-ingestions (TCAs), no seizures, significant AMS, need CV monitoring, may need infusion

Question 7

Cholinergic Toxicity

Answer 7

Increased PANS activity

muscarinic, nicotinic, and CNS effect

Question 8

Cholinergics

Answer 8

Organophosphates (pesticides)
Carbamates (physostigmine)
Iatrogenic (edrophonium)
Nerve gas (VX)
Mushroom species

Question 9

Muscarinic Toxidrome

Answer 9

Diarrhea, diaphoresis, urination, miosis, bradycardia, bronchorrhea, bronchospasm, emesis, lacrimation, salivation

Question 10

Nicotinic Toxidrome

Answer 10

Myadriasis, Tachycardia, weakness, Hypertension, Fasciculations

Question 11

CNS Cholinergic Tox

Answer 11

Agitation, seizures, coma

Question 12

Cholinergic Tox treatment

Answer 12

Atropine, Pralidoxime, BZDs

Question 13

Atropine

Answer 13

Cholinergic tox treatment
1-2 mg IV every 5-10 mins, short acting
May need infusion

Question 14

Pralidoxime

Answer 14

VX gas antidote

1-2 grams infused over 30 mins

Question 15

Diazepam

Answer 15

Benzodiazepine - cholinergic tox treatment

Helps CNS effects

Question 16

Adrenergic Toxidrome

Answer 16

Increases SANS
CNS: AMS, increase temp, seizures
Myadriasis, increased BP and HR, diaphoresis, nausea, vomiting, urine retention

Question 17

Adrenergic treatment

Answer 17

BZDs, temperature regulation, fluid administration, BP management (verapamil IV, NTG) maybe labetalol - NO BETA only BLOCKERS

Question 18

BB/CCB toxicity

Answer 18

Myocardium transitions from FFA to glucose substrate = anaerobic metabolism
hypoglycemia
BB: blockade of both B1 and B2 receptors, high dose = blockade of Na channels, decreased entry of Ca and decrease cAMP release, decreased BP and HR
CCB: Decrease SA/AV conduction, reduced CO and BP

Question 19

Salicylate (ASA) TOX

Answer 19

Antiplatelet Agent
MOA: irreversibly binds COX-1 and inhibits prostaglandin synthesis. uncoupling of oxidative phosphorylation (aerobic metabolism) and disruption of cellular metabolism.
SEs: gastric bleeding, ulcers
Metabolized into salicylic acid and acetic acid metabolites
*triad of hyperventilation and dizziness, GI upset (vomiting), tinnitus
Treatment: gastric decontamination (activated charcoal), LOW Vd, Hemodialysis!

Question 20

Acetamenophine (APAP)

Answer 20

active metabolite = N-acetyl-p-benzoquinone
Glutathione required to detoxify NAPQI from liver, glutathione depletion = CYP2E1 saturation and tox
Treatment = N-acetylcystine (NAC) usually IV
MOA tox: covalent binding of protein adducts, Kupffer cells and formation of IL, damage is mainly irreversible

Question 21

Toxic Alcohols

Answer 21

Methanol, ethylene glycol, ethanol, propylene glycol = hyperosmolality AND metabolic acidosis
Isopropranol only = hyperosmolality
HD used as treatment

Question 22

Unfractionated Heparin

Answer 22

MOA: short half life (2 hours), administered SQ or IV.

Frequent monitoring with activated partial thrombinplastin time (aPTT) UFH tox reversed with Protamine

Question 23

Protamine

Answer 23

Heparin OD treatment

Slightly basic pH, large dose will result in paradoxical bleeding and CV changes

Question 24

Ticlopidine

Answer 24

Antiplatelet Agent
ADP antagonist
*not as commonly used
MOA: interferes with the binding of ADP to its receptor on platelets and therefore inhibits the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and bind to each other.
Results in reduced platelet aggregation
Use: Alternative to aspirin in TIA, post-MI, and unstable angina, post-coronary artery stent procedure
Side Effects: GI bleed, neutropenia *RARE side effect of thrombocytopenia

Question 25

Clopidogrel

Answer 25

Antiplatelet Agent ADP antagonist MOA: interferes with the binding of ADP to its receptor on platelets and therefore inhibits the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and bind to each other. Results in reduced platelet aggregation Use: Alternative to aspirin in TIA, post-MI, and unstable angina, post-coronary artery stent procedure Side Effects: GI bleed, neutropenia

Question 26

Prasugrel

Answer 26

Antiplatelet Agent ADP antagonist MOA: interferes with the binding of ADP to its receptor on platelets and therefore inhibits the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and bind to each other. Results in reduced platelet aggregation Use: Alternative to aspirin in TIA, post-MI, and unstable angina, post-coronary artery stent procedure Side Effects: GI bleed, neutropenia

Question 27

Ticagrelor

Answer 27

Antiplatelet Agent ADP antagonist MOA: interferes with the binding of ADP to its receptor on platelets and therefore inhibits the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and bind to each other. Results in reduced platelet aggregation Use: Alternative to aspirin in TIA, post-MI, and unstable angina, post-coronary artery stent procedure Side Effects: GI bleed, neutropenia

Question 28

Antiplatelet Agents

Answer 28

Aspirin (ASA), ticlopidine, clopidogrel, prasugrel, ticagrelor

Question 29

Glycoprotein IIb/IIIa inhibitors

Answer 29

Abciximab, Tirofiban, Eptifibatide

Question 30

Abciximab

Answer 30

GP IIb/IIIa inhibitor MOA: monoclonal antibody against GP IIb/IIIa receptors on platelets. Prevents the binding of fibrinogen and other adhesive molecules to GP IIb/IIIa = prevention of platelet aggregation. IV administered Indication: in patients undergoing percutaneous coronary intervention, unstable angina, and post MI SEs: Bleeding and thrombocytopenia *Long acting 18-24 hrs *Hepatic metabolism no dose adjustment for renal dysfunation

Question 31

Tirofiban

Answer 31

GP IIb/IIIa inhibitor Indication: in patients undergoing percutaneous coronary intervention, unstable angina, and post MI SEs: Bleeding and thrombocytopenia *Short acting 6-12 hrs *IV and infusion, requires dose adjustment for renal dysfunction

Question 32

Eptifibatide

Answer 32

GP IIb/IIIa inhibitor Indication: in patients undergoing percutaneous coronary intervention, unstable angina, and post MI SEs: Bleeding and thrombocytopenia *Short acting 6-12 hrs *IV and infusion, require dose adjustment for renal dysfunction

Question 33

Direct Thrombin inhibitors

Answer 33

Argatroban, Bivalirudin, Dabigatran

Question 34

Argatroban

Answer 34

Direct Thrombin Inhibitors MOA: synthetic manufactured, IV infusion. Half life 0.5-1 hr Use: patient that do not react to UFH or ADR SEs: bleeding dependent of dose *need dose adjust for hepatic dysfunction *dose titrated to aPTT monitoring

Question 35

Bivalirudin

Answer 35

Direct Thrombin Inhibitor MOA: synthetic manufactured, IV infusion, bolus. Half life 25 min. cleared hepatic and some renal Use: patient that do not react to UFH or ADR, ACS treatment via PCI SEs: bleeding dependent of dose *Monitored via ACT

Question 36

Dabigatran

Answer 36

Direct Thrombin Inhibitor Novel oral agent MOA: pro-drug, no need for extensive monitoring and low drug interactions. Target is thrombin inhibition. Low bioavailability, 1/2 life 14-17 hrs, mainly renal clearance USE: evaluating outpatient use in DVT and PE

Question 37

Xa Inhibitors

Answer 37

Enoxaparin, Rivaroxaban, Apixaban

Question 38

Enoxaparin

Answer 38

Xa inhibitor

Question 39

Rivaroxaban

Answer 39

Xa inhibitor MOA: inhibit factor Xa, high bioavailability, half life 7-11 hrs, no monitoring required, hepatic and renal clearance USE: outpatient treatment of DVT and PE *may have drug ixn with CYP450 3A4 and P-gp

Question 40

Apixaban

Answer 40

Xa inhibitor MOA: inhibit factor Xa, medium bioavailability, half life 12 hrs, no monitoring required, mainly hepatic clearance USE: outpatient treatment of DVT and PE *May have drug interaction with CYP450 3A4

Question 41

Fonsaparinux

Answer 41

Synthetic Anticoagulant

Question 42

Warfarin

Answer 42

Anticoagulant MOA: inhibition of hepatic-vitamin K dependent clotting factors (II, VII, IX, and X), long acting therapy, primarily protein bound, liver metabolism (CYP2C9 and CYP3A4). S-isomer is more potent and is 2C9, R is 3A4. Crosses placenta CONTRAINDICATED IN PREGNANCY *Monitored with prothrombin time (PT) and international normalized ratio (INR) indications: Long-term outpatient anticoagulation for DVT, PE, stroke, AF, and inherited clotting disorders (Protein C and S deficiencies) AEs/SEs: bleeding, GI bleed, skin necrosis, multiple drug interactions, teratogenic *Toxicity reverse with vitamin K and blood products Drug ixn: Acidic molecule so oral cholestyramine can decrease absorption, protein binding drugs can displace (ASA, sulfonamides, and phenytoin) increasing active drug, inducers and inhibitors of CYP2C9 and 3A4 will alter drug concentrations

Question 43

Phytonadione

Answer 43

Vitamin K clotting agonist | Warfarin OD treatment (?)

Question 44

aminocaproic acid

Answer 44

Lysine derivative | Inhibitor of fibrinolysis

Question 45

Tranexamic acid

Answer 45

Lysine derivative | Inhibitor of fibrinolysis

Question 46

Thrombolytics

Answer 46

Streptokinase, Alteplase, Tenecteplase, Reteplase | USE: Coronary thrombosis, PE, DVT, AMI, Stroke

Question 47

Streptokinase

Answer 47

Thrombolytic derived from B-hemolytic streptococcus bacteria (antigenic activity) MOA: inhibits thrombin, promotes conversion of plasminogen to plasmin Indication: AMI, stroke, and PE

Question 48

Alteplase (tPA)

Answer 48

Thrombolytic Often used in non-hemorrhagic strokes but time of administration is key MOA: inhibits thrombin, promotes conversion of plasminogen to plasmin = clot lysis Selectively activates plasminogen that is bound to fibrin (selective clot lysis) Indication: AMI, stroke, and PE (time critical) *Less hemorrhagic episodes than other thrombolytics due to specificity.

Question 49

Reteplase

Answer 49

Thrombolytic MOA: synthetic agent, inhibits thrombin, activates conversion of plasminogen to plasmin = clot lysis Indication: AMI, stroke, and PE More use in cardiology

Question 50

Tenecteplase

Answer 50

Thrombolytic MOA: Synthetic agent, activates plasminogen to plasmin = clot lysis Indication: mainly AMI, can be used for stroke and PE too more use in cardiology

Question 51

Heparin Immune Mediated Thrombocytopenia (HIT)

Answer 51

More severe thrombocytopenia MOA: antigen-antibody reaction, onset 7-14 days, diagnostic testing, PLT less than 150,000 or >50% decrease from baseline *Needs additional therapy: DTI (short-term), Warfarin (home)

Question 52

Heparin Associated Thrombocytopenia (HAT)

Answer 52

MOA: onset less that 7 days, temporary, requires supportive care but no additional therapy, may continue heparin therapy and monitor PLT

Question 53

Rapid Preparation Insulin

Answer 53

Drugs: Lispro, Aspart, glulisine MOA: rapid onset of action/control, but do not last long. ~4 hrs, control for meal time

Question 54

Short Preparation Insulin

Answer 54

Regular insulin | MOA: onset of 30 mins, SQ administration or IV

Question 55

Intermediate preparation Insulin

Answer 55

Neutral Protamine Hagedorn (NPD) or Isophae | MOA: onset ~2 hrs, duration of 4-12 hrs

Question 56

Long preparation insulin

Answer 56

Drug: Glargine and Detemir MOA: Slow onset (1 hr), and lasts 12-24 hrs

Question 57

Sulfonylureas

Answer 57

2nd gen: Glyburide, Glipizide, Glimepiride MOA: alteration of the K dependent channel to result in increased depolarization. This = indirect increase in Ca entry into the cell and insulin release. Toxicity: Hypoglycemia and increased drug activity due to secondary organ dysfunction (liver or kidney)

Question 58

Glyburide

Answer 58

Sulfonylureas Oral insulin therapy

Question 59

Glipizide

Answer 59

Sulfonylureas Oral insulin therapy

Question 60

Glimepiride

Answer 60

Sulfonylureas Oral insulin therapy

Question 61

Insulin Secretagogues

Answer 61

Meglitinide class: repaglinide D-Phenylalanine: Nateglinide Metabolized in liver

Question 62

Repaglinide

Answer 62

``` Insulin Secretagogue, Meglitinide class MOA: similar to sulfonylureas but with faster onset (60 mins) and metabolism via 3A4 Absent of sulfur structure so can be utilized in patients with sulfur allergy ```

Question 63

Nateglinide

Answer 63

Insulin secretagogue, D-Phenylalanine MOA: Similar to sulfonylureas, and no sulfur allergy Metabolized via 2C9 and 3A4

Question 64

Metformin

Answer 64

Biguanide Oral insulin agent MOA: reduce hepatic glucose production via activation of an enzyme AMP - activated protein kinase (AMPK) Tox: GI (N/V, abdominal pain), lactic acidosis**, CONTRAINDICATED IN PATIENT WITH LIVER OR RENAL DISEASE

Question 65

Thiazolidinediones

Answer 65

Pioglitazone Rosiglitazone MOA: regulation of peroxisome proliferator-activated receptor-gamma (PPAR-g) which regulated muscle, fat, and muscle tissue expression. (targets mostly adipose cells in diabetics) Benefits of cholesterol profile (pioglitazone) Tox: lower risk of hypoglycemic episodes, but increase cardiac events (rosiglitazone)

Question 66

Alpha-glucosidase inhibitors

Answer 66

Acarbose, Miglitol MOA: inhibition of intestinal alpha-glucosidase thereby delaying the absorption of starch and disaccarhides. taken prior to meals. Tox: GI (diarrhea, abdominal pain, flatulence) Caution in renal impairment

Question 67

Pioglitazone

Answer 67

Thiazolidinedione | *Benefits cholesterol profile with long term therapy

Question 68

Rosiglitazone

Answer 68

Thiazolidinedione | *increased risk of cardiac events

Question 69

Acarbose

Answer 69

Alpha-glucosidase inhibitor MOA: inhibits the function of intestinal alpha-glucosidase thereby delaying absorption of starches and disaccarhides Taken prior to meal Tox: GI, caution in renal impairment

Question 70

Miglitol

Answer 70

Alpha-Glucosidase Inhibitor MOA: inhibits intestinal alpha-glucosidase thereby slowing the absorption of starches and disaccarhides Tox: GI taken prior to meal

Question 71

Amylin analog

Answer 71

Pramlintide MOA: Suppression of glucagon release, delayed gastric emptying, and CNS anorectic effects USE: patient taking insulin that need addition therapy adjunct Injectable, to be given right before meal Tox: Hypoglycemia

Question 72

Incretin therapy

Answer 72

Exenatide | Sitagliptin

Question 73

Exenatide

Answer 73

``` Incretin therapy oral insulin therapy MOA: is an analog of glucagon-polypeptide 1 [GLP-1] USE: Injectable adjunct therapy for T2D *Dose adjust for renal dysfunction TOX: GI! ```

Question 74

Stiagliptin

Answer 74

Incretin therapy oral insulin agent MOA: is an inhibitor of dipeptidyl peptidase-4 (DDP-4) which will increase levels on GLP-1 and GIP USE: Oral prep given to T2D, 1x/day

Question 75

Cholestyramine

Answer 75

Bile Acid Resin MOA: Effects cholesterol absorption. Anion exchange resins bind negatively charged bile salts in the small intestine, loss of bile leads to compensatory increase in hepatic LDL receptors = reduced plasma cholesterol. HMG CoA reductase activity is increased which reduces cholesterol loss (temporarily), Triglyceride synthesis enhanced (temporarily), Temporary increase in VLDL then eliminated. AEs: temp increase in TGs, bad taste, inconvenient to swallow, abdominal bloating, constipation/steatorrhea, anal leakage, anal fissures, impairment of other drug absorption, decrease in fat soluble vitamin absorption *poor compliance due to bloating and steatorrhea

Question 76

Colestipol

Answer 76

Bile Acid Resin | Analog to Cholestyramine

Question 77

Zetia

Answer 77

Transport inhibitor MOA: Effects Cholesterol Absorption. Acts as a transport inhibitor, blocking the absorption of cholesterol by the brush border cells of the intestine USE: minor decrease in LDL, smaller decrease in TGs, and almost no effect on HDL AEs: Not recommended for those with moderate-severe hepatic insufficiency, drug ixn with cyclosporine, can cause increase in transanimase liver enzymes with statins *Often used as combination therapy with statins

Question 78

Statins

Answer 78

HMG CoA Reductase Inhibitors MOA: interfere with cholesterol synthesis. clearance by liver. Inhibit the enzyme HMG CoA Reductase which catalyzes the conversion of Acetyl CoA to melvonic acid a key step in cholesterol synthesis *Some upregulation of HMG CoA reductase levels but does not overcome effect. Results in liver LDL receptor upregulation and decrease in LDL plasma levels. May also be anti-inflammatory by reducing c reactive protein. USE: Most potent LDL lowering drugs and most preferred. AEs: Check liver enzymes before and after starting treatment. Myopathy is a major concern and Rhabdomyolysis, transaminase hepatitis Contraindicated in renal failure and with cyclosporine, microlide antibiotic, antifungal agent, or other CYP450 inhibitor useage.

Question 79

Nicotinic Acid (Niacin)

Answer 79

Acid form drug MOA: higher doses have hypolipidemic effect, eliminated via kidneys. Inhibition of VLDL secretion. Increased clearance of VLDL = decreased TGs and increase in HDL. USE: Most effective agent used for the increase of HDL levels (15-35%) AEs: Intense flushing and pruritis, nausea/abdominal pain, hyperuricemia, hyperglycemia (decreased glucose tolerance shows Acanthosis Nigricans), Hepatotoxicity (increased transaminase and ALT, flu-like fatigue

Question 80

Clofibrate (Gemfibrozil)

Answer 80

Fibric acid derivative MOA: well absorbed, 95% protein bound and can displace Warfarin. Decreases fatty acid synthesis, and lipoprotein lipase-enhanced hydrolysis, stimulates synthesis of apoA-1 (gemfibrozil) USE: decreases TGs and increases HDL, lower LDL effect *Most effective for TGs AEs: Dyspepsia, Gallstones, Myopathy- when used with statins enhanced risk for rhabdomyolysis! *Not commonly used for this reason

Question 81

Dinoprostone

Answer 81

Prostaglandin (PGE2) | USE: to induce labor, 2nd trimester abortion

Question 82

Misoprostol

Answer 82

Prostaglandin (PGE1) USE: used to decrease gastric ulceration, can prevent or reverse gastric SEs due to NSAIDs *also abortifacient properties Contraindicated in pregnancy Commonly combined with NSAIDs to reduce GI side effects

Question 83

Alprostadil

Answer 83

Prostaglandin (PGE1) MOA: improves blood flow at in peripheral vascular disease (vasodilator), platelet anti-aggregant USE: can be used as direct injection for male impotence (ED), and can maintain open ductus arteriosus

Question 84

Latanoprost

Answer 84

Prostaglandin(PGF2) USE: topically for the treatment of glaucoma *Topical only due to bronchoconstrictive properties

Question 85

Epoprostenol

Answer 85

Prostacyclin (PGI2) | USE: Rapid reversal of pulmonary hypertension

Question 86

Aspirin (ASA) General

Answer 86

NSAID prototypical MOA: non-selective COX-1 and COX-2 inhibitor, acetylates COX on a serine resulting in an irreversible inhibition (important in platelets because they cannot regenerate COX). Readily metabolized into salicylic acid which reversibly inhibits COX. Mainly metabolized in liver USE: Analgesic - mild to moderate musculo-skeletal pain and post-op pain, Antipyretic (adults only), Polyarthritic conditions*, Prevention of MI, unstable angina, and TIA (antiplatelet) *Not recommended in children (Reye's syndrome) SEs: GI upset (burping, cramps, nausea, ulceration, pH burning), PGI2 and PGE2 inhibition (decreases gastric mucus production) = upset *Ok in pregnancy, but avoid in last trimester

Question 87

Acetaminophen (APAP)

Answer 87

COX inhibitor, not NSAID! MOA: Is a weak inhibitor of COX in the presence of peroxides which accumulate during inflammation, therefore lacks anti-inflammatory properties. Is good for analgesia and antipyretic USE: pain without inflammation, those who can't take aspirin (ulcers/GI, hematologic issues, sensitivity to NSAIDs) SEs: little CV effects, respiratory, GI, or platelet function. Tox: Dose dependent hepatic toxicity (glutathione) GSH depletion = metabolite build up and hepatocyte damage. *Tox treatment: n-acetylcysteine (time dependent) *Tox increases with alcohol use in conjunction and excessive fasting

Question 88

Non selective COX NSAIDs

Answer 88

Aspirin, Ibuprofen, Indomethacin, Ketoprofen, Naproxen, Ketorolac, Sulindac

Question 89

COX-2 selective drugs

Answer 89

Rofecoxib, Celecoxib, Valdecoxib

Question 90

DMARDS

Answer 90

Methotrexate, Leflunomide, Gold salts, Sulfasalazine, Hydroxy-chloroquine

Question 91

Anti TNF

Answer 91

Infliximab, Adalimumad, Etanercept

Question 92

Rituximab

Answer 92

Anti CD 20 MOA: monoclonal antibody that targets CD20 antigen on the surface of B cells. USE: RA (for people that do not respond to anti-TNF therapy, B cell lymphomas SEs: similar to Infliximab: cytokine release syndrome (headache, fever, chills) -rare, lupus like syndrome (discontinue), infections (contraindicated in TB), myalgia or back pain *Expensive usually 3rd line

Question 93

Anakinra

Answer 93

IL-1 receptor blocker MOA: IL-1 blocker, onset 4-6 weeks, less efficient than TNF blocker, but may retard bone erosion USE: moderate to severe RA SE: injection site issues, infection (Rare), neutropenia

Question 94

Ibuprofen

Answer 94

Non-selective COX inhibitor, NSAID MOA: non-selective, propionic acid metabolite USE: primary dysmenorrhea, minor aches/pains, fever, tooth ache, backache, minor arthritic pain SEs: GI (less severe than aspirin), dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances

Question 95

Indomethacin

Answer 95

Non-selective COX inhibitor, NSAID MOA: non-selective, acetic acid metabolite USE: closure of patent ductus arteriosus, not often used for pain - more for inflammation SEs: GI (less severe than aspirin), dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances *Acute renal toxicity

Question 96

Ketoprofen

Answer 96

Non-selective COX inhibitor, NSAID MOA: non-selective, propionic acid metabolite USE: primary dysmenorrhea SEs: GI (less severe than aspirin), dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances

Question 97

Naproxen

Answer 97

Non-selective COX inhibitor, NSAID MOA: propionic acid metabolite USE: dysmenorrhea, SEs: GI (less severe than aspirin), can increase BP! dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances

Question 98

Ketorolac

Answer 98

Non-selective COX inhibitor, NSAID MOA: acetic acid metabolite, USE: moderate to severe pain management, NOT RA/OA SEs: GI (less severe than aspirin), dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances *can cause renal failure

Question 99

Sulindac

Answer 99

Non-selective COX inhibitor, NSAID MOA: acetic acid metabolite USE: not for pain, used in inflammation SEs: GI (less severe than aspirin), dose dependent, minor inhibition of platelet coagulation, N/V, some renal toxicity TOX: amblyopia, other ocular disturbances *only non-selective with NO renal effects

Question 100

Rofecoxib

Answer 100

COX-2 Selective inhibitor drug MOA: high COX-2 selectivity, not more effective analgesia or anti-inflammatory USE: OA/RA treatment, acute pain and dysmenorrhea SE: reduced GI/platelet effects, abdominal pain, diarrhea, nausea, headache, upper respiratory *Cardiotoxic! decreases release of anti-thrombotic PGI2, so COX-1 mediated thromboxane A2 takes over and is pro-thrombotic

Question 101

Celecoxib

Answer 101

COX-2 Selective inhibitor drug MOA: significant COX-2 selectivity, not more effective analgesia or anti-inflammatory USE: OA/RA treatment, acute pain and dysmenorrhea SE: reduced GI/platelet effects, abdominal pain, diarrhea, nausea, headache, upper respiratory *Cardiotoxic! decreases release of anti-thrombotic PGI2, so COX-1 mediated thromboxane A2 takes over and is pro-thrombotic

Question 102

Valdecoxib

Answer 102

COX-2 Selective inhibitor drug MOA: high COX-2 selectivity, not more effective analgesia or anti-inflammatory USE: OA/RA treatment, acute pain and dysmenorrhea SE: reduced GI/platelet effects, abdominal pain, diarrhea, nausea, headache, upper respiratory *Cardiotoxic! decreases release of anti-thrombotic PGI2, so COX-1 mediated thromboxane A2 takes over and is pro-thrombotic

Question 103

Methotrexate (MTX)

Answer 103

DMARD MOA: immunosuppressive, in higher doses inhibits dihydrofolate reductase. Doses used here may inhibit adenosine and TNF-alpha USE: RA SEs: stomatitis, nausea, GI, thrombocytopenia, pulmonary fibrosis, hepatotoxicity *Contraindicated in pregnancy, LIVER tox, immunodeficiency

Question 104

Leflunomide

Answer 104

DMARD MOA: Inhibits synthesis of uridine phosphate (1 month) USE: RA SEs: hepatotoxicity, immunesuppression, alopecia, diarrhea, hypertension, respiratory infections *Contraindicated in pregnancy - teratogenic *Works better with MTX

Question 105

Gold Salts

Answer 105

DMARD MOA: Taken up by macrophages, inhibits phagocytosis and decreases rheumatoid factor, decreased IgG (injection at joint) SEs: Stomatitis, rashes (discontinue), renal toxicity, immunosuppression *long onset, oral and IM as well

Question 106

Sulfasalazine

Answer 106

DMARD MOA: Sulfa drug, RA treatment MOA not known. Impairs secretion of myofibroblasts that prevent the breakdown of scar tissue USE: RA SEs: Stomatitis, nausea, GI, rare thrombocytopenia, decrease WBC

Question 107

Hydroxy-chloroquine

Answer 107

DMARD

Question 108

Infliximab

Answer 108

Anti TNF MAO: monoclonal antibody to TNF-alpha, binds to TNF and clears from the joint and blood stream. Prevents TNF from binding to its cellular receptor: there is reduced activation/infiltration of inflammatory cells. Reduces clinical symptoms and slows/stops progression USE: RA and Crohn's *Co-treat with methotrexate to reduce Ab formation SEs: cytokine release syndrome (headache, fever, chills) -rare, lupus like syndrome (discontinue), infections (contraindicated in TB), myalgia or back pain

Question 109

Adalimumab

Answer 109

Anti TNF MOA: monoclonal antibody to TNF-alpha, binds to TNF and clears from the joint and blood stream. Prevents TNF from binding to its cellular receptor: there is reduced activation/infiltration of inflammatory cells. Reduces clinical symptoms and slows/stops progression. Completely human Ab Less likely to develop Ab response USE: RA SEs: injection site reactions, infection (TB),

Question 110

Etanercept

Answer 110

Anti TNF MOA: soluble dimeric form of the p75 TNF receptor, binds TNF and prevents from binding cellular receptors USE: RA, ankylosing spondylitis, psoriatic arthritis SEs: sepsis/infection (deadly), injection site issues, and abdominal pain

Question 111

COX-1

Answer 111

PGH synthase I found in blood vessels, GI, mucosa Constitutive - prostaglandins have a role in normal physiological function

Question 112

COX-2

Answer 112

PGH synthase II Found in macrophages, Mast cells, and other cells associated with the immune or inflammatory response. Inducible - up regulated in inflammation

Question 113

Glucocorticoids drugs

Answer 113

Hydrocortisone, cortisone, prednisone, methylprednisolone, Triamcinolone, Dexamethasone, Betamethasone

Question 114

Mineralcorticoid drugs

Answer 114

Aldosterone, Fludrocortisone

Question 115

Glutocorticoids general

Answer 115

MOA: Stimulates synthesis of lipocortin which inhibits phospholipase A2 - reduces arachidonic acid production (starting point for prostaglandin and leukotriene synthesis) Effect: increased apoptosis of lymphocytes (reduced activation of NF-kB), inhibits cytokine production, inhibits activation of neutrophils and leukocytes - decreased ICAM, selectins, and integrins, stabalizes leukocyte lysosomal membranes, reduces capillary permeability and edema, antagonism to histamine and edema USE: Rheumatoid and collagen diseases, allergic - angioedema, serum sickness, contact dermatitis, hypersensitivity, UC, corticoid replacement SEs: few side effects, but short term activity, hypertension, lethargy, amenorrhea, "steroid diabetes", Cushing's syndrome, growth suppression, muscle wasting, N/V, osteoporosis, cataracts, Na retention, Ca and K loss, increased RBCs, WBC increase, CNS

Question 116

Metyrapone

Answer 116

MOA: inhibits 11B-hydroxylation, interferes with cortisol and corticosterone synthesis USE: Cushing's treatment

Question 117

Trilostane

Answer 117

MOA: Inhibits 3B-dehydrogenase USE: cushing's treatment

Question 118

Sympathomimetic

Answer 118

Epinephrine, isoproterenol, metaproterenol, albuterol, terbutaline, salmeterol

Question 119

Mast cell stabalizer

Answer 119

Cromolyn sodium, nedocromil

Question 120

Corticosteroids (asthma)

Answer 120

Hydrocortisone, prednisone, methylprednisolone, beclomethacone, triamcinolone, fluticasone

Question 121

Xanthine

Answer 121

Theophylline, aminophylline,

Question 122

Antimuscarinic

Answer 122

Ipratropium, tiotropium

Question 123

Leukotriene modifiers

Answer 123

Zafirlukast, montelukast, zileuton

Question 124

IGE antibody

Answer 124

Oalizumab

Question 125

Epinephrine

Answer 125

Emergency bronchodilator MOA: a1, b1, b2 non-selective, relaxes bronchial smooth muscles, increased mucus clearance, prevent mast cell mediator release USE: emergency relief of bronchospasm in acute asthma or anaphylaxis SEs: muscle tremors, tachycardia, palpitations due to cardiac stim, peripheral vasodilation (hypotension), tolerance developed of long term use, metabolic effects (increase FFA, glucose, lactate after large dose) *inhalation = minimal SEs

Question 126

Metaproterenol

Answer 126

Inhaled bronchodilator of choice MOA: b2 agonist (3-4hr) Relaxes bronchial smooth muscles, increased mucus clearance, prevents mast cell mediator release USE: episodic relief of bronchospasm, rapid short acting SEs: muscle tremors, tachycardia, palpitations due to cardiac stim, peripheral vasodilation (hypotension), tolerance developed of long term use, metabolic effects (increase FFA, glucose, lactate after large dose) *inhalation = minimal SEs

Question 127

Albuterol

Answer 127

Inhaled bronchodilator of choice MOA: b2 agonist (3-4hr) Relaxes bronchial smooth muscles, increased mucus clearance, prevents mast cell mediator release USE: episodic relief of bronchospasm, rapid short acting SEs: muscle tremors, tachycardia, palpitations due to cardiac stim, peripheral vasodilation (hypotension), tolerance developed of long term use, metabolic effects (increase FFA, glucose, lactate after large dose) *inhalation = minimal SEs

Question 128

Terbutaline

Answer 128

Inhaled bronchodilator of choice MOA: b2 agonist (3-4hr) Relaxes bronchial smooth muscles, increased mucus clearance, prevents mast cell mediator release USE: episodic relief of bronchospasm, rapid short acting SEs: muscle tremors, tachycardia, palpitations due to cardiac stim, peripheral vasodilation (hypotension), tolerance developed of long term use, metabolic effects (increase FFA, glucose, lactate after large dose) *inhalation = minimal SEs

Question 129

Salmeterol

Answer 129

Long Acting Beta2-agonist MOA: b2 agonist, long duration (12-24hrs) long onset (2 hrs) USE: Suppression of night time asthma *Does NOT replace a rescue inhaler (long onset) SEs: muscle tremors, tachycardia, palpitations due to cardiac stim, peripheral vasodilation (hypotension), tolerance developed of long term use, metabolic effects (increase FFA, glucose, lactate after large dose) *inhalation = minimal SEs

Question 130

Isoproterenol

Answer 130

Sympathomimetic asthma drug MOA: b1 and b2 non-selective agonist, inhaled short acting (60-90mins) Use: asthma SE: cardiac due to b1, muscle tremors, tachycardia, palpitations, peripheral vasodilation, direct stim of b1 cardiac receptors, tolerance over time, metabolic

Question 131

Cromolyn Sodium

Answer 131

Mast cell stabilizer (asthma) MOA: Inhibition of mast cell degranulation by stimuli (including cell bound IgE), alter function of delayed Chloride channel in cell membranes inhibiting activation. Suppresses activation of chemoattractant peptides on PMN, eosinophils, and monocytes, reverses elevated receptor expression on leukocytes. No bronchodilator or antihistamine activity. USE: Prophylactic treatment of asthma (mild to moderate) especially allergic asthma, allergic rhinitis. Often used prior to challenge (exercise, allergen, cold) Long term treatment. Prevents early and late response to allergen - decreases bronchial response *Coadministered with b2 agonist (albuterol) to assure access of cromolyn to airways SE: very few (likely due to low absorption rate), often used in childhood asthma *not as often used due to greater effect of leukotriene inhibitors

Question 132

Nedocromil

Answer 132

Mast cell stabilizer (asthma) MOA: Inhibition of mast cell degranulation by stimuli (including cell bound IgE), alter function of delayed Chloride channel in cell membranes inhibiting activation. Suppresses activation of chemoattractant peptides on PMN, eosinophils, and monocytes, reverses elevated receptor expression on leukocytes. No bronchodilator or antihistamine activity. USE: Prophylactic treatment of asthma (mild to moderate) especially allergic asthma, allergic rhinitis. Often used prior to challenge (exercise, allergen, cold) Long term treatment. Prevents early and late response to allergen - decreases bronchial response *Coadministered with b2 agonist (albuterol) to assure access of cromolyn to airways SE: very few (likely due to low absorption rate), often used in childhood asthma *not as often used due to greater effect of leukotriene inhibitors

Question 133

Corticosteroids (asthma general)

Answer 133

Anti-inflammatory agents (asthma) Systemic: prednisone - po, methylpednisolone - inj MOA: potent anti-inflammatory, inhaled is less absorbed = fewer SEs. Reduces number and activity of inflammatory cells in the airway, inhibits release of arachidonic acid metabolites in airway, prevent vascular permeability, suppresses IgE binding, decreases severity of disease and increases bronchodilator effect *Not bronchodilator USE: Patients who require b2 agonist use more than 4x per week, suppresses late response Systemic use for short term "burst" in persistent severe asthma Inhaled: long term use, suppression, control, and reversal of inflammation, reduces need for oral corticosteroids *Often used with LABA SE: inhaled= dysphonia, Oropharyngeal candidiasis, systemic=short term: reversible glucose metabolism abnormalities, increased appetite, fluid retention, weight gain, mood alteration, hypertension, peptic ulcer, rare necrosis of femur long term: adrenal axis suppression, growth suppression, hypertension, diabetes, osteoporosis, infection

Question 134

Theophylline

Answer 134

Xanthine MOA: inhibition of phosphodiesterases, increases cellular cAMP, adenosine receptor antagonism, blocks adenosine receptor which mediates bronchoconstriction, bronchodilation independent -mainly blocks constriction 6-12hrs PO USE: reverses and block bronchoconstriction, less potent than b2 agonist, additive effect with b2 agonist (bronchodilation) *often coadministered sustained release for night time asthma SE: VERY NARROW THERAPEUTIC INDEX, TI=1.3! significant SE with plasma over 20 mg/L, low dose to reach required plasma levels Low: headache, N/V, restlessness, increased acid secretion, diuresis High: convulsions, arrhythmias

Question 135

Aminophylline

Answer 135

Xanthine MOA: inhibition of phosphodiesterases, increases cellular cAMP, adenosine receptor antagonism, blocks adenosine receptor which mediates bronchoconstriction, bronchodilation independent -mainly blocks constriction 6-12hrs IV USE: reverses and block bronchoconstriction, less potent than b2 agonist, additive effect with b2 agonist (bronchodilation) *often coadministered sustained release for night time asthma SE: VERY NARROW THERAPEUTIC INDEX, TI=1.3! significant SE with plasma over 20 mg/L, low dose to reach required plasma levels Low: headache, N/V, restlessness, increased acid secretion, diuresis High: convulsions, arrhythmias

Question 136

Ipratropium

Answer 136

``` Antimuscarinic MOA: muscarinic antagonist, parasympathetic pathway (can induce bronchospasms) USE: combined therapy with b2 agonist *drug of choice for COPD SEs: few side effects, ```

Question 137

Zafirlukast

Answer 137

Leukotriene Modifiers MOA: selective leukotriene receptor (LKT4) antagonist, 12 hr PO USE: alternative to low dose inhaled corticosteroids, cromolyn or medocromil, beneficial in allergen related asthma SEs: diarrhea, dizziness, cough, headache, N/V, difficulty sleeping (mild or rare) uncommon: earache, fever, sore throat, muscle weakness, mood change, hallucination, suicide ideation, other neuropsychiatric events

Question 138

Zileuton

Answer 138

Leukotriene Modifier MOA: 5 lipoxygenase inhibitor, decreases leukotriene synthesis, 6 hrs PO USE: alternative to low dose inhaled corticosteroids, cromolyn or medocromil, beneficial in allergen related asthma SEs: diarrhea, dizziness, cough, headache, N/V, difficulty sleeping (mild or rare) uncommon: earache, fever, sore throat, muscle weakness, mood change, hallucination, suicide ideation, other neuropsychiatric events

Question 139

Montelukast

Answer 139

Leukotriene Modifier MOA: N/A - inhaled USE: alternative to low dose inhaled corticosteroids, cromolyn or medocromil, beneficial in allergen related asthma SEs: diarrhea, dizziness, cough, headache, N/V, difficulty sleeping (mild or rare) uncommon: earache, fever, sore throat, muscle weakness, mood change, hallucination, suicide ideation, other neuropsychiatric events

Question 140

Omalizumab

Answer 140

Anti IgE antibody (asthma) MOA: antibody that binds to IgE in circulation and prevents its binding to cellular receptors. Does not activate IgE already on cells, 2x SQ USE: chronic severe asthma not controlled by other medications (b2 agonists, corticosteroids, LABA, etc), most effective for precipitated allergen or seasonal asthma, reduces frequency and severity of attacks *Very expensive, last line treatment for severe persistent asthmatics SEs: injection site, anaphylaxis (rare)