Interacting drugs- Summary

+ Barbiturate anesthetics- 

Narcotics 

Barbiturate dose required to induce anaesthesia may be reduced. Apnea may be more common with combination

Phenothiazines                                                                                                               Preanaesthetic use of pnenothiazines may raise the frequency and severitity of neuromuscular excitation and hypotension in patients who receive barbiturate      anesthesia

Probenecid                                                                                                                  anesthesia produced by thiopental may be extended or acheived at lower rate

Sulfisoxazole                                                                                                            sulfisoxazole may enhance the anaesthetic effects of the barbiturate.

Barbiturates (sedative/Hypnotics) +

Alcohol                                                                                                                   concomittant use may produce additive CNS effects and death

Charcoal                                                                                                                        charcoal can reduce the absorption of barbiturates, and can reduce efficacy                   and toxicity

Barbiturate +  chloramphenicol/ chloramphenicol + barbiturate-                                     Chloraamphenicol    may inihibit phenobarbiturate metabolism.  Barbiturate                    may enhance chloramphenicol metabolism

Rifampicin                                                                                                                    rifampicin induces hepatic microsomal enzymes decrease the effectiveness of barbiturates

Valproic acid                                                                                                                   valproic acid decrease barbiturate metabolism, resulting in an increased effect.

Barbiturates +

Acetaminophen                                                                                                                      risk of increased hepatotoicity exist with large or chronic barbiturate doses

Anticoagulants                                                                                                                      barbiturate increase metabolism of anticoagulants resulting in a decreased response. Patients stabilised on anticoagulants may require dosage adjustments if barbiturates            are added to or withdrawn from their regimen

Betablockers                                                                                                               pharmacokinetic parameters of beta blockers (metoprolol and propranol ) altered by barbiturates. Timolol not appear to be affected

Carbamazepine                                                                                                             decreased serum carbamazepine levels occur

Clonazepam                                                                                                                           increased clonazepam clearance occur, leading to lower steady-state levels and          loss of efficacy

Contraceptives                                                                                                                    decreased contraceptive effect occur due to induction of microsomal Oral enzymes. Menstrual irregularities (spotting, brakthrough bleeding) or pregnancy occur .

Corticosteroids                                                                                                               barbiturates enhance corticosteroid metabolism through induction of microsomal enzymes

Digitoxin                                                                                                                      barbiturates increase digitoxin metabolism

Doxorubicin                                                                                                                        total doxorubicin plasma clearance increased

Doxycycline                                                                                                               phenobarbital decreases doxycycline half l;ife and serum levels which may persist for 2 weeks after barbiturate therapy is discontinued

Felodipine                                                                                                                        Felodipine plasma levels and bioavailabilty reduced

Fenoprofen                                                                                                               fenoprofen bioavailability may be decreased

Griseofluvin                                                                                                                 phenobarbital interferes with metabolism of oral griseofluvin, decreasing its blood level, effect on its therapeutic response not established

Hydantoins                                                                                                                              the effect of barbiturates on metabolism is unpredictable, monitor hydantoin and barbiturate blood levels frequently, if given concurrently

Methoxyfurane                                                                                                                      enhanced renal toxicity may occur Metronidazole decr barbiturates decrease the antimicrobial effectiveness of metronidazole

Narcotics                                                                                                                           methadone actions reduced. CNS depressive effects of meperidine prolonged

Phenmetrazine                                                                                                                effects of phenmetrazine decreased by amobarbital

Quinidine                                                                                                                  Phenobarbital significantly reduce the serum level & half-life of quinidine.

Theophylline                                                                                                                   barbiturates decrease theophylline levels, resulting in decreased effects

Verapramil                                                                                                                   clearance of Verapramil increased and its bioavailability decreased

Hypnotic, sedation

Barbiturates- sedatives/Hypnotics CNS- somnolence, ( 1 to 3% )agitation, confusion, hyerkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomina, anxiety, dizziness, abnormal thinking, headache, fever( especially with chronic phenobarbital use) ( < 1% ) vertigo, lethargy, residual sedation, drowsiness.

Emotional disturbances and phobias may be accentuated with phenobarbital use in some persons, barbiturates repeatedly produce excitement rather than depression, irritabilitry and hyperactivity can occur in children

Respiratory: Hypoventilation, apna, ( < 1% )circulatory collapse, respiratory depresion

Cardiovascular- Bradycardia, hypotension, syncope ( < 1% )

GI- Nausea, vomiting, constipation, liver damage, particularly with chronic phenobarbital use. ( < 1% )

Hypersensaitivity- Skin rashes, angioedema( particulaerly following phenobarbital use), exfoliative dermatitis, (Stevens Johnson syndrome and toxic epidermal necrolysis) may be caused by phenobarbital and may be fatal (rare)

Acquired hypersensitivity to barbiturates consists chiefly in allergic reactions that occur especially in persons who tend to have asthma, urticaria, angioedema and similar conditions. Hypersensitivity include localised swelling, particularly of the eyelids, cheeks or lips, and erythematous dermatitis.

The skin eruption may be associated with fever, delirium and marked degenearative changes in the liver and other parenchymatous organs

Local- Inadvertant intra-arterial injection may produce spasms with resultant thrombosis and gangrene of an extremity Reactions range from transcient pain to severe tissue necrosis and neurological deficit. Injection SC may produce tissue necrosis, pain, tenderness and redness. Injection into near peripheral nerves may result in permanent neurological deficit.

Thrombophebitis after IV use and pain at injection site have been reported.

Hematologic: Megaloblastic anemia (rarely following chronic phenobarbital use)

Pre-existing CNS depression,coma,severe hepatic/respiratory impairment.

Special precautions:

Elderly,children,acute pain,gradual withdrawal. Monitoring- During prolonged therapy perform periodic laboratory evalution of organ syste, including hematopoietic, renal and hepatic systems

Special risk patients- Untoward reactions may occur in the presence of fever, hyperthyroidism, diabetes mellitus and severe anemia. Use with caution.                        

Drug abuse and dependence- Barbiturates may inhibit habit forming. Tolerance,psychological dependence and physical dependence may occur.

Intoxication- Symptoms of acute intoxification include unsteady gait, slurred speech and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgement, irritabilty, insomnia and somatic complaints

Dependence- Symptoms are similar to those of chronic alcoholism and include a strong desire to continue taking the drug, tendency to increase the dose, psychic dependence on the effects of the drug related to subjective and individual appreciation of these effects.

Warnings-                                                                                                                            Status asthmaticus- use methohexital and thiamylal with extreme caution in patients with status asthmaticus.

Repeated or continous infusion - may cause cumulative effects resulting in prolonged somnolence and respiratory depression.

Resusctitative and endotracheal intubation equipment and oxygen should be immediately available.

Pregnancy- safety for use during pregnancy has not been established. Use onlt whennclaerly needed or when the potential benefits outweigh the potentail hazards to the fetus.

Lactation- excercise caution when administering barbiturates to a nursing woman.

Indication 

Hynotics, sedatives

Sedative Dosage:

Individualise dosage                                                                                                          Adults day time sedation - 30 to 120 mg/day in 2 or 3 divided doses.                      Hypnotic - 100 to 320mg                                                                                            Children preoperative sedation - 1 to 3 mg/kg                

Overdosage-

Symptoms :On set of symptoms may not occur until several hours after ingestion     .Acute barbiturate overdosage is manifested by CNS and respiratory depression          which may progress to Cheyne-Strokes respiration, areflexia, constriction of pupils            to a slight degree (though in severe poisoning they may show paralytic dilation)  nystagmus, ataxia, oliguria, tachycardia, hypotension, lowered body temperature            and coma.

Treatment :

1. Treatment is mainly supportive.

2. Maintain an adequate airway, with assisted respiration and oxygen administration as necessary.

3. Monitor vital signs and fluid balance.

4. If a patient is conscious and has not lost the gag reflex, emesis may be induced with ipecac.

5. Take care to prevent pulmonary aspiration of vomitus.

6. After completion of vomiting administer 30g activated charcoal in a glass of water.

7. Nasogastric administratrion of multiple doses of activated charcoal has been successful in accelerating the elimination of phenobarbital from the body.

8. If emesis is contraindicated, perform gastric lavage with a cuffed endotracheal tube in place with the patient in the face down.

9. Activated charcoal may be left in the emptied stomach and a saline catharter administered.

10. Administer fluid and other standard treatments for shock

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.

1. Do not increase the dose of the drug without consulting physician.

2. Barbiturates may impair mental or physical abilities required for the performance of potentially hazardous tasks(driving,operating machinery).

3.Alcohol should not be consumed while consuming barbiturates. Concurrent use of alcohol. and other CNS antidepressants may result in in additional CNS depressant effects.

4.Notify physician if the following occurs; fever,sore throat,mouth sores,easy bruising or bleeding.

5. Allergies- Tell your doctor if you have ever had any unusual or allergic reaction to barbiturates. Also tell your doctor if you are allergic to other substances such as foods, preservatives or dyes

3. Pregnancy- taking barbiturates regularly during pregnancy may cause bleeding problems in the newborn infant

4. Breast-feeding- barbiturates pass into breast milk and may cause drowsiness,         slow heartbeat, shortness of breath or troubled breathing in babies of nursing mothers.

5. Children- unusual excitement may be more likely to occur inchildren, who are           more unusally sensitive to the effects of barbiturates.

6. Elderly- confusion, mental depression, and unusual excitement may be more likely to occur in the elderly.

7. Other medicines- Tell your doctor if you are taking any of the following-   Adrenocorticoids or Anticoagulants or Carbamazepine or Corticotropin -               barbiturates  may decrease the efects of these medicines                                                CNS depressants-  that cause drowsines- using these medicines with                    barbiturates may result in increased CNS depressant effects                                  Diavalprox sodium or Valproic acid - using these medicines with barbiturates                 may change the amount of either medicines that you need to take                                    Oral contraceptives- containing estrogens- barbturates may decrease the                 effectiveness of oral contraceptives

8. Other medical problems- Tell your doctor if you any medical problems-                Alcohol abuse or Drug abuse or Anemia or Asthma , emphsyema, or other  chronic lung disease or Diabetes mellitus or Hyperactivity in children or Overactive thyroid or Porphyria- barbiturates may make the conditons worse                                                                   Kidney disease - higher blood levels of barbiturates may result in increasing chance of side effects Liver disease- higher blood levels of barbiturates may result Pain- barbiturates ay cause unexpected excitement or mask inportant symptoms or Underactive adrenal gland- barbiturates may interfere with the effects of other medicines needed for this condition.

Pharmacology:

Barbiturates depress the sensory cortex,decrease motor activity,alter cerebellar function and produce drowsiness,sedation and hypnosis.

Pharmacokinetics:

Barbiurates are absorbed in varying degrees following oral,rectal or parentral administration. The salts are more readily absorbed than the acids.

Pregnancy:

Barbiturates can cause fetal damage when administered to a pregnant woman. If the drug is used during pregnancy or if the patient becomes pregnant while taking the drug,advise her of the potential hazards to the fetus.

Lactation:

Excercise caution while administering to the nursing mother,since small amounts are excreted in the breast milk.