Teratology , Drugs And Medication Flashcards
This refers to agents that produces STRUCTURAL ABNORMALITIES
Teratogen
Teratogen is derived from Greek word teratos which means?
Monsters
Most of the major structural abnormalities are easily seen at ___ and an association with a specific ___ exposure is likely to be suspected
Birth
Prenatal
Agent that interferes with normal MATURATION and FUNCTION of an organ
Hadegen
This refers to an agent that alters growth
Trophogen
Criteria for proof of human teratogenicity: (7)
- Careful delineation of clinical cases
- Rare environment exposure associated with rare defect with at least three reported cases
- Proof that agents acts on embryo or fetus, direct or indirectly
- Proven exposure to agent at critical times in prenatal development
- Association must be biologically plausible
- Consistent findings by two or more epidemiological studies of high quality
- Teratogenicity in experimental animals especially primates
This is the period of 2 weeks from fertilization to implantation
Preimplantation period
This is called the “all or none” period
Preimplantation period
Teratogens in the preimplantation period in animals can produce a ___ dependent diminution in ___ or ____
Dose dependent
Body length and size
This is the critical period from the 2nd to the 8th week following conception
Embryonic period
This is the most crucial with regard to structural malformations
Embryonic period
This pertains to the 9th week to term, in which functional maturation may be involved
Fetal period
Alteration in the cardiac blood flow can result in ___ an example of which involves (2)
Deformations
Hypoplastic left heart or aortic coarctation
Category of drugs that shows studies in pregnant women have not shown an increased risk for fetal abnormalities
Category A
This category of drugs if administered during the first, second, and third trimester of pregnancy the possibility of fetal harm appears remote
Category A
Fewer than __ percentage of all medication are within the category A
1
Examples of category A drug
Levothyroxine
Potassium supplementation
Prenatal multivitamins
This category shows that animal reproduction studies have shown adverse effect but adequate and well controlled studies in pregnant women have failed to demonstrate a risk to the fetus during the first trimester and in the later trimesters
Category B
Drugs under the category B
Antibiotics: Penicillins, Macrolides, Cephalosporins
This category shows that animal reproduction studies have shown that this medication is TERATOGENIC or EMBRYOCIDAL or Adverse effect and there are no adequate and well controlled studies in pregnant woman
Category C
Examples of drugs under category C
Albuterol Zidovudine Lamivudine Beta blocker Calcium channel blocker
Category of this medication causes fetal harm when administered to pregnant woman
Category D
If this drug categories is used during pregnancy or if a woman becomes pregnant while taking this medication, she would be apprised to the potential hazard to the fetus
Category D and X
This category of drugs usually contains medications used to treat potentially life threatening medical conditions
Category D
Examples of category D
Systemic corticosteroids Azathioprine Phenytoin Carbamazepine Lithium Valproic acid
This category of medication is contraindicated in women who are or may become
Category X
An example of a category X medications
Rubella vaccines
List the possible disturbances of specific pathogenic processes
Cell death
Altered tissue growth
Abnormal cellular differentiation
Abnormal development
Folic acid metabolism can cause the following:
Neural tube defects
Cardiac defects
Cleft lip and palate
Drugs that can interfere with folic acid metabolism
Hydration
Phenobarbital
Valproic acid
Carbamazepine
Treatment for folic acid metabolism distrubances
Folic acid supplementation
The mutations of this gene can cause neural tube defects
Tetrahydrofolate reductase 677C
Hydantoin can cause a homolozygous gene mutation of low ____
Epoxied hydroxylase activity
Cigarette smoking and cleft palate cause the polymorphism in the gene of __
Transforming growth factor alpha-1
This are regulatory genes that encodes nuclear proteins to control the expression of other developmentally important genes
Homeobox genes
Retinoic acid can prematurely activate the homeobox gene that can cause _____
Severe hindbrain and limb abnormalities
Valproic acids activates the homeobox genes that regulates the ___ skeletal patterning in turns causes ___ in the ___
Axial
Neural tube defects
Lumbosacral region
Paternal exposure may either involve:
Genetic mutation or chromosomal anomaly in the sperm
Drug in the seminal fluid can expose the fetus during intercourse
Drugs that can cause changes in the gene expression and imprinting in the paternal exposure
Ethyl alcohol Cyclophosphamide Lead Opiates Mercury Solvents Pesticide Anesthetic gases Hydrocarbons
Fetal alcohol syndrome diagnostic criteria
Dysmorphic facial feature
Prenatal and/or postnatal growth impairment
CNS abnormalities
Dysmorphic facial features in fetal alcohol syndrome involves:
Small palpebral fissure
Thin vermilion border
Smooth philtrum
Women ingesting ___ or more drinks of alcohol per day throughout pregnancy have a ____ risk of fetal alcohol syndrome
8
30-50%
Most frequent abnormalities brought about by anticonvulsant ingestion:
Orzo facial clefts
Congenital heart defects
This drug’s teratogenicity is strongly influenced by genetic make up of low activity of fetal epoxied hydroxylase
Phenytoin
The used of phenytoin will show 7-10% have sufficient features of the ______ and one third show ____ and ____ anomalies
Fetal hydantoin syndrome
Minor craniofacial
Digital anomalies
Features of a fetal hydantoin syndrome
Upturned nose Mild midfacial hyplasia Longer upper lip Thin vermillion border Lower distal digital hyplasia
Used to be considered as the epileptic drug of choice during pregnancy, teratogenic potential unclear
Carbamazepine
High potential for teratogenicity, abnormalities characteristic of anticonvulsant embryopathy
Trimethadone
Paramethadone
This drug when given in the 1st trimester exposure has a 1-2% risk of spina bifida in the lumbosacral region, also acts directly in the homeobox gene governing caudal structure development
Valproic acid
This drug when given in the first trimester there will be no structural abnormalities, usually occurs during the fetal period
ACE inhibitors
Examples of ACE inhibitors
Enalapril
Captopril
Lisinopril
ACE inhibitors causes anomalies as a result from prolonged fetal ___ and ____
Hypotension
Hypoperfusion
This drug is associated with conjoined twins, and in animal studies shows CNS and Skeletal anomalies
Griseofulvin
This anti fungal drug is used in immune compromised patients and several reports shows congenital malformation associated with this
Fluconazole
Fluconazole is associated with this syndrome:
Antley Bixler syndrome
Antley Bixler syndrome is composed of the following:
Skull abnormalities
Cleft palate
Humoral radial fusion and other arm abnormalities
Itraconzole is associated with this defect
Limb defects
In the exposure of exogenous sex hormones prior to ____ completed weeks of gestation has no effect on external structures
7
The exposure of exogenous sex hormone between ___ to ___ weeks can result to full masculinization of the female fetus and partial effects and genital ambiguity thereafter up to about ___
7-12
20
Hormonal influence on behavior occurs much ___ than on the ____ genitalia and the degree if behavioral alteration is _____ to the ___ and _____ of exposure
Later External Proportional Dose Length
This disease has an enzymatic deficiency that causes the inability to hydroxylase cortisol precursors which eventually cause female masculinization
Congenital adrenal hyperplasia
This drug cause the virilization of female fetus wherein there is labioscrotal fusion after first trimester exposure and phallic enlargement later
Testosterone
Anabolic steroids
The presence of this drug and specifically this metabolite can cause the virilization of the female fetus and slight increased risk for cardiac defects
Androgenic progestin
Medroxyprogesterone Acetate
Weak androgen that may cause female fetus virilization such as CLITOROMEGALY, FUSED LABIA, UROGENITAL SINUS MALFORMATIONS
Danazol
Virilization of Danazol
Clitoromegaly
Fused labia
Urogenital sinus malformations
Virilization of the female fetus by Testoterone and Anabolic steroids
Labioscrotal fusion
Phallic enlargement
Both a carcinogen and teratogen used to vaginal and cervical clear cell adenocarcinoma in prenatally exposed women
Diethystilbestrol
The anomalies associated with Diethylstilbestrol
Muller own structural anomalies Epididymal cysts Microphallus Cryptochordism Testicular hypoplasia
Category of corticosteroids and in animal studies causes ____
Category
Cleft palate
Facial clefts
Mycophenolate mofetil has this enzyme inhibitor
Inosine monophosphate dehydrogenase inhibitors
This drug is used to prevent rejection in kidneys recipients and treatment of autoimmune disease
Mycophenolate mofetil
The use of Mycophenolate mofetil will increased the risk of the following:
Spontaneous abortions
Ear bilateral microtia
Antonia
Atresia of external auditory canals
Category of Mycophenolate mofetil
Category D
To drug is used to treat thyroid malignancies that can ablate the fetal thyroid which increase risk of childhood thyroid carcinoma
Radioactive iodine 131
This is a known teratogen which the it’s effect can hinders the development of the nervous system
Methyl mercury
Prenatal exposure to methyl mercury can appear yo cause a disturbance in the neuronal cell division and migration which results to range of defects from:
Developmental delay
Mild neurological abnormalities
Microcephaly and severe brain damage
This psychiatric medications can cause Ebstein anomaly
Lithium
Lithium can cause transient neonatal toxicity such as:
Hypothyroidism Diabetes insipidus Cardiomegaly Bradycardia ECG abnormalities Cyanosis Hypotonia
This psychoactive drug can cause cardiovascular anomalies, omphalocele, craniosynostosis, and anacephaly
Paroxetine
Fluoxetine
Neonatal behavioral syndrome includes the following:
Jitteriness Shivering Increased muscle tone Feeding or digestive distrubances Irritability or agitation Respiratory distress
Maternal use of SSRI can cause persistent _____ in newborn
Persistent pulmonary hypertension
Two forms of vitamin A
Beta carotene
Retinol
A precursor of provitamin A found in fruits and vegetables and has never been shown to cause birth defects
Beta carotene
Preformed vitamin A uncertain whether a high dose of vitamin A are teratogenic
Retinol
Constriction of the fetal ductus arteriosus and persistent fetal circulation and pulmonary hypertension in neonate
Indomethacin and other PGI
With prolonged used of Indomethacin and other PGI, this will ___ urine output and amniotic fluid volume
Decreased
NSAIDS are not considered teratogenic but may have reversible fetal effects during the ___ trimester
3rd
These are the greatest risk if infant is born within 48 hours after starting the NSAID therapy
Intraverntricular hemorrhage
Pulmonary dysplasia
Necrotizing enterocolitis
This can precipitate as neonate withdrawal syndrome
Narcotic analgesic
Butorphanol can cause the following:
Respiratory distress
Neonatal withdrawal with sinusoidal heart pattern
Exposure during pregnancy is generally brief and not at toxic levels
Local analgesia and anesthesia
This is a pyrimidine synthesis inhibitor used in the treatment of RA
Leflunomide
Leflunomide is contraindicated in pregnancy because this shows ___ in animal experiments
Hydrocephalus
Eye anomalies
Skeletal abnormalities
Fetal death
Valuable as the first line anti malarial treatment and for chemoprophylaxis
Chloroquine
This is reserved for severely ill women and chloroquine resistant malaria
Quinine and quinidine
Are there any occurrence of congenital anomalies in mothers using anti malarial drugs in therapeutic dose?
None
Daily use of chloroquine for lupus and connective tissue disease has been shown to cause ___
Maternal retinopathy
This is used for a symptomatic malaria treatment
Mefloquine
This is associated with a five fold increased risk for STILLBIRTH
Mefloquine
Dose exposure to quinine and quinidine can cause
CNS anomalies
Limb and Urogenital anomalies
Induce abortions
This can cause yellowish discolorization of the deciduous teeth
Tetracycline
This drug can cause deposition in the fetal long bones
Tetracyclines
This drug can cause CN 8 damage
Streptomycin
This drug has a 1-2% risk of having ototoxicity
Streptomycin
Hyperbilirubinemia if used near delivery of a preterm infant
Sulfonamide
Alkylating agent that cause cell death or heritable DNA alterations in surviving cells
Cyclophosphamide
This is commonly reported in cyclophosphamide used:
Hypoplastic digits on hands and feet
Cyclophosphamide can be given during ___ but not during ___
2nd and 3rd trimester
1st trimester
Anomalies seen in cyclophosphamide:
Cleft palate Single coronary artery Imperforated anus Fetal growth restriction Microcephalic
What is the Methotrexate and Amniopterin syndrome:
Growth restriction Failure of calvarial ossification Craniosynostosis Hypoplastic supra orbital ridges Small posteriorly of rotated ears Micrognathia Severe limb anomalies
Antiviral drug used as an inhalational agent for RSV infection in children
Ribavirin
Ribavirin is contraindicated in pregnancy because it can cause
Hydrocephalus
Limb deformities
This is an endothelin receptor antagonist used to treat pulmonary hypertension
Boss tan
Bosentan cause abnormalities in the ___, ____ and _____
Head
Face
Large coronary artery
Dose higher than the recommended daily allowance of ___ of vitamins A should be avoided
5000 IU
An anti-acne medication considered one of the most POTENT teratogen in common use
Isotretinoin
1st trimester the exposure to isotretinoin can cause craniofacial anomaly: _____ and cardiac anomaly: _____, CNS: _____, Thymus:____
- bilateral, symmetrical microtia, anotia, agenesis, stenosis of external ear canal
- conotruncal
- hydrocephalus
- agenesis, aplasia, hypoplasia of the thymus
An antipsoriatic drug similar anomalies to isotretinoin but does so even when conception occurs after drug discontinuation
Eat retinae
It is recommended that woman stop the use of etretinate for at least ___ years prior to attempting conception
2 years
This is an all trans retinoids acid usually prepared in gel treatment of acne vulgaris
Tretinoin
Anxiolytics and sedative agent that is notorious teratogen producing limb reduction defects
Thalidomide
Thalidomide affect structures derived from the mesodermal layer this includes:
Limbs
Ear
Cardiovascular system
Bowel musculature
Days of upper limb phocomelia
Day 27-30
Days of lower limb phocomelia
Days 30-33
Warfarin exposure during this age will cause warfarin embryopathy
6-9th week
What is the components of warfarin embryopathy
Nasal hypoplasia
Stippled vertebral and femoral epiphyses
Mechanism of warfarin embryopathy:
No posttranslational carboxylation of coagulation protein
Warfarin exposure at 2nd and 3rd trimester can cause:
Dorsal midline CNS dysplasia Micropthalmia Optic atrophy Blindness Developmental delay and mental retardation
Sympathomimetic agent associated with symmetrical growth restriction, minor congenital anomalies
Amphetamines
This drug has vasoactive and hypertensive effect
Cocaine
Risk of vascular interruption is highest after 1st trimester can cause placental abruption
Cocaine
Miscellaneous drugs that can manifest with jitteriness, tremors, and irritablity
Phenycyclidine
Miscellaneous drug that can cause chromosomal breakage
Lysergic Acid Diethylamide
This drug is best documented reproductive effect that cause fetal growth restriction
Tobacco
Preterm fetuses exposed to this drug can cause gray baby syndrome
Chloramphenicol
This drug when used in the 1st trimester has been associated limb defects and fetal cardiac depression and arrest
Verapamil
This drug is associated with neonatal thrombocytopenia, bleeding and electrolyte disturbance
Thiazides diuretics
This may stimulate renal PGE2 production that cause patent ductus arteriosus
Furosemide
Maternal therapy associated with neonatal hematologic abnormalities such as fatal pancytopenia
Azathioprine
