pharmacology workshop Flashcards
- 10mg/L = concentration of drug in tank
- 100mg/10 = 10L (drug stays within fish tank)
Less water soluble
This time concentration is 1mg/l
Vd: 100/1 = 100l
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
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.
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
What is a loading dose and how is it determined?
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).
Define distribution
Movement of drugs in & out of blood
Define clearance
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
How does elimination rate differ to clearance
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
What biological factors can influence the clearance of drugs by the liver? Think about efficiency of the liver to metabolise chemicals
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)
What could happen to plasma concentrations of phenobarbital in a patient with hepatic failure?
Liver dysfunction = reduced clearance → higher plasma concentrations
Risk of toxicity due to drug accumulation
Solutions:
- Lower dose or increase dosing interval (give less often)
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
What are some determinants of a dosing regimen?
What is the goal of multiple dosing?
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
What is normal vs saturating kinetics
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
If the half-life of phenobarbital is 76h in dogs. How long will it take to reach the steady state in the dog?
Steady state = ~5 half-lives
Phenobarbital t1/2 = 76h → steady state in ~16 days
Loading dose may be used to reach therapeutic levels faster.
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?
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
Why is it common for dose adjustments to have to be made when treating dogs with phenobarbital?
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
