Pharmacodynamics - Sinal 1 Flashcards
What is pharmacology?
What drugs are, how they work and what they do
Divided into pharmacodynamics and pharmacokinetics
Drugs
Therapeutic agent
Any substance other than food, used in prevention, diagnosis, alleviation and treatment or cure of disease
Pharmacy
Concerns with scientific, legal and managerial aspects of dispensing drugs
Pharmacodynamics
Study of relationship of drug concentrations to drug effects
Biological effect is proportional to amount of drug-receptor complex
Major classes of receptors targeted
- Ligand-gated ion channels
- Enzyme-linked receptors
- G-protein coupled receptors
- Ligand-activated transcription factors
Agonist
A drug causing receptor to respond in same way as naturally occurring substance
Independent impact on receptor activity
Antagonist
Drug that binds to receptor but does not produce a response
Inhibitory effect on naturally occurring substance
Impacts receptor activity only in presence of agonist (lacks efficacy)
B
Fraction of total receptors bound
Bmax
Maximal faction of total receptors bound
Kd
Equilibrium dissociation constant
Drug concentration at which 1/2 of Bmax is achieved
A measure of the inherent affinity of the drug-receptor interaction
Constant and not altered by concentration of drug or receptor number
Saturation point
Level out of B/[D] graph because all receptors are saturated
High Kd
Low affinity
Low Kd
High affinity
Graded dose-response curves
Drug dose/Biological effect (%)
Emax
Maximum response achieved by the drug
ED50
Drug dose where 1/2 Emax is achieved
Also referred to as drug potency
Concentration-Binding Curve
Drug concentration/fraction of receptors bound
Quantal Dose-Response Curves
Used to describe population rather than single individual responses to drugs
Based on plotting cumulative frequency distribution of responders against the log drug dose, adding bars of histogram
Graded phenomena
Infinite number of intermediate states
ie. vessel dilation, blood pressure change, heart rate change
Quantal phenomena
All or none
ie. death, pregnancy, pain relief
Potency
Amount of agonist needed to produce an effect of a given magnitude
Usually expressed as ED50: dose to achieve 50% of the maximum effect achievable with that agonist
Efficacy
Maximum effect that can be achieved with a particular agonist
Usually expressed as Emax: maximum effect that can be achieved with that drug
Full agonist
High/low potency, maximum efficacy
Partial agonist
High/low potency, reduced efficacy
Inverse agonists
Stabilize the inactive state or destabilizes the active state
Reduces constitutive receptor activation
Has an independent impact on receptor activity
Opposite effect of agonist: classified as an agonist as it has a functional impact on the receptor
Chemical antagonism
Direct interaction of two substances in solution such that the effects of one or both is lost
ie. acid and base anticoagulant
Physiological antagonism
Indirect interaction of two substances with opposing physiological actions
ie. Histamine vs. EN
Pharmacological antagonism
Blockage of interaction of one substance with receptor by another substance
Pharmacological antagonists
Bind to receptors but do not activate signal transduction mechanisms
Biological effects derived from blocking ability of agonist to bind/activate receptor
Competitive antagonists
Bind reversibly to receptor
Inhibition can be overcome by increasing agonist concentration
Primarily affect agonist potency but can still achieve same magnitude of biological affect
Non-competitive antagonists
Bind irreversibly to receptor or reversibly/irreversibly to allosteric site
Inhibition cannot be overcome by increasing agonist concentration
Primarily affect efficacy
IC50
Inhibitory concentration
Endogenous receptor ligands
Such as hormones and neurotransmitters Mostly are agonists Inverse agonists are rare Antagonists are rare Some drugs mimic effect of endogenous agonists and some block
Epinephrine
Full agonist of cardiac beta2-adrenergic receptor to increase rate and force of heart contraction
Agouti-related Peptide
AGRP
Endogenous inverse agonist
Reduces constitutive receptor activity of melanocortin receptor
Kynurenic Acid
Endogenous pure antagonist
NMDA receptor antagonist
Physiological role unclear but may play a role in neurotransmission and neuropathologies
Isoproterenol
Full agonist that mimics epinephrine at cardiac beta2 adrenergic receptor
Buprenorphine
Partial agonist that mimics endogenous endorphins at n-opiod receptor
Safer analgesic than morphine due to less rest of respiratory depression
Superagonists
> 100% Emax
Uncommon in clinical practice
Propranolol
Pure antagonist of epinephrine at cardiac beta2-adrenergi receptor
Drug desensitization
Effect of drug often diminishes when given continuously or repeatedly
Receptor-mediated and non-receptor mediated mechanisms
Receptor mediated drug desensitization
Loss of receptor function due to change in receptor conformation
Reduction of receptor number
Non-receptor mediated drug desensitization
Reduction of receptor-coupled signalling components
Increased metabolic degradation
Physiological adaptation
Adverse drug effects
- Side effect
- Toxic reaction
- Allergic reaction
Side effect
Dose dependent
Not directly related to desired effect of drug
Action of drug at other sites to produce undesirable effects
Toxic reaction
Dose-dependent
Directly related to desired effect of drug
Excessive action of drug at intended target site
Allergic reaction
Not dose-dependent
Not related to desired effect of drug
Immunologic response to drug and largely unpredictable
Cyclosporine
Promotes survival of transplanted organs
Increased susceptibility to infection, kidney damage, rash/hives/itching/breathing difficulties
Paracelsus
It is not the nature of the drug that determines toxicity, but rather the amount
Everything in excess is potentially toxic
Therapeutic index
Measure of drug safety
Considers dose required for a toxic or other adverse drug effect versus that required for the desired beneficial effect
Toxic ED50/Beneficial ED50
A larger TI indicated a clinically safer drug
Therapeutic window
Measure of drug safety that considers the range of blood concentration of a drug that are associated with toxic, therapeutic benefit or lack of effect within a population
If drug falls between window, it fulfills clinical role
