PHARMACOLOGY 3 Flashcards
what is Pharmacodynamics?
Study of how drugs affect the body
what does Pharmacodynamics involve?
qualitative (descriptive) and quantitative (numbers) research to identify potential drug targets
what does Qualitative research do?
determines the mechanisms of action drugs
what does Quantitative research do?
to determine dosage, safety, contraindications, side effects and drug interactions
what are the 4 major drug targets?
ion channels
receptors
transporter proteins
enzymes
what do ion channels target?
can target Na+, K+, Ca2+, and Cl-
what do receptors target?
can target Type 1 (ionotropic), Type 2 (G-coupled receptors), Type 3 (receptor tyrosine kinase) and Type 4 (nuclear receptors) receptors
what do transporter proteins target?
Can target release of neurotransmitters
what do enzymes target?
can target re-uptake of neurotransmitters , ie acetylcholinesterase
what are the 4 major drug properties?
Selectivity
Specificity
Potency
Efficacy
what is Drug Selectivity?
describes the ability of a drug to bind to a particular receptor. However some drugs bind to more than 1 receptor - thus have low selectivity.
give an example of Drug Selectivity
propranolol – a β-blocker
Binds to β1 and β2 adrenergic receptors
what does blockage of β1 receptor do?
decreases heart rate and the force of contraction of the heart
what does blockage of β2 receptor do?
inhibits bronchial smooth muscle relaxation – thus can cause a bronchospasm in asthmatics and sufferers of COPD
what is Drug Specificity?
refers to how drugs interact with a receptor when bound
what is ligand specificity?
Drug targets such as receptors have a configuration giving them a specificity for specific signaling molecules (ligands)
can receptors bind with ligands that have slightly different configurations?
yes
what happens when ligands with high specificity bind to a receptor?
give rise to a specific effect
what effect so low specificity ligands have?
have different effects on that receptor. If combined with low selectivity may have different effects on other receptors.
what is Drug Potency?
Refers to dosage of drug needed to induce an effect.
what is Drug Potency dependent on?
receptor affinity
how will a drug with low affinity bind?
weakly bind to a receptor and will readily dissociate from that receptor
how so low affinity drugs have an effect?
need large doses
how will a drug with high affinity bind?
will bind strongly to a receptor and stay bound to that receptor giving rise to a large physiological response at low conc
what is Drug Efficacy?
describes the ability of a drug to induce an effect
what effect does Drug Efficacy have?
Can have full agonists and partial agonists effect
what is full agonist?
at specific doses can induce a full physiological response, i.e. a full and maximal muscle contraction
what is partial agonist?
describes a drug that cannot induce a full physiological response regardless of the dose
how are partial agonist useful?
useful in healthcare because they can have a therapeutic effect without a risk of overdose
what is studied by Dose Response Curves?
Potency and efficacy
what does creating a Dose Response Curves involve?
Involves measuring tissue response (force of contractions) to treatment with increasing drug conc until a maximum response is reached (Emax)
what is the quantal response?
all or nothing response i.e. a patient responding or not responding to a drug.
how can you examine a quantal response to a drug?
by taking a sample of the population and determining the dose at which a drug has an effect
what is Median lethal dose (LD50)?
Lethal dose for 50% of users
what is Medial toxic dose (TD50)?
Toxic dose for 50% of users
what is Therapeutic Ratio?
Therapeutic dose that produces a therapeutic effect in half of treated – Median effective dose (ED50)
what are the 5 main mechanisms of drug antagonism?
Chemical antagonism Receptor antagonism Non- competitive antagonism Pharmacokinetic antagonism Physiological antagonism
what is Chemical antagonism?
when drugs reduce the concentration of an agonist
what is Receptor antagonism also known as?
Competitive antagonism
what is Receptor antagonism?
Describes the blockade of a receptor by a drug molecule.
what are antagonists?
compete with the agonist for receptor site (competitive antagonism)
have no efficacy, but have an affinity
what is low affinity?
Reversible competitive antagonism
what is high affinity?
Irreversible competitive antagonism
what is non-competitive antagonist?
Drug binds to an allosteric site (non-agonist) site on the receptor and prevent activation
may activate singling pathways
Converts a full agonist into a partial agonist.
what is Pharmacokinetic Antagonism?
Antagonist drug that acts to increase clearance, reduce plasma concentrations and effect half life of active drug in the body
what is Physiological Antagonism?
Interaction between 2 drugs that initiate opposing effects via different receptors in the same target tissue
what is tolerance?
associated with maintenance of drug response requiring increasing doses
what is tolerance caused by?
Pharmacokinetic mechanisms
Pharmacodynamic mechanisms
how does Pharmacokinetic mechanisms cause tolerance?
Metabolism of drug increasing because of up regulation of enzymes that breakdown the drug and it is rapid eliminated from the body.
how does Pharmacodynamic mechanisms cause tolerance?
down regulation of receptors
what is cross tolerance?
repeated use of a drug effects the therapeutic function of another drug
what is cross tolerance caused by?
caused by shared signaling pathways or metabolic pathways
what is Desensitisation?
Lack of receptor response after prolonged stimulation. Can be short term or long term.
what is Short term Desensitisation?
due to post-translation modification of the receptor – deactivation
what is Long term Desensitisation?
Associated with changes in gene regulation
what is Tachyphylaxis?
Describes desensitisation associated with the depletion an intermediate signaling molecule or depletion of the pool of neurotransmitter in the synaptic vesicles arising from over stimulation
