Speth Final (Opioids, Ligand & Voltage Gated Channels) Flashcards
What classification of drugs are alkaloids found in the opium poppy?
opiates
(e.g. codeine and morphine)
What is the major cause of death of opioid use?
respiratory depression
List 4 clinical problems associated with opioid use:
- constipation
- endocrine disturbances
- tolerance to analgesic effect
- interactions with other CNS-depressant drugs
In proopiomelanocortin (POMC), what amino acid is a critical part of the peptide that stimulates opioid receptors?
methionine (Met)
What two amino acids are found in the first 5 sequences of endogenous ligands?
Met or Leu
Which endogenous ligand is the “exception to the rule” and only has a 4 amino acid sequence instead of 5?
endomorphins
The overall effect of u-opioid receptor actions at these effectors is to inhibit neuronal activity. What g-coupled protein receptor is it acting on? (the “u” is pronounced “mu”).
Gsub-i (aka Gai)
List 3 generic and proprietary names of opioid agonists:
- Fentanyl (Duragesic = skin, Sublimate = pill form)
- Hydrocodone (Hycodan = potent analgesic)
- Oxycodone (oxycontin, Roxicodone)
Name a prototypical opioid partial agonist that is often used to help patients in withdraw.
Buprenorphine (Buprenex, Subutex)
Name two opioid antagonist. Which one is most popular?
- Naloxone (Narcan) = most popular
- Naltrexone (Revia, Depade)
Give an example of each opioid classification by origin: natural, semisynthetic, synthetic.
- natural = morphine
- semisynthetic = heroin
- synthetic = fentanyl
Which opioid receptor has “good and bad effects” in terms of response?
mu (u) receptor
List the three opioid receptors:
- mu (u)
- delta
- kappa
List 4 pharmacological actions of opioids that are considered “good”:
- analgesia
- cough suppression
- sedation
- constipation
- miosis
List 4 pharmacological actions of opioids that are considered “bad”:
- respiratory depression
- euphoria
- tolerance
- physical dependence
- increased body temp
- convulsions
The first cultivation of opium was from which plant?
Hul Gil “the joy plant”
Morphine was derived from which Greek god?
Morpheus (God of Dreams)
What did the patent medicines in the 1900s like snake oil contain?
opium, morphine, cocaine, alcohol
What Pharma company aggressively marketed opioids by fear-mongering the public with “it’s important to control pain to speed recovery”?
Purdue Pharma
Why does hardly anyone die from a drug overdose in Portugal?
they decided to treat possession and use of small quantities as a public health issue, not a criminal one
What is another name for drug dealer?
a criminal
Between 1998 and 2008, how much did the production of oxycodone increase?
nearly 6-fold
What two drugs are considered the “most common killers”?
fentanyl and methamphetamine
What is the HB21 bill?
a prescriber or dispenser must consult the PDMP database to review a patient’s controlled substance dispensing history before prescribing or dispensing a controlled substance for a patient who is 16 years or older.
What complaint is the most common reason for seeking health care?
acute and chronic pain-related complaints
The HB21 bill also provides that a prescription for a schedule II opioid for treatment of acute pain may not exceed a ___ day supply.
3-day supply
Paracetamol and Ibuprofen are combined into a tablet called “combogesic”. What is the rule for oral administration of this tablet?
for short term use ONLY (not more than 3 days)
Name two types of ion channels:
- ligand gated
- voltage gated
What is the main neurotransmitter excitatory ligand-gated channels act on?
glutamate
What is the main neurotransmitter inhibitory ligand-gated channels act on?
GABA
What are inhibitory interneurons and what do they do?
short axons that inhibit neurotransmission balance
Activation of the GABA receptor ________ neurons by increasing Cl- permeability.
hyperpolarizes
If a patient is suffering from seizure, which neurotransmitter do you want to increase?
GABA
T/F all GABA receptors are ion channels
FALSE
How many GABA binding sites are there per receptor?
two
Name two depressants that act on GABA receptors:
benzodiazepines and barbiturates
Z drugs bind to ______ sites on the GABA A receptor to potentiate GABA mediated channel opening.
allosteric
What blocks the GABA-gated chloride channel?
Picrotoxin
Benzodiazepine (BZD) effects on anxiety are blocked by ______ antagonists.
GABA
List 3 Benzodiazepine (BZD) actions on the body:
- muscle relaxation
- sedation
- anticonvulsant action
What is the difference between Benzodiazepines (BZD) and Phenobarbital?
BZD doesn’t do anything without GABA, phenobarbital can activate channels without GABA
Name two GABA receptor blockers:
Picrotoxin and Bicuculline
Z drugs are selective to which GABA receptor subunit?
GABA a1 subunit
High levels of GABA subunit a5 receptor is found where in the brain?
hippocampus
What drug is a selective competitive antagonist of Benzodiazepine (BZD) binding site?
Flumazenil (Romazicon)
(reverses sedative effects of BZDs in overdoses)
Name one GABA A receptor agonist and one antagonist.
agonist = Muscimol
antagonist = Bicuculline
Which Benzodiazepine (BZD) was a prototype for all BZD?
Diazepam (Valium)
In the Rolling Stones song “Mother’s Little Helper” there’s a little yellow pill. What drug is this song about?
Valium
Give two examples of “Z drugs”.
- Ambien
- Sonesta
Z drugs are more selective than ______ and bind to the BZD binding site of the _____ receptor.
benzodiazepines; GABA
Z drugs are more selective than BZD because they bind only to the _____1 _____2 subunit interface associated with sedation and ______.
alpha1; gamma2; amnesia
T/F Z drugs can be used for short-term and chronic use.
TRUE AND FALSE
should be used for only short-term but many people use them chronically
Z drugs are primarily for the treatment of what?
insomnia
Which Z drug has a very short duration of action and is for initiating sleep?
Zaleplon (Sonata)
Which Z drug has a shorter duration in men more than women?
Zolpidem (Ambien)
Some sleeping pills have strange effects like sleep walking. What is another name for sleep walking?
somnambulism
The Beers Criteria Medication List is a list of drugs not recommended for who?
older people
What drug at high concentrations can be a full agonist of the GABA A receptor?
barbiturates
What drug was administered by IV to induce anesthesia and used to kill people for executions?
Thiopental
What was “Mother’s Little Helper?”
Valium (Diazepam)
What receptor reacts with MDMA?
glycine receptor
What was the first performance enhancing drug?
Strychnine (nut vomica)
What are two major groups of ionotropic glutamate receptors?
NDMA and AMPA
_____ receptor activation enhances inhibitory GABA transmission.
NMDA
Which receptors need to open first before NMDA is open?
AMPA
Name two NMDA antagonists:
- ketamine
- phencyclidine (PCP)
Name one NMDA agonist
glutamate
What are the two glutamate receptor subtypes and which one is a GPCR?
- ionotropic
- metabotropic (GPCR)
What are the functional classes of the inotropic glutamate receptor?
AMPA, Kainate, NMDA
What are the functional classes of the metabotropic glutamate receptor?
class I, class II, class III
What two ion channels do AMPA receptors work on?
Na+ and K+
AMPA receptors act on Na+ and K+ ion channels, which mediate the majority of _____ ______ neurotransmission.
fast excitatory
(AMPA receptors has fast kinetics)
What subunit makes most AMPA receptors calcium impermeable?
the GluR2 subunit
(has arginine instead of glutamine)
I think this will def be a question
Do NMDA receptors or AMPA receptors have slower kinetics?
AMPA
What receptors require glycine or D-serine as a co-agonist?
NMDA
Depolarization by AMPA receptors is stimulated by what?
glutamate
What drug is a great antidepressant because it acts instantly but unfortunately causes hallucinations?
ketamine
In seizure disorders, excessive stimulation by glutamate will cause neuronal cell death by elevating _____ levels in the cell.
calcium
What drug can sustain cognitive gentian for a short time in Alzheimers patients and is a unique antagonist at NMDA receptors?
Memantine (Namenda)
(weak agonist, doesn’t completely block NMDA)
What amino acid will you find in excess in Alzheimers disease?
glutamate
The NMDA receptor has involvement in _____ and _____ and long-term potentiation.
learning; memory
In the long-term potentiation (LTP) of Namenda, LTP requires what?
activation of synapses and depolarization of postsynaptic membrane
In the long-term potentiation (LTP) of Namenda, LTP involves what?
Hint: 4 things
- release of glutamate
- activation of NMDA receptors in depolarized membrane
- entry of calcium ions
- new AMPA receptors in the postsynaptic membrane
PCP and Ketamine block what channel?
NMDA
Which serotonin receptor is a nonselective ion channel and is not a GPCR?
5HT3
Name the 3 primary voltage-gated ion channels and the 1 secondary voltage-gated ion channel:
- calcium
- sodium
- potassium
- chloride (secondary)
Which voltage-gated ion channel is responsible for neurotransmission, secretion, cardiac pacemaker activity and contraction of muscle cells?
calcium
Which voltage-gated ion channel is responsible for neurotransmission and conduction of nerve impulses?
sodium
Which voltage-gated ion channel is reestablished the membrane potential?
potassium
Which voltage-gated ion channel is responsible for the regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation?
chloride
Where is potassium stored?
in the cytoplasm
the Cav1 subfamily mediates what type of calcium currents?
L-type
The Cav2 subfamily mediates what type of calcium currents?
P/Q-type, N-type, R-type
What type of calcium currents are mainly on the heart?
L-type
Most drugs work on what type of calcium currents?
L-type
A strong change in membrane potential can shorten the _______ period.
refractory
_______ refractory period is the time after opening of channel when it is unable to open again.
absolute
_______ refractory period is the time after opening of a channel when only a strong depolarization can reactivate it.
relative
What mV does it take for an action potential to get activated?
-55 mV
What is a neurotoxin with potential analgesic activity?
Tetrodoxin (TTX)
What does TTX do that makes it so toxic?
inhibits nerve action potentials and blocks nerve transmission
Pyrethroids are synthetic chemicals that act like ______.
pyrethrin
What is a natural extract from the chrysanthemum flower that is a “secondary metabolite” that has no other function other than to protect the plant from insects?
pyrethrin
Permethrin can be used on food, crops, livestock, and pets but NOT _____.
cats
Some permethrin products can be used to treat ______ and ______ on people.
scabies; head lice
Local anesthetics bind to the inside of ______ channels.
sodium
Local anesthetics bind with higher affinity to “activated” and “inactivated” states of channel use ________ inhibition.
dependent
Which local anesthetics are esters?
- cocaine
- procaine (novocaine)
- benzocaine
- tetracaine
Which local anesthetics are amides?
- lidocaine
- bupivacaine
- mepivacaine
- ropivacaine
Which local anesthetics (amides or esters) tend to be short acting because they are quickly metabolized by plasma cholinesterase?
esters
Which local anesthetics (amides or esters) tend to be more resistant to metabolic inactivation which occurs in the liver via P450s?
amides
What will limit the systemic distribution of a local anesthetic?
potent vasoconstrictor
(epi or phenylephrine)
High concentrations of local anesthetics can cause what?
Hint: 4 things
- weakness
- methemoglobinemia
- convulsions
- dysrhythmias
Gabapentin is a synthetic analogue of the neurotransmitter ______-________ acid.
gamma-aminobutyric acid
gamma-aminobutyric acid can have anticonvulsant activity but can also be used for the treatment of _________ pain and _______ _____ syndrome.
neuropathic pain; restless legs syndrome
Pregabalin selectively binds to alpha2delta subunits of presynaptic voltage-dependent ______ channels.
calcium
The drug action of B-adrenergic receptor blockade treats what abnormal cardiac condition?
atrial fibrillation or flutter
_______ is a short-term inhibitory neurotransmitter that treats paroxysmal supra ventricular tachycardia.
adenosine
Name a Class II B-adrenergic receptor blocker.
propranolol
Does the drug Diltiazem have an increased or decreased effect on action potential duration?
decreased
Does lidocaine have an increased or decreased effect on action potential duration?
decreased
Lidocaine rapidly blocks both activated and inactivated ______ channels, though there is some preference for the inactivated state.
sodium
In partially depolarized cells, lidocaine significantly _______ membrane responsiveness.
depresses
Lidocaine also elevates the ________ _______ threshold.
ventricular fibrillation
What is a derivative of lidocaine that is orally active?
Mexiletine
Mexiletine ______ the maximal rate of depolarization of the cardiac action potential and exerts a negligible effect on depolarization.
slows
T/F lidocaine is not orally active:
TRUE
Drugs that act upon calcium channels are almost exclusively _______ of calcium channel function aka calcium channel blockers.
antagonists
What are the 3 calcium channel blocker drug classes?
- dihydropyridines
- phenylalkylamines
- benzothiazepines
What calcium channel blocker drug class preferentially block vascular smooth muscle calcium channels and doesn’t have cardiac effects at therapeutic doses?
dihydropyridines
What calcium channel blocker drug class acts on the heart as well as vascular smooth muscle?
phenylalkylamines
What calcium channel blocker drug class acts on heart as well as vascular smooth muscle?
benzothiazepines
The molecular structure of CL- channel types varies from ___ to ___ transmembrane segments.
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