Sesh 7: Pharmacodynamics Flashcards
Name 3 enteral administration routes.
- Oral
- Sublingual
- Rectal
What is the ‘most addictive’ method of administration, and why?
Intranasal, as drug can enter the brain rapidly.
Why is the oral drug administration route the most common?
It is the safest and most convenient.
Where does most drug absorption take place?
Jejunum
What is the typical small intestine transit time and pH?
About 3-5 hrs, with pH 6-7.
What physicochemical factors can affect drug absorption?
- GIT surface area
- Drug lipophilicity/ pKa
- Density of GI SLC expression
Where does first pass metabolism mainly occur?
Liver
What are the 2 major metabolising enzyme groups in the liver?
- Phase 1-CYP450s
2. Phase II- Conjugating enzymes
Define bioavailability.
The fraction of a defined dose of a drug that reaches a specific body compartment (usually the circulation).
How is oral bioavailability calculated?
Amount reaching systemic circulation (area under curve via oral route) / total drug given IV (area under curve IV route).
What are the 3 types of capillary endothelium, and what can they affect?
- Continuous
- Fenestrated
- Sinusoidal-incomplete basement membrane
Can affect drug distribution if hydrophilic.
What is the volume of distribution (Vd)?
A model summarising the movement of a drug from the plasma, to interstitial fluid, to intracellular compartments. Units= L or L/kg
What effect will increasing drug penetration into interstitial and intracellular compartments have on:
A) plasma concentration of the drug
B) volume of distribution of the drug
A) reduced
B) increased
What is the action of hepatic phase I enzymes on a drug?
CYP450s increase the ionic charge on a drug via modifying its existing functional groups, e.g. Via redox reactions, to increase their renal elimination.
Can also convert pro-drugs into their active form e.g. Codeine to morphine.
What action do phase II enzymes have on drugs?
Conjugating enzymes further increase the ionic charge of drugs by adding new functional groups on to the drug, to increase their renal elimination.
By what 3 mechanisms can CYP450 enzymes be induced?
- Increased transcription
- Increased translation
- Reduced degradation
What effect will it have if a drug is metabolised by a CYP450 that is induced?
Will reduce the plasma levels of the drug, and reduce its therapeutic efficacy.
By what mechanisms can CYP450 inhibition occur?
Competitive/non-competitive inhibition.
If a drug is metabolised by a CYP450 that is inhibited, what may happen?
Drug plasma levels will increase, potentially leading to side effects/ toxicity.
What are the 3 main stages of renal elimination?
- Glomerular filtration
- Proximal tubular secretion-ACTIVE
- Distal tubular reabsorption-PASSIVE
The glomerulus receives __% of renal bloodflow, whilst the peritubular capillaries receive __%.
- 20
2. 80
What type of transporters are highly expressed in the kidney, and transport ionised molecules across the membrane?
OATs and OCTs (solute-linked carriers).
What is clearance?
The volume of plasma completely cleared of drug per unit time (mL.min-1) i.e. Rate of elimination of drug from body.
Which 2 values can, together, provide an estimate of drug half life (t 1/2)?
Volume of distribution and clearance.
T0.5=0.7 X Vd / CL
