Antiadrenergic agents ( Peripherally acting )include-

Reserpine, Guanithidine monosulphate, Guandrel sulfate, ( Alpha-1- blockers), Prazosin,Terazosin, Doxazosin, Tamsulosin, Silodosin, Alfuzosin Hcl

Refer - Prazosin

Interacting drugs - summary

 Betablockers + Alpha blockrs  -

Beta-blockers may enhance the acute postural hypotensive reaction following the first dose of prazosin 

  Indomethicin +  Alpha blockrs  -  

 Antihyertensive action of prazosin may be decreased.  No interaction occured in patients receiving doxazosin and NSAIDs

 Verapramil +  Alpha blkrs -  

Verapramil appears to increase serum prazosin levels and may Alpha blkrs increase the sensitivity to prazosin -induced postural hypotension

 Alpha blockers+  Clonidine  -   

Antihypertensive effect of clonidine may be decreased 

Hypertension

 Antiadrenergic agents ( Peripherally acting )include-

Reserpine, Guanithidine monosulphate, Guandrel sulfate, ( Alpha-1- blockers), Prazosin,Terazosin, Doxazosin, Tamsulosin, Silodosin, Alfuzosin Hcl

Refer- Prazosin

New Drugs Approved by (DCI) Drug Controller  GENERAL -  India  For Marketing                                                                                                   (Ref- IDMA Publication)

Adverse Reactions-
               

Alpha- 1 - adrenergic Blocker Adverse Reactions 

PRAZOSIN-

CARDIOVASCULAR -             Palpitations  5% , Postural hypotenson,
                                                 Syncope 4% , Tachycardia  1 % 

CNS-                                        Depression 4%  Dizziness 10% , Asthenia 7%,
                                                 Drowsiness 8 %  Nervousness 4%,
                                                 Paresthesia  1%
                                                

DERMATOLOGIC-                  Rash 4% Pruritus  1%

GI -                                          Nausea 5%, Vomiting 4%, Dry mouth 4%,
                                                Diarrhoea 4% Constipation 4%
                                                Abdominal discomfort 1%

GU-                                       Urinary frequency 4%  Impotence < 1%
                                               Incontinence < 1%

MUSCULOSKELETAL -         Arthalgia < 1% 

RESPIRATORY -                  Dyspnea 4%, Nasal congestion 4%
                                                Epistaxis 4%

SPECIAL SENSES-               Conjuntivitis 4% Blurred vision 4%
                                                 Vertigo 4% Tinnitus  1%

MISCELLANEOUS -             Headache  8% Lack of energy 7 % Weakness 6 %
                                              Edema 4% Fever < 1%
                                              

CHF due to mechanical obstruction,hypersens.

Special precautions:

Phaeochromocytoma.Abrupt withdrawal.Impaired renal function

Children below 12 years.

Pregnancy,lactation.Concurrent administration of other antihypertensives.

Hemodilution- small but stastitically significant decreases in hemotocrit hemoglobin, white cells, total protein and albumin were observed,

Leukopenia/neutropenia- in hypertensive patients receiving doxazosin mean WBC and neutrophil count were decreased by 2.4% and 1% respy, compared to placebo. No patient became symptomatic as a result of the low counts.

Weight gain- there was a tendency for patients to agin weight during terazosin therapy.

Cholesterol- during clinical studies patients receiving terazosin monotherapy had a small but statistically significant decrease in total cholesterol and the combined LDL and VLDL fractions. No significant changes were observed in HDL fraction and triglycerides.

Cardiotoxicity- an increased incidence of myocardial necrosis or fibrosis occured in rats and mice following 6 to 18 months of doxazosin 40 to 80kg/day. There is no evidence thatsimilar lesions occur in humans.

Prostatic cancer- carcinoma of the prostate and BPH cause many of the same symptoms and frequency coexist. Therefore, examine patients thought to have BPH prior to starting terazosin therapy to rule out prostrate cancer.

Drug/Lab interactions- false positive results may occur in screening tests for pheochromocytoma in patients who are being treated with prazosin. If an elevated VMA is found, discontinue prazosin and retest the patient after a month.

Warnings-

First-dose effect- prazosin, terazosin, and doxazosin like other alpha-adrenergic blocking agents, can cause marked hypotension (especially postural hypotension ) and syncope with sudden loss of consciousness with a few doses, if dosage is increased rapidly, or ifanother antihypertensive drug is introduced.

BPH complications- long term effects of terazosin on the incidence of surgery ,acute urinary obstruction or other complications of BPH are yet to be detremined.

Hepatic function impairment- administer dozazosin with caution to patients with evidence of impaired hepatic function or to patients receiving drugs known to influence hepatic metabolism.

Pregnancy- safety for use during pregnancy has not been established. Use onlywhen clearly needed.

Lactation- excercise caution when administering these drugs to a nursing woman. Children- safety and efficacy for use in children have not been established.

Date of Approval         June 1990

Indications:

Hypertension

Dosage:

1mg 2 or 3 times daily. When increasing doses, give the first dose each at bed time to reduce syncopal episodes.

Maintenance - 6 to 15mg/day in divided doses.

Overdosage- Symptoms

Most likely manifestation of overdosage would be hypotension Treatment

1. Restore blood pressure and normal heart rate by keeping the patient supine

2. Treat shock with volume expanders

3. If necesary, use vasopresors and monitor and support renal function.

4. These drugs are highly protein bound,dialysis may not be of benefit.

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

Management of Benign Prostatic Hypertrophy (BPH)

Comparative effectiveness of various interventions

Beneficial

1. Aplha blockers (parzosin, alfuzosin, indoramin, terazosin, doxazosin,tamsulosin)

2. 5-alpha -reductase inhibitors (e.g. finastreride)

3. Transureythral resection (TURP)

4. Transurethral microwave thermotherapy (TUMT)

5. Trnasurethral needle ablation (TUNA)

Unknown effectiveness

1. TURP versus less invasive techniques

KEY POINTS

1. Randomised controlled trials (RCTs) have found that both alpha-blockers and 5-alpha-reductase-inhibitors are more effective than placebo in improving lower urinary tract symptoms in men with BPH.

2. One trial found that alpha-blockers (e.g.prazosin ) were more effective than 5-alpha- reductase inhibitors (finasteride) in men not selected for having large prostrates.

3. Neither drug has been compared directly with surgical treatment

4. There is limited evidence from one trial that TURP is more effective than watchful waiting in improving symptoms and reducing complications, and does not increase the risk of ercetile dysfunction or incontinuence.

5. TURP has not yet been adequately compared with medical treatments or with newer less invasive techniques.

6. TUMT is more effective than sham treatment at reducing symptoms. There is no difference beween TURP and TUMT with regard to short term relief

7. One trial found that TURP was more effective than TUNA in men with BPH.

PRAZOSIN- ANTIADRENERGIC AGENTS

1. Inform patients of the possibility of syncopal and orthostatic symptoms, especially at the initiation of therapy

2. Avoid driving or hazardoustasks for 12 to 24 hrs after the first dose, after dosage increase and interruption of therapy when treatment is resumed

3. Use caution when rising from a sitting or lying position

4. If dizziness or palpitation are bothersome, report to the physician so that dose adjustment can be considered.

5.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to prazosin, doxazosin or terazosin. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6.Pregnancy - limited use of prazosin to control high blood pressure in prergnant women has not shown that prazosin causes birth defects or other problems.

7.Breast feeding- prazosin pass into breast milk in small amount , and not reported to cause problems in nursing babies.

8.Children - no specific information comparing use of prazosin in children with use in other age groups

9.Elderly- dizziness, lightheadednessor fainting may be more likely to occur in the elderrly. In addition prazosin may reduce tolerance to cold temperatures in elderly patients

10. Other medicines - non-prescription drugs or OTC medicines

11. Other medical problems - Tell your doctor of your  other medical problems especially - Angina or chest pain or Heart disease -prazosin may make these conditions worse Kidney disease -possible increased sensitivity to the effects of prazosin

12. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

14. Date Expired  medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Not available

Pregnancy-

Safety for use during pregnancy has not been established. Use onlywhen clearly needed.

Lactation-

Excercise caution when administering these drugs to a nursing woman.

Children-

Safety and efficacy for use in children have not been established.