tetratology and clinical chemistry Flashcards
Lab tests can be used for:
Diagnosis Prognosis Treatment Screening Research into biochemical basis of disease Clinical trial of new drugs
Plasma =
Blood with all cells removed
Serum =
Blood with cells and coagulation proteins removed
Biological testing can be divided into 2 groups:
- Selective requesting
2. Screening
Selective requesting =
Carried out on basis of individual patient’s clinical situation
Screening tests =
Look for disease without there being a necessary clinical indiciation
Newborn screening progaramme looks for how many conditions?
9
Conditions looked for in newborn screening program:
Sickle cell disease Cystic fibrosis Congenital hypothyroidism Phenylketonuria Medium-chain acyl-CoA dehydrogenase deficiency Maple syrup urine sidase Isovaleric acidaemia Glutaric aciduria type 1 Homocystinuria
PKU is the absence of =
Phenylalanine hydroxylase
Test for PKU
Guthrie test
Background risk of congenital defects =
2-3%
Teratogens can induce =
Chromosomal abnormalities Structural abnormalities Impairment of implantation Abortion Fetal death IUGR Functional impairment Behavioural problems Mental retardation
Ex of teratogens:
Medicines Chemicals Radiation Infection Maternal metabolic disorder
Birth defects seen in T21 =
Mental retardation Muscle weakness Downward slant of eyes Misformed, lowset ears Abnormal crease in palm of hand Heart and intestine defects
Defects seen in turner’s syndrome =
Short stature
No ovaries
Learning disabilities
Teratogen =
Agent that, if administered to pregnant mother, causes structural or functional abonormalities in foetus.
Behavioural teratology =
Effects behaviour or functional adaptation of the offspring to its environment
FAS symptoms =
IUGR
Behaviour issues
Learning difficulities
Facial dysmorphia: low nasal bridge, flat midface, thin upper lip, small chin
No adverse effects on mother but cancer in offspring =
Transplacental carcinogenicity
Ex of drug that has transplacental carcinogenicity
Diethysiboestrol Synthetic oestrogen (vaginal)
General principles of teratogens:
May be harmless to mother Time of exposure important Duration and dose important Genetically determined susceptibility Synergistic Placental barrier doesn't exist
Mendelial inheritence and defects =
Single gene, recognisable patterns, risk to future babies doesn’t change
Ex of monogenic problems =
CF, sickle cell, Marfan’s, DMD
Multifactoral inheritience =
Multiple genes and environment.
Risk changes
Ex of defect that risk changes/increases
Spina bifida
Spina bifida =
Failure of fusion of the caudal neural tube
Causes of spina bifida =
Chromosome abnormalities
Single gene disorder
Teratogen exposure
What % of spina bifida can be prevented with folic acid?
70%
Ex of drug with steep dose-response curve
Methotrexate
Why is route of exposure important?
Lower systemic exposure best
What should be avoided due to synergy?
Poly-pharmacy
Anti-epileptic drug that should not be taken:
Valporate
Why is detection of teratogenic effects difficult?
Lack of data
Lack of research
Background risk
Where does info come from?
Epidemiological study
Human case reports
Preclinical studies in animals or in vitro
Period of max susceptibility =
First 10 weeks post conception (12 weeks LMP)
Neural tube closes at
25-28 days
Drugs that shouldn’t be taken in T1
Androgens Oestrogens Warfarin Retinoids Diethystilboestrol Antiepileptics
Androgens in T1 =
Virilisation of female
Oestrogens in T1 =
Feminisation of male fetus
Warfarin in T1 =
Nasal hypoplasia, skeletal defects
Retinoids in T1 =
Craniofacial, cardio and CNS defects
Diethylstilboestrol in T1 =
Uterine lesions
Transplacental carcinogen
Antiepileptis in T1 =
Facial defects, mental retardation, neural tube defects
Drugs not to be given after T1 =
Antiepileptics Warfarin Benzodiazepines Antidepressants Narcotics ACE inhibitors
ACE inhibitors after T1 =
Oligohydraminous, growth retardation, lung and kidney hypoplasia, hypocalacaria, convulsions, hypotension, anuria
Critical factors when assessing risk to fetus =
Stage of pregnancy
Drug/chemical exposure
Clinical condition of mother
Previous OB HX (HX of malformations, recurrent abortions)
Principles of prescribing in pregnancy =
- Only if needed (risk vs benefit)
- Avoid in T1
- Avoid polypharmacy
- SOP
- Lowest effective dose, shortest possible time
- Avoid new drugs
Pain in pregnancy =
- non-pharma
2. paracetamol - codeine - ibuprofen - paracetamol + codein - codeine + ibuprofen - tramadol - amitriptiline - oramorph
When should NSAIDS not be given?
After 28 weeks
Non-pharma management of nausea and vomiting =
small, high carbohydrate, low fat frequent meals
1st choice for pharma management of nausea =
Cyclizine or promethazine
Recommendations for hyperemesis gravidarum =
Hospital
Fluid and electrolyte
Non-pharma management of constipation
Increase: fiber, fluid, exercise
Recommened antibiotics:
Amoxicillin, cephalosporins
Erythromycin, clindamycin
Nitroduratoin and timethoprim if indicated
