Drugs Flashcards
1
Q
What is acetylcholine?
A
- neuromodulator in the CNS, often at axoaxonic synapses
- primary neurotransmitter released by motor neurons at the neuromuscular junction
- activates excitatory ionotropic receptors on muscle cells, causing fast EPSPs and muscle contraction
2
Q
What do motor neurons generally release as their main neurotransmitter?
A
- acetylcholine
3
Q
What do sensory neurons generally release as their main neurotransmitter?
A
- glutamate
4
Q
What is black widow spider venom?
A
- Poison produced by the black widow spider that triggers the release of acetylcholine from motor neurons
- causes muscle cramps, spasms, pain, nausea
5
Q
What is botulunim toxin?
A
- botox
- Produced by bacteria that grow in improperly canned food
- prevents acetylcholine release from motor neurons, causing muscle paralysis
6
Q
What do many natural toxins target?
A
- the vesicle release machinery
7
Q
What is neostigmine?
A
- Drug that inhibits acetylcholinesterase, which is the enzyme that breaks down acetylcholine in the synapse
- causes acetylcholine to stay around longer in the synapse, causing prolonged muscle contraction, spams
8
Q
What is Myasthenia Gravis?
A
- autoimmune disorder in which a person’s immune system attacks healthy acetylcholine receptors
- weaker over time
- neostigmine keep acetylcholine in the synapse for longer periods of time
9
Q
What is a receptor agonist?
A
- drug that directly or indirectly increases the activity of postsynaptic receptor proteins
10
Q
What is a receptor antagonist?
A
- drug that directly or indirectly decreases the activity of postsynaptic receptor proteins
11
Q
What are direct agonists/antagonists?
A
- bind directly to postsynaptic receptors
12
Q
What are indirect agonists/antagonists?
A
- affect the activity of postsynaptic receptors in an indirect manner
- agonist: neostigmine, black widow venom
- antagonist: botox
13
Q
What are antipsychotics (neuroleptics)?
A
- Class of drugs used to treat psychosis
- mostly dirty drugs, which means they bind to more than one type of receptor
- the one action they all have in common is they directly block the dopamine D2 receptor, which is an inhibitory metabotropic receptor expressed by neurons all over the brain
- direct dopamine receptor antagonists (dopamine receptor blockers)
14
Q
What are drugs that cause hallucinations?
A
- most popular ones directly activate serotonin 2A receptors, which are expressed by neurons all over the brain
- Direct serotonin receptor agonists (serotonin receptor activators)
- not all serotonin 2A receptor agonists cause hallucinations
15
Q
What 4 drugs directly activate the serotonin receptor 5HT-2A?
A
- mescaline
- psilocybin
- LSD
- lisuride
16
Q
Which serotonin receptor activators are not hallucinogens?
A
- lisuride
17
Q
How do hallucinogens work?
A
- the drugs activate the 5HT-2A receptor, which is metabotropic, they launch an intracellular signaling cascade that starts with the g protein Gq/11
- also trigger the receptor to activate a different g protein: Gi/o
- Hallucinations seem to result from 5HT-2A receptor activation of Gi/o proteins
18
Q
What is biased agonism?
A
- when a ligand causes a metabotropic receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
- way receptor activates biases which g protein inside cell gets turned on
19
Q
How can direct agonists/antagonists be classified?
A
- competitive binding
- non competitive binding
20
Q
What is a competitive agonist?
A
- acts similarly to the endogenous neurotransmitter
- activates the receptor by binding where the neurotransmitter normally binds
- can be full (activate as much as neurotransmitter) or partial agonists (half activate)
21
Q
What is a competitive antagonist?
A
- attaches to the same binding where the neurotransmitter normally binds
- it doesn’t activate the receptor
- always full
22
Q
What is affinity?
A
- probability and tightness of ligand receptor binding
- competition for a binding site between an endogenous neurotransmitter and an exogenous drug will depend on their relative concentrations and their affinity for the binding site
23
Q
What is a non competitive agonist?
A
- drug binds to a receptor at a site that does not interfere with the binding site of the normal ligand
- neurotransmitter to bind on one site of a receptor while a drug binds on another
- fully or partially activates the receptor
24
Q
What is a non competitive antagonist?
A
- drug binds to a receptor at a site that does not interfere with the binding site of the normal ligand
- neurotransmitter to bind on one site of a receptor while a drug binds on another
- fully blocks receptor activation
- “wins” without competing by binding to an alternative site
25
Q
What are allosteric modulators?
A
- Non-competitive drugs that only influence receptor activity when the neurotransmitter is also bound to the receptor
- negative allosteric modulators reduce the effect of the primary ligand
- positive amplify the effect of the primary ligand
26
Q
What is Parkinson’s disease?
A
- neurological disorder
- tremors, rigidity of limbs, poor balance, and difficulty initiating movements
- caused by the degeneration (death) of dopamine neurons in the midbrain
27
Q
How is Parkinson’s treated?
A
- amino acid L-Dopa is used as a drug to treat Parkinson’s disease
- it increases dopamine production in the brain and thus acts as an indirect dopamine receptor agonist
28
Q
How do indirect agonists work?
A
- Conventional neurotransmitters are made in axon terminals, where an enzyme converts a precursor molecule (typically an amino acid) into a neurotransmitter
- the precursor molecule can be given as a drug, since it can increase the amount of neurotransmitter that is made and released
- the precursor molecule is an indirect receptor agonist
29
Q
How do indirect antagonists work?
A
- Enzymes synthesize neurotransmitter from precursor molecules
- Some antagonists work by blocking these enzymes, thus reducing production of the neurotransmitter so there is less in each synaptic vesicle
OR - Once made, neurotransmitters are packaged into synaptic vesicles
- Some antagonists work by blocking the transporter proteins that package neurotransmitter into vesicles
- the synaptic vesicles can remain empty, so nothing is released when they fuse with the presynaptic membrane
30
Q
How do drugs affect neurotransmitter release?
A
- Some antagonists work by blocking the vesicular release machinery, so no neurotransmitter is ever released (botox)
- Some agonists work by activating the vesicular release machinery, causing neurotransmitter release (black widow venom)
31
Q
How do drugs affect enzymatic deactivation?
A
- Some agonists block the enzymatic deactivation of neurotransmitter in the synaptic cleft (neostigmine)
- stays longer in synapse
32
Q
How do drugs affect reuptake transporter proteins?
A
- Some agonists block neurotransmitter reuptake transporters (stays longer)
- Some agonists can even reverse the direction of reuptake transporters, so they push neurotransmitter into the synapse as soon as it is made (without being packaged into a synaptic vesicle)
33
Q
What is Methylphenidate/cocaine?
A
- Drugs that block catecholamine reuptake transporters, meaning they block the reuptake of dopamine & norepinephrine
34
Q
What is Adderall/crystal meth?
A
- Drugs that reverse catecholamine reuptake transporters, causing dopamine and norepinephrine to flow out of the axon terminal before being packaged into a vesicle
- action potential-independent, non-vesicular release
- Ecstasy (MDMA) has a similar effect on all the monoamine reuptake transporters (causing them to run backwards)
35
Q
What are the ways agonists affect synaptic transmission?
A
- drug serves as precursor
- drug stimulates release of neurotransmitter
- drug stimulates postsynaptic receptors
- drug blocks autoreceptors, increases synthesis/release of NT
- drug blocks reuptake
- drug inactivates acetylcholinesterase
36
Q
What are the ways antagonists affect synaptic transmission?
A
- drug inactivates synthesis enzyme, inhibits synthesis of NT
- drug prevents storage of NT in vesicles
- drug inhibits release of NT
- drug blocks postsynaptic receptors
- drug stimulates autoreceptors, inhibits synthesis/release of NT
37
Q
How can drugs be categorized?
A
- according to their effects on postsynaptic receptor activity
- according to their behavioural effects
- according to their physiological effects
- according to their actions on specific proteins
38
Q
Can heroin enter the brain?
A
- very easily crosses the blood-brain barrier (because an enzyme in the blood makes it very lipid/fat soluble)
39
Q
Can morphine enter the brain?
A
- less easily crosses the blood-brain barrier (it is less lipid soluble than heroin
40
Q
Can imodium anti-diarrheal enter the brain?
A
- does not cross the blood-brain barrier
41
Q
What do heroin, morphine, and imodium anti-diarrheal have in common?
A
- They are all very strong opiates (opioids) that cause constipation
42
Q
What are opioid receptors?
A
- inhibitory metabotropic receptors
- found throughout the body and brain
- normally get activated by endogenous opioid peptides that function as hormones in the body and as neuropeptides in the CNS
43
Q
What is tolerance?
A
- when a drug effect gets smaller with repeated administration
- body becomes used to the drug and actively counteracts its effects
44
Q
What are withdrawal symptoms?
A
- opposite the effects of the drug
45
Q
What is sensitization?
A
- when a drug effect becomes larger with repeated use
