I3 TEST 1 - PHARMACOLOGY

Drug Therapeutic Use Mechanism of Action Drug/Drug

Interactions

Adverse Effects Phys. Disposition

(ADME)

Aspirin

(acetylsalicylic

acid)

Low dose: protection against

cardiovascular disease

Platelet aggregation

protection (MIs, strokes, etc.)

Inflammatory bowel disease

See also NSAID uses.

Non-selective irreversible

inhibitor of COX-1/2.

For COX-1, alters active

binding site to prevent

substrate entry.

Probenecid blocks

elimination.

- Contraindicated in

children with fever due

to virus (may cause

Reye’s syndrome).

- GI bleeding/uclers

- Analgesic nephropathy,

progressive renal failure

- Hepatic injury

- Respiratory and

metabolic acidosis if at

toxic levels.

Aspirin hydrolyzed in

plasma to salicylate.

Conjugated by

glutathione, glucoronic

acid, and sulfate…

eliminated renally.

Salicylate Cogener for aspirin. See aspirin. Interacts with lithium

and fluconazole drugs.

More adverse effects

than aspirin.

Metabolized by CYP

Ibuprofen (Advil)

NSAID

Low dose: analgesia (pain

relief), antipyretic (fever

reducer)

High dose: anti-

inflammation, closure of

patent ductus arteriosus for

newborn’s circulation

May reduce risk for colon

cancer.

Reversible competitive

inhibitor of COX-1/2.

Inhibition of prostaglandin

synthesis.

Compete against the

protective effects of

low-dose aspirin.

Adverse effects with

ACE inhibitor (HT

drug)

GI discomfort and stress

hemorrhage and

perforation.

Analgesic nephropathy

Postpartum hemorrhage

for pregnant users (also

prolonged gestation and

inhibition of labor)

Acidic so well absorbed.

Renal excretion,

extensively metabolized,

undergo EH circulation.

Highly protein bound

Found in synovial fluid

(useful for joint pain)

Naproxen has longer

half-life than ibuprofen.

Naproxen (Aleve)

Indomethacin

(Idocin)

Celecoxib NSAID

(anti-inflammation)

Inhibits COX-2 Cardiovascular disease

(uncontrolled platelet

aggregation).

Black box warning.

Misoprostol Prevents peptic ulcers that

result from NSAIDs

PGE1analog (replaces lost

PGs in GI from

NSAIDs/COX inhibition)

Heparin

Anti-coagulant

Prevent PE, DVT; acute MI,

Catalysts for antithrombin

III inhibition of both

thrombin and FXa.

Protamine sulfate –

antagonist.

- Bleeding

- Hypersensitivity

(sometimes)

Not easily absorbed

because large IV or

subcutaneous injection.

Drug Therapeutic Use Mechanism of Action Drug/Drug

Interactions

Adverse Effects Phys. Disposition

(ADME)

unstable angina; prevent

thrombosis in extracorporeal

devices

Long chains wrap

thrombin and anti-

thrombin together.

- Transient

thrombocytopenia

- Heparin-induced

thrombocytopenia

- Contraindications:

history of

hypersensitivity to

heparins, active

bleeding, threatened

abortion, surgical

procedures in general,

infective endocarditis

Does not cross into

placenta.

Must routinely monitor

Pt. because drug is

mixture of

unfractionated peptides.

Enoxaparin

(Lovenox)

Anti-coagulant

Prevent DVT,

thromboembolism, Pts with

HIT

Catalysts for antithrombin

III inhibition of FXa (can’t

wrap around thrombin).

- Bleeding

- Hypersensitivity

(sometimes)

- Transient

thrombocytopenia

See above for

contraindications.

Subcutaneous injection

Fondaparinux

(Arixtra)

Anti-coagulant

Prevent PE, DVT;

thromboprophylaxis for Pts

undergoing hip/knee surgery,

Pts with HIT

Catalysts for antithrombin

III inhibition of FXa:

synthesized

pentasaccharide mimics

the binding site on

antithrombin III,

enhancing FXa binding

and inhibition.

- Bleeding

- Hypersensitivity

(sometimes)

- Transient

thrombocytopenia

See above for

contraindications.

Oral dose

Dabigatran (PRADAXA)

Anti-coagulant Inhibits FII (thrombin) via

blocking active site

Transported by P-

glyocoprotein (drugs

that inhibit PGP will

enhance dabigatran,

drugs that induce will

inhibit)

Bleeding Administered as

dabigatran etexilate

(prodrug).

Rivaroxaban

(Xarelto) Anti-coagulant Inhibits FXa via blocking

active site

Bleeding Metabolized by CYP-

3A4

Apixaban

(Eliquis) Anti-coagulant Indirect inhibition of FXa

active site

Bleeding

Warfarin

(Coumadin)

Anti-coagulant Vitamin K analog

inhibits VKOR prevents

MANY. See last page. Bleeding

100% bioavailable;

highly bound to plasma

Drug Therapeutic Use Mechanism of Action Drug/Drug

Interactions

Adverse Effects Phys. Disposition

(ADME)

Gla modifications in

clotting factors factors

inactive

Can be overcome by

excess Vitamin K.

Pro-cogulative states

(inhibition of protein C

and S)

protein; long half-life.

Extensively metabolized

(CYP-2C9), excreted in

urine.

Crosses placenta can

be teratogen.

Desirudin Anti-coagulant Direct acting inhibitor of

thrombin

Bivalrudin Anti-coagulant Direct acting inhibitor of

thrombin

Agratroban Anti-coagulant Direct acting inhibitor of

thrombin (blocks catalytic

active site)

Clopidogrel

(Plavix)

Anti-coagulant (anti-platelet)

Use with Pt who are allergic

to aspirin or need synergic

effect with aspirin.

Irreversibly binds to

P2Y12 receptor no

ADP activation of platelet

aggregation

Rash, diarrhea,

abdominal pain,

dyspepsia, bleeding,

thrombotic

thrombocytopenia

Well absorbed;

extensive metabolism by

liver; 8 hr half life; urine

and fecal elimination

Needs to get

metabolized to be active.

Aspirin Anti-coagulant (anti-platelet)

NSAID

No TXA2 formation.

No hemostasis (platelet

change initiation).

See above. See above. See above.

Abciximab Anti-coagulant (anti-platelet) Ig that inhibits GP2b/3a

receptor on platelets no

fibrinogen binding no

aggregation

Cortisol Anti-inflammatory steroid;

immuno-suppressant

- Inhibit phospholipase A2

(AA mobilization) via

increased synthesis of

annexin-1

- Decrease production of

PG and LT

- Inhibit COX-2 up-

regulation/synthesis

- Decrease TNF-α

production by inhibiting

May cause

hypertension because

also interacts with

mineralcorticoid

receptor with high

affinity.

(Licorice has

glycyrrhizic acid

which inhibits 11β-

HSD 2 from

Abrupt cessation of

therapy acute adrenal

insufficiency (fever,

myalgia, arthralgia,

malaise).

High doses: HPA

suppression,

hypertension,

hyperglycemia,

Fat soluble, go through

membranes. Prepared as

nasal sprays, inhalers,

topical, injectable,

sprays well absorbed.

Inactivated by liver

conjugation into inactive

metabolites, excreted in

liver

Drug Therapeutic Use Mechanism of Action Drug/Drug

Interactions

Adverse Effects Phys. Disposition

(ADME)

NFκB (TNF-α

transcription factor)

regulating high

cortisol levels.)

increased susceptibility

to infection, peptic ulcer

disease, osteoporosis,

osteonecrosis,

myopathy,

cataracts,behavior

disturbance, growth

suppression, Cushing’s

syndrome

Use the lowest dose

possible to achieve

desired result because

not specific/curative.

Prednisolone Anti-inflammatory steroid;

immuno-suppressant

Cortisol analog with

intermediate half life (4x

more potent)

See Cortisol. See Cortisol. See Cortisol.

Active ingredient for

prednisone. If Pt has

hepatic failure,

administer prednisolone

straight.

Dexamethasone Anti-inflammatory steroid;

immuno-suppressant

Diagnose causes of

hypercorticism

Cortisol analog with longer

half life (25x more potent)

See Cortisol. See Cortisol. See Cortisol.

Aldosterone Mineralcorticoid (low blood

pressure)

Retains Na+

Flurocortisone Replacement therapy of

mineralcorticoid (low blood

pressure, aldosterone

deficiency)

Retains Na+

(125x

potency)

Sodium and water

retention, high blood

pressure, edema, low

potassium, muscle

weakness, fatigue,

increase susceptibility to

infection, peptic ulcer,

cataracts, hyperglycemia

Moderate glucocorticoid

potency.

Fat soluble, go through

membranes. Well

absorbed.

Hepatic metabolism.

Chlorpheniramine (Chlortrimeton)

Anti-histamine (1st

generation)

Allergic rhinitis,

conjunctivitis, itching, atopic

& contact dermatitis,

urticaria, drug reactions,

motion sickness, local

Inverse agonists to H1

receptor on smooth

muscle, endothelial

vessels, and CNS.

Depression drugs

inhibit MAO more

histamine

accumulation

Impairment of alertness,

cognition, learning,

memory, and

performance. Sinus

tachycardia, reflex

tachycardia,

antimuscurinic effects

(pupil dilation, blurred

Liposoluble, well

absorbed. Metabolized

by liver. Renal

excretion.

Crosses placenta and

breast milk.

Penetrates BBB anti-

Diphenhydramine

(Benadryl)

Dimenhydrinate

(Dramamine)

Drug Therapeutic Use Mechanism of Action Drug/Drug

Interactions

Adverse Effects Phys. Disposition

(ADME)

anesthetic, insomnia, some

symptom relief for colds

vision, dry eyes, dry

mouth, urinary retention,

constipation, ED),

fatality in young

children

Contraindicated for

people with glaucoma,

prostatic hypertrophy,

impaired renal function,

elderly (impairs their

cognition), pregnant and

lactating women,

neonates, infants and

young children.

Ach and sedation.

Loratadine

(Claritin)

Anti-histamine (2nd

generation)

Allergic rhinitis,

conjunctivitis, itching, atopic

& contact dermatitis,

urticaria, drug reactions

Inverse agonists to H1

receptor on smooth muscle

and endothelial vessels

Depression drugs

inhibit MAO more

histamine

accumulation

Even 30x overdose has

not seen any adverse

effects or fatality!

Contraindicated for

pregnant and lactating

women.

Liposoluble, well

absorbed. Metabolized

by liver. Renal

excretion.

Crosses placenta and

breast milk.

Differences:

Does not penetrate BBB,

longer lasting, some

metabolized by CYP-

3A4

Cetirizine is metabolite

of hydroxyzine.

Fexofenadine excreted

by bile and abs is

inhibited by some fruit

juices.

Cetirizine

(Zyrtec)

Fexofenadine

(Allegra)

Cromolyn sodium

(Nasalcrom)

Mast cell stabilizer Blocks ion channels on

mast cells directly

inhibits degranulation

no histamine release

ADVERSE EFFECTS OF WARFARIN.

1. Phenobarital – induces microsomal enzymes that increase warfarin metabolism

2. Sulfinpyrazone – inhibition of CYP-450 will cause inhibition of warfarin metabolism

3. Decrease of binding to plasma protein-sulfonamides increase in free warfarin

4. Aspirin – interference with normal platelet function intensified anticoagulation function

5. Cholestyramine – binds to warfarin and inhibits absorption in GI