Interacting drugs- summary

+ Bromocriptine -

Erythromycin -

serum bromocriptine levels increased, resulting in an increase in pharmacologic and toxic effects

Phenothiazine 

efficacy of bromocriptine ,when used for prolactin secreting tumors, inhibited

Sympathomimetics- isometheptene-phenylpropranolamine -

 exacerbation of bromocriptine side effecs, during concurrent use.  Ventricular tachycardia and cardiac dysfunction have occured  

 possible exacerbation of bromocriptine side effecs, during concurrent use.  Ventricular tachycardia and cardiac dysfunction have occured

Bioavailability increased if given along with erythromycin. Alcohol reduces tolerance to bromocriptine & vice versa. Anti-hypertensives potentiated. Avoid psychotropics.

New drugs approved For Marketing by Drug Controller General of India(DCGI )                                     during the period January 1988 to November 2014                                                                                  (Ref- IDMA Annual Publication 2015)

Parkinsons disease. 

Hyperprolacinemic indications-

Incidence of adverse effects are high (69% ) but they are generally mild to moderate Therapy discontinued in approx 5% of patients

Adverse reactions include- Nausea 49% Headache 19% Dizziness 17% Fatigue 7% Lightheadedness, vomiting 5% Abdominal cramps 4% Nasal congestion , constipation, diarrhea, drowsiness 3% Physosis, hypotension, cerebrospinal fluid rhiinorrhea, Occurance of these effects may be lesened by temporarily reducing dosage to 1/2 tablet 2 to 3 times daily

Lab test abnormalities- elevations in BUN, AST, ALT, GGPT, CPK, alkaline phosphatase abnduric acid are usually transcient and not clinically significant

Ca breast,pregnancy,sensitivity to ergot alkaloids.

Special precautions:

Since hyperprolactinema is found in patients with pituitary trumors, evaluate sella turcica before treatment. Psychiatric disturbances reported in patients treated for Parkinsons disease.

Smaller doses to minimise postural hypotension. Women not wishing to conceive should take conterceptive. Pituitary adenoma. Discontinue when conception occurs.

Care while driving vehicles or operating machinery. Diabetes, diabetic retinopathy. Patients presenting with unexplained pleuro-pulmonary signs or symptoms impaired hepatic or renal function. Safety during long-term therapy of more than 2 yrs at the doses reqd for Parkinsonism not established.

Pulmonary effects- long term treatment (6 to 36 months) in doses of 20 to 100mg/day is assoociated with pulmonary infiltrates, pleural thickening. When treatment was terminated the changes slowly reverted toward normal.

Warnings-

Pituitary tumors- since bromocriptine causes hypotension and rarely hypertension, do not initiate therapy until the vital signs are stabilized and no sooner than 4 hours after delivery.

Rhinorrhea- a few cases of cerebrospinal fluid rhinorrhea occured in patients receiving bromocriptine for treatment of large prolactinomas.

Pregnancy- safe use of bromocriptine has not been demonstrated in pregnancy and use in pregnancy is contraindicated

Lactation- since bromocriptine prevents lactation do not administer to mothers who will breast feed.

Children- safety and efficacy in children < 15 years of age have not been established.

Indicated as an adjunct to diet and excercise to improve glycemic

Indications:

Parkinsons disease.

Dosage:

Individualise dose. Start at a low dose. One half of a 2.5mg tablet twice daily with meals. If necessary, increase dosage every 2 to 4 weeks by 2.mg/day with meals. If necessary, to reduce because of adverse reaction,reduce gradually in 2.5mh increments.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

EVIDENCE BASED MEDICINE (April 2003) Premenstrual sydrome Comparative effectiveness of various intreventions Beneficial Overall Premenstrual Syndrome

Symptoms

1. Prostagalndin inhibitors (e.g. Indomethicin)

2. Selective serotonin Reuptake Inhibitors (e.g. Fluoxetine, Seratinine, Fluvoxamine)

Breast symptoms only

1. Leuteal phase control

2. Bromocriptine

Bloatedness and Swelling

1. Spironolactone/ diuretics Likely to be beneficial 1. Tobolone 2. Oestrogen 3. Vitamin B-6 4. Evening primrose B-6 Trade-off between Benefits and Harms 1. Danazol 2. Gonodotropin-releasing hormone (GnRH analogues) 3. Non-SSRI antidepressants/ anxiolytics 4. Hysterectomy with/without oophorectomy

Unknown effectiveness

1. Progesterone

2. Progestogens

3. Oral contraceotives

4. Cognitive behaviour treatment

5. Dietary supplements

6. Relaxation treatment

7. Endometrial ablation

8. Laproscipic bilateral oophorectomy

KEY POINTS

1. Trials have found that SSRIs and prostagalndin inhibitors relieve premenstrual symptoms. Antidepressants and ovulation suppression with danazol and GnRH analoges are also effective but have significant adverse effects, including the masculanising effects of danazol and the menopausal effects of GnHR analogues.

2. There is a limited evidence suggesting that oestrogen, viatmin-B6 , evening Primrose Oil and excercise may also be beneficoial

3. Trials have found that bromocriptine is effective for breast symptoms and diuretics are effective for bloatedness and swelling. Both can have adverse efects.

4. There is no good evidence to support the use of progesterone or oral contraceptives

5. Few treatments have been adequately validated in trials. 

Galactorrhea ( 1787 ) ------------------------------- Galactorrhea can be defined as an iaapropiate production of milk that is persistent or worrisome to the patient , recognizing that in some instances no underkying pathoilogy will be demonstrated. Milky discharges must be distinguished from dark or bloody secretions that may be present with neoplasm of the breast. Drugs causing Adverse reactions- ( also may cause ammenorrhea ( 386 )

1. Methyldopa 2. Phenothiazines 3. Reserpine 4. Tricyclic antidepressants 5. Dexamphetamine

Pharmacology-

Bromocriptine is a semisynthetic ergot alkaloid derivative which inhibits prolactin secretion with no effect on other pituitary hormones except inacromegaly where it lowers elevated blood vessels of growth hormone. It is a dopamine receptor agonist that activates postsynaptic dopamine receptors.

Pharmacokinetics-

Twenty-eight percent of an oral dose is absorbed from GI tract. The drug is completely metabolised prior to excretion, 84% of the dose is excreted in the feces. Only 2.5% to 5.5% is excreted in the urine. The major route of excretion of absorbed drug is via the bile.

Take with food

Pregnancy-

Safe use of bromocriptine has not been demonstrated in pregnancy and use in pregnancy is contraindicated

Lactation-

Since bromocriptine prevents lactation do not administer to mothers who will breast feed.

Children-

Safety and efficacy in children < 15 years of age have not been established.