Part 7

-Drugs

           Ehibiting 1st pass effect                          

          Liver microsomal enzyme inducers&inhibitors

-Drugs and Pregnancy

-Drugs of Choice for some diseases

-Antioxidants

-Aphrodisiacs

-Ant-helmintics -Ergot alkaloids     -General drug categories

-OTC drugs"Antidiarrheal/Mucolytics/Expectorants/Antitussives"

-Poly-drug use

First pass effect

The first-pass effect (or first-pass metabolism) is a phenomenon of drug metabolism.

After a drug is swallowed, it is absorbed by the digestive system and enters the portal circulation. The absorbed drug is carried through the portal vein into the liver.

The liver is responsible for metabolizing many drugs. Some drugs are so extensively metabolized by the liver that only a small amount of unchanged drug may enter the systemic circulation, so the bioavailability of the drug is reduced.

Alternative routes of administration (e.g., intravenous, intramuscular, sublingual) avoid the first-pass effect.

First pass metabolism may be caused by or feature of the following
Drugs, hormones and mediators

-Amitriptyline &Aspirin &Chlorpromazine

-Clomethiazole &Imipramine &Labetalol

-Nortriptyline &Oxprenolol &Paracetamol

-Pentazocine &Pethidine &Propranolol

Cyt-P450 inhibitors: cimetidine, erythromycin, ciprofloxacin, fluoxetine (Prozac ®), grapefruit juice

Cyt-P450 inducers: rifampin, barbiturates, phenytoin, carbamezepine, St. John's wort, (ethanol in large amounts), thyroid hormone

Cyt-P450 substrates: warfarin, theophylline, oral contraceptives

Cyt-P450 drug interactions: sulfa drugs & phenobarbital, ethanol & tolbutamide, phenobarbital & warfarin, phenobarbital & phenytoin

Other metabolism related drug interactions: ethanol & disulfuram, MAO inibitors & tyramine

Drug usage during pregnancy

        Pregnancy induces significant changes in the functions of the body’s systems and in its fluid and tissue composition. It is helpful to consider how these changes are likely to affect drug dosing and drug interactions in the pregnant women.

Drugs have effects on developing fetuses. Administered as an anti-anxiety and anti-nausea agent in the first trimester, thalidomide caused limb-reduction defects in one third of the fetuses exposed. The drug had been determined safe initially so several years passed and thousands of deformed infants were born before this was recognized.

The definition of a teratogen includes a broad range of abnormal development, including complete pregnancy loss, structural abnormalities, abnormal growth and long-term functional defects. Drug effects can be unexpected and delayed and can affect target organs at their time of most rapid development.

Drugs affecting the unborn child

• Alcohol
• Chemotherapeutic agents (i.e., antimetabolites and alkylating agents)
• Anticonvulsants (i.e., trimethadione, valproic acid, phenytoin, and carbamezapine)
• Androgens
• Warfarin
• Danazol
• Diethylstilboestrol
• Lithium
• Isotretinoin and other retinoids
• Thalidomide

Athough nearly all drugs are present in breast milk following maternal ingestion, few are absolutely contraindicated or should be avoided by nursing mothers (i.e., amiodarone, aspirin, barbiturates, benzodiazepines, carbimazole, combined oral contraceptives, cytotoxic drugs, ephedrine, and tetracyclines).

The FDA has established five drug categories known to cause birth defects if taken during pregnancy

• Studies in women fail to demonstrate a risk to the fetus in the first trimester and the possibility of fetal harm seems remote (e.g., folic acid and levothyroxine).
• Studies have shown an adverse effect that is not yet confirmed in women in the first trimester (e.g., amoxycillin and ceftriaxone).
• Drugs to be given only if there is significant benefit ie. after seeking medical advice, as these dugs might have potential risk to the fetus (eg., nifedipine and omeprazole).
• There is enough evidence of human fetal risk and only to be used in special medical conditions only if the doctor recommends (e.g., phenytoin and propylthiouracil).
• These drugs should not to be used in women who are pregnant (e. g., misoprostol, warfarin, and isotretinoin). Their usage poses fetal abnormalities, or evidence of fetal risk.

Antibiotics during pregnancy:

1. Those considered safe (i.e., penicillin and erythromycin base, stearate or ethylsuccinate)
2. Those that probably are safe but to be used with caution (i.e., azithromycin, metronidazole, nitrofurantoin)
3. Those that are contraindicated in pregnancy (i.e., tetracycline, fluroquinones, and erythromycin estolate)

Drugs that should be avoided or used with caution during pregnancy Drugs Comments Alcohol High dose may affect the infant Aminophylline Try to avoid Amiodarone Significant amounts present in milk Aminoglycosides Try to avoid Antibiotics Use with caution Aspirin Avoid high repeated doses Atropine Try to avoid Benzodiazepines Sedation with repeated doses Calciferol Hypercalcaemia in high doses Carbimazole Thyroid problems Chlorpromazine Drowsiness Clindamycin Bloody stools Corticosteroids Avoid high doses Corticosteroids Avoid high doses Diuretics Some may suppress lactation Iodine It is concentrated in milk Isoniazid Convulsions Laxatives Try to avoid them Lithium Avoid, but if used careful monitoring is required Meprobamate High milk concentration Metronidazole Discontinue breast feeding for 12-24 hours after a single dose, avoid breast feeding if repeated doses used Nalidixic acid Avoid as far as possible Nitrofurantoin Avoid them Opioid analgesics Withdrawal symptoms may occur in infants of addicted mothers Penicillin Safe except for allergy Phenobarbitone Drowsiness if used in high concentrations Currently 60/5 Stars. 1 2 3 4 5 20 تصويتات / 117 مشاهدة نشرت فى 13 فبراير 2007 بواسطة eagle احفظ ساحة النقاش شارك فى النقاش... عدد زيارات الموقع 9,812