Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
79 Cards in this Set
- Front
- Back
What is an agonist?
|
a ligand that binds to a receptor and alters the receptor state
|
|
What is an antagonist?
|
a drug that reduces the action of another drug
|
|
How is the potency of a drug measured?
|
it is the amount of the drug necessary to reach the ED50 (not very important)
|
|
What is the efficacy of a drug?
|
the efficacy refers to the response that a drug elicits
|
|
What is desensitization?
|
a spontaneous decline in the response to an agonist due to a change in receptor activation
|
|
What is the difference between "fade" and "tachyphylaxis"?
|
-fade refers to the decline in response to continued application of agonist
-tachyphylaxis refers to the decline in response to repeated applications of agonist |
|
What is a full agonist?
|
an agonist capable of producing the system maximal response in a tissue
|
|
What is a partial agonist?
|
an agonist that cannot elicit the maximum effect, compared to another agonist that acts through the same receptors.
|
|
What are spare receptors?
|
a system has spare receptors if an agonist does not need to occupy all the receptors to elicit the maximum response
|
|
What is competitive antagonism?
|
the binding of the agonist and antagonist is mutually exclusive
|
|
What is noncompetitive antagonism?
|
agonist and antagonist can be bound to the receptor simultaneously, but the antagonist prevents the action of the agonist
|
|
What is the difference between pharmacokinetics and pharmacodynamics?
|
pharmacokinetics: study of [drug/metabolite] in body fluids
pharmacodynamics: study of drug-target interactions |
|
What factors determine drug response?
|
-number of receptors
-receptor occupancy -efficacy -duration of drug exposure |
|
How is the dissociation constant (Kd) measured?
|
it is the [Dfree] present when 50% of the receptors are occupied
|
|
What usually causes sensitization?
|
prolonged exposure to antagonists (left shift in dose-response curve)
|
|
What is one molecular explanation for partial agonists?
|
the inactive drug-receptor conformation is more stable than the active conformation
|
|
How can competitive and noncompetitive inhibition be distinguished on dose-response curves?
|
in competitive inhibition, the maximum response can be achieved regardless of inhibitor concentration.
in noncompetitive inhibition, the possible response is dependent on inhibitor concentration |
|
How is the therapeutic index calculated? What is it for?
|
toxic dose for 50% population / effective dose for 50% population
-it measures safety → large TI = safe, small TI = not safe |
|
What are some amino acid transmitters?
|
-glutamate
-GABA -glycine |
|
What are some amine transmitters?
|
-dopamine
-norepinephrine -epinephrine -serotonin -histamine |
|
What are some neuropeptides?
|
-substance P
-vasopressin |
|
What are the precursors of acetylcholine? What enzyme catalyzes this reaction and where?
|
-acetyl-CoA and choline are precursors
-choline acetyltransferase catalyzes this reaction in the cytoplasm |
|
What is the limiting factor in acetylcholine synthesis?
|
availability of choline (provided by choline/Na+ cotransporter in presynaptic terminal)
|
|
What terminates acetylcholine action?
|
acetylcholinesterase in the synapse
|
|
What is the precursor of norepinephrine, epinephrine, and dopamine?
|
tyrosine
|
|
What is the major regulatory step in the synthesis of biogenic amines? What enzyme catalyzes this step?
|
hydroxylation of tyrosine by tyrosine hydroxylase to produce dihydroxyphenylalanine (DOPA)
|
|
What is the immediate precursor of dopamine? What enzyme catalyzes its conversion into dopamine?
|
DOPA; the enzyme is DOPA decarboxylase
|
|
What is the immediate precursor of norepinephrine? What enzyme catalyzes its conversion into norepinephrine?
|
dopamine; the enzyme is dopamine β-hydroxylase
|
|
What is the immediate precursor of epinephrine? What enzyme catalyzes its conversion into epinephrine?
|
norepinephrine; the enzyme is phenylethanol-amine N-methyl-transferase
|
|
How is the action of biogenic amines terminated?
|
reuptake by pumps in the presynaptic membrane
|
|
What does monoamine oxidase (MAO) do? Where in the cell is it found?
|
converts amine group into aldehyde in catecholamine metabolism; it is found in mitochondria
|
|
What does catechol-O-methyltransferase do?
|
converts a hydroxyl group into a methyl ether in catecholamine metabolism
|
|
How does the amount of time per cell cycle differ in a cancer cell and a normal cell?
|
it doesn't; cancer cells divide more often (more cell cycles) but each cell cycle takes the same amount of time as in a normal cell
|
|
How many cancer cells must be present in order for the cancer to be clinically detected?
|
10^9
|
|
At the time of host death from cancer, how many cancer cells are usually present?
|
10^12
|
|
At what point in the cell cycle can the cell undergo death from differentiation?
|
mitosis
|
|
Which cells in a tumor are drug sensitive?
|
clonogenic proliferating cells
|
|
Which cells in a tumor are in G0?
|
clonogenic nonproliferating cells
|
|
Which cells in a tumor are "doomed" cells?
|
nonclonogenic proliferating cells
|
|
Which cells in a tumor are "end" cells?
|
nonclonogenic nonproliferating cells
|
|
What are some categories of cell cycle-specific agents? What is their general mechanism of action?
|
-antimetabolites (interfere with synthesis)
-vinca alkaloids (destroy mitotic spindle) -topoisomerase inhibitors (disrupt transcription and duplication) |
|
What are some categories of cell cycle nonspecific agents? What is their general mechanism of action?
|
-alkylating agents (covalently crosslink DNA)
-antibiotics (intercalation, DNA scission, block RNA production) -platinum salts (inhibits DNA synthesis, DNA crosslinking) |
|
What are the pathologic processes involved in rheumatoid arthritis?
|
-inflammation
-synoviocyte proliferation → cartilage destruction -angiogenesis -matrix metalloproteinases → irreversibly degrade cartilage matrix -chondrocytes → impaired cartilage synthesis |
|
What is palliative treatment?
|
treatment of symptoms rather than the cause
|
|
What is the mechanism of action of gold salts?
|
-block prostaglandin synthesis
-suppress mononuclear phagocytes -inhibit lysosomal hydrolases |
|
How do corticosteroids work?
|
alter gene expression (downregulate expression of cytokines)
|
|
How do antimalarials work?
|
inhibit cyclooxygenase
|
|
What DNA sequence is frequently methylated?
|
5'-CG-3' (C is methylated at position 5 of the pyrimidine ring)
|
|
How does methylation regulate transcription?
|
heavy methylation of CG-rich islands → low transcription of downstream genes
|
|
How can methylation lead to mutations?
|
methylated C can spontaneously deaminate to yield T
|
|
What is Lepore hemoglobin?
|
caused by fusion of δ and β genes and driven by the δ promoter (weaker)
|
|
How are Alu repeats involved in familial hypercholesterolemia?
|
aberrant recombination between Alu repeats causes a deletion
|
|
What are transgenic mice? How are they generated?
|
-mice which have had mutated/altered genes introduced into their genome
-foreign DNA is injected into fertilized mouse egg before male and female pronuclei fuse -injected eggs are transferred to a foster mother -offspring are selectively bred |
|
What is gene knockout? How is it accomplished? What are the
|
-a technique for selectively inactivating a gene by replacing it with a mutant allele
-mutant alleles are introduced into embryonic stem cell by homologous recombination -embryonic stem cells with the mutation are introduced into a mouse embryo -offspring are selectively bred |
|
How do G16 and R16 variants of the β2 adrenergic receptor affect its interactions with agonist?
|
-R16/R16 variant has full response to albuterol
-G16/R16 variant has 75% response -G16/G16 variant has 50% response |
|
How does N-acetyl transferase affect isoniazid metabolism? What happens to slow acetylators?
|
Acetylation of isoniazid inactivates it. Slow acetylators have a greater risk for adverse side effects.
|
|
What drugs (categories) are metabolized by CYP2D6?
|
-beta-blockers
-tricyclic antidepressants -anti-arrhythmic agents -anti-psychotic agents and selective serotonin-reuptake inhibitors -opioids |
|
What happens to patients with serum cholinesterase deficiency?
|
potentially fatal adverse reaction to the muscle relaxant succinyl choline → prolonged apnea requiring artificial respiratory support
|
|
What is the most common enzyme deficiency in humans? Why? What is the mode of inheritance for this deficiency?
|
-glucose-6-phosphate dehydrogenase deficiency
-confers resistance to malaria -X-linked recessive |
|
What happens to people with deficiency in glucose-6-phosphate dehydrogenase? Why?
|
-decreased ability to dispose of oxidants because glutathione peroxidase activity is low (needs glutathione)
-things that increase oxidants are primaquine, xenobiotics, fava beans -hemolysis |
|
What does the ryanodine receptor (RYR1) do? What happens if it is mutated?
|
-it is a calcium ion release channel in sarcoplasmic reticulum
-if it is mutated (dominant), inhalation anesthetics cause malignant hyperthermia → death (preventable with dantrolene sodium) |
|
How is a retrovirus made?
|
-start with RNA virus (usually Moloney murine leukemia virus)
-replace the genes that code for capsid, replication, and envelope with desired gene - |
|
What are the problems with using retrovirus gene therapy?
|
-only works in dividing cells (useless in neurons for example)
-only ex-vivo currently possible -gradual turn-off of gene over months -transgene can interrupt another gene, or viral LTR can overexpress another gene |
|
What is an adeno-associated virus?
|
-small defective DNA virus
-needs adenovirus or herpes simplex virus -in absence of helper virus, integrates into specific region of chromosome 19 -recombinant AAV rarely integrates |
|
What are the problems with using recombinant AAV therapy?
|
-small cloning capacity
-difficult to obtain high titer stocks -immune response to viral capsid antigens |
|
What is the problem with delivering DNA without a viral vector?
|
it is inefficient
|
|
Why was the treatment of SCID using retroviral vector halted?
|
insertional mutagenesis caused 3 out of the 10 patients to develop leukemia (from LMO2 oncogene), and 2 died
|
|
How is recombinant AAV used to treat hemophilia B? What were the problems with this therapy?
|
-hepatic portal vein infusion
-destruction of transduced hepatocytes by immune system -immunomodulatory treatment proposed |
|
What are the targets of most antiarrhythmic drugs?
|
-voltage-dependent Na+ channels
-voltage-dependent K+ channels -voltage-dependent L-type Ca2+ channels |
|
What is the target of one class of vasodilators?
|
voltage-dependent L-type Ca2+ channels (inactive conformation)
|
|
What is the target of local anesthetics?
|
voltage-dependent Na+ channels (open conformation)
|
|
What are the targets of many antiepileptic drugs?
|
-voltage-dependent Na+ channels (slow recovery from "inactive" to "rest")
-voltage-dependent Ca2+ N-type or low-threshold channels |
|
What are the two types of Ca2+ channel vasodilators?
|
-nonselective
-vasoselective (preferentially bind "inactive") |
|
What are the differences between cardiac and vascular smooth muscle cells?
|
-cardiac cells have high resting membrane potential, vascular cells have low
-cardiac cells have an AP range of -70-100 → 0-25 mV, vascular of -50 → 0 mV -cardiac cells have "open" channels more often, vascular have "inactive" more often |
|
What is the difference between use-dependent binding and voltage-dependent binding?
|
Use-dependent: binds "open" and "resting" preferentially
Voltage-dependent: binds "inactive" preferentially |
|
What is an HMO? Where do their income and costs come from?
|
Health Maintenance Organization; contracts with a primary care provider, group, or Independent Provider Association (IPA)
Income: patients Costs: -administration -IPA -pharmacy -hospital -risk pool |
|
Where do the income and costs for an IPA come from?
|
Income:
-HMO contract -risk pool Costs: -management -primary care physician fee -specialists -lab -medical equipment -x rays |
|
What is a PPO?
|
Preferred Provider Organization - network of physicians that agree to accept a guaranteed discounted fee
|
|
What type of family makes up the majority of the uninsured population?
|
more than 1 adult, no children, with worker(s)
|