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BOT 380 > Stimulants 1 > Flashcards

Stimulants 1 Flashcards

1
Q

what are three widely used stimulant drugs?

A

caffeine: from coffee, tea (legal, socially acceptable)

Nicotine: (legal, socially unacceptable??)

Cocaine: illegal, socially unacceptable depending on location

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2
Q

stimulant containing plants create a _______?

A
  • state of well being
    -self confidence
    -euphoria
    -increased alertness
    -mental functioning
    -alleviate fatigue and drowsiness

-peripheral organs may be effected
-increased heart rate, blood pressure

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3
Q

____________ is common with some stimulants?

A

addiction

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4
Q

continued use of stimulant drugs may lead to…..?

A

increased agitation, apprehension, and anxiety

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5
Q

what is the mechanism of action of stimulants?

A

increases the activity of the sympathetic nervous system

neurotransmitter action is regulated

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6
Q

stimulant plants can be organized based on their compounds mechanism of action…. list the three

A

cholinergic

adrenergic

purinergic

-these terms refer to the type of neurotransmitter or neuron that is affected by the plant compound

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7
Q

chemical and electrical signals are received by the ________?

A

dendrites

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8
Q

information is transmitted down the _____ by an action potential

A

axon

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9
Q

neurons are organized into pathways and transfer information at ________?

A

synapses

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10
Q

chemical and electrical signals leave the neuron from the ____________?

A

terminal bulb

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11
Q

central nervous system

A

-consists of the brain and the spinal cord

-the brain is subdivided into anatomically and functionally distinct areas

-neurons are organized into pathways that link the brain areas to each other

-the CNC receives and processes information and relays it back to the peripheral nervous system to create an appropriate response

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12
Q

peripheral nervous system

A

the somatic branch
-consciously controlled
-movement, respiration, posture
-skeletal muscle contraction

autonomic branch
-unconsciously controlled
-cardiac action
-blood flow
-digestion
-the autonomic branch is divided into the sympathetic and parasympathetic systems
-the difference would be the locations of neurons along the spinal cord
-organs are controlled by neurons from both systems

-actions are often opposing

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13
Q

parasympathetic projections originate from:

A

-cranial nerves

-sacral portion of the spinal cord

-‘breed or feed response’

-constricts pupils
-stimulate salivation
-slow heartbeat
-stimulate digestion
-inhibit hormone and enzyme release
-dilate blood vessels
-stimulate urinary bladder to contract
-stimulate penile or clitoral arousal
-stimulate gut motility and secretions
-stimulate gallbladder to release bile

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14
Q

sympathetic projections originate from the:

A

-thoracic and lumbar portions of the spinal cord

-‘fight or flight response’

-dilate pupils
-inhibit salivation
-constrict blood vessels
-relax airways
accelerate heartbeat
-stimulate secretion by sweat glands
-celiac ganglion
-inhibit digestion
-stimulate secretion of epinephrine and norepinephrine
-inhibit gut motility and secretions
-relax the urinary bladder system
-stimulates orgasm
-stimulate glucose production and release

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15
Q

pharmacokinetics

A

-an organism’s normal body systems relate to how rapidly and how long a drug will appear at a target organ

-absorption of the drug
-distribution of drugs in the body
-elimination or clearance of drugs from the body

-these factors determine the appropriate concentration, route of administration, or dose of the drug that is to be given

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16
Q

pharmacodynamics

A

-the nature of the drug/ target interaction is essential in determining the dose of a specific drug that is to be given

-how readily it will bind, dictated by its chemistry

-dose-response curves determine how drugs interact with specific receptors

-this information can be used to help determine the appropriate dosage of a drug

  • we can see the tradeoff between toxicity and efficacy
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17
Q

receptors

A

-normal cellular processes work due to the interaction of endogenous chemicals with receptors

-may inhibit or activate

-drug structures relate to receptor binding –> the structures matter because they control how quickly they will bind

-drugs may bind permanently or reversibly

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18
Q

the normal or endogenous molecule is an _________?

A

endorphin

-it binds to a receptor in the brain in order to elicit a pain-relieving response

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19
Q

morphine is a ___________ of an endorphin molecule and binds to the same receptor?

A

structural mimic (analog)

-morphine is found in the opium poppy

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20
Q

morphine also elicits a _________________?

A

pain-relieving response through receptor activation

-it is labeled as an agonist at the endorphin receptor

-the pharmacodynamic and pharmacokinetic properties of morphine will determine the strength of this response

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21
Q

morphine has a lower __________?

A

dissociation rate and does not go away as quickly, this triggers the pathways more intensely

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22
Q

the final effect of a drug is based on:

A

-how much makes it to the target

-how the action of the drug at the target leads to an outcome

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23
Q

interactions of drug with receptor

A

-agonist or antagonist (or mixed)

-may bind better or worse than endogenous molecule

-drugs may outcome endogenous molecules

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24
Q

possible outcome of drug/receptor interaction?

A

-activation of neuronal action potentials

-activation of signalling pathways

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25
Q

neurotransmitters

A

-chemicals used to relay, amplify, and modulate signals between cells

-synthesized in presynaptic neurons

-released in response to action potentials (electrical signalling)

-elicit physiological effects depending receptor(s) they bind to and activate

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26
Q

agonist

A

activates the receptor to produce a biological response

27
Q

antagonist

A

blocks or dampens a biological response by binding to and blocking a receptor

28
Q

neurotransmitters are important chemicals that regulate nervous system function

A

-relevant in both CNS and PNS activities

-plant drugs often change the normal action of neurotransmitters

29
Q

neurotransmitters examples

A

acetylcholine –> functional class: excitatory to vertebrate skeletal muscles; excitatory or inhibitory at other sites

secretion sites–> CNS, PNS, vertebrate neuromuscular junction

30
Q

Biogenic amines

A

-norepinephrine –> excitatory or inhibitory–> CNS, PNS

-dopamine–> excitatory, could be inhibitory at some sites –> CNS, PNS

-serotonin –> generally inhibitory–> secretion sites : CNS

31
Q

amino acids

A

-GABA (gamma aminobutyric acid) –> inhibitory –> CNS, invertebrate neuromuscular junction -

Glycine –> inhibitory–> CNS

Glutamate–> excitatory –> CNS, invertebrate neuromuscular junction

asparate –> excitatory–> CNS

32
Q

step process of chemical neurotransmission

A
  1. action potentials arrive at axon terminal
  2. voltage gated Ca2+ channels open
  3. Ca2+ enters the cell
  4. Ca2+ signals to vesicles
  5. vesicles move to the membrane
  6. docked vesicles release neurotransmitter by exocytosis
  7. neurotransmitter diffuses across the synaptic cleft and binds to receptors
  8. binding of neurotransmitter to receptor activates signal transduction pathways
33
Q

what are the three types of synapses?

A

cholinergic synapse:
-produce and release acetylcholine (Ach)
-receptors are nicotinic and muscarinic

adrenergic synapse
-produce and release catecholamines
-norepinephrine
-epinephrine
-dopamine
-receptors: alpha and beta-adrenergic receptors and dopamine receptors

  1. purinergic synapse
    -release urine nucleotides or nucleosides
    -e.g. adenosine or ATP
    -P1 and P2 receptors
34
Q

cholinergic synapse process

A
  1. acetyl coA is synthesized in the mitochondria
  2. choline acetyltransferase catalyzes the conversion of choline and acetyl coA to acetylcholine (Ach)
  3. the Ach is packaged into synaptic vesicles
  4. Ach is released into the synapse
  5. Ach binds to its receptor on the postsynaptic cell
  6. AChe breaks down ACh into choline and acetate, terminating the signal in the postsynaptic cell
  7. the presynaptic cell takes up and recycles the choline and the acetate diffused out of the synapse
35
Q

Pilocarpine: a cholinergic agonist

A

-this is a treatment for glaucoma and dry mouth

-pilocarpus microphyllus (jaborandi)

-imidazole alkaloid

-native to brazil

-first recorded use in 1648

-concentrations of pilocarpine can reach up to avg of about 1.0% of the leaf dry mass (range 0.2%- 2.2%)

36
Q

Physostigmine

A

-cholinergic agonist
-treatment for glaucoma
-alkaloid
-native to western africa
-Physostigma venenosum (calabar bean)

Hippomane mancinella (Manicheel tree)
-native to south america
“little apple of death”
-all parts of the tree contain toxins
-standing beneath the tree during rain will cause blistering of the skin from mere contact with any tree sap

37
Q

Galantamine

A

cholinergic agonist

treatment for Alzheimers

Galanthus nivalis (caucasian snowdrop)

alkaloid

found across europe and middle east

grown in gardens as an ornamental

38
Q

Cocaine

A

-adrenergic agonist
-pain killer
-Erythroxin coca –> coca plant
-tropane alkaloid
-native to south america
-Nicolas Monardes –> describes effects and use of coca leaves by indigenous peoples
-Friedrich Gaedcke–> isolation of cocaine alkaloid

-Richard Willstatter –> synthesis of cocaine

39
Q

Ephedrine

A

-adrenergic agonists
-treatment of low blood pressure, asthma, narcolepsy

-ephedra sinica ( Ma Huang)

-native to northeastern China
-documented by Han dynasty as an anti asthmatic and stimulant

40
Q

caffeine

A

purinergic antagonist

-can enhance pain relief

-coffea arabica (coffee)

-methylxanthine alkaloid

-native to yemen and Ethiopia

-most heavily used drug in the world

-part of a class of compounds called Methylxanthines

-found in coffee, cocoa, Guarana, Mate, and Kola plants

-binds to adenosine receptors

41
Q

purinergic summary

A

adenosine

P1 and p2 receptors

key compounds: caffeine, Theobromaine cacao, cola nitida (camellia sinensis)

plants producing caffeine or other methylxanthines

42
Q

adrenergic summary

A

-norepi, epi, dopamine
-a and B adrenergic receptors
-and dopamine receptors

key compounds: cocaine, ephedrine, cathinone

synthetic stimulant drugs: amphetamine, methylphenidate, MDMA

43
Q

cholinergic summary

A

acetylcholine

-nicotinic and muscarinic receptors

-key plant compounds: nicotine, arecoline, pilocarpine, physostigmine, galantamine

44
Q

purinergic stimulants

A

-methylxanthines are among the most commonly used stimulants worldwide –> possibly the most commonly consumed drugs

stimulate CNS at all levels
-milder than other stimulants like cocaine or ephedrine

found in many plants:
-coffee, cocoa, guarana, mate, kola
-often taken in the form of a beverage

45
Q

methylxanthines

A

in 1821 caffeine was discovered

-search for quinine alternatives

-three closely related methylated xanthine compounds
-caffeine
-theophylline
-theobromine

compounds have purinergic activity
-modulate (inhibit or activate) purine neurotransmitter action

-The endogenous neurotransmitter is adenosine

46
Q

physiological effects of caffeine

A

-CNS stimulant

-increases alertness, induces insomnia, improves energy and mood

-stimulates skeletal muscles: slight increase in muscle endurance

-diuretic

-dilutes bronchial tubes and coronary arteries –> relax smooth muscle

-improves psychomotor performance

-increases heart rate and blood pressure

-increases metabolism

47
Q

methylxanthine mechanism

A

adenosine
-endogenous inhibitory neurotransmitter
-causes behavioural sedation
-inhibits the release of most neurotransmitters into synapse

caffeine binds to adenosine receptors
-competes for receptor binding sites
-a similar structure to adenosine
-antagonizes normal adenosine function

methylxanthines
-have other documented mechanisms of action
-multiple physiological effects depending on which methylxanthine is used, which receptor is bound, or which mechanism of action is occurring

-elicit similar effects on the body, but to varying degrees

-CNS and skeletal stimulators
-caffeine» theophylline» theobromine

cardiovascular stimulators
-theophylline» theobromine» caffeine

48
Q

camellia sinensis is…..?

A

tea

49
Q

theobroma cacao is…?

A

cocoa tree

chocolate

cola acuminata –> caffeine

50
Q

medicinal uses of methylxanthines

A

historical use: cure for measles

modern use: component of many non prescription pain remedies

-methylxanthines like theophylline have been used to treat asthma

-the mechanism is to dilate bronchioles

-caffeine is the compound most often used for CNS stimulant effects
-effects heightened by carbonation

51
Q

coffea arabica: a coffee containing plant

A
  • ethiopia
    -a goat herder notices lively goat behavior and correlates it with eating the kaffa plant

yemen
-goats
-drink ‘K’hawah’
-toasted and crushed berries plant water mixed

-drink was supposed to further mental alertness

-mix coffee beans with fat as a food source

-coffee: more widely consumed than wheat corn, and rice, and more traded than steel

coffee bean: seed, found inside a fruit
-Berry or dupe
-berries, red when ripe
- two coffee seeds per berry
-edible fleshy pulp surrounds seeds
-green –> to red on ripening

52
Q

evolution of the coffee drink

A

-originally the whole berry was steeped in hot water

-13th century, yemen –> roasting seeds

-1500s–> coffee tree cultivation
-coffee drinking spreads through arabian world
-16th century coffee houses
-schools of the cultured

53
Q

evolution of coffee production

A

-initially, arabia has monopoly on coffee
-port of mocha: yemen

1690: dutch viable beans
-set up coffee plantations in their colonies
-Ceylon ( now Sri Linka)
-java

-Arabian monopoly

-Columbia and brazil are currently the leading producers of coffee

54
Q

growth of other coffea species

A

genus Coffea
-other species grown in areas that climates unsuited for coffea arabica

Africa
- C.iberica
-c. canephora
-used to produce instant and decaffeinated coffee

-these species are resistant to a fungal pathogen that causes coffee rust that kills coffea arabica

-this pathogen destroyed dutch coffee plantations in Ceylon

55
Q

coffee fruit development

A

after fertilization

seeds and surrounding fleshy tissue develop

caffeine synthesis begins

maximum caffeine concentration reached when the berry is red color (2% of dry weight)
-seed and fruit tissues, fully hydrated)
-berries picked

56
Q

caffeine and plant biology

if berries are left on tree?

A

undergo maturation

seeds and fruit tissues lose water

30% to 60% relative water content

desiccation is a natural process–> desiccated seeds can germinate and produce a seedling

maturation–> caffeine concentration falls
-2%–> 0.03% of dry weight

57
Q

why do plants produce caffeine?

A

-soft, ripe fruits are vulnerable to insects

-but they contain caffeine at 2% dry weight

-caffeine is at lethal dose for tobacco hornworm/ causes sterility in some beetles

caffeine levels increases in soft, developing shoots and young leaves
-up to 4% of dry weight
-caffeine levels fall as leaves mature

other plants produce caffeine and methylxanthines in addition to coffea sp.

58
Q

the cola tree

A

genus cola

rain forests of tropical west africa

seeds in form in fruit pods

cola nuts are natural stimulants
-high caffeine content
-historically used to depress appetite as part of religious rites and thought to have aphrodisiac properties

initially used for flavoring in beverages but many manufacturers now use synthetic versions

cola nitida and cola acuminata
-commercially important species
-cultivated in west indies, brazil, india, sudan

59
Q

theobroma cacao

A

-chocolate beverage is prized drink among Aztecs

-plant produces pod shaped fruits containing large seeds

-seeds are dried, roasted., ground to make chocolate liquor and cocoa butter

-higher levels of theobromine than caffeine

60
Q

so how is caffeine made?

A

the N-methyltransferases from the caffeine biosynthetic pathway have high protein sequence homology (<80% identity) yet exhibit remarkable substrate selectivity

61
Q

genetic engineering of caffeine production?

A

-can use genetic engineering to either increase caffeine levels in coffee?

can use it to make caffeine in plants that do not normally make this compounds?

can use it to reduce the levels of caffeine by knocking out the key enzymatic steps

62
Q

effects of caffeine on leaf borer

A

transgenic caffeine producing tobacco plants repel tobacco cutoworm (spodoptera litura)

-tobacco cutworm larvae at the third instar stage of development

-larvae were starved for 3 hr then allowed to feed for 3 hr in darkness on three wild type and three transgenic leaf discs producing 5g caffeine/g

quantification of feeding behavior

63
Q

genetic engineering to alter purine alkaloid metabolism

A

production of decaffeinated coffee plates

RNAi mediated gene silencing

target MXMT gene

building caffeine metabolism into new plant species

-expression of CaMXMT, DXMT genes in tobacco

significant increases in resistance to tobacco cutworm

BOT 380 (3 decks)

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