The I's of geriatrics

• Immobility, Incontinence, Infection, Impaction, Impaired senses, Instability, Impotence, Insomnia

• MI: Chest pain (50%), weakness, confusion, syncope, abdominal pain
• Pneumonia: lethargy, confusion, anorexia (fever, chills, and productive cough may or may not be present)
• UTI: incontinence, confusion, abdominal pain, nausea/vomiting

• no change in bioavailability for most drugs
• ↓ first-pass extraction and ↑ bioavailability for some durgs

• changes in receptor numbers (lower density of muscarinic, adrenergic and opioid receptors)
• changes in receptor affinity
• postreceptor alterations
• age related impairment of homeostatic mechanisms

used to determine potentially inappropriate medication use in older people

1. Medication classes that should generally be avoided in persons 65+ b/c they are either ineffective or may pose unnecessarily high risk and a safer alternative is available
2. Medications that should not be used in older persons known to have specific medical conditions

• e.g benzphetamine, diethylpropion, phendimetrazine, phentermine
• act by modulating central norepi receptors by promoting catecholamine release
• all except Phentermine are infrequently used
• older adrenergic weight loss drugs (amphetamine, ...) engage in dopamine pathways and are not recommended b/c of risk of abuse

• avoid the use of medications that may negatively interact with anesthetic agents
• know whether the drug will negatively affect the procedure

• when to restart medications in order to avoid the potential for withdrawal, progression of the underlying disease state, and other adverse events

• restart agents as soon as pts is stable
• if unable to take PO, switch to equivalent dose of same agent in IV form. know PO to IV conversions
• if agent not available in IV form, give IV drug from same class or from another class

%25

this % and the # of those on the wait list has remained relatively steady

• Hyperacute
• accelerated 
• acute chronic

• 1st agents appeared around 1962
• cyclophosphamide: 1970
• survival rate increased between 1994-95 with the use of new agents (ie tacrolimus)

• graft rejections
• Renal failure
• GI
• Diabetes
• infections 
• malignancy 
• osteoporosis
• hypertension
• hyperlipidemia
• psychiatric disorders
• recurrent disease (e.g hep C)
• noncompliance

• polyclonal Abs > steroids
  • reversing rejection
  • preventing graft loss
• Polyclonal Abs = steroids
  • preventing subsequent rejections
  • Death
• Polyclonal Abs are all equal

patient education

simplify drug regimen

intervention programs

1. phychiochemical properties of the drug
2. rate the drug crosses placenta and amount of drug that reaches fetus
3. duration of exposure
4. distribution in different fetal tissues
5. stage of placental and fetal development
6. effects of drugs used in combination

• Highly ionized drugs diffuse slowly (Succinylcholine and Tubocurarine, therefore safer to use for C-section)
• Some agents i.e Salycylates (aspirin) cross BPB readily, event though ionized (do not give to pregnant women)

• small molecules (250-500): readily cross placenta
• larger molecules (500-1000): difficulty crossing 
• >1000 poor crossing
• Large molecules may cross via transporters
• Maternal Abs are large but may cause Rh incompatibility and death

• Use heparin as apposed to Warfarin
• heparin is larger and will not cross BPB as readily
• Warfarin is contraindicated during pregnancy

• carry large molecules through the placenta to the fetus
• examples p-Glycoprotein transporter, BCRP (ABCT)/ MRT 3 transporter

• encoded by MDR 1 gene in the placenta 
• pumps drugs back into maternal circulation
• vinblastine, Doxorubicin (Anticancer)
• Saquinavir (viral protease inhibitors)
• increased risk of vertical transmission (HIV)

MRP 3 transporter

effluxes glyburide (glibenclamide)

• albumin binding affects free drug availability
• not as effective for very lipid soluble drugs
• some drugs bind more to maternal plasma proteins than to fetal proteins (more free drug in fetus) : sulfonamides, barbiturates, phenytoin, local anesthetics (lidocaine)

• hydroxylation, dealkylation, and demethylation occurs in placental tissue (pentobarb)
• toxic metabolites may be created (ethanol)

• drugs crossing placenta enter the fetus through the umbilical vein
• 60% of this passes through fetal liver
• remainder enters general fetal blood circulation
• Umbilical artery shunts to umbilical vein and may activate prodrugs

• breast, uterus undergo endocrinal changes
• maternal tissues (heart, liver, etc) may not change but physiological changes such as cardiac output, renal blood flow may 
• cardiac glycosides and diuretics may be needed for heart failure of pregnancy
• insulin may be needed for pregnancy induced diabetes

• emerging branch which treats the baby through the mother
• corticosteroids, phenobarbital, antiarrhythmics
• chronic opioid use may cause dependence
• neonatal withdrawal syndrome
• ACE-I may cause irreversible renal damage in fetus
• 
  

• can be caused by a single exposure
• Ex: thalidomide during limb formationE

Mechanisms of teratogenecity

1. drugs may have different effects on developing tissues or secondary effects on fetal cells
2. they may alter O2 and nutrient availability thus effecting rapidly metabolizing tissues or may alter cell differentiation

• Vitamin A and Isotretinoin
• Folic acid deficiency: neural tube defects
• fetal alcohol syndrome: CNS, face and growth

• substance that results in a characteristic set of malformations indicating tissue selectivity
• exerts effects at a stage of fetal development
• resultant effects may be intrauterine growth retardant (IUGR)(cigarettes), miscarriages (alcohol), stillbirth, cognition

• 1/2 of pregnancies are unplanned
• 3% of babies have genetic defects

• continue drug
• chance of birth defect increased from 3 to 10%