Module I Flashcards
The four primary types of receptors
Ion channel linked, G Protein-coupled, and Enzyme-linked receptors, Steroid receptors (intracellular receptors)
Receptors that have no change at the receptor, have affinity but no efficacy at a receptor and block the effects of other drugs.
Antagonist
The enzyme that is homozygous in 7-10% of white individuals that affects the metabolism of at least 40 drugs, notably many opioids.
CYP2D6
A specific protein that recognizes one or a few specific ligands that, when attached, and causes a biological response.
Receptor
Most genetic variations in the human genome (polymorphisms) occur in these?
Drug-metabolizing enzyme genes
Continued stimulation of cells with an AGONIST that generally results in a state of desensitization. Also referred to as refractoriness.
Down-Regulation
Half of all drugs are metabolized by this cytochrome P-450 (CYP) isoenzyme in the liver and intestines. Notably many of the ones used in anesthesia practice.
CYP3A4
Type of compound that binds to and activates a receptor, yielding a cellular effect
Agonist
Type of GPCR that activates phospholipase C to increase DiaAcylGlycerol (DAG) and inositol triphosphate to release Ca2+ from cells.
Gq (mnemonic: “Q” quivers, calcium ions are second messengers in muscle contraction)
Compound that that contains two enantiomers in equal proportion
Racemic mixture
Receptor subtypes that cause post-synaptic inhibition in the CNS
GABA receptors
Most numerous family type of receptors; largest class of membrane receptors.
G protein-coupled receptors
Type of GPCR that increases Adenylcyclase, and produces cAMP from ATP.
Gs (mnemonic: “S” stimulates, cAMP is key second-messenger in many CNS neurotransmitters)
Largest class of membrane receptors targeted for medications that have 7 transmembrane alpha helices.
G-protein coupled receptors
Three types of opioid receptors
- Mu (MOR)
- Kappa (KOR)
- Delta (DOR)
The GPCR that works in the Phospholipase C, inositol triphosphate-DiAcylGlycerol pathway to release Ca2+ ions.
Gq
Adrenergic receptors located in vascular smooth muscle, bronchi, GI, and GU systems
Beta-2 adrenergic receptors (bronchodilators)
The non-hydrolyzed form of this signaling protein is bound at a target site in its active state.
Guanosine triphosphate (GTP)
Psychoactive drugs work on these receptors by modulating serotonin release and uptake.
Serotonin (5-HT) receptors
The form of a guanine nucleotide signaling protein that is considered inactive when bound to its’ target site.
Guanosine diphosphate (GDP)
Ion channels that open when bound by a ligand
Ligand-gated ion channels
What is a drug’s LD50?
The lethal dose of a drug in 50% of patients
Type of compound that binds to a receptor that has a rival compound but produces no net cellular effect.
Competitive antagonist
Molecules that are associated with having no net charge
Non-polar Molecules
In this type of receptor, phosphorylated (has attached phosphate molecules) receptors in its’ intracellular domain act as docking stations for other types of proteins to send intracellular signals.
Receptor Tyrosine Kinase
B-1 and B-2 agonists increase what second-messengers
cyclic aminophophate (cAMP)
A chloride ion, ligand-gated ion channel receptor that is a major inhibitory neurotransmitter in the CNS.
GABA-A
The attenuated response to the repeated use of beta-adrenergic agonists, such as bronchodilators for the treatment of asthma. Clinically the patient experiences “tolerance.”
Down-Regulation
Genetic polymorphisms occur in most, possibly all of this protein:
cytochrome P-450
Cell-surface receptors with intracellular domains that are associated with a specific enzyme.
Enzyme-linked receptors, notably Receptor Tyrosine Kinases (RTKs)
The target receptor for the antispasmodic agent, Baclofen
GABA-B (Baclofen)
Receptor proteins found on the inside of the cell (cytoplasm or nucleus)
Intracellular receptor
The process of the cell increasing the number of receptors in attempt to sense the missing ligand.
Up-regulation
True or False: Voltage-Gated Ion Channel Receptors can be excitatory or inhibitory
TRUE
The study of how molecules are structured in three dimensions.
Stereochemistry
Cell surface receptors with seven different protein segments that cross the membrane that send signals to the inside of the cell through a specific type of protein.
G protein-coupled receptors (GPCR). (G-Protein)
GPCR types that are most associated with the sympathetic branch of the Autonomic Nervous System.
Adrenergic receptors
Three types of adrenergic receptors:
- Alpha
- Beta
- Dopaminergic
Type of receptor that cause an effect by increasing or decreasing production of proteins.
G protein-coupled receptors
Receptor subtype located in pancreatic islet cells (B cells), platelets, nerve terminals, Central Nervous System, and pre- and postsynaptic smooth muscle
Alpha-2 receptors (think cloinidine)
How many types of dopamine receptors are there?
- 5
- D1, D2, D3, D4, D5
The two GPCR types that work within the cyclic adenosine monophosphate (cAMP) pathway
Gs, Gi (stimulate or inhibit pathway)
Two main types of nicotinic receptors:
- Nm (mnemonic- M for Muscular)
- Nn (mnemonic- N for autoNomic)
Receptor subtype located in vascular smooth muscle, GU smooth muscle, liver, and is post-synaptic in the Central Nervous System. GPCR-Gq (Stimulatory) (Vasoconstriction)
Alpha-1 receptors
When a molecule binds to a GPCR, this subunit of G-proteins exchanges GDP for GTP to elicit a response in the cell.
Alpha unit
Two types of cholinergic receptors:
- Muscarinic
- Nicotinic
Type of receptor that, when bound to a ligand, allows certain types of ions to pass through. (e.g. Neurons)
Ligand-gated ion channels
Nicotonic receptor type found in the post-synaptic skeletal neuromuscular junction
-Nm
Type of receptor that opens or closes in response to voltage changes in the cell
Voltage-gated ion channel receptors
An opioid receptor with several subtypes that can be located in the substantia gelatinosa in the spinal cord, brain, and involves respiratory depression and reduced GI motility
Mu receptors
Muscarinic receptor involved in the inositol triphosphate- diacylglycerol mechanism and is mainly involved in dopamine neurons.
M5
Set of genes carried by an organism that is inherited from parents.
Genotype
Component of the cell that is composed of a phospholipid bilayer that is in turn composed of a hydrophilic glycerol head, and a fatty acid hydrophobic tail.
Cell membrane
In GPCRs, long-term treatments with antagonists can lead to…
Hypersensitization
Opioid receptor type that is co-located with Mu receptors that do not cause respiratory depression, but can cause reduced GI motility and dysphoria.
Kappa receptors
Muscarinic receptor involved in Inhibition of cyclase adenosine monophosphate (cAMP) and activation of K+ channel and are located in the CNS, heart, smooth muscle, and autonomic nerve terminals.
M2
Postsynaptic Alpha-2 receptors in blood vessels have what effect?
- Vasoconstriction
- Platelet aggregation
Type of compound that binds to a receptor and prevents a normal response
Antagonist
In GPCRs, long-term treatment with agonists can lead to…
Desensitization
Type of GPCR that inhibits adenylcyclase and the production of cAMP from ATP
Gi (mnemonic: “I” inhibits)
An enzyme that transfers a phosphate group from ATP to a protein or other target
Kinase
The target receptors for barbiturates and benzodiazepenes
GABA-A
A G protein-coupled receptor that is found primarily in peripheral tissues and a few in the CNS
GABA-B (Gi)
Molecules such as cAMP, cGMP, calcium calmodulin, inositol triphosphate, DiaAcylGlycerol (DAG) that cause responses in the cell when activated by alpha G-proteins bound to GTP and are tissue-specific
Second messengers
Acetylcholine activates which type of receptor by opening Na+ and K+ depolarizing ion channels?
- Nicotinic cholinergic receptors
Beta-blockers normally have their effect on these receptors
- Beta-1 receptors
- B1 antagonists
Adrenergic receptors located in the heart and kidneys (juxtaglomerular cells)…
Beta-1 adrenergic receptors (inotropes and chronotropes)
Chronic Administration of an ANTAGONIST that causes an increase in the number and sensitivity of receptors. Clinically the patient develops tolerance, requiring higher doses to counteract the increase in number of receptors.
Up-Regulation
Opioid receptor subtypes are all what type of receptor?
G protein-coupled receptors
The Heterotrimeric subunits of G proteins
Alpha, Beta, and Gamma
Binding of a ligand to it results in receptor dimerization and phosphorylation of the intracellular kinase domain.
Receptor Tyrosine Kinase
Three ways agonists can create cellular effects
- Enzme activation/inhibition
- ion channel modulation
- DNA transcription
Subtypes of adrenergic dopamine receptors that when activated decrease cyclic adenosine monophosphate (cAMP) and have the opposite effect as receptors in the same family
- D2, D3, D4
In its resting state (inactive form) the GPCR (ex: Adrenergic Receptor) is bound by this guanosine nucleotide.
GDP
What are the 3 types of G Protein-coupled receptors?
Gs, Gi, Gq (mnemonic: G’s are SIQ “Sick”)
Muscarinic receptors are what type of cell membrane receptors?
- G protein-coupled receptors
Arguably the most important role of RTKs is their ability to bind to and act on these type of vital substances.
Growth factors
Agonists come in what two types?
Full and partial
All Serotonin receptors, with the exception of 5-HT3 are this type of receptor.
G protein-coupled receptors
Small, hydrophobic ligands that pass through the cell membrane and bind to intracellular receptors on the nucleus or cytoplasm.
Steroid hormones
Receptor type that can attach and DIRECTLY alter DNA and transcription
Intracellular receptor
A ligand-gated ion channel that is directly coupled to fast NA+ and K+ ion channels and is the target site for ondansetron/Zofran, an antagonist.
5-HT3 serotonin receptor
Its affect is only observable in the presence of an agonist. It will interact with (or bind to) the receptor but NOT change the receptor
Antagonist
Nicotinic receptor type that is post-ganglionic, found in the autonomic ganglia and the adrenal medulla
- Nn
Molecules associated with having no net charge, are water soluble, and have regions with partial negative and positive charges.
Polar Molecules
Muscarininc receptor that initiates the inositol triphosphate (IP3) and diacylglycerol (DAG) mechanisms, and are located in the CNS/PNS, smooth muscle and glands.
M3
Presynaptic Alpha-2 receptors inhibit the release of what hormone?
Norepinephrine (action of clonidine)
Receptors that are located in the brain, peripheral tissues, kidneys, increase cyclic adenosine monophosphate(cAMP), and have the agonistic effect of vasodilation
- D1 and D5
Type of receptor that, when ligand bound to a signaling molecule, forms crosslinked dimers of the same type of receptor
Receptor Tyrosine Kinase
Type of receptor associated with causing excitatory effects in its’ nicotinic and glutamate variants, or inhibitory effects in its’ GABA-A and Glycine variants.
Ligand-gated ion channels
Which muscarininc recptor activates the inositol triphosphate (IP3)-Diacylglycerol (DAG) mechanism (and thus involved in release of (Ca2+), and is located in the CNS, autonomic ganglia, salivary and gastric glands, and enteric nerves?
M1
The process of the cell decreasing the number of receptors in the presence of increased stimulation by ligands.
Down-regulation
Receptor type that is activated through chloride channel channel activation and causes CNS depression through post-synaptic inhibition
GABA receptors
Four environmental factors that affect drug pathways.
- Smoking
- Alcohol
- Dietary supplements
- Diet
5 Types of chemical bonds and attractive forces between molecules in order of decreasing strength
- Covalent,
- Ionic
- Hydrogen
- Hydrophobic
- Van der Waals
This type of receptor is named after the ion they are permeable to, they open and close in response to voltage changes in the cell and play a role in muscle contraction and propagation of action potentials.
Voltage-gated ion channel receptors
Alpha-2 agonists decrease what type of intracellular secondary messenger?
- Cyclic adenosine monophosphate (cAMP)
- This, in turn, decreases norepinephrine (think action of clonidine)
Small compounds that are _____ can cross the cell membrane through diffusion.
hydrophobic
An intrinsic enzyme linked receptor attaches phosphates to a certain amino acid in its’ intracellular domain. When phosphorylated (attaches phosphate molecules) types of its’ amino acid can then send intracellular signals.
Receptor Tyrosine Kinase
Molecules that are mirror images of each other but cannot be superimposed
Enantiomers
Alpha-1 agonists increase these types of secondary messengers…
- Phospholipid-C
- Diacylglycerol (DAG)
- Inositol Triphosphate(IP3)
Muscarinic receptor involved in the inhibition of of cyclic adenosine triphosphate and is located in the forebrain.
M4 (mnemonic= 4-Brain)
Location of adrenergic receptors.
Central Nervous System and peripheral tissues
5-HT3 serotonin receptor is what type of receptor?
HINT: Directly coupled to fast Na+ and K+ ion channels.
ligand-gated ion channel
Type of compound that binds to a receptor, producing a paradoxical effect (opposite/contradictory of the desired effect).
Inverse agonist
Nicotinic receptors are what type of cell membrane receptors?
- ligand-gated ion channel receptors
A compound that binds to the receptor and produces the opposite of the desired/expected effect. Ex: a medication binds to GABA resulting in anxiety.
Inverse Agonist
Membrane-anchored proteins that bind to ligands on the outside surface of the cell
Cell-surface receptors
A difference in a DNA sequence that is more frequent than 1% in population
Polymorphism
A signaling molecule that when attached to receptor, activates the receptor, and causes a biological response.
Ligand
Adrenergic receptors that bronchodilate, vasodilate muscle and liver, release insulin, and relax uterine muscle influence their effect on these receptors…
- Beta-2 receptors
- B2 agonists
Crucial cell membrane protein structures that are necessary in order to allow ions and large molecules into the cell.
Receptors
Opioid receptors involved in spinal and supraspinal analgesia. Modulates neurotransmitter and hormone release.
Delta
A compound (or ligand) that has affinity but no efficacy.
Antagonist
Carbon-based compounds that have same chemical structure but different arrangement of bonds; has implications for receptor bonding and drug effects.
Stereoisomers
Type of compound that binds to a different/discrete receptor site that contradicts the cellular effect of other compounds.
Noncompetitive antagonist
Physical and physiologic characteristics that are based on genotypes and are influenced by the environment
Phenotype
