Hormonal Warfarin

Indirect response models have been successfully applied for a number of drugs that display a relatively slow onset of effect compared to their distribution to the site of action. Examples are corticosteroids, warfarin, furosemide and terbutalin. Such models are also particularly appropriate if the measured response is a change in circulating blood cells or endogenous proteins (e.g. hormones or cytokines). 

Uses Breast/endometrial CAs appetite stimulant in cachexia (CA HIV) Action Hormone progesterone analog Dose CA 40-320 mg/d PO in + doses Appetite 800 mg/d PO + dose Caution [X, -] Thromboembolism Contra PRG Disp Tabs, soln SE DVT edema, menstrual bleeding photosens, insomnia, rash, 4- BM Interactions T Effects OF warfarin EMS T Risk of CV problems, esp in smokers T effects of warfarin may T glucose T risk of photosensitivity Rxns OD Unlikely to cause life-threatening Sxs... 

Antagonists of vitamin K substances include dicoumarol, sulfonamides, antibiotics, a-tocopherol quinone, dihydroxysteanc acid glycide, salicylates, iodinin, warfarin. Synergists include ascorbic acid, somatotropinn (growth hormone), and vitamins A and E. 

It is reasonable to use proprietary names when dosage, and therefore pharmaceutical bioavadability, are critical so that small variations in the amoimt of drug available for absorption can have big effects on the patient, e.g. drugs with low therapeutic ratio, digoxin, hormone replacement therapy, adrenocortical steroids (oral), antiepileptics, cardiac anti-arrhythmics, warfarin. Also, with the introduction of complex formulations, e.g. sustained-release, it is important clearly to identify these, and use of proprietary names has a role. 

About half the patients who take colestyramine experience constipation and some complain of anorexia, abdominal fullness and occasionally of diarrhoea these effects are dose-related but may limit or prevent its use. Because the drug binds anions, drugs such as warfarin, digoxin, thiazide diuretics, phenobarbitone and thyroid hormones should be taken 1 h before or 4 h after colestyramine to avoid impairment of their absorption. 

Sex hormones and hormone antagonists. Oestrogens increase the synthesis of some vitamin K dependent clotting factors and progestogen-only contraceptives are preferred. The hormone antagonists danazol, flutamide and tamoxifen enhance the effect of warfarin. 

Tablets (e.g., quinapril hydrochloride) Capsules (e.g., pancrease) Oral suspensions (e.g., cefuroxime axetil) Injectables (e.g., coumadin) Sterile powders (e.g., cefoxitin) Topicals (e.g., zinc oxide powder) Anti-infectives (e.g., erythromycin ethyl succinate) Anti-coagulants (e.g., warfarin sodium) Anti-asthmatics (e.g., montelukast sodium) Anti-psychotics and anxiolytics Hypnotics and anticonvulsants (e.g., barbiturates) Anti-hypertensives Anti-inflammatories (e.g., indomethacin) Analgesics (e.g., aspirin) Antacids (e.g., aluminum hydroxide) Diuretics Enzymes (e.g., pancreatin) Hormones...

In 13 men with advanced hormone-refractory prostate cancer the interaction between suramin and warfarin was studied because of potential worries that suramin may affect blood coagulation (38). After initial stabilization to an International Normalized Ratio (INR) of about 2.0 suramin plus hydrocortisone was started, after which warfarin requirements fell by 0.50-0.78 mg/day. The difference did not reach statistical significance. There were no bleeding problems. These results suggest that suramin and warfarin can be safely co-administered, provided that coagulation status is monitored. 

A 28-year-old woman took thalidomide 100 mg/day for Behget s disease and after 3 months developed amenorrhea (89). She took an oral contraceptive for 8 months, but then had a deep vein thrombosis in association with a factor V Leiden mutation the oral contraceptive was withdrawn and she was given warfarin. She remained amenorrheic. She had a raised serum concentration of follicle-stimulating hormone but all other laboratory tests were normal. Ultrasonography showed a normal uterus and an endometrial lining of 4 mm. The amenorrhea was attributed to thahdomide, which she decided to continue taking she remained amenorrheic. 

A patient with a mechanical prosthetic mitral valve is seen in the clinic. He has been stable on 5 mg of warfarin taken every evening. His INRs have been ranging from 2.5 to 2.7 for the past 6 months. He was started on amiodarone 2 weeks ago for an arrhythmia. Today his INR is 5.1 and thyroid-stimulating hormone (TSH) level is 2.1 mlU/L. How does amiodarone play a part in this patient s anticoagulation therapy ... 

Model I has been applied to a wide variety of drug responses, such as the reduction of fever (8, 20) or pain (19) by anti-inflammatory drugs, anticoagulant action of warfarin (3,9), reduction in blood sorbitol levels by inhibitors of aldose reductase (21), cortisol suppressive effects of corticosteroids (22), luteinizing hormone suppression by the synthetic hormone cetrorelix (23), reduction in the levels of tumoral phospho-EGFR (epidermal growth factor receptor) by cetuximab (24), inhibition of dihydrotestosterone (25), the suppression of T-lymphocyte influx into the blood by corticosteroids (26), and the acid-inhibitory effects of H2-receptor antagonists (27). 

Quinestrol has the potential to decrease the effects of warfarin-type anticoagulants. Patients receiving this drug concurrently with an adrenocorticosteroid or adrenocorticotropic hormone are at greater risk for fluid and electrolyte accumulation. 

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