Pharma Flashcards
What are pharmacodynamics?
The actions of the drug on the body. Drug-Receptor interactions.
What is ADME?
Absorption, Distribution, Metabolism and Excretion (Elimination)
What do receptors do?
Determine the relationship between dose and effect.
Responsible for selectivity of drug response
Responsible for agonist and antagonist activity
What are the different types of receptors?
Ion channels, G Protein coupled receptors, enzyme linked receptors and steroid receptors
What does signal transduction and secondary messengers do?
Amplify the signal. But there must also be a way to turn off or desensitize the signal.
What are ion channel receptors?
A channel through the phospholipid bilayer that allows lipid insoluble molecules through to cause cellular polarization or depolarization. Opens when receptor is activated.
Nicotine activates a sodium ion channel. The influx of sodium depolarizes the cell. In the brain this leads to increased alertness.
What are G Protein coupled receptors?
Transmembrane receptor, quick
An agonist binds to a receptor on the G Protein which undergoes a change. GTP replaces GDP and then the GDP joins a subunit to go and power an effector protein.
There are many different types of effector proteins (ion channels, secondary messengers-Ca)
Can cause polarization, depolarization, protein phosphorylation, Ca release, etc.)
The biggest family of receptors, 60% of drugs work on this type of receptors. Morphine acts on this type to reduce pain
What does the G Protein subtype determine?
Determines the receptor effects.
Gs has a stimulatory effect by increasing cAMP.
Gi has an inhibitory effect by decreasing cAMP, increased K efflux. Both are activated by the pertussis bug.
Golf is for smelling and increases cAMP. Activated by cholera toxin
What are the types of enzyme linked receptors?
Guanylyl cyclase, tyrosine kinase receptors and tyrosine kinase associated receptors
How does guanylyl cyclase work?
The drug (nitroglycerin) must pass through the cellular membrane in order to reach the receptor (intracellular). The interaction causes guanylyl cyclase to convert GTP to cGMP. Activation causes vasodilation and relief of cardiac pain
How do tyrosine kinase receptors work?
Transmembrane. The drug (insulin) binds to the receptor on tyrosine kinase, which then phosphorylates proteins on tyrosine (Y) residues.
How do tyrosine kinase associated receptors work?
Transmembrane. A drug binds to a receptor that then activates a tyrosine kinase. An additional domain on the receptor, intermediate.
The immune system (cytokines) use this type of receptors.
What are steroid (nuclear) receptors?
The drug must pass through the cellular membrane and then pass through the nuclear pores into the nucleus of the cell. Binds to DNA and can turn a gene on and off to cause different protein synthesis (DNA transcription).
Hydrocortisone decreases cell proliferation.
How long do drug effects last?
The effects last as long as the drug is bound to the receptor. Depends drug-receptor affinities.
How do enantiomers affect carvedilol?
+ carvedilol is a selective beta-blocker. - carvedilol is selective for alpha receptors.
What is Kd?
The concentration that binds 50% of the available receptors.
What is affinity?
The degree of attraction between drug and receptor. Determines drug properties.
The dual arrows between D+R and DR
What is efficacy?
How good the response is to the drug. Used in clinical trials.
Effectiveness is used for the wider population.
Emax is the maximum possible efficacious.
The one way arrow between DR and response.
The y axis of a response vs. dose graph.
What is an agonist?
Drugs that bind to and activate the receptor.
What is a partial agonist?
Drugs that bind to the same receptors and activate them in the same way with a lower response.
Has affinity, but low efficacy.
Emax is not as high
Pindolol on heart rate
What is an antagonist?
Drugs that bind to a receptor, compete with and prevent the binding by other molecules. Blocks out response
Straight line on response vs. concentration graph
What is the law of mass action?
The drug receptor interaction is directly dependent upon the concentration of the drug and the concentration of the receptor.
More pronounced in the beginning.
What is EC50?
The effective concentration for 50% effectiveness.
Graph can be transformed by taking the log.
What is potency?
The concentration or dose of a drug required to produce maximum effect.
The x axis of a response vs dose graph
What is an inverse agonist?
Binds to the receptor but does not cause a response. Lowers efficacy by creating a negative response
What happens when a partial agonist is administered in the presence of a full agonist?
The partial agonist will simply reduce the effects of the full agonist.
What happens when an antagonist is administer in the presence of a full or partial agonist?
It will reduce the effects of the agonist to a very low levels, less than just a partial agonist. Will be the same level no matter whether it is full or partial.
What are the types of antagonists?
Competitive reversible, irreversible, physiological, chemical and allosteric modulators.
How do competitive reversible antagonists work?
They compete with agonists for the receptors and make the site inactive when they bind. If the concentration of agonists is increased, the antagonists can be “bumped” out.
The curves are shifted to the left (less potent) so EC50 is shifted to the right but Emax does not change.
How do irreversible antagonists work?
They covalently bond to the active site, making it inactive. They reduce efficacy by reducing the total number of receptors.
Makes curve higher.
How do physiological antagonists work?
The effects of one agonist counteracts the effects of another agonist. Doesn’t involve binding to a receptor
Diminishes efficacy
How do chemical antagonists work?
A chemical interaction reduces the effect of the agonist. No receptors are involved
How do allosteric modulators work?
Bind to a site separate from the receptor. Don’t compete with agonist for binding or interfere with agonist binding.
Can increase or decrease agonist induced response
How does the Ca Phosphoinositide signaling pathway work?
A G protein stimulates PLC (phospholipase-C) which breaks down membrane bound PIP2 into 2 molecules (DAG and IP3)
IP3 interacts with vesicles of Ca in the cell to create a cellular response.
DAG becomes PK-C which helps a substrate become phosphorylated to create a cellular response.
How does desensitization and resesitization work?
When you continue to add an agonist over a long period of time, the receptor response wanes (desensitization).
By leaving a period of rest in between administrations, you’ll get a response of original magnitude (resensitization).
The length of rest time depends on the receptor.
What is tachyphylaxis?
When tissue response to an agonist wanes over time.
What causes phosphorylation and dephosphorylation?
Kinases cause phosphorylation. Phosphatases cause dephosphorylation.
How does desensitization and resensitization work with G coupled proteins?
When a G coupled protein receptor is repeatedly administered an agonist, the beta-art will interact with the coated pit to promote endocytosis. The G Protein then leaves the membrane, surrounded by its membrane. This leaves less receptors to interact with the drug.
The G Protein vesicle can then go back into the membrane or be broken down by lysozyme.
What is passive diffusion?
The movement of a drug from an area of high concentration to an area of low concentration through aqueous channels. Does not require ATP.