Therapeutic decision making in special situations Flashcards
Give an example of some special situations
-Pregnancy
What affect does pregnancy have on physiology and drug choosing?
- Increases plasma volume
- Chronic metabolic alkalosis
- Increased volume of distribution
- Altered protein binding (increase free fraction)
- Increased gastric pH
- Decreased GI motility
- Altered cytochrome function
What is fetal trapping?
As fetus is more acidic than the dam, weak base drugs that are partially ionised in dam’s circulation become more heavily ionised in the fetal circulation and struggle to cross back over placenta.
e.g. bupivacaine
What detrimental effects can therapeutic drugs have on thee fetus?
- Teratogenic effects
- Prevention of implantation
- Early termination
- Mutagenesis
What effects can prostaglandins have on the fetus?
-Can impact on implantation and cause early termination
What considerations should you take into account when treating a neonate?
- Have altered GI function ( more permeable mucosa/ altered gastric emptying)
- Increased metabolic rate but decreased metabolic function
- Less enzymes present
- Increased Vd for non-lipophilic drugs as increased water content and lower albumin levels so less PPB
- Incomplete BBB
- Lower adipose content so need to watch dosing. frequency
- Reduced hepatic function
What alterations would you make to a drug regime in a neonate?
Often reduce dosage and be careful for contraindications!
Discuss changes in elderly patients that impact on drug therapy
- Age increases gastric pH
- Delayed absorption from gut due to less microvilli
- Gastric emptying slowed/ motility decreased: tablets take longer to degrade, altered ionisation, slower absorption
- Less lean muscle and less water conent BUT more fat
- Increased Vd for fat soluble: increased half life
- Decreased half life of hydrophilic drugs
How does decrease PPB in geriatric patients affect drugs?
- Decreased albumin and less binding can cause more free (active drug), possible toxicity issues (IV administration)
What should you consider about geriatric patient’s kidneys?
- have decreased renal elimination due to lower GFR, decreased renal mass
- Lower expression of OATs and OCTs
Which special considerations should be made when treating animals with liver disease?
- content/ activity of phase 1 and 2 reactions decreased
- little effect of drug metabolism until 80% loss
Discuss giving drugs to patients with renal disease
- Gradual loss of urine concentrating ability
- Less acidic urine
- Change in acid.base balance
- Uraemia (chronic acidosis -reduced albumin drug binding)
- Careful with renal cleared drugs, lower dose to compensate for decreased GFR)
What considerations should you take into account when giving drugs to animals with chronic CVS disease?
-Decreased mentation so sedatives have increase efficacy
What considerations should you make when treating animals with respiratory disease?
Have altered serum pH and protein binding
List some drugs with a high therapeutic index
- NSAIDs
- Benzodiazepines
- Beta blockers
List drugs with a low therapeutic index
Lithium
Phenobarbital
Digoxin
What factors affect the margin of drug safety?
-Receptor saturation: e.g. medetomidine - binds to pre synaptic membrane and works by a negative feedback affect causing release of norepi and hence sedation. If you overdose the process is saturated so you reach max effects.
How do you calculate the Vd?
Vd=A/C
C= concentration and A= amount
Why are drugs with a high Vd more dangerous?
They tend to have a low therapeutic window as they are very lipophilic so hit more targets and are less selective.
Why must you monitor plasma drug concentrations?
- Avert toxicity
- Optimize drug/ therapeutic response
- Detect changes in pharmacokinetics
- Monitor compliance
Describe monitoring therapy
- Steady state provides best correlation between serum/ drug concentrations and clinical status
- Remember need about 5 half lives to reach steady state
- If testing for toxicity need to measure at peak and efficacy need to measure at trough
