pharmacology workshop

Question 1

Answer 1

1. 10mg/L = concentration of drug in tank
2. 100mg/10 = 10L (drug stays within fish tank)

Question 2

Answer 2

Less water soluble
This time concentration is 1mg/l

Vd: 100/1 = 100l

Question 3

Answer 3

Bioavailability = % of drug reaching circulation

IV drugs = 100% bioavailable (fast but irreversible)

Oral drugs must be absorbed in SI, cross plasma membranes & pass through liver (first-pass metabolism)

Phenobarbital (90% bioavailable) mostly reaches circulation

Ruminants poorly absorb oral drugs due to their digestion process

Question 4

Answer 4

Vd (L/kg) compares drug distribution across species/weights

Warfarin (0.1L/kg) & phenobarbital (0.75L/kg) mostly stay in plasma (water-soluble, protein-bound)

Propofol (5L/kg) distributes widely (lipophilic, crosses membranes)

Fat animals = lower plasma concentration for lipophilic drugs, affecting anesthesia.

Question 5

Answer 5

Formula: t1/2 = (0.693 × Vd) / Cl

Higher clearance = shorter half-life (drug removed faster)

Lower Vd = shorter half-life (stays in blood, cleared faster)

Phenobarbital (76h) vs. Levetiracetam (4h) → different Vd & Cl

Question 6

What is a loading dose and how is it determined?

Answer 6

Formula: Loading dose = Vd × desired concentration

Given to reach therapeutic levels quickly, followed by lower maintenance dose

Long half-life drugs (e.g., phenobarbital) need loading dose to avoid delays

Higher Vd = higher loading dose (more drug distributes into tissues).

Question 7

Define distribution

Answer 7

Movement of drugs in & out of blood

Question 8

Define clearance

Answer 8

Efficiency of body to remove drug

Volume of plasma/blood irreversibly cleared of parent drug during specified time period (e.g. ml/hr)

Key determinant of maintenance dose rate

Question 9

How does elimination rate differ to clearance

Answer 9

Clearance (CL):
- Measures efficiency of drug removal (L/h)
- Constant value regardless of drug concentration.

Elimination Rate:
- Measures amount of drug removed (mg/h)
- Changes with plasma concentration (↓ Cp = ↓ ER)
- Formula: ER = CL × Cp

Key Difference:
- CL stays constant, ER decreases as drug levels drop

Question 10

What biological factors can influence the clearance of drugs by the liver? Think about efficiency of the liver to metabolise chemicals

Answer 10

Solubility:
- Water-soluble drugs = lower hepatic clearance (can’t cross plasma membrane into liver).
- Lipid-soluble drugs = better clearance (easily enter hepatocytes for metabolism)
- Water-soluble drugs cleared faster by kidneys instead.

CYP Enzymes:
- Liver metabolizing enzymes (CYP450) break down drugs
- More active CYP enzymes = higher clearance.

Liver Blood Flow:
- Higher blood flow = more clearance (faster drug metabolism)

Plasma Protein Binding:
- Highly bound drugs = lower clearance (only free drug can be metabolized)

Question 11

What could happen to plasma concentrations of phenobarbital in a patient with hepatic failure?

Answer 11

Liver dysfunction = reduced clearance → higher plasma concentrations

Risk of toxicity due to drug accumulation

Solutions:
- Lower dose or increase dosing interval (give less often)

Question 12

Answer 12

Phenobarbital = weak acid

In alkaline urine (↑ pH), drug ionizes (A⁻ form) → can’t cross membranes → trapped in nephron → increased excretion

Urine alkalization enhances drug elimination

Question 13

What are some determinants of a dosing regimen?

Answer 13

Question 14

What is the goal of multiple dosing?

Answer 14

Aim for steady state where drug levels remain stable
- achieved within 5 half lives

Perfectly flat levels are impractical, so fluctuations occur

Frequent dosing = smaller peaks & troughs, better stability

Less frequent dosing = larger fluctuations, risk of toxicity or inefficacy

Too frequent dosing → harder for owners to follow, increasing non-compliance

Question 15

What is normal vs saturating kinetics

Answer 15

Normal Kinetics
- Most drugs follow linear elimination
- Higher therapeutic index = safer dosing

Saturating Kinetics:
- Small dose increase → large plasma concentration jump (system overwhelmed)
- E.g.: Ethanol (enzymes saturate, causing drug buildup)
- Higher risk of toxicity & adverse effects
- Require careful dosing

Question 16

If the half-life of phenobarbital is 76h in dogs. How long will it take to reach the steady state in the dog?

Answer 16

Steady state = ~5 half-lives

Phenobarbital t1/2 = 76h → steady state in ~16 days

Loading dose may be used to reach therapeutic levels faster.

Question 17

The owner administers their dog 50 mg phenobarbital every 12 h. They call you saying that they have forgotten to give a single dose 8h ago. What would you suggest?

Answer 17

Concern: Plasma levels dropping too low

Options:
- Give dose now + another in 4h (risk of toxicity)
- Give dose now & reset schedule (Awkward timing).
- Skip dose! (t1/2 is long, so missing 1 dose has minimal impact)

Frequent dosing reduces risk of big concentration drops

Question 18

Why is it common for dose adjustments to have to be made when treating dogs with phenobarbital?

Answer 18

Drug tolerance develops over time (esp. with agonists)

Clearance can change → body upregulates CYP enzymes, making liver more efficient

Increased metabolism may require higher doses to maintain effect