Lecture 2: Drug/ Target Interactions Flashcards
What are the drug characteristics that affect absorption? (4)
Molecular weight, ionisation, solubility and formulation
What patient factors affect absorption?
- Route of administration
- Contents of GI tract
Do drugs bound to plasma proteins cross the membrane?
No
How does malnutrition lead to an increase in free drug?
Malnutrition means a decrease in albumin so an increase in free drug.
Where do lipophilic drugs accumulate?
Adipose tissue
How much of digoxin is absorbed?
70-80%
What is the half life of digoxin?
26-45 hours
What is the primary route of metabolism?
Liver
What can statins interact with? (4)
- Grapefruit
- Warfarin
- Courmarins
- Certain antimycotics
How do you calculate the therapeutic index?
minimum toxic dose/ minimum effective dose
What drugs are renally cleared? (8)
- Aminoglycosides
- Glycopeptides
- Amikacin
- Gentaminic
- Vancomycin
- Digoxin
- Lithium
- morphine 6-glucuronide
What is steady state?
Drug administered is equal to the amount of drug eliminated within one dosing interval resulting in a plateau or contant serum drug level
How many half lifes does it take to reach 100% steady state?
5
What is efficacy?
The degree to which a drug is able to produce the desires response
What is the effective concentration 50% ?
Concentration of the drug which induces a specified clinical effect in 50% of subjects
What is the lethal dose 50%
Concentration of the drug which induces death in 50% of subjects
What is the theraputic index?
Measure of the safety of the drug
What is the margin of safety?
Margin between the theraputic and lethal doses
What is an agonist?
A ligand that binds and actiavtes a receptor
Give examples of endogenous ligands?
- Neaurotransmitters
- Hormones
How long do ion channel linked receptors take to exert an effect?
Milliseconds
How long do G-protien linked receptors take to exert an effect?
Seconds
How long do tyrosine kinase linked linked receptors take to exert an effect?
Minutes
How long do DNA linked receptors take to exert an effect?
Hours to days
Give an example of an ion channel linked receptor?
Nicotinic acetylecholine receptor
Give an example of a G-protien linked receptor?
B-adrenergic receptor
Give an example of a tyrosine kinase linked receptor?
Insulin receptor
Give an example of an DNA linked linked receptor?
Steroid receptor
Where are cell surface receptors found?
- Cell surface
- On an organelle within the cell
- In the cytoplasm
What can cell surface receptors be?
Proteins or glucoprotiens
What actions can occur when a drug binds to its receptor?
- Ions channel opens and closes
- Second messenger is activated: cAMP, Calcium, inositol phosphates etc. This initiates a series of chemical reactions
- Cellular function can be turned on/ off
What is the treatment for cardiovascular disease?
Manipulation of cardiac output, peripheral vascular resistance and blood volume
What is the prevention for cardiovascular disease?
- Reduce platelet adhesion
- Reduce cholesterol
How do you reduce atherogenesis?
Reduce platelet adhesion
What is used to reduce platelet adhesion?
- Irreversible cyclooxygenase inhibitors: aspirin
- Adenosine diphosphate receptor inhibitor: clopidogrel
What drugs cause contraction?
- calcium channel blocker
- Agonst
- Noradraline
- Histamine
- angiotensin
What drugs cause relaxation?
- Potassium channel activators
- Adenosine
- B agonist
- Prostaglandins
What causes cell relaxation?
- Noradrenaline
- Histamine
- Angiotensin
What agonists cause cell relaxation and hyperpolarisation?
- Adenosine
- B agonists
- Prostaglandins
- PDE Inhibitor
