Pharmacology: Therapeutics

Question 1

Define and adverse event?

Answer 1

Unintended or noxious response to a drug that occurs within a reasonable time frame following administration”

Question 2

What are the risk factors associated with ADE?

Answer 2

Use of human-label drugs
Drugs with low therapeutic indices
Inappropriate (trivial) use
Lack of therapeutic goals
Multiple drugs
Young, old, altered PK

Question 3

What are the types of ADE?

Answer 3

1) Lack of efficacy
2) Exaggerated normal response e.g.
3) Hypersensitivity - non dose related
4) Toxic effects not related to pharmacological action
5) Idiosyncratic

Question 4

Where must we report ADE?

Answer 4

BMD website

Question 5

Give examples of the altered physiology of pregnant animals?

Answer 5

Increased plasma volume – due to greater size of animal
Chronic metabolic alkalosis- due to morning sickness losing acid from stomach
Acidosis due to increased histamine in the latter stages of pregnancy
Increased volume of distribution
Altered protein binding (increased free fraction)
Increased gastric pH
Decreased GI motility
Altered cytochrome function

Question 6

What is fetal trapping?

Answer 6

eg. with bupivacaine a which is a weak base with a pKa of > 7.4. Therefore according to: pH = pKa + log [A]/[HA+] it is partly ionised in the plasma.

In the fetus (which tends to be more acid) it is more heavily ionised, and therefore less able to cross the placenta and exit the fetus

Question 7

What are the detrimental effects drugs can have on the foetus?

Answer 7

Teratogenic (could halt development) effects - Nitrous oxide
Prevention of implantation
Early termination
Mutagenesis

Question 8

What is the altered physiology in paediatric animals?

Answer 8

– Increased surface area to volume ratio: Affects allometric scaling
– Increased metabolic rate/decreased metabolic function
– GI absorption is variable which causes altered gastric emptying, Irregular peristalsis and Increased permeability of mucosa
– Reduced hepatic function: Very species specific for example biotransformation normal within a few days in foals and around 3-6 weeks in other domestic species
– GFR becomes normal within a few days

Question 9

Why do neonates have a more rapid topical uptake?

Answer 9

An immature percutaneous. barrier

Question 10

Why do neonates have an increased vd?

Answer 10

Increased volume of distribution for non-lipophilic drugs:
Greater water content
Decreased plasma protein binding

Question 11

When is the BB formed in neonates?

Answer 11

after a few days

Question 12

Neonates have a low adipose content, what does this mean for drugs?

Answer 12

less fat uptake and sequestration - may affect maintenance of plasma level

Question 13

What type of excretion takes longer in neonates?

Answer 13

Tubular secretion takes a lot longer - for many acid or basic drugs may take 3-4 weeks

Question 14

What are the physiological changes in geriatric patients?

Answer 14

– Gastric pH increased
– Less microvilli
– Gastric emptying slowed and motility decreased
– Body mass decreases
– Less water content
– Increased adipose tissue
– Less volume of distribution for water soluble drugs - decreases half
– Decreased plasma albumin and less binding may lead to more free (active drug)

Question 15

What does the increase in adipose tissue have on drug metabolism in geriatric patients?

Answer 15

Increased volume of distribution for fat soluble drugs -increases half life

Question 16

What does the decrease in albumin have on drug metabolism in geriatric patients?

Answer 16

Increased potential toxicity

Only of concern for IV administration

Question 17

What does decreased renal mass in geriatric patients mean for drug metabolism?

Answer 17

Decreased GFR and thus decreased renal excretion

Question 18

What is the effect of liver disease on drug metabolism?

Answer 18

Content and activity of phase I and II reactions is decreased
No adequate functional tests - bile acids closest
Most antimicrobials are well tolerated: Not licosamides, macrolides, sulphonamides and chloramphenicol

Question 19

How much of the liver must be lost until drug metabolism is affected?

Answer 19

80% functional loss

Question 20

What is the effect of uraemia on drug metabolism?

Answer 20

Uraemia -chronic acidosis - reduced albumin binding of drug & less hepatic metabolism

Question 21

What is the effect of chronic cardiovascular disease on drug metabolism?

Answer 21

Decreased mentation - increased effects of sedatives etc

Question 22

What is the effect of chronic respiratory disease on drug metabolism?

Answer 22

Altered serum pH and protein binding

Question 23

What drugs have a high therapeutic index?

Answer 23

NSAID’s: aspirin, Tylenol, ibuprofen
Sedatives: Benzodiazapines
Most antibiotics
Beta-blockers

Question 24

What drugs have a low therapeutic index?

Answer 24

Lithium
Neuroleptics: Phenobarbitol
Some antibiotics: Gent/vanco/amikacin
Digoxin
Immunosuppressants

Question 25

Drugs are made more dangerous where Vd is large this is because…

Answer 25

….high Vd drugs are likely to be lipophilic and most receptors have a lipid region- so it will bind to most targets in the body = side effects

Question 26

Drugs with low Vd are contained mostly in the plasma, because . . .

Answer 26

They are highly water soluble (plasma water content is higher than tissues), or
They are highly protein bound (which prevents them from freely diffusing into tissues)

Question 27

Drugs with high Vd are mostly in…

Answer 27

…tissues, and plasma levels may not reflect body burden

Question 28

Digoxin is used to improve CO in CHF patients, what is its Vd of it?

Answer 28

Vd = 500 - 600 L/Kg

Highly bound to tissues

Question 29

When is steady state usually achieved?

Answer 29

3-5 half lives of a given drug