Teratology , Drugs And Medication Flashcards by Arielle Dellosa

This refers to agents that produces STRUCTURAL ABNORMALITIES

Teratogen

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Teratogen is derived from Greek word teratos which means?

Monsters

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Most of the major structural abnormalities are easily seen at ___ and an association with a specific ___ exposure is likely to be suspected

Birth

Prenatal

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Agent that interferes with normal MATURATION and FUNCTION of an organ

Hadegen

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This refers to an agent that alters growth

Trophogen

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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

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This is the period of 2 weeks from fertilization to implantation

Preimplantation period

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This is called the “all or none” period

Preimplantation period

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Teratogens in the preimplantation period in animals can produce a ___ dependent diminution in ___ or ____

Dose dependent

Body length and size

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This is the critical period from the 2nd to the 8th week following conception

Embryonic period

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This is the most crucial with regard to structural malformations

Embryonic period

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This pertains to the 9th week to term, in which functional maturation may be involved

Fetal period

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Alteration in the cardiac blood flow can result in ___ an example of which involves (2)

Deformations

Hypoplastic left heart or aortic coarctation

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Category of drugs that shows studies in pregnant women have not shown an increased risk for fetal abnormalities

Category A

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This category of drugs if administered during the first, second, and third trimester of pregnancy the possibility of fetal harm appears remote

Category A

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Fewer than __ percentage of all medication are within the category A

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Examples of category A drug

Levothyroxine
Potassium supplementation
Prenatal multivitamins

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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

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Drugs under the category B

Antibiotics: Penicillins, Macrolides, Cephalosporins

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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

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Examples of drugs under category C

Albuterol
Zidovudine
Lamivudine
Beta blocker
Calcium channel blocker

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Category of this medication causes fetal harm when administered to pregnant woman

Category D

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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

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This category of drugs usually contains medications used to treat potentially life threatening medical conditions

Category D

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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

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