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Questions and Answers
What does pharmacokinetics study?
What does pharmacokinetics study?
What the body does to the drug
What properties are studied under pharmacodynamics?
What properties are studied under pharmacodynamics?
What the drug does to the body
Which of the following is considered a physicochemical property affecting pharmacokinetics?
Which of the following is considered a physicochemical property affecting pharmacokinetics?
Name one parental route of drug administration.
Name one parental route of drug administration.
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The stomach pH ranges from _____ to _____.
The stomach pH ranges from _____ to _____.
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What does the Henderson-Hasselbalch equation relate?
What does the Henderson-Hasselbalch equation relate?
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What are the two main processes involved in absorption?
What are the two main processes involved in absorption?
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Passive diffusion of drugs requires energy.
Passive diffusion of drugs requires energy.
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Which factor does NOT affect the rate of passive diffusion?
Which factor does NOT affect the rate of passive diffusion?
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What is meant by 'log P' in pharmacokinetics?
What is meant by 'log P' in pharmacokinetics?
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Study Notes
Pharmacokinetic (ADME) Properties
- The study of how the body affects a drug.
- It's essential for medicinal chemists to analyze a drug's absorption, distribution, metabolism, and excretion at an early stage.
Pharmacodynamic Properties
- The study of how a drug affects the body.
- Focuses on the physiological response, mechanism of drug action, and dose-response curve.
Physicochemical Properties and Drug Action
- Minor modifications in chemical structure can cause significant changes in activity.
- This is influenced by physical factors, such as:
- Partition coefficient (log P)
- Dissociation constant (PKa)
- Steric factor
- Solubility
- Polymorphism
Physicochemical Properties and ADME
- The physicochemical properties of a drug impact its pharmacokinetic profile by affecting its ADME.
Routes of Administration
-
Parentral route: IV, IA, intraspinal (direct access to blood, no absorption barrier)
- IM, SC, IP: (Drugs need to pass through membranes)
-
GIT route:
- Drug dissolution in GIT fluids is crucial for absorption, and the dissolution rate is affected by:
- Particle size: Smaller particles have larger surface areas, leading to faster dissolution (example: Spironolactone in micronized form).
-
pH of the medium: Weakly acidic drugs dissolve better in basic regions of the GIT, and vice versa.
- Stomach pH (1- 3.5), duodenum (6 - 7), ileum (8)
- Drug dissolution in GIT fluids is crucial for absorption, and the dissolution rate is affected by:
Absorption
-
Active transport or carrier-mediated:
- Requires energy
- Moves against concentration gradient
- Requires similarity between the drug and the natural substrate.
-
Passive diffusion:
- Does not require energy
- Moves according to concentration gradient
- No specific substrate requirement.
-
Convective absorption:
- Small molecules (molecular radius < 4A°) pass through water-filled pores
- Does not require energy
Passive Diffusion
- Rate of diffusion is proportional to the drug concentration on the other side of the membrane.
- -dC / dt: rate of diffusion
- C1: concentration of drug at the site of absorption
- K: proportionality constant (depends on the membrane)
Rate of Passive Diffusion
- Depends on:
- Area of the membrane
- Thickness of the membrane
- Partition coefficient of the drug
Dissociation Constant (pKa)
- Most drugs are either weak acids or bases.
-
Henderson-Hasselbach Equation:
-
Weak acids:
- pH = pKa + log ([salt] / [acid])
-
Weak bases:
- pH = pKw - pKb + log ([base] / [salt])
-
Weak acids:
Partition Coefficient (log P)
- The logarithmic ratio between the concentration of a compound in the organic phase and its concentration in the aqueous phase at equilibrium.
- log P = log (CO / CW)
- Example: Barbital (pKa = 7.8, log P = 0.7) and secobarbital (pKa = 7.9, log P = 23.3) - secobarbital has better absorption due to its higher log P value.
Sites of Loss
-
Protein binding:
- Drug-protein complex: Large, inactive form
- Protein + free drug: Active form
-
Advantages:
- Storage site: Slow release of free drug
- Contributes to long duration of action (ME)
- Metabolism:
- Excretion:
- Storage sites:
Neutral Fat
-
Partition into neutral fats depends on:
- Log P
- pKa
Excretion
-
For a drug to be excreted in urine:
- The drug must be polar to be soluble in urine.
- Weakly acidic drugs are better excreted in alkaline urine and vice versa.
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