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![References
Carachi and Doss. Clinical Embryology – An Atlas of Congenital Malformations.
2019. Springer Internataional Publishing AG, United Kingdom.
Currie, D. Drug Therapy During Pregnancy [PowerPoint slides]. SlideShare
Donald Mattison. Clinical Pharmacology During Pregnancy. 2013. Alsevier Inc,
London, UK.
Karch, A. Lippincott’s Nursing Drug Guide. 2011. Wolters Kluwer – Lippincott
Williams & Wilkins, Philadelphia, US.
Manjuprasad. Drug Therapy in Pregnancy [PowerPoint slides]. slideShare](https://image.slidesharecdn.com/pharmacologyinpregnancy-230818121557-18239405/75/Pharmacology-in-Pregnancy-pptx-26-2048.jpg)
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Pharmacology in Pregnancy.pptx
The document discusses pharmacology and medications during pregnancy, highlighting physiological changes that affect drug therapy and the importance of careful medication use to avoid fetal harm. It covers drug transfer across the placenta, the classification of drugs by FDA in pregnancy, and examples of teratogenic agents. Additionally, it lists commonly used medications, potential risks, and contraindications for pregnant women, emphasizing the need for medical guidance in drug administration.
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Pharmacology in Pregnancy.pptx
- 1. Pharmacology and Medications inPregnancy M. TENO MBBS, DGO 31st July 2023
- 2. Outline Introduction PhysiologicalChanges in Pregnancy Placental transfer of drugs Critical period in fetal development and teratogenesis FDA categories of drug use in pregnancy Commonly used drugs References
- 3. Introduction Medications ordrugs are only used in pregnancy when “indicated.” Physiological changes during pregnancy affect drug therapy including pharmacokinetics Use of drugs is associated with 2-3% of all birth defects other than alcohol. Medications are essential when medical conditions are superimposed on pregnancy.
- 4. Physiologcial Changes inPregnancy System Changes GIT Nausea & vomiting, ↓ gastric motility and emptying CVS CO ↑ 30-50%, SBP & DBP ↓ in T2, plasma volume ↑ 45% Resp ↑O2 consumption (32-58mls), ↑ TV 40%, ↓PaCO2 27% Liver No change in size/blood flow. ↓ serum albumin levels, ↓ colloid osmotic pressure Renal ↑ in size/blood flow 60-80%, ↑ GFR Coagulation System Hyper-coagulable state Weight ↑ BMR 15-20%, weight gain
- 5. Impact of Pregnancyon maternal pharmacokinetics PHARMACOKINETIC PROPERTY PHYSIOLOGOGICAL PARAMETER EFFECT Absorption ↓ GI motility ↓ gastric emptying time Hypertrophy of duodenal villi ↑ gastric acid pH ↑ systemic absorption of medications Distribution ↑ palsma vol ↑ adipose tissue volume ↑ cardiac output ↑ volume distribution ↓ plasma drug concentration Excretion ↑ GFR and renal blood flow ↑ clearance of drugs that are cleared through the kidney (especially in T3) Protein binding ↓ albumin concentration ↑ free drug concentration of high protein bound drugs ↑ drugs total clearance Metabolism & bioavailability Blood flow to liver is unchanged ↑ hepatic metabolism occurs for some drugs, ↓ bioavailability or no change
- 6. TRANSFER OF DRUGSACROSS PLACENTA Rate of transfer of a drug depends on: Molecular size Lipid solubility pH difference (7.0 vs 7.4): ionic trapping of weak basic drugs (e.g. morphine) Ionization of drugs
- 7. William’s Obstetrics (22ndEdition). 2005. McGraw-Hill Companies. Inc • Placenta is capable of metabolizing drugs • Little relevance to mother • Protective effect on fetus
- 8. Drugs can affectthe fetus in several ways: 1. Act directly on the fetus, causing damage, abnormal development (birth defects, or death. 2. Alter function of placenta, by constricting blood vessels and ↓ oxygen and nutrient supply. 3. Stimulate forceful uterine contractions, which can affect the fetus by ↓ blood supply and stimulating preterm delivery
- 9. Effect of toxicDrugs on the fetus No effect Little effect Serious fetal toxicity Spontaneous abortion Death Fetal malfunction/malformation
- 10. Harmful effects dependson Nature of drug, dose and route of administration Trimester of pregnancy at which drug is administered Genetic constitution and susceptibility of fetus Directly on the fetus – birth defects or death Alter the function of the placenta - by constricting blood vessels, ↓ blood supply of O2 and nutrients to the fetus Contract uterus: ↓ blood supply to fetus Trigger pre-term labour and delivery
- 11. Gestation is dividedinto 4 stages Blastocyst formation (0-16days or first 2 weeks) Teratogen(s) can either: Inhibit cell division and kill embryo or Normal subsequent development, if embryo survives exposure to drug Organogenesis (17-60days or week 3 to 8) Teratogen causes gross structural malformation
- 12. Histogenesis andmaturation (final stage) Teratogens have a deleterious effect on growth and maturation e.g. DES (diethylstilbesterol)– dysplasia, vaginal Ca in female offsprings Androgen exposure - masculinization of female infants Short labour and delivery Drug administration poses the risk of neonatal toxicity.
- 14. What is ateratogen? Terato = teras (Greek) + gen = genesis ----- teratogen Something unsual or abnormal in size, composition or appearance Congenital anomalies caused by teratogens and visible at birth Exert its effect on a particular stage of fetal development Show dose dependent incidence Include radiation, maternal infections, chemicals and drugs.
- 15. Examples of teratogenicagents Drugs • Thaliomide • Sodium Valproate • Methotrexate • Lithium • Warfarin Environmental agents • Ionizing radiation • fever Infections • Rubella • Cytomegalovirus (CMV) • Parvovirus • Syphilis Toxins • Alcohol • Phenylalanine • Lead • Mercury Nutrients • Folic Acid • Vitamin A
- 16. Fetal Warfarin Syndrome: ChondrodysplasiaPunctata Aminopterin Thalidomide Disorders of musculoskeletal system: phocomelia or amelia Anencephaly, hydrocephalus, cleft lip and palate Nasal hypoplasia, limb hypoplasia, optic atrophy, bone abnormalities, neurological impairement Clinical Pharamcology during Pregnancy. 2013
- 17. Rubella Syphillis Classic triad ofrubella: cataract, cardiac abnormalities & deafness Anomalies and deformations of musculoskeletal system: Amelia Clinical Pharamcology during Pregnancy. 2013
- 18.
- 19. (U.S Food andDrug Administration) • Folic Acid • Vitamin B12 • Acetaminophen or paracetamol • Insulin • Famotidine • Fluconazole • ciprofloxacin • Phenytoin Medications that are contraindicated: Warfarin, Methotrexate, Medroxyprogesterone (Depo) Medications that can be used
- 20. DRUGS WITH PROVENTERATOGENIC EFFCTS DRUGS EFFECTS Phenytoin • Fetal Hydantoin Syndrome • Cleft Lip/palate and CHD Vitamin A- derivatives • Isotretinon, etretinate • ↑ risk of miscarriage and other significant anomalies ACEIs • Renal damage and oligohydramnios in T2/T3 • Anomalies of face, limbs and lungs Valproate and carbamazepine • CNS defects: spina bifida, anencephaly, encephalocele Warfarin • Fetal warfarin syndrome • Nasal hypoplasia, depressed nasa; bridge & hemorrhagic disorders in fetus NSAID’s (diclofenac, ibuprofen, naproxen) After 20 weeks: • Premature closure of ductus arteriosus • Kidney problems Oligohydramnios (Aspirin is only used when indicated)
- 21. Clinical Pharamcology duringPregnancy. 2013 Bilateral cleft Lip Palate
- 22. Clinical Pharamcology duringPregnancy. 2013 Meningocele Mylomeningocele
- 23. COMMONLY USED DRUGSIN PREGNANCY
- 24. Category Drugs usedContraindications Developed Countries LMICs Analgesics & antipyeretics Acetaminophen, phenacetin, aspirin Acetaminophen (panadol) NSAID’s avoided towards end of pregnancy: risk of PDA Anti-emetics Cyclizine, meclizine, ondansteron Metoclopromide (maxalon) Antibiotics Beta-lactam, nitrofurantoin, erythromicin Antiamoebic Metronidazole Antimalarials Coartem, Quinine Primaquine (for mixed infection) Anti-TB FDC: Isoniazid, Rifampicin and Ethambutol Streptomycin and Kanamycin – ototoxicity, , Amikacin – congenital otoxicity Anti-fungal Nystatin, miconazole Nystatin, miconazole, clotrimazole Ketoconazole – fetal malformation
- 25. Category Drugs usedContraindications Developed Countries LMICs Anti-asthmatic Beta-agonist, glucocorticoids (salbutamol, prednisolone, dexamethasone, cortisone) Cardiac Digoxin and quinidine Anti- hypertensives Methyldopa, labetalol Methyldopa, Nifedipine Enalapril - oligohydramnios Anti-coaguant Low molecular weight heparin (LMWH) Warfarin Anti- Helminithic Piperazine, pyrantel Albendazole Anti- convulsants Magnesium Sulphate (MgSo4) Phenytoin, carbamazepine, phenobarbiturate
- 26. References Carachi andDoss. Clinical Embryology – An Atlas of Congenital Malformations. 2019. Springer Internataional Publishing AG, United Kingdom. Currie, D. Drug Therapy During Pregnancy [PowerPoint slides]. SlideShare Donald Mattison. Clinical Pharmacology During Pregnancy. 2013. Alsevier Inc, London, UK. Karch, A. Lippincott’s Nursing Drug Guide. 2011. Wolters Kluwer – Lippincott Williams & Wilkins, Philadelphia, US. Manjuprasad. Drug Therapy in Pregnancy [PowerPoint slides]. slideShare
Editor's Notes
- #5 GIT: effect of PG4 and endogenous opiods’ effect. ↑ Na + H2O absorption (aldosterone effect). ↑Vit B12 & Fe absorption. Hypercoagulable state: prone to develop blood clots. Physiologically adaptive mechanism to prevent PPH. Increased production of VII and fibrinogen.
- #7 Ionization of drug: ionized drugs are not absorbed as efficiently as un-ionized drugs. Drug that is a weak acid is absorbed primarily in the acidic environment Weak base drugs will be absorbed in the alkaline environment.
- #8 Fetus blood vessels = villi extend into uterine wall. Mothers blood passes through the intervillous space and diffuses into the villi. Thin placental membrane separates the mothers blood from fetal blood Drugs in the mothers blood cross this membrane into the fetal blood vessels in the villi and into the umbilical cord.
- #13 DES: diethylstilbesterol: synthetic form of estrogen. Prescribe to women between 1940 and 1971 to prevent miscarriage and PTL. Associated with birth defects in T1, during formation of fetal genitalia.
- #14 Red indicates periods that have the greatest sensitivity to teratogens
- #17 Thalidomide: marked in Germany in 1950’s as a sedative and anti-emetic. 1961 – first phocomelia case reported. Embryonic sensitivity to drug occurs betweeb 20-36 days after fertilization. Produced limb abnormalities, CHD, eye and ear abnormality, intestinal atresia, renal malformation and facial palsies Day 20-24: affects eyes + ears Day 24-31: upper limbs Days 27-33: lower limbs Aminopterin: derivative of folic acid used in chemotherapy. Competes for folate binding site of dihydrofolate reductase. Anencephaly: failed closure of rostral end of neural tube. Characterized by total or partial absence of cranial vault & cerebral hemisphere.
- #20 A: controlled studies in pregnant women that demonstrate no harm to the fetus in T1 and no evidence of further risk in T2/T3. B: animal studies failed to demonstrate risk to fetus, but no adequate or well controlled studies in pregnant women Famotidine: H2 receptor anatgonist, treats GERD or peptic ulcer. C: potential benefits may warrant use of drug in pregnant women despite potential risks. Fluconazole: antifungal Rx for candidiasis, cryptococcosis. Cirpofloxacin: fluroquinolone that Rx bacterial infections, diarrhoea, UTI, RTI, skin infections. D: Phenytoin (dilantin) – anti-seizure Rx for tonic clonic or focal seizures.
- #23 sac prtotruding from the spinal column. Contains spinal fluid, but no neural tissue. May be covered with skin or meninges