Pharmacodynamics Flashcards
Define Pharmacodynamics
Studies of action of the drug from its interacrtion with receptors, to the effect on animal populations.
Types of Drug Targets
- Enzymes
- Carriers
- Ion Channels
- Receptors
- DNA and Nucleic Acid
Inhibition of this drug leads to suppression of proinflammatory prostaglandins
Cyclooxygenases
An enzyme that metabolizes ACh
Acetylcholine esterase
An enzyme that breaks down Trimetoprim and Acetylcholine
Dihydrofolate reductase
A type of drug target, also known as membrane transport systems
Carriers
Types of Neurotransmitters
- Endogenous
- Exogenous
A molecule or a polymeric structure on the surface / inside the cell that specifically recognizes and binds an endogenous compound.
Receptor
Moleculrs without signal transduction pathways, binding will not trigger a physiological response
Acceptor
Receptors posses an effector system also called?
signal-transduction pathways
A three-dimensional structure, forms pockets/grooves on the surface of protein that allowns specific interactions with compounds known as ligands
Binding site
Molecules of compilementary shape to the protein binding site, follows “locka and key” analogy
Ligands
A neurotransmitter that acts as molecular messenger, hormones are example of this neurotransmitter
Endogenous
A neurotransmitter that may produce a cascade of biochemical events that results in drug interaction, example: drugs
Exogenous
Drug Characteristics
- Intrinsic Activity
- Affinity
The property of drug that permits it to initiate post-receptor processes, which lead to a response
Intrinsic Activity
Ability of a drug to bind to its receptors
Affinity
Drugs that produce measurable pharmacological response and physiological response. Drugs that have both affinity and intrinsic ability.
Agonist
Types of Agonist Drugs
- Primary agonist
- Allosteric agonist
- Full agonist
- Partial agonist
- Inverse agonist
A drug that binds to the same site as the endogenous ligands
Primary agonist
A drug that binds to a different region of the receptor
Allosteric agonist
An agonist that produces a maximal effect under a given set of condition.
Full agonist
Drugs that bind to the receptor, suppressing the constitutive signaling activity
Inverse agonist
Drugs that are unable to trigger any action on their own but are able to block the action on other agonist, has affinity but no intrinsic activity. Also called “silent drugs”, most drugs are antagonist.
Antagonist
An interaction between 2 drugs such that the response of one drug (the agonist) is reduced in the presence of the second drug (the antagonist)
Antagonism
Types of Antagonism
- Receptor antagonism
- Physiologic antagonism
- Chemical antagonist
Forms of Antagonism
- Competitive
- Non-competitive
Occurs on same receptor protein such that two drugs compete and bind to the same receptor protein.
Receptor antagonism
Occurs as a result of activating receptors with opposite phyiologic effect
Physiologic antagonism
Occurs as a result of drug combining with 2 or more molecules via the formation of chemical bonds
Chemical antagonist
Antagonist acts on the same receptor as the agonist, usually reversible, can be surmounted by increasing the concentration of the agonist
Competitive
Occurs when the antagonist is bound covalently / irreversibly to its receptor binding site
Irreversible Competitive
Refers to the situation where a drug blocks the cascade of events, normally leading to an agonist response at some downstream point
Non-competetive
Ability of the drug to bind to its receptor
Affinity
The drug’s ability, once bound, to initiate changes that lead to the production of responses. A property of a ligand/receptor pair.
Efficacy
Define Potency
Coresponds to the concentration of drugs required to achieve a given effect.
The maximum possible effct that can be obtained regardless of how large a dose is administered.
High Ceiling Effect
Drugs that act only on single target. Linked to the nature of the drug-receptor interaction, considered rare.
Specificity
Related to the concentration range of drugs. A drug may be specific at low concentration if it activates only one type of target whereas several targets may be involved simultaneously if the drug concentration is increased.
Selectivity
Reversible Bonds
- Ioninc Bond
- Hydrogwn bond
- Van der Waals forces
Strongest known non-covalent bond
Ionic bond
An irreversible bond
Covalent bond
A very tight bond, unable to dissosiate, rare
Covalent bond
Activation leads to direct opening or closing an ion channel
Ionotropic Receptors
Activation leads to some changes in metabolic processes within the cell. When activated, a series of intracellular events is first triggered that may also subsequently result in ion channel opening
Metabotropic receptors
G-protein coupled receptor is also called?
Seven Transmembrane Receptors
May act directly on an ionic channel or activate an enzymatic system to release a range of second messengers which ultimately permits certain ions to enter or leave the cell.
G-proteins
A class of metabotropic cell surface receptors which exerts their regulatory effect by phosphorylating different effector proteins.
Tyrosine-Kinase Receptor
Primary chemicals that act on RTKs
Hormones and growth factors
Activates transmembrane ion channels , contains central pore (functions as ligand-gated ion channel)
Ionotropic receptors
After binding the ligand, the activated receptors translocate to the nucleus and bind to a DNA sequence called the response element and initiate transcription of specific gene(s)
Transcription Factor Receptor
The effect of the drug diminishes when it is given repeatedly
Tolerance and Tachyphylaxis
Term used to describe a gradual decrease in responsiveness to chronic drug administration, can take from days to months
Tolerance
An acute form of tolerance
Tachyphylaxis
Common reasons for tachyphylaxis/tolerance
Pharmacodynamic mechanism: desensitization, loss of receptor, exhaustion of mediator
Pharmacokinetic mechanism: metabolism induction, active extrusion of the drug
Tolerance phenomenon known for diuretics. Results from activation of the renin-angiotensin-aldosterone system and the parasympathetic nervous system
Braking Phenomenon
Results from the chronic stimulation of receptors with drug results in a state of long term desensitization. Often due to a decrease in number of receptors.
Down Regulation
Under stimulation of receptors (due to an increase in the number of receptors and a functional super sensitivity)
Up Regulation
Four main levels of pharmacodynamic description
- Drug action
- Drug effect
- Clinical response
- The final drug effectiveness at the population level.
The Four main levels of pharmacodynamic description are influenced by:
- Physiological factors
- Genetic Background of the animal
- The disease and its progression
- The treatment itself
Define therapeutic window
A concept coined to describe the range of useful plasma concentrations in which expeced clinical response is obtained with minimal risk of adverse effect.
Drugs with this therapeutic index requires drug monitoring to ensure treatment with a reaseonable margin of safety.
Narrow therapeutic index
Drugs witht his therapeutic index allows more flexibility for the design of a dose regimen
Wide therapeutic index
Define therapeutic index
a ratio that expresses the relationship between useful and toxic drugs.
