MOA: 

for heme/heme-containing protein synthesis(hemoglobin and myoglobin)

INDICATION/Uses: 

iron deficiency=> microcytic anemia

Adverse effects

Acute OD: lethargy, GI and dyspnea 

Chronic od: hemochromatosis 

Notes:  

Deficiency=>inadequate heme production

Elemental Fe= 30%

Route: 

 most popular= oral 

MOA:Iron Chelator

INDICATION/Uses: Remove XS Fe from blood transfusions: B-thalassemia, sickle cell DZ, myelodysplastic syndrome.  hemochromatosis not adequately tx'd by phlebotomy

Adverse effects:Rapid IV = hypotension LongIV= distress Long-term: neurotox, ↑infection susceptibility

Notes: Repeated transfusions= Fe accumulation, hemosiderin formation & CHF.↓ADR than deferoxamine

Route: Oral: dissolve in water/juice

MOA: MP1 receptor agonist = incr platelets production

Indication: ITP (idiopathic thrombocytopenic purpura)* *used for pts not responding to steroids, immunoglobulins or splenctomy

BLACK BOX WARNING: hepatotoxic, HA on day of therapy, reticullin accumulation in bone marrow

Monitoring: liver baseline

Delayed absorption w/ food and antacids

MOA: Iron chelator = decr acute/chronic iron overload

Indication: acute iron posioning, aquired/inherited hemachromatosis not responding to phlebotomy

SE:

• hypoTN w/ rapid IV
• acute respiratory distress w/ long infusions
• neurotoxicity and incr infections w/ longterm use

Forms: IM and SC preferred

MOA: inhibits IMPDH and other synthetic enzymes, therby interfering with AMP and GMP synthesis 

Effects: inhibits purine synthesis in lymphocytes

Uses: immunosuppression in renal transplant, RA, IBD, antineoplastic drug of choice

Common Side Effects: Gastritis

Serious Side Effects: Pancreatitis, myelosuppression, hepatotoxicity, infection

Contraindication: Pregnancy

MOA: binds and neutralizes TNF α

Uses: RA (with methotrexate), PsA (w or wo methotrexate). AS (w or wo methotrexate)

Can be used with corticosteroids, non-biological DMARDs, and/or NSAIDs

Multiple glycoforms, not able to fix complement

MOA: Binds to CD20 that causes B cell lysis through numerous possible reactions

Uses: B cell non-Hodgkin's lymphoma, RA (when TNFs fail), used with methotrexate

Common side effects: infusion reactions

Serious side effects: increased risk of infection (less than other DMARDs), pancytopenia

MOA: stimulate the Mp1 receptor to increase platelet number

Uses: treatment of idiopathic thrombocytopenic purpura

Common Side Effects: fatigue, HA, dizziness, anemia

Serious Side Effects: fluid accumulation in the lungs and transient atrial arrhythmia

Possible Side Effect: reticulin accumulation in bone marrow

Dose: SC once a week

MOA: drug enters macs of liver, spleen and bone marrow, iron released in 2 forms: storage pool as ferritin or incorporated into Hb

Uses: treatment of iron deficiency in adults with CKD (on or off dialysis)

Side Effects: compared with oral preparations, higher incidence of hypotension and dizziness, less diarrhea, nausea, constipation, and peripheral edema

Can be administered at a quicker rate compared to other parenteral forms and dose can be readministered after 1 month if anemia persists

MOA: Required for biosynthesis of heme and heme containing proteins (including hemo and myoglobin)

Uses:Microcytic anemia (iron deficiency)

ADE:

Acute: lethargy, abdominal pain dyspnea (necrotizing gastroenteritis)

Chronic iron overload: hemochromatosis

Elemental Iron: 12%

ORAL

MAO: cofactor required for:

• form tertahydrofolate
• convert homocysteine to methionine
• metabolize L-methylmalonyl-CoA

Uses: Vitamin 12 deficiency

ADE: None

• ORAL OR PARENTERAL (IM or SQ)
• orally used when injections aren't tolerated
• parenteral when anemic or malabsorbed

AKA: A77-1726

MOA: DHOD inhibitor = pyrimidine synthesis inhibition

Specificity: B cells

Indication: RA

Common SE: diarrhea, alopecia

Serious SE: hepatotoxicity, HTN, interstitial lung disease

AVOID: pregnancy

**major enterohepatic circulation = incr effect, use cholestyramine to remove

Recombinant humanized anti-human IL-6 receptor antibody

MOA: binds to IL-6 receptors specifically

Indication: RA monotherapy or combo with methotrexate

Common SE: URTI, HA, HTN, incr ALT

Serious: infections, GI perforation, neutropenia, thrombocytopenia

AVOID: live vaccines, biological DMARDS (restores p450 levels)

Prescreen for TB

**Humanized antibody to CD52

MOA: lympholysis of mature lymphocytes due to CD52 binding

Specificity: T and Bcells

Indication: Bcell chronic lymphocytic leukemia

Dosing: IV 3x wk for 12 wks

SE: same as anti-thrombocyte globulin w/o cytokine release 

AVOID: systemic infection, underlying immunodeficiency

MOA: Myeloid growth factor

stimulates G-CSF (recombinant form) receptors expressed on mature neutrophils and progenitors. Its a non-glysylated protein.

CA: Approved:

~decr infection in nonmyeloid malignant pt receiving myelosuppresive chemo drugs,

~reduces time to neutrophil recovery and duration of fever after induction or consolidation chemo in adults with AML (acute myelogeous leukemia)
~reduce duration of neturopenia and neutropenia-related clinical sequelate in nonmyeloid malignancy pts undergoing myeloblative chemo after bone marrow transplant

~mobilization of peripheral blood progenitor cell

Overall, in chemo: stimulates myelopoiesis

used in combo with Plerixafor to mobilize hematopoietic stem cells into peripheral blood for collection

AE:

injection site rash
mild bone pain

fewer SE compared to sargramostim

Notes: t1/2 = 2-4 hrs SC/IV

daily dosing during chemo

produced by E.Coli

MOA: Used for biosynthesis of heme and heme-containing proteins (hemoglobin and myoglobin)

Indication: Iron-deficiency anemia for chronic hemodialysis pts receiving supplemental erythropoietin therapy

AE: hypersensitivity, cramps, NV, flushing, hypTN, rash, pruitus

-Acute OD: lethargy, abdominal pain, dyspnea (necrotizing gastroenteritis, bloody diarrhea, shock)
-Chronic iron overload: hemochromatosis (damage to heart, liver, pancreas, other organs, organ failure and death)

Notes:

Dosage form parenteral (safest of three)

Safer than iron dextran due to fewer anaphylactic rxns 

primarily taken up by reticuloendothelial system

MOA: Tacrolimus binds to FK-binding protein (FKBP) and the tacrolimus-FKBP complex inhibis cacineurin. 

Specificity: activated t cells, inhibits IL3, IL4, IFNy and TNF alpha secretion. inhibit cell-mediated immunity. Doesn't suppress B cell or NK cell activity.

Uses: Organ transplantaition. widely used for Atopic dermatitis and eczematous diseases (topical preparation)

AE: common- alopecia GI, anemia, thrombocytopenia. Serious- nephrotoxicity, hypertension, prolonged QT interval, hyperglycemia, infection. Skin irritation is common (topical preparation)

MOA: Recombinant anti-human IL-1Beta monoclonal antibody- IgG1 form. Binds to and sequesters IL-1beta

Uses: Cryopyrin associated periodic syndromes- 4 years and older, Familiar cold autoinflammatory synddeom and muckle-Wells synfrom.

AE: Common:minor infections, Nasopharygitis, diarrhea, Nausea, HA, Flu. Serious- Severe infections(from every other agent that was discussed) -vertigo.

Interactions: TNF blockers, IL-1 blockers not recommended (kinda the same for the entire class). Avoid live vaccines.

Notes: Pre-screen of TB, stop treatment if serious infection develops. P450 normalization.

MOA:synthetic ACTH

Indication: dx of 1º adrenocortical failure 2º adrenal insufficiency, occasionally non-endocrine dzs responsive to glucocorticoids

Adverse Effects: rare hypersensitivity rxns, Consequences of ↑corticosteroid

Notes:IM, IV, SubQ (not PO)

Target: NOT Clacineurin Inhibitor

MOA: Binds FK-binding protien mTOR, regulator of protein translation

Effects: mTOR activation is necessary to allow IL-2 receptor stimulation leading to T cell proliferation ultimately T cell stuck in G1 cannot proliferate

Use: Organ transplant; Coronary artery disease (cardiac stent)

ADE: Common: anemia, thrombocytopenia, arthralgia, asthenia, HA

Serious: HTN, peripheral edema, thromboembolic disorder, hyperlipidemia

• Sirolimus-eluting stents are used in Tx of coronary artery disease
• oral: coadmin with voriconazole increases serum levels

MOA: Human IgG1 alpha monoclonal antibody against the p40 subunit of the IL-12 and IL-23

Effect: Decreases T cell infiltration into the skin tissue with minimal impact on the immune system

Uses: Moderate to severe PsO (18+), candidate for phototherapy or systemic therapy

ADE: Common: Nasopharyngitis, URIs, HA, fatigue, diarrhea

Serious: infections, malignancies, reversible posterioir leukoencephalopathy syndrome

• Supervised SubQ injection every 12 weeks after initial dosing
• Cannot get Tx if serious infectin is present or develops
• Pt genetically deficient in IL-23 susceptible to myobacteria
• Prescreen for Tb
• Contraindicated with live vaccines

MOA: AZA is prodrug of 6-MP; Drug metabolites inhibit IMDPH and other synthetic enzymes, interfering with AMP and GMP synthesis 

Clinical Application: Immunosuppression in renal transplantation; Rheumatoid arthritis; Inflammatory bowel disease; Myasthenia gravis, psoriasis, inflammatory bowel disease

 Route: Oral or IV

Side Effects:  (Common:) Gastritis
(Serious:) Pancreatitis, Myelosuppression, Hepatotoxicity; infection 

MOA: Binds TNF-alpha; a cytokine produced by macrophages and other cells that is a mediator of inflammation

Clincal Application: Rheumatoid Arthritis; Crohn's Dx; Ankylosing Spondylitis; Psoriatic Arthritis; Plague Psoriasis; Juvenile arthritis

Side Effects: 

Common: Injection site rxn, URI, abdominal pain, vomiting

Serious: Myelosuppresion, HF, optic neuritis, reactivate Tb, Increased risk of infection

MOA: Binds e chain of CD3 and promotes Ab mediated activation of complement and phagocytosis 

Clincal Application: Organ Transplant

Side Effects:

 Common: Ab, chest and bladder pain, diarrheea, dizziness

Serious: Cytokine release syndrome (fever, shivering, myalgia, HA) HTN, anemia, leukopenia, thromboytopenia, infection

Contraindication: CI: HF, Sz, Pregnancy/breastfeeding, uncontrolled HTN 

MOA:  activates the phagocytic activity of mature neutrophils and extends their survivial; mobilizes hemato stem cells.

USES:  aplastic anemia

AE:  Bone pain (rare), injection site rash (splenic rupture

ROUTES:  T1/2 15-80 hours (SQ or IV)- this long half time allows the use of one dose/chemotherapy cycle.

NOTES: 
A G-CSF, produced by recombinant DNA using E coli; generallly well tolerated

MOA: Binds to alpha-4 integrin that inhibits immune cell interaction with cells expressing VCAM-1 and MAdCAM-1

Effects: A4B1 and VCAM-1 interactions occur for immune cell homing in the CNS vasculature; A4B7 and MAdCAM-1 interactions occur for homing in the GI microvasculature

Uses: MS

ADE: Common: rash, arthralgia, HA, fatigue, UTI, lower resp tract infection

Serious: Cholelithiasis, PML, depression, pneumonia

• Monoclonal antibody against alpha-1 integrin that inhibits immune cell interaction with cells expressing VCAM-1 and MAdCAM-1
• IV every 4 weeks
• Contraindications: History of PML or existing PML

MOA

Orally inhaled glucocorticoids causes local suppression of eosinophils

Indication

Asthma, Severe (inflammatory bowel disease: ulcerative
colitis and Crohn’s disease

Notes

Nasally-inhaled glucocorticoids are also used for allergic rhinitis

MOA:  Required for the biosynthesis of heme and heme-containing proteins (including hemoglobin and myoglobin)

USES: iron-deficiency

AE:  Black-box warning: anaphylactic-type reactions(Can cause hypersensitivity); Common: Leg cramps, hypotension

ROUTE:  usually given IV

USES: contains 20mg elemental iron/ml

MOA: Inhibitor of IMPDH

SPECIFICITY:  IMDPH is essential to purine synthesis in the de novo pathway,

USES:  Solid organ transplantation (better than Azathioprine), Lupus Nephritis,
Rheumatoid Arthritis; Myasthenia gravis, psoriasis, inflammatory bowel
disease

AE:  Common: GI disturbances, HA Serious:HTN, GI hemorrhage, leukopenia, myelosuppression, neutropenia, increased risk of infection

INTERACTIONS:  Avoid concurrent admin of oral iron bc it reduces bioavail

NOTES:  May be given oral or IV

MOA:  binds TNF-Alpha

SPECIFICITY: Chimeric antibody with pieces of murine antibody and human FC gamma

INDICATION: RA (with methotrexate); Crohns disease (refractory in adults and kids) ulcerative colitis; PsA; PsO; AS

AE:  Common: Injection site reaction, URI, abdominal pain, vomiting

INTERACTIONS:  Avoid doses >5mg/kg in severe heart failure

NOTES: IV

MOA:  Binds to multiple epitopes on T cells

SPECIFICItY:  Binding to T cells causes depletion of T cells (opsonizes T cells for phagocytosis)

INDICATION:  Organ Transplant

DOSING:  IV daily over 4 hours for 1-2 weeks

AE: Common: Abdomina, chest and bladder pain, diarrheea, dizziness Serious: Cytokine release syndrome (fever, shivering, ,myalgia, HA) HTN, anemia, leukopenia, thromboytopenia, infection

NOTES:  Tx is limited b/c pt develpantibodies against rabbit epitopes; ATG Tx can result in a broad immunosuppression;

MOA: Binds IL-11 receptors, stimulates megakarocyte progenitors, increases platelet production.

USE: To prevent thrombocytopenia. esp during chemotherapy.

Therapy: Given daily SubQ, adverse effects are all reversible.

SE: Fatigue, fluid retention, edema, tachycarda

MOA: Comples of ferric hydroxide and dextran. Required for synthesis of heme groups.

USE: Iron deficiency, manifest as microcytic anemia

Therapy: Associated with anaphylactic reaction deaths, give a test dose first, used when oral is not possible (IV,IM)

MOA: Folate analogue that inhibits DHFR, GAR transformylase and AICAR transformylase.

Specificity: T-cells.

USE:Psoriasis, GRAFT vs Host diseases, Rheumatoid arthritis.

Dosing: Oral and Injection

Note: Use with caution in pts using NSAIDs

SE: Stomach ulcers, bone marrow toxicity

MOA: Specifically binds to TNF-alpha

Specificity: TNF-alpha cytokine mediator of inflammation produced by macrophages.

USE: Rheumatoid arthritis, Crohn's Dx

Notes: Recombinant, humanized antibody Fab fragment made by E.coli, often used with methotrexate.

SE:URI, myelosuppresion, HF, optic neuritis, increase risk of infection.

MOA: Binds to high affinity CD25 of IL-2 receptors and block cytokine activation.

Specificity: IL-2 receptors stimulation needed to increase  T-cell ; only to MHC-antigen stimulated Tcells

USE: Organ transplant.

Notes: Usded for induction therapy. Daclizumab is humanized antibody against CD25

Basilximab: Chimeric antiboty against human CD25  

Second generation Antihistamine

No Anti-Ach

Active Metabolite of loratidine

idiopathic urticaria

allergic rhinitis

Used in the treatment of Acute Gouty Arthritis

NSAID

High Doses for 3-4 days; tapper for 7-10

FDA Approved

MOA: Non-purine xanthine oxidase inhibitor

-Treats the intercritical period/chronic tophaceous gout (decreases uric acid formation)

ADE: Diarrhea, Headache, nausea, liver function abnormalities

1st generation Piperazine derivative

anti-emetic

some anxiolytic effects

1st generation antihistamine

anti-motion sickness

glucocorticoid

MOA: local suppression of enosinophils

Indications: Asthma (oral inhaled), allergic rhinitis (nasal inhalation)

glucocoriticoid

MOA: local suppression of enosinophils

Indication: asthma, severe inflammatory bowel dz, Crohn's dz, allergic rhinitis (nasal form)

glucocorticoid receptor antagonist

weak progestrone receptor antagonist

Indication: rescue for life-threatening glucocorticoid levels, ectopic ACTH syndrome

anti-inflammatory

Indication: acute gout

Dosing:high dose therapy, must taper

Xanthine oxidase inhibitor = ↓uric acid formation

• Structural analog of xanthine

Indication: chronic gout

Common AE: pruiris/rash, GI effects

Serious AE: Steven-Johnson syndrome, agranulocytosis, hepatic necrosis

Drug Intx: azathioprine and 6-mercaptopurine

NOT EXAM II

Enolic acid class

Selective COX-2 inhibitor

long half life = 1xday dosing

Less GI SE than piroxicam

NOT EXAM II 

Gold Salts Class

Immunomodulator = ↓ complement activation

Targets synovium/RES phagocytes

Indication: refractory Rheumatoid arthritis

SE: mucous membrane lesions, nephrosis w/ proteinuria

**NOT anti-inflammatory

Class

1st Generation

Family

Alkylamines

Anti-Ach

Yes

Sedation

slight sedation

Other

Common component of OTC cold meds

Class

1st Generation Antihistamine

Family

Piperazine derivative

Anti-ach

none

Sedation

Slight Sedation

Motion Sickness

Anti-Motion Sickness

Other

Used in Meniere's Disease

MOA

Orally inhaled glucocorticoids=local suppression of eosinophils

Indication

Asthma, Severe (inflammatory bowel disease: ulcerative
colitis and Crohn’s disease

Notes

Nasally-inhaled glucocorticoids=> allergic rhinitis

Indications: psoriasis, dermatitis, rheumatic disorders, allergic diseases, serious asthma, spinal cord injury

Dosing: Topical, IA injection

Potency G:M- 5:0.5

Indications: Asthma, rheumatic disorders

Dosing: Inhaled, IA

Potency G:M- 5:0

MOA: Inhibits CYP17 and 11A1 at high doses

Indications: MOST EFFECTIVE FOR CUSHINGS

Adverse Effects: Hepatic dysfunction, drug interactions

MOA

Orally inhaled glucocorticoids=local suppression of eosinophils

Indication

Asthma

Notes

Nasally-inhaled glucocorticoids=>allergic rhinitis

1st Generation Antihistamine

Ethanolamine

Sedating: +++

Only an OTC sleep aid or nighttime cold remedy

2nd Generation Antihistamine

Piperazine

Indications: Rhinitis, urticaria

Glucocorticoid

Use: Acute Gout

Dosing: most common oral (high doses initially, then taper)

Enhance uric acid metabolism (recombinant uricase)

Use: Intercritical period/chronic tophaceous gout

MOA: converts uric acid to more water-soluble allantoin

Use when refractory to conventional therapy

Adverse Effects: anaphylaxis and infusion rxn (pre med with antihistamine), gout flares, GI, chest pain, nasopharyngitis

NOT EXAM II

Off the market- increased MI and stroke

Least COX2 selectivity of all the coxibs

Tx uses: RA, Osteoarthritis, dental pain, chemoprevention of polyposis coli

Considerations: No platelet effects, Kidney effects

BROAD MOA:Inflammation (Acute gouty arthritis)

MOA:Binds to tubulin=prevents microtubule polymerize -Inhibits cell division-intracell trafficking

INDICATION:acute gouty attacks-gout prophylaxis -familial Mediterranean fever

DOSING:Oral/IV (FDA ordered-stop compound IV)

ADVERSE EFFECTS: Serious: bone marrow, renal complications,neuromyopathies Other: acute toxicity/chronic use

NOTES:↑ levels: cyclosporine, tacrolimus, verapamil

Broad MOA:↑uric acid mtblsm

MOA:uric acid=>water-soluble allantoin (↓crystals)

Indication:tumor lysis syndrome

Adverse Effects:Not for -G6PDpnts: methemoglobinemia, hypersensitivity (mild-anaphylaxis), GI, mucositis 

Notes:Well-tol in allopurinol-intol pnts; ↓SE than allopurinol

CLASS:Propionic Acid, nonselective

 MOA:Inhibits neutrophil oxidative burst (↓NADPH oxidase); ↓amyloidogenic proteins; Inhibits RhoA-ROCK ,↓contraction.

DOSING:t1/2 2hrs

INDICATION:1st choice: inflammatory joint DZ(↓est SE).

 RA, OA, AS, 1º dysmenorrhea.

 NOTES:Better tol than ASA/indomethacin.

CLASS:Acetic Acid

SELECTIVITY:COX-2, COX1

MOA:inhibitor of neutrophil. ↓Arachidonic metabs(PGE2 &PGI2)↑urate crystal phagocystosis.↓inflam effects. Inhibit RhoA-ROCK,↓contraction.

DOSING:For gout: @high doses 3-4 dys, taper off 7-10 days.

INDICATION:Inflamation (+++), GOUT, Osteoarthritis, ankylosing spondylits

ADR: Airway hyperreactivity (Aspirin-sensitive asthma).ulcer, Hepatitis,jaundice (rare)

NOTES:Potent inhibit of COX in vitro. t1/2=2hrs. 20x more potent than ASA on joint pain. Prodrug= Sulindac.

2nd generation antihistamine

Longer acting
Idiopathic urticaria
allergic rhinitis

Broad MOA: agent that increases uric acid excreation URICOSURIC 

MOA: ARB 

Clinical Application: Chronic gout

SE: dizziness, cough, angioedema, hyperkalemia

NOT EXAM II

Immunomodulating agent

MOA: Chelates trace metals; Dissociation of antigent-antibody reactions; decreased IL-1; Modulation of T Cell proliferation

Indication: Rheumatoid arthritis (75% response rate but can take weeks to months)

AE: Nephropathy with proteinuria, skin rash, GI symptoms, Hematologic effects

NOT EXAM II 

SELECTIVITY: monospecific anti-IGE antibody

MOA: Omalizumab neutralizes the free IgE in the serum by binding to the Fc regions of the heavy chains to form high-affinity IgE-anti-IgE complexes. (This prevents the IgE from binding to FcεRI, thereby blocking allergen-induced cell activation)

Indication:  Allergies, Moderate-severe persistent asthma

AE: Well-tolerated, Injection site rashes, Possible malignancies

2nd generation anti-histamine

no anti-cholinergic activity

fixed combo with decongestants

Alkylamines

Oral/topical

long acting

use for: fetal lung maturation, psoriasis, dermatitis, outer and anterior eye disease

and diagnose Cushing's Syndrome

increased IOP when given topically

naturally occurring steroid hormone

interacts with type 2 glucocorticoid R

synthetic glucocorticoid

intermediate acting

topical or IM

Treat: severe asthma, spinal cord injury, severe allergy dz

"Severe rheumatic disorders:SLE, polyarteritisnodosa, Wegener’s granulomatosis, Churg-Strauss syndrome, giant cell arteritis

NOT EXAM II 

competitive blocker of CysLT1 R

Uses: prevent for mild asthma

NOT EXAM II 

gold salt (po)

Use if NSAIDS not working for RA pts.

SE: GI, dermatitis, nephrosis with proteinuria

MOA:Targets phagocytic cells taken up in synovium & RES. Decreases phagocytic activity, inhibits IL-1 production by monocytes, reduces complement activation

MOA: stimulate BFU/CFU in bone marrow via Jak-stat to increase RBC production

Ind: CKD pts, non-myeloid malignancies with anemis due to concomitant chemotherapy (prevent need for transfusion in pts undergoing elective surgery)

SE: HTN, thrombosis, allergic (red cell aplasia, rare)

Route: IV OR SubQ (1x week)

longer t.5 than epoetin(20hrs IV, 49 subq)

SE: GI, N&D, constipation,

Acute overdose:lethargy, sob

Chronic overdose: damage organs

Use: treat Fe deficiency

MOA:

Increase Iron absorption to increase serum iron levels. Required for the biosynthesis of heme and heme-containing proteins

Elemental iron percentage 100%

Route: Expensive, oral preparation.

Route: po (prefered)-well absorbed, IM injection

MOA:donor of CH3 for synthesis of AA, DNA, purines,

Use:Trmt for folic acid deficiency, megaloblastic anemia(General tiredness, weakness, dyspnea). Prevention of congenital neural tube defects. Primary uses are for malnutrition, malabsorption, alcohol-liver disease and pregnancy.

1st generation antihistamines

Classificaiton- phenothiazine

anticholinergic effect(+++)

S/E-marked sedation, anti-emetic effets

1st generation antihistamine

classification- piperidine

limited anticholinergic effect (+)

moderate sedation and anti-serotonin

antihistamine

does not relieve an alergic response once it has begun

decrease the activity of the mast cells

taken several times per day

good safety profile

aspirin interferes with effect

use with NSAIDS/colchine to avoid attack

S/E- well tolerated, GI effects

serious bronchoconstrition in pts w/ asthma

*Sulfinpyrazone was a similar drug (D/C)

NOT EXAM II

NSAID

 Cox-2 selectivity

more potent than naproxen and indomethacin

reduces intracellular arachidonic acid

uses-RA, ankylosing spondylitis, osteoarthritis, pain associated with renal stones

NOT EXAM II

NSAID
a pro-drug converted in the liver

A/E are more than with aspirin

some COX-2 selectivity

long t1/2

uses- RA, osteoarthritis 

Steroid

Long duration of action

high anti-inflamatory activity

promotes fetal lung maturation

Steroid

orally inhaled glucocorticod used for asthma

nasal is used for alergic rhinitis

causes local supresion of esinophils

Steroid

specific effects on adrenal hormone

Class:  1st Generation Anti-histamine

Family:  Ethanolamines

ANTI-ACH:  Yes

Sedation:  Yes

For: Acute Gout
Class: NSAID

MOA: decrease arachidonic metabolites, decrease inflammation

SE: GI

Other: Some NSAIDS wont work (ASA, salicylates, tolmetin)
 

Use: Chronic Gout

MOA: structural analog of xanthine, inhibits formation of uric acid

SE: GI, Steven-Johnson syndrome, agranulocytosis, aplastic anemia, renal failure, etc

Other: Metabolite of Allopurinol 

1st generation antihistamine; Ethanolamine

Anticholinergic Effect: +++

Effects: Sedation
 

2nd Gen Antihistamine

Class: Piperanzine

Effect: No anticholinergic activity

MOA: Glucocorticoid

Use: Basically anything you could use a steroid for

SE: Increase IOP

Other: Can give to mother without fetal SE 

MOA: Inhibits CYP11A1 and 11B1, inhibits aromatase

Use: Cushing syndrome, hormonally responsive tumors

SE: rash, GI, neuro 

MOA: Glucocoritcoid

Use: Severe rheumatic disorders:

SLE, polyarteritisnodosa, Wegener’s granulomatosis, Churg-Strauss syndrome

Potency: 4 

Other: In pregnancy, mother's liver converts prednisone to prednisolone

NOT EXAM II 

Non-selective

Less GI SE than others, chronic use causes kidney damage, OD causes hepatotoxicity

Crosses BBB

NOT EXAM II 

Selective COX-2 Inhibitor

Use: Rheumatoid arthritis, dental pain, etc

MI & STROKE = OFF THE MARKET

NON-selective COX-inhibitor

MOA: ROCK pathway inhibitor = ↓ contraction, amyloigenic proteins

Prodrug of indomethacin

 Indications: RA, ankolysing spondylitis

Anti-ACh: Yes, Strong activity

Sedation:  Yes, Marked Sedadtion

Antimotion sickness activity

Used for meniere's disease

1st generation Anti-hist

Anti-ACh:  No Activity

2nd generation anti-hist

MOA:  Converted to the inactive cortisone by 11-B HSDII

No Glucocorticoid action

Duration of Action:  Short

Other:  Kidney inactivates cortisol to cortisone; cortisone will not bind to the mineralcorticoid recept

MOA:  mineralocorticoid receptor agonists

SE:  HTN, hypokalemia, cardiac failure

Other:  Minimal 1st pass metabolism

****Has a high mineralcorticoid to glucorticoid potency ratio

Class: 1st generation,

Family: Alkylamines,

Action:Weak anti-ACh activity, slight sedation

Class: 2nd generation

Family: Piperidines

Other: Low risk of arrythmia

Glucocorticoid

Indication: Dermatologic applications and less severe skin conditions (psoriasis, lichen planus, atopic dermatitis); primary and secondary adrenal insufficiency (oral in daily divided doses [primary needs mineralocorticoid concurrent and secondary does not]; Enema = Mild IBS, ulcerative colitis and crohn's

Notes: active form of the drug with high local drug concentration (topical) -- very low percentage of drug is delivered systemically when given topically ---

MOA: selectively kills adrenocortical cells
~possible mitochondria toxin

Indication: pallation of inoperable adrenocortical carcinoma

(chemical adrenalectomy)

Adverse Effects: anorexia, nausea(80%), somnolence, lethargy (34%), dermatitis (17%)

Notes: effects on early synthetic enzymes, ? toxicity to P450 enzymes

Other: must give adrenocorticosteriods because of cell killing, WHILE on Mitotane? pg 36

Broad MOA: inflammation

Specific MOA: terminates acute attack, and controls pain by limiting inflammation

Dosing: Delivered intraarticular injection

Class: salicylates

Selectivity: nonselective COX 1 and COX2

MOA: *BIG PICTURE: inhibits COX-1 and COX2, NF-kB acitivity, Reduction of COX-2 induation through NF-kB, acetylates COX-2 leading to epi-lipoxins, activates PPARy. Has analgesic (+,integumental structures), antipyretic (+), and antiplatelet effect (+, 8-12 days).*** MECHANISMS, Figure 4 in notes:acetylation of COX serine=> blocks formation of thromboxane A2 (in platelets) and prostagcylin (in vascular cells) *Epi-lipoxins via COX-2 acetylation by aspirin, See figure 5 in notes: can trigger lipoxins (ATLS)=>causes conversion of arachidonic acid to 15R-HETE via aspirin-triggered Cox2 acetylation in endothel/epithel cells. 15RHETE=>to 5,6 epoxytetraene intermediate by 5-LO in adherent leukocytes then => 15-LXA4 or 15epi-LXB4*blocks Cox-1 @ low doses *inhibitor of NFKB activation- normally lead to inflammatory proteins=> activation of PPAR & interacte w/IkB to block NFkB-initiated transcription of inflammatory molecules.*Figure 14arachidonic acid(AA) gains access to catalytic site of COX-1 through a hydrophobic channel that leads to core of enzyme by irreversibly acetylating a serine residue at position 529 in platelet COX-1, near but not w/in catalytic site=>prevents metabolism of AA to cyclic endoperoxide prostaglandin G2 and prostaglandin H2 for the lifetime of platelet. Because prostaglandin H2 is metabolized by thromboxane synthase to thromboxane A2, aspirin prevents formation of thromboxane A2 by the platelets until new platelets generated. Prior occupancy of catalytic site by ibuprofen prevents aspirin from gaining access to target serine.**LOW DOSE: TXA2 production decreased- COX-1 irreverible inihibited. PGI2 much less affected and dominated (vasodilatin and decreased platelet aggregation.

Indication: Anti-inflammatory effects, inflammatory bowel disease. A drug
of first choice for mild analgesia.

Adverse Effects: *Keratolytic action (destroys epithelial cells, tissue swells, softens, and desquamates) *Salicylism (condition of moderate toxicity, w/ repeated ingestion of large doses) **Neurological effects (CNS stimulation w/ depression, tinnitus, dizziness, decreased hearing, NA&V)**Epidemiological association between aspirin intake and Reyes syndrome (follows acute viral illness)*renal effects *respiration and Acid-base balance **ASA-induced airway hyperractivity (ocular/nasal congestion, aiway obstruction, may include increased leukotriene production) **fairly marked GI upset and Hemorrhages.

Notes: AKA acetylsalicylic acid, therapeutic agents are currently in development for epi-lipoxins. Can be be applied rectally**Use of salicylates in children w/ chicken pox/influenza *t1/2: 3-5 hours**Comparison w/ other NSAIDS; Diflusinal (less GI than ASA), Nabumentone (ADR more marked), Indomethacin (20X more potent joint pain), Naproxen (20X more potent/less GI), Ibuprofen (better tolerated), Enolic Acids(similar efficacy)

Class: propionic acid 

Selectivity: nonselective

MOA: COX inhibitor

anti-inflammatory > anti-pyretic & analgesic
some NKκB inhibition
NSAIDs inhibit the ATP binding necessary for IκBαphosphorylation to mark it for ubiquination.

Indication: TREATMENT OF ACUTE GOUTY ARTHRITIS

Rheumatoid arthritis
ankylosing spondylitis (chronic inflammatory disease of the axial skeleton)
osteoarthritis
juvenile arthritis

Adverse Effects: less severe GI SE than aspirin

Notes: ibuprofen analogue

20X more potent than ASA
ASA-induced airway hyperreactivity also usually sensitive to naproxen
t1/2=13 hrs
liver mtblized
better tolerated than other NSAIDs
reduce dose for elderly

MOA: Agonist of erythropoietin receptors, primarily through a Jak-Stat signaling mechanism which regulates transcription of erythroid cells (BFU-E and CFU-E), expressed by red cell progenitors

Indication: Non–dialysis-dependent CKD patients, Dialysis-dependent CKD patients, HIV-infected patients with anemia related to zidovudine, Patients with non–myeloid malignancies with anemia due to concomitant chemotherapy, and Transfusion reduction in patients scheduled to undergo surgery

Adverse Effect: Hypertension, thrombotic complications, allergic reactions

Notes: Half-life: 4–11 hours (intravenous) and 19–25 hours (subcutaneous);To reduce the risk of serious CV events, hemoglobin levels should be maintained < 12 g/dL

Route: IV or SC administration 1–3 times per week

Other: Classified as a growth factor

-is a glycosylated protein made in mammal cells
-contains more sialylated carbs than human erythropoietin

MOA: Required for the biosynthesis of heme and heme-containing proteins
(including hemoglobin and myoglobin); elemntal iron is absorbed in
ferrous state primarily in the duodenum and much of the ferrous state is
oxidized to the ferric form

Indications/uses: Iron Deficiency Anemia

Adverse Effects: Acute overdose: lethargy, abdominal pain and dyspnea (necrotizing gastroenteritis, bloody diarrhea, shock); Chronic iron overload: results

in hemochromatosis (damage to the heart, liver, pancreas, other organs,
organ failure and death)

Notes: Elmental Iron Percentage = 33%

Route: Available as a tablet, drop, and suspension.

MOA: Chelate excess iron. Reduces the toxicity associated with acute or chronic iron overload.

Indications: treatment of acute iron poisoning and for inherited or acquired hemachromatosis that is not adequately treated by phlebotomy. 

Adverse Effects: Rapid IV: will cause hypoTN. Long infusions: cause acute respiratory distress. Long term use: can cause neurotoxicity and increase susceptibility to certain infections.

Notes: Signs of toxicity:  cyanosis, hyperventilation, cardiovascular collapse.  If pills are in system induce vomiting.  In this case excess iron can build up if patient has numerous blood transfusions.

Cyclosporin A

Class: IL2

Target: Calcinuerin inhibitor

MOA: Per Collier notes:

TNF inhibitor, DMARD (disease modifying anti-rheumatic drug)

DMARDs decr inflammation, improves symptoms, slows bone/joint damage, slow acting and effective longterm (6wk-6mths) protection of worsening damage

Per Oakes notes:
Calcineurin inhibitor

binds to cyclophilin to form CSA-cyclophilin complex inhibitor of phosphatase calcineurin, Calcineurin cannot dephosphorylate NFAT. NFAT cannot enter the nucleus so IL-2 synt is inhibited by activated Tcells

Specificity: specific to ACTIVATED Tcells

-blunts production of anti-apopotic proteins
-incr transforming growthfactor-beta (TGF-B) - basis for toxicity.incr cell production of extracellular matrix leading to fibrosis

Indication: RA (rheumatoid arthritis) inflammation

organ transplant, psoriasis, keratoconjunctivitis sicca (ophthalmic prep)

Dosing: Oral, IV, opthalmic suspension (Restasis)

Adverse Effects: Common: gingival hyperplasia, hyperlipidemia, hirsutism, GI disturbances Serious: nephrotoxicity, hypertension, neurotoxicity, hepatotoxicity, infection

Interactions: Contraindicated in active ocular infections (ophthalmic preparation)

danazol/other androgens can incr serum levels

rifampin and SJW reduce serum levels

Notes:

Forms: capsule, IV, topical, oral, oral solution.

Calcineurin activation is needed in Tcells to generate NFAT to cause IL2 production to stimulate IL2 receptors *neoral and Sandimmune- are not bioequivalent

Class: Cytokine Inhibitor

Class: IL-1 inhibitor

Adverse Effects: Common: injection site rxn, URI

Serious: severe infections, GI bleeding and colitis

Interactions: Caution/avoid in: other IL-1 blockers

monitor: lipids, screen TB baseline and test for latent TB (Follow CDC guidelines)
will normalize p450 levels (during inflammaiton, p450 decreases, therefore, when inflammation is resolved, p450 levels will normalize)

Notes: 'cept'=mimics receptor to bind and sequester agents

Abatecept

Target: block costimulation

MOA: B7 of CD80/86 anatgonist = T cell activation inhibitor

B7 is on APC

~prevents T cells' CD28 from making "signal 2".

forms a complex w/ cell surface B7 molecules preventing normal costimulatory signal (normally, Tcell activation needs binding of B7 and CD28)

T cell develops anergy or undergoes apoptosis

Specificity: CD52 is expressed on T and B cells

Indication: Rheumatoid arthritis, used for refractory to methotrexate and anti-TNFs

Dosing: 3 dose q2wks, then monthly

Adverse Effects: common: nausea, HA, UTI

Serious: COPD exacerbation, incr susceptibiity to infection

Notes: do not give concurrently with anti-TNFs (anticytokines) or anakinra (incr infections

Notes: IV