Session 2 - Basic Pharmo Concepts Flashcards
Equation of Oral Bioavailability
ral Bioavailability (F)=(AUC oral)/(AUC IV) × 100
Equation for Volume of distribution
Volume of Distribution (Vd)= (Total Amount of Drug in Body)/(Plasma Concentration of Drug at Time=Zero)
What is total clearance
Total Clearance = Hepatic Clearance + Renal Clearance
How is clearance calculated?
Clearance=(Amount in urine × Urine flow rate)/(Arterial Plasma Concentration)
HOw is half life calculated/
(0.693 × Volume of Distribution)/Clearance
How is first order kinetics calculated?
Rate of Metabolism=(Vmax [C])/Km
How are 0 order kinetics calculated?
Rate of Metabolism=(Vmax [C])/([C])
HOw is steady state conc in plasma calculated?
Steady State Concentration in Plasma (CpSS)= (Dose Rate)/Clearance
How is loading dose calculated?
Loading Dose (Dose L)= Vd ×CpSS
Define agonist, antagonist and partial ag/antag
Agonist – Bind to and stabilise receptor sites in the Active conformation
Antagonist – Bind to and stabilise receptor sites in the Inactive conformation
Partial Agonist/Antagonist – When drugs act as a mixture of both of the above, they are said to act as Partial Agonists or Partial Antagonists. The overall action of the drugs is dependent on the proportion of receptor sites it stabilises in the Active or Inactive confirmation.
What is affinity?
Affinity – The tendency of a drug to bind to a specific receptor site.
What are kd and ki?
o Kd – Concentration at which half available agonist receptors are bound
o Ki – Concentration at which half available antagonist receptors are bound
WHat is efficacy?
Efficacy – The maximal effect of a drug when bound to a receptor.
What is agonist potency?
Potency (Agonist) – Concentration that produces 50% of maximal response
What overcomes competitive antagonism?
In competitive antagonism agonist efficacy can be restored, by increasing agonist concentration. This increases the competition for receptor sites.
What is non competitive antagonism?
In non-competitive antagonism the antagonist can bind in two ways:
1. At the same site for the agonist binding irreversibly or unbinding very slowly
2. At a separate site to the agonist either reversibly or irreversibly
In this case, no matter how much agonist is added, the maximal effect will be depressed proportional to the degree of antagonist binding. However, because the agonist does not have to compete to occupy its binding site, the EC50 remains the same.
What is a therapeutic window?
The therapeutic window is the concentration of drug that is high enough to have a therapeutic effect, but not so high that is has a toxic effect.
Some drugs have extremely narrow therapeutic windows, e.g. Phenytoin meaning they have to be closely monitored.
What is the calculation for therapeutic index?
Therapeutic Index= (Toxic Dose in 50% of People (TD50))/(Effective Dose in 50% of People (ED50))
What two factors can effect absorption of drugs?
Gut motility
Passive or active absorption
What effects metabolism?
Induction and inhibition of the CYP450 enzymes
What effects elimination? (3)
Level of protein binding
- Decreased binding increases the amount of free, unbound rug, accelerating its removal
Tubular secretion
Urinary pH
Give 5 clsaees of drugs which commonly interact with other drugs
o Anticonvulsants Phenytoin Carbamezepine o Anticoagulants Warfarin o Antidepressants Monoaimine Oxidases o Antibiotics Rifampicin Macrolides Quinolones o Antiarrhythmics Amiodarone
Give three ways in which CYP450 can induced?
Increased transcription
Increased translation
Slower degradation
What two bad things can happen if CYP enzymes are induced?
o Withdrawal of the inducing agent without a change in the therapeutic agent can lead to toxicity if dosing is not re-adjusted.
o Induction may lead to increased production of a toxic metabolite
What two bad things can happen if CYP enzymes are inhibited?
o Introduction of an inhibiting agent without a change in the therapeutic agent can lead to toxicity if dosing is not re-adjusted
o Withdrawal of an inhibiting agent without a change in the therapeutic agent can lead to concentrations falling to a sub-therapeutic level
How does hepatic disease cause drug metabolism to go awry? 3
o Reduced clearance of hepatic metabolised drugs
o Reduced CYP450 activity
This leads to drugs having much longer half-lives, which in turn leads to toxicity.
E.g. Opiates in Cirrhosis – Small doses accumulate, leading to coma.
o Hypoalbuminaemia (malnutrition, nephrotic syndrome)
Less albumin for drugs to bind to, free drug plasma levels higher
How does renal disease mess up drugs?
o Reduced clearance of hepatic metabolised drugs
o Reduced CYP450 activity
This leads to drugs having much longer half-lives, which in turn leads to toxicity.
E.g. Opiates in Cirrhosis – Small doses accumulate, leading to coma.
o Hypoalbuminaemia (malnutrition, nephrotic syndrome)
Less albumin for drugs to bind to, free drug plasma levels higher
How does cardiac disease effect drugs?
Reduce organ perfusion
What is an on target ADR?
On Target ADRs are due to an exaggerated therapeutic effect of the drug, most likely due to increased dosing or another factor affecting the drugs pharmacokinetics or pharmacodynamics.
o Hypertension treatment leading to hypotension
Dizziness, unsteadiness, syncope
On Target ADRs often consist of effects on the same effector, but in different tissues.
o Antihistamine H1 receptor antagonists acting on Immune System H1 Receptors
Also act on CNS H1 Receptors causing drowsiness
What is an off target ADR?
Off Target ADRs are interactions with other receptor types secondarily to the one intended for therapeutic effect. Virtually all drugs do this.
Off Target ADRs can also occur with metabolites that subsequently act as a toxin.
o Paracetamol in overdose
NAPQI
Give four groups prone to drug ADRs
o Pregnant Women
Teratogenicity
Thalidomide
o Breast Feeding Women
Man drugs can be passed on in the breast milk
o Elderly
Polypharmacy
Reduced renal clearance
Nervous system is more sensitive to drugs
o Patients with genetic enzyme defects
Glucose-6-Phosphate Dehydrogenase deficiency, resulting in haemolysis if an oxidant drug (e.g. aspirin) is taken
What is polypharmacy?
The risk of adverse drug reactions increases with every drug a patient takes. Hospital patients are often on a cocktail of 8 or more drugs, which takes the overall chance of an ADR to 80%.
