Drugs I3-1 (Emmeline).pdf
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Transcript of Drugs I3-1 (Emmeline).pdf
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