Pharmacology Flashcards
How do drugs work? Targets from drug mechanism?
- Receptors
- Carriers
- Channels
- Enzymes
- Neutralisation (Physiochemical)
- Chelation (Physiochemical)
Example of drug mechanism of action?
- Acetylcholinesterase inhibitor (Neostigmine)
- Pyridostigmine - Myasthenia gravis
- Voltage gated sodium channels - LA
- Na/K-ATPase - Digoxin inhibition - Myocardial Stabilization
- Chelation - Roc + Sugammadex
- Neutralization - Citrate / activated charcoal
Properties of agonists?
- Increasing the dose increaes the effect
- They produce maximal effect
Properties of partial agonists?
- Produce submaximal effect
- Low efficacy
Properties of antagonists?
- Bind to receptor with no intrinsic activity
- May displace agonists from receptors
- No efficacy
What is drug efficacy?
- Ability to produce maximal effect
What is potency?
- Dose required to generate effect
What is the semilogarithmic plot?
- Used to assess efficacy and potency
- Assesses concentration and receptor response
- Negative log of conc of drug at which half-maximal response occurs is used to compare drug potency.
What is oral bioavailability?
This is the fraction of drug reaching the systemic circulation unchanged after oral administration.
It is the ratio of the area under the plasma concentration-time curve for oral and IV doses
Factors affecting bioavailability?
- Impaired GIT motility or rapid transit
- Neutralisation - Activated charcoal
- Mucosal surface area
- Blood flow
- Hepatic function & 1st pass metabolism
- Drug - SR preparations
Patient factors influencing drug effects? in relation to Absorption, distribution, metabolism and elimination.
- Acquired or inherited
- Physiological
- Pathological
Physiological changes affecting drug effetcs? Especially volume of distribution?
- TBW
- Fat
- Compartment size
- Protein binding
- Age-related decline in organ function
Patholgical changes aftecting drug action?
- Renal impairment
- Hepatic impairment
- Pyrexia & acidosis
Examples of drugs affected by pathological conditions?
- Atracurium rapid breakdown with pyrexia & acidosis (Short duration of action)
- Intropes and vasopressors - Acidosis
- Codeine - CYP2D6 mutation
- Sux apnoea- Defective plasma cholinesterase
How is codeine converted?
Converted to Morphine by O-demethylation by CYP2D6
What is the structure of GABAa receptor?
- It is a pentameric structure
- Its a ligand-gated ion channel
- It contains 5 protein subunits - 2A/2B/1G
- Inward conductance of chloride ions
- Hyperpolarisation + Inhibition of synaptic transmission
- Propofol, Etomidate, Thiopental and Benzo
What are the determinants of the speed of onset of IV induction agents?
- Speed of injection
- CBF
- Protein binding, pH & pKa
- Lipid solubility
Termintion of action of IV hypnotics?
- Diffusion out of the brain
- Diffusion into the tissue
- Slow release back into plasma
- Transfer to the liver for metabolism
After terminatio of infusion, what influences the CSHT? - Prolongs the effect
- Fatty tissue - Slow blood flow
- Hepatic metabolism
- A reverse gradient is produced
Action of propofol?
- Direct vasodilatory effect
- Loss of sympathetic tone
- Decreased venous return, RV filling & CO
What patients are suscptible to the hypotensive response seen with propofol?
- Cardiomyopathy
- Stenotic valvular lesions
- Constrictive pericardial disease
- Right - Left intracardiac shunts
- Antihypertensive medications
What is an enzyme?
This is a biological catalyst which increases the speed of chemical reaction without being consumed in the reaction itself.
List drugs which induce hepatic cytochrome P450 enzyme system?
- Barbiturates
- Phenytoin
- Carbamazepine
List drugs which inhibit hepatic cytochrome P450 enzyme system?
- Amiodarone
- Oral hypoglycaemics
- Antibiotics
What is a first order reaction?
The reaction is dependent on the concentration of the components of the reaction. This is an exponential process.
What is a zero order reaction ?
The rate of reaction is independent of concentration, hence it is constant
What happens when an enzyme system is saturated ?
A first order reaction may become a zero order reaction once enzyme system is saturated
what is the Meyer-Overton hypothesis ?
The potency of an anaesthetic agent is related to its lipid solubility
List common anaesthetic agents in order of increasing potency ?
- Nitrous
- Xenon
- Desflurane
- Sevoflurane
- Enflurane
- Isoflurane
- Halothane
What is a summative reaction?
The action of both drugs are additive but have actions of their own. Example: Midazolam & Propofol
What is potentiation?
The action of one drug is amplified by another which has no independent action of its own . Example: Penicillin & Heparin
what is synergism?
The combined action of two drugs is greater than one alone - Propofol & Remifentanil
What is a Ligand?
This is a chemical messenger that is able to bind to a receptor. May be endogenous or exogenous
What is a receptor?
This is the component of a cell which is able to interact with a compound selectively to initiate a biochemical change
What is the law of mass action?
The rate of a reaction is proportional to the concentration of the reacting compounds
What is affinity?
A measure of how avidly a drug binds to a receptor
How can affinity be measured?
This can be measured as concentration of a drug that occupies 50% of the available receptor
What is efficacy?
- Intrinsic activity
- Measure of magnitude of effect
What is potency ?
This is the measure of the quantity of drug needed to produce maximal effect.
How is potency measured?
It is measured using the median effective dose (ED50)
What is the median effective concentration?
The concentration of a drug that induces effect halfway between baseline and maximal effect
What is the median effective dose?
The dose of a drug that induces effect in 50% of the population (ED 50)
Describe EC50 & ED50 in relation to potency?
A drug with a low EC50 or ED50 will have a higher potency
Draw the log-dose response curve?
The attached image can be used to define drug interaction
What is the median lethal dose?
This is the dose of drug that is lethal in 50% of the population (LD50)
What is the therapeutic index?
This is the balance between beneficial and toxic effect. It is LD50/ED50
What is an agonist?
- It has affinity
- It has intrinsic activity
- Induces a response
What is an antagonist?
- Affinity
- No intrinsic activity
What is a full agonist ?
This is a drug which produces maximal response once bound to receptor.
What is a partial agonist?
This is a drug with significant affinity but submaximal intrinsic activity. They lack efficacy
Agonist curves, please see attached diagrams..
Review the potency of the different drugs in the curve
Describe an alternative partial agonist?
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