This document summarizes key points about pharmacokinetic and pharmacodynamic changes during pregnancy and their implications for drug use. It discusses how physiological changes can impact absorption, distribution, metabolism and excretion of drugs in pregnant women. It also describes placental drug transfer and factors that can influence fetal drug effects. The document emphasizes that drug use during pregnancy requires careful consideration of benefits versus risks to both the mother and fetus. Definitive dosing guidelines are often limited due to lack of clinical trials in pregnant women.
Pharmacodynamics and kinetics during pregnancyReem Alyahya
This presentation discuss the following objectives:
-Drug therapy during pregnancy, childbirth, and lactation.
-Physiological changes of drugs in pregnant women.
-Drug toxicity
-Cross-placental transfer of drugs
-Exertion of drugs in breast milk
-Drug safety + ABCDX
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
hi there .. this poerpoint deal with drugs usage in pregnent women .. th pharmacokinetics .. drug effects on the fetus .. FDA category .. with thanks to my collegues mariam and sherin .. wish to be useful .. enjoy:)
Pharmacodynamics and kinetics during pregnancyReem Alyahya
This presentation discuss the following objectives:
-Drug therapy during pregnancy, childbirth, and lactation.
-Physiological changes of drugs in pregnant women.
-Drug toxicity
-Cross-placental transfer of drugs
-Exertion of drugs in breast milk
-Drug safety + ABCDX
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
hi there .. this poerpoint deal with drugs usage in pregnent women .. th pharmacokinetics .. drug effects on the fetus .. FDA category .. with thanks to my collegues mariam and sherin .. wish to be useful .. enjoy:)
Drug therapy in pregnancy and lactationVishnupriya K
This slide share will provide drugs which are used and which are contraindicated during pregnancy and lactation, also give information about side effects and malformations if pregnant women's used some drugs.
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
There are several physiological changes occuring in pregnancy which leads to altered pharmacodynamics. Placenta is an incomplete barrier which allows drug transfer to the fetus.
Drug therapy in pregnancy and lactationVishnupriya K
This slide share will provide drugs which are used and which are contraindicated during pregnancy and lactation, also give information about side effects and malformations if pregnant women's used some drugs.
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
There are several physiological changes occuring in pregnancy which leads to altered pharmacodynamics. Placenta is an incomplete barrier which allows drug transfer to the fetus.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
2. Introduction…
• Every minute a woman is giving birth to a baby
• Each pregnancy is a precious pregnancy
• Mother and fetus are non-separable unit
• Maternal well being is absolute prerequisite
• Important to treat the mother while protecting the
unborn fetus.
3. Drugs are used for…
• Conceiving
• Maintaining pregnancy
• Preventing diseases
• Treating ailments and illness in pregnancy
4. Intake of Drugs During Pregnancy
• A prescription for a pregnant female contains 4
drugs on an average.
• Increased incidence of Hypertension and
Diabetes in late age pregnancy, for which
treatment is imperative
5. Unsupervised use of drugs and environmental
agents in expectant mothers can lead to
spontaneous abortions, low birth weight or….
Fetal Malformations
6. The facts are ..
• Only 2-3% of birth defects are due to drug
exposure
• 60-70% of birth defects are due to unknown
reasons.
7. On the other hand…
• Scarcity of data about safety and PK of various
drugs in mother and fetus.
• Fetal effects of drugs differ widely between
animals and humans.
• As pregnant females are excluded from clinical
trials on ethical grounds, case control and cohort
studies are the main sources of information.
• Unnecessary termination of wanted pregnancies
due to fear about drug intake in pregnancy.
9. Definitions
• Pharmacokinetics means “ what body does to
the drug”
• Includes absorption, distribution, metabolism and
elimination of drugs
• It tells you how and when drug reaches the site
of action
10. • Pharmacodynamics means “ what a drug does
to the body”
• Study of biochemical and physiological effects
of drugs and their mode of action
• It deals with the relationship between the plasma
concentration of the drug and its response as
well as its duration of action
11. Changes in Maternal Pharmacokinetics
• A result of physiological changes
• Progressive in nature
• High intra and interindividual variability
• Therapeutic drug monitoring in case of doubt
12. • Cmax: Highest drug concentration observed in plasma
after administration of an extravascular single dose.
• Tmax: time taken to reach Cmax
• T1/2 means the time duration in which the plasma
conc. of the drug falls by 50% of the earlier value.
• Vd (volume of distribution) is the total space
apparently available in the body to contain the known
amount of the drug. If a drug has high Vd, then it is
widely distributed and attains a lower plasma conc.
13. Physiological Changes in Pregnancy
Body System Physiological change Extent of change
Cardiovascular System Cardiac output
Heart rate
Stroke volume
Blood Pressure
40%
20%
10%
Blood Flow
Uterus
Kidney & Liver
Skin
15 times
60-80%
600-700%
Hematological System Plasma volume
Red cell mass
Plasma albumin conc
50%
18-30%
30%
Respiratory System Tidal Volume
RR
Oxygen consumption
40%
15-20%
14. Body System Physiological change Extent of change
Respiratory System Compensated respiratory
Alkalosis, pH 7.4
Lowered PaCO2
Gastrointestinal
system
Gastric motility
Intestinal motility
Relaxation of LES
Kidney Function GFR
BUN
Creatinine
50%
8-9 mg/dL
0.5-0.6 mg/dL
Body Composition Water
Fat
(6-8 Lit)
25%
16. ↓H+ secretion
↓
↑ gastric PH & ↑ mucus production
↓
Weak acids ionize and their absorption ↓
↓
Multiple dose weak acids shows no change
but
Single dose (analgesic, antiemetic) shows ↓ Cmax
and↑ Tmax
Weak bases show less ionization so no effect
17. Nausea and vomiting
↓
↓ absorption
↓
If single oral dose to be given, administer in the
evening, when nausea is less
Vasodilatation
↑ tissue perfusion so IM absorption ↑
↑ transdermal absorption
18. ↑ cardiac output, ↑ tidal volume, ↑ alveolar
uptake
↓
↑ absorption of drugs by inhalation
E.g.: low dose halothane is required for
anesthesia
23. Metabolism
• Estrogen/progesterone induces cyP450 so
elimination ↑ e.g. Phenytoin
• Inhibit some other isoenzymes so elimination ↓
e.g. theophylline, caffeine
• Estrogen causes cholestasis and so reduced
clearance of some drug eg. Rifampicin
• Less activity of cholinesterase
24. Excretion
• Renal blood flow ↑ by 60-80%
• GFR ↑ by 50 % in 1st
trimester and 80 % in 2nd
trimester
• Elimination of penicillin and digoxin ↑
• Also of amino glycosides and cephalexin ↑
• Required increase in dose
25. Placental excretion
• Mainly by simple diffusion
• Facilitated diffusion e.g. is cephalexin, glucose
• Active transport e.g. is 5- FU, alpha methyl dopa
26. • Follow Fick’s Equation
∆q/∆t = KA (Cm-Cf)/d
K – Diffusion constant
A – Area of absorption
Cm – Cf – Conc. gradient
d – thickness of the membrane
28. Lipid solubility
• Thiopental (anaesthetic) crosses placenta and
causes sedation and apnea in newborn
• Highly ionized drug doesn’t cross placenta e.g.
tubocurarine, scholine
• Salicylates (highly ionized) metabolites or free
fraction is highly lipid soluble and readily crosses
placenta
29. Molecular size
Molecular size crossing of
placenta
< 500 D Very easily
500-1000 D With difficulty
>1000 D poorly
• controls rate and amount of drug transfer
30. Placental transporters
• Increased number of specific drug
transporters identified
• P-glycoprotein transporter encoded by MDR-
1 gene e.g. vinblastin, doxorubicin, digoxin
31. Few points…
• Placental blood flow is a rate limiting step
• Placenta not crossed by
1) high mol. Wt 2) protein bound
e.g. heparin, insulin
• Metabolism by placenta and fetal liver.
Develop in fetus by 8 weeks post conception
32. Metabolism in placenta…
• Prednisolone & hydrocotisone will be converted
to prednisone and cortisone respectively and
thus, they are harmless to the fetus
• Ethanol and benzpyrine toxicity is augmented by
metabolism in placenta
33. Factors affecting placental drug
transfer and effects on fetus
• Stage of gestation
• Uterine blood flow
• Conc. gradient
• Physicochemical properties of
drug and its metabolites of
protein binding
• Metabolism
• Placental absorption of
drugs e.g. coccaine
34. Hepatic metabolism in fetus
• All enzymes for phase I and phase II metabolism
are present
• By 11-18 weeks, CYP450 level reaches adult
value
• CYP3A4 absent and CYP3A7 present (30%)
• Glucoronisation absent and sulphation present
36. • Changes in maternal physiology during
pregnancy impact on pharmacokinetics with a
tendency to reduced plasma concentrations.
• Definitive information from studies that could be
used to formulate therapeutic guidelines for the
safe use of drugs in pregnancy is, however,
limited.
• At present there is little evidence to formulate
clear-cut guidelines with respect to dosing
schedules for individual drugs.
37. • In order to design evidence-based guidelines for drug-
dosing in pregnancy, high-quality pharmacokinetic
studies of adequate sample size which incorporate a
non-pregnant control group are required.
• On current evidence, dose requirements are likely to
be higher for drugs with increased clearance during
pregnancy.
• Dose titration for protein-bound drugs should be
based on monitoring of free drug concentration.
38. Drugs in pregnancy…
Fever and pain
Paracetamol
• It crosses placenta
• Reduces t1/2 with increased
clearance
• PCM toxicity occurs after hepatic
oxygenation by cyto P450
39. • At week 18-23 of gestation the mean activity of
CYP450 in fetal liver is 10% of adult values, which
increase with gestation
• So potential for fetal toxicity increases with
gestational age
• N acetylcysteine can be given to pregnants as
neglible placental transfer and no teratogenicity
• If maternal PCM conc. are in toxic range, then
delivery of mature fetus is considered to allow for
40. Aspirin
• Avoided in 3rd
trimester
• Salicylic acid crosses placenta
• Conc. in fetus is more than mother as salicylic acid
has more affinity for fetal proteins
41. • Crosses cell membrane and causes CNS toxicity
• It interfere with thromboxane A2 synthesis of
maternal platelets and may interfere with fetal
prostaglandin synthesis
• Can cause peripartum bleeding and CND
haemorrhage
• 40-150 mg/day can be given for the prevention of
42. Other NSAIDs
• Avoided in 3rd
trimester as it can inhibit fetal COX
• May be assosciated with oligohydramnios,
constriction of the ductus arterious, PDA, and PPH
after birth
• Indomethacin is given as tocolytic
43. Opiod analgesics
Pethidine:
• Most commonly used during delivery (1st
phase of labour)
• Longer T1/2 in pregnancy
• Maternal –fetal equilibrium reaches in 6 mins after i.v
administration
44. • hypertonic uterine constriction may occur with its use
• So, given intrathecally with/without LA during labour
or IM
• Morphine can be used for the same purpose
• Prolnged use of them causes resp. depression and
addiction in pregnancy
45. • Pentazocine, fentanyl, oxymorphone can be
used as analgesics in late pregnancy
• Codeine , oxycodone and hydromorphone are
safe when used in pharmacological dose during
pregnancy
• Naloxone used to couneract resp depresssion in
neonate caused by opioid agonist
46. Anticaogulants
• Heparin and Aspirin are given
Heparin
• Do not cross placenta as large size
• On the day of delivery, the dosage should be
reduced to 7500 U or less every 12 hrs to reduce the
danger of excessive bleeding
• If Aptt if prolonged , then administer protamine
47. Anaesthesia
• Pre mixed Nitrous oxide and O2(entonox) is used
as inhalational agent
• Enflurane and halothane is also safe
• Dose requirement may be less
48. •Duration of anaesthesia before delivery is kept as
low as possible as fetal conc. of nitrous oxide
increases with continuous administration
•During labor i.v. thiopental and methohexital
•Peak fetal conc. in 2 mins
•Bupivacaine or lignocaine are given for regional
anaesthesia
50. Bacterial infection
Penicillin
• Safe and preferred Antibiotic
• Dose need to be increased during pregnancy as
renal clearance is increased
Ampicillin, amox and methicillin (i.v.)
• Clerance ↑ so dose need to be ↑
51. • Β lactams are low protein bound and crosses
placenta and reaches amniotic fluid and
reabsorbed in the gut of fetus
Cephalosporins
• Increased dose is required of 1st
and 2nd
gen.
• Unchanged dose of 3rd
gen like ceftriaxone
Erythromycin
• Erythrmycin esolate is hepatotoxic in pregnants
52. Clindamycin,
• Can be given in anaerobic infections as it
crosses placenta
Nitrofurantin
• Given in UTI in femlaes
Metronidazole and cotrimoxazole are safe
Tertacyclines and sulphonamides are avoided
53. Asthma
• Inhalational salbutamol, corticosteroids, sodium
cromoglycate and ipratropium bromide
• Systemic theophylline and corticosteroids
Diabetes mellitus
Human insulin
Antacid & Antiemetic
H2 blocker and Metoclopramide are choices
54. Antihypertensives
Methyldopa
• Easily crosses placenta and drug of choice
Labetaolol
• T1/2 is shorter in pregnants, so frequent doses are
required as compared to non-pregnants
Nifedipine
• Clearance of nifedipine ↑ in pregnants than non-
58. Arrythmia
Digoxin
Quinidine
• accumulate in amniotic fluid
Procainamide
• Weak base and low protein so placental
transport and ion trapping occurs
60. • Drug
use
Benefits mother or fetus
Dangers to mother or
fetus
Fetal adverse effects are difficult to manage
• They are difficult to diagnose
• Most of the effects are irreversible
61. So our objectives should be
• Prevent the adverse effects
• Diagnose these effects as soon as possible
• Treat them before they reach an irreversible state
63. Teratology
• Definition: The study of all environmental
contributions to abnormal development
Teratogen
‘ Any agent that acts during embryonic or fetal
development to produce a permanent alteration
of form or function.’
64. Principles of teratogenicity
1 Time of exposure (window of opportunity)
• Thalidomide – 22 to 36 post conceptional day
• Carbamazepine – 1st
week
2 Dose and duration
• Severity of teraotogenicity increase with dose
and duration
• e.g. Alkylating agents, Actinomycin D etc.
65. 3. Species difference
• Coumarins - teratogenic in man only
• Thalidomide – teratogenic in higher primates
4.Mechanism
a)Direct fetal toxicity
e.g. chemotherapeutic agents, radiation
b) Genetic suseptibility
Fetal hydantoin syndrome is associated with the
expression and activity of epoxide hydrolase
66. C) Maternal-fetal unit dysfunction
Cadmium interferes with placental zinc transport
d) Multifactorial effects
e.g. Fetal hydantoin syndrome caused by alcohol
e) Other factors
Concurrent exposures
Concurrent illness
Degree of organ specificity
68. Mechanisms
• Folic acid deficiency
• Epoxides or arenaoxides- metabolites(CBZ)
• Environment & genes
• Maternal disease and drugs-ex. Epilepsy
• Homeobox genes –regulate normal development
& growth (Hox gene) affected by teratogen
69. Slice 1
Slice 2
Slice 3
Fetal period
Embryonic period
(organogenesis)
Pre-
implantation
period
Gestational clock
70. Stages of fetal growth & development
Period of cell division( pre-implantation period)
• The period of one week from fertilisation to
implantation of fertilized egg is called the
preimplantation period
• Zygote transforms into embryonic disk
• No birth defects as systems not developed
• But fetal loss can occur
• So called ‘all-or-none’ period i.e. an insult can either
cause death or complete recovery can occur
71. Embryonic period
• The period from 8th
day to the end of 8th
week(2nd
month) is the period of organogenesis during which
organs are formed in the fetus
• most vulnerable for major birth defects
72. Fetal period
• from 3rd
month 1st
week to the end of 9 months s
the period of fetal maturation.Intake of drugs
during this period may modify the function of the
fetal organs rather than causing gross structural
malformation in the fetus
• Period of growth
• Birth defects usually not severe.
73. Criteria for proof of human
teratogenicity
• Careful delineation of clinical cases
• Rare exposure a/w rare defect (at least 3
reported cases)
• Proof of embryopathic action direct or indirect
• Proven exposure at critical stages
• Association must be biological plausible.
• Epidemiological studies consistency
• Teratogenicity in experimental animals
74. Evaluation of Teratogenicity
• Pregnant animals treated with drugs during
embryonic period (organogenesis)
• Mice & rats – 6-15 days of gestation
• Rabbits – 6-18 days of gestation
• Fetuses removed few days before parturition.
75. Evaluation parameters
• Litter size (no of implantation)
• Lethal effect (no. of resorbed embryo & dead
fetuses
• Teratogenic effects (no. of malformed live fetuses)
83. Do’s and Don’ts of prescription
Do’sDo’s
• Only prescribe for valid indications.
• Use lowest therapeutic dose.
• Treat minor ailments without drugs.
• Avoid medications during the first trimester when the
fetus is at greatest risk from teratogens.
• Do not use combinations of drugs. Use one agent at a
time.
• Use topical treatments when available as you get less
systemic absorption.
• Use the medication only if the benefits outweigh the
risks.
84. Don’tsDon’ts -
• Do not add drugs
unnecessarily.
• Never be the first one to
use the new & the last
one to use old drugs.
• If decision to treat, do
not use sub-therapeutic
doses.
• Don’t encourage pt. to
take OTC or herbal
preparations.
85. US-FDA GUIDELINES
CATEGORY DESCRIPTION
A Well controlled studies show no fetal
risk. ex. Niacin, riboflavine, thiamine
B Animal studies indicated no fetal risk,
but human inadequate or animal
studies show some risk not supported
by human studies. Ex. Metro.,
cefotaxime, penicillin
C Animal studies shows risk but human
studies inadequate of no studies in
humans or animals. Ex. mebendazole,
acyclovir
86. US-FDA GUIDELINES
CATEGORY DESCRIPTION
D Definite fetal abnormalities human
studies but potential benefits may
outweigh risks. Ex. Phenytoin,
alprazolam
X Contraindiacated in pregnancy. Fetal
abnormalities in animals or humans
proven. Risks clearly outweigh any
benefits. Ex. Isotretinoin, danazol
88. Justification
Should not be deprived of beneficial drugs,
vaccines, investigations because of lack of
data
88
89. General Ethical Consensus
Pregnant or nursing women should in no
circumstances be the subject of any research
unless the research carries no more than
minimal risk to the fetus or nursing infant
89
90. Ethical aspects
NWCPT 12/03/2013
Should only be included if object of the research is to
obtain new knowledge about the fetus, pregnancy and
lactation
trials as are designed to protect or advance the health of
pregnant or nursing women or fetuses or nursing infant
Data obtained from the non-pregnant are not suitably
extrapolated to pregnant women
No discontinuation of nursing for the sake of
participating in trial
90
91. Recommended safeguards
NWCPT 12/03/2013
– All female reproduction toxicity studies and
genotoxicity studies should be complete
– All female reproduction toxicity data to be
reviewed
91
92. Are they Therapeutic orphans
NWCPT 12/03/2013
• Actively excluded from the studies evaluating
safety and efficacy of NCEs
• Very few data available to decide
The right drug
The right dose and
The right dosing regimen
92
93. NWCPT 12/03/2013
• Safety and efficacy data :
observational studies
Pregnancy registries
• Studies on women who desire to undergo
MTP
93
94. Typical Clinical Trials (1/2)
NWCPT 12/03/2013
• Randomized controlled trials
– Two preparation of iron for anemia
• Placebo-controlled trials
– Antidepressant drug Vs placebo
– TRH Vs placebo for threatened premature delivery
– Vit D supplementation Vs placebo
94
95. Typical Clinical Trials (2/2)
NWCPT 12/03/2013
• PK studies, PK-PD studies
– Normal pregnant volunteers ?
– Pre-requisites for initiation
– A typical study:
Study of PK-PD of anti HT drug on a woman who
is already taking the drug for PIH
95
96. Trials related to Prenatal diagnostic
techniques
NWCPT 12/03/2013
• Prenatal Diagnostic Techniques (Regulation
and Prevention of Misuse) Act, GOI, 1994
96
97. Conclusion
• Pregnancy not a disease which require
multidrug therapy.
• Based on reliable info. drug use should be
cautious & minimal.
• Systematic generation of reliable data is
desperately sought commodity .
• Always strive for better & safer therapies in
years to come.