Drugs causing FOLATE deficiency

Drugs causing FOLATE deficiency

Medications can interfere with folate metabolism, including:

anticonvulsant medications (such as phenytoin, primidone, carbamazepine or valproate)
metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
methotrexate, an anti-cancer drug also used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis.
5-fluorouracil
Hydroxyurea
trimethoprim
sulfasalazine (used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis)
triamterene (a diuretic)
birth control pills

Related Questions Haemato-pharmacology

Medications can interfere with folate metabolism, including:

anticonvulsant medications (such as phenytoin, primidone, carbamazepine or valproate)
metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
methotrexate, an anti-cancer drug also used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis.
5-fluorouracil
Hydroxyurea
trimethoprim
sulfasalazine (used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis)
triamterene (a diuretic)
birth control pills

Antiplatelet Drugs

Aspirin/ASA

- Works on Cyclo-oxygenase (AA -> thromboxane)

- Low dose (80-160 mg/day) irreversibly inhibits plt COX, and they can’t make new COX b/c they have no nucleus

- Some inhibition of endothelial COX but not much, therefore prostacyclin (anti-coag) synthesis isn’t  affected much
- Benefit is greater after thrombolysis

- SE is bleeding

- Prophylaxis for MI or TIA (80mg/day), higher doses for post-MI/TIA (160-325mg/day)

- Contraindications (bleeding risk):  Vit. K def., Hemophilia, Hypoprothombinemia, pregnancy & childbirth

Clopidogrel/Plavix

- ADP antagonist

- Competes with ADP for P2Y receptor (prevents lowering of cAMP)

- Less incidence of neutropenia/thrombocytopenia

- Used in combo with ASA

 Ticlopidine

- ADP antagonist, prodrug

- Often used in combo with ASA (synergistic)

- May cause severe neutropenia (1%)

 

Dipyridamole

- phosphodiesterase inhibitor (prevents cAMP breakdown)

 

GpIIb-IIIa inhibitors

-  Eptifibatide, Abciximab, Tirofiban

-  Block the receptor for fibrinogen blocking plt Aggregation

 

Heparin (& derivatives)

- Stimulates natural anticoags (antithrombin)

Heparin

- Monitor using aPTT (add negative charges)

- Negatively charged, therefore cannot cross membranes (given IM, IV, parentally)

- Good for pregnancy

- Eliminated by RES & macrophages

- Potentiates AT III (in the plasma) – inhibits IIa, Xa, IXa and VIIa

- Toxicity – hemorrhage

- Antidote – protamine sulfate (1mg for every 100 units of heparin)

Heparin-Induced Thrombocytopenia (HIT) – occurs 5-10 days after, stop heparin immediately;  use alternatives lepirudin/danaparoid

- Good for PE and DVT and during pregnancy

 

LMWH – better bioavailability, can be given subcut. w/o lab monitoring as outpatient, less risk of bleeding

- More expensive, not good in renal failure, not for pregnancy

- DOES NOT inhibit IIa (but inhibit Xa)

- Good for DVT, PE and UA

Danaparoid – promotes inhibition of Xa by AT (for HIT)

Lepirudin – direct thrombin inhibitor (for HIT)

 

Coumarin (Oral) anticoags

Warfarin

- Monitored using PT (add tissue factor)

- Inhibit Vit. K Epoxide reductase in liver

-Prevents carboxylation of Vit.K dependent factors

-Takes 4-5 days to get effective (carboxylated fx’s in plasma need to be cleared before inactive ones take over)

-Small volume of distribution, steep dose-response curve (small therapeutic window)

-Teratogenic

- For DVT and PE, prosthetic heart valves or Afib, MI

-Metabolized by CYP1A and CYP2C9

-Efficacy measured by INR, pt’s PT time divided by PT time in pooled plasma

- INR = (PTpt/PTref)^ISI (target is 2.0 – 3.0)

- Warfarin overdose

- Give Excess Vit.K, goes through a diff  enzyme that isn’t inhibited by warfarin  (Diaphorase)

Fibrinolytics (lyse formed thrombi)

Streptokinase – turns plasminogen -> plasmin

-Plasmin breaks down fibrin (lysis of formed clot) Dissolves clots post-MI/DVT/PE

- SE – bleeding (systemic plasminogen activation), allergy, hTN, fever

- Streptokinase has an additive effect with ASA

Tissue plasminogen activator (tPA) – acts on fibrin and circulating plasminogen -> plasmin

- Less systemic plasmin

- Same indications as streptokinase

- More expensive