Therapeutic decision making in special situations

Question 1

Give an example of some special situations

Answer 1

-Pregnancy

Question 2

What affect does pregnancy have on physiology and drug choosing?

Answer 2

• 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

Question 3

What is fetal trapping?

Answer 3

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

Question 4

What detrimental effects can therapeutic drugs have on thee fetus?

Answer 4

• Teratogenic effects
• Prevention of implantation
• Early termination
• Mutagenesis

Question 5

What effects can prostaglandins have on the fetus?

Answer 5

-Can impact on implantation and cause early termination

Question 6

What considerations should you take into account when treating a neonate?

Answer 6

• 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

Question 7

What alterations would you make to a drug regime in a neonate?

Answer 7

Often reduce dosage and be careful for contraindications!

Question 8

Discuss changes in elderly patients that impact on drug therapy

Answer 8

• 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

Question 9

How does decrease PPB in geriatric patients affect drugs?

Answer 9

• Decreased albumin and less binding can cause more free (active drug), possible toxicity issues (IV administration)

Question 10

What should you consider about geriatric patient’s kidneys?

Answer 10

• have decreased renal elimination due to lower GFR, decreased renal mass
• Lower expression of OATs and OCTs

Question 11

Which special considerations should be made when treating animals with liver disease?

Answer 11

• content/ activity of phase 1 and 2 reactions decreased

- little effect of drug metabolism until 80% loss

Question 12

Discuss giving drugs to patients with renal disease

Answer 12

• 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)

Question 13

What considerations should you take into account when giving drugs to animals with chronic CVS disease?

Answer 13

-Decreased mentation so sedatives have increase efficacy

Question 14

What considerations should you make when treating animals with respiratory disease?

Answer 14

Have altered serum pH and protein binding

Question 15

List some drugs with a high therapeutic index

Answer 15

• NSAIDs
• Benzodiazepines
• Beta blockers

Question 16

List drugs with a low therapeutic index

Answer 16

Lithium
Phenobarbital
Digoxin

Question 17

What factors affect the margin of drug safety?

Answer 17

-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.

Question 18

How do you calculate the Vd?

Answer 18

Vd=A/C

C= concentration and A= amount

Question 19

Why are drugs with a high Vd more dangerous?

Answer 19

They tend to have a low therapeutic window as they are very lipophilic so hit more targets and are less selective.

Question 20

Why must you monitor plasma drug concentrations?

Answer 20

• Avert toxicity
• Optimize drug/ therapeutic response
• Detect changes in pharmacokinetics
• Monitor compliance

Question 21

Describe monitoring therapy

Answer 21

• 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