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142 Cards in this Set
- Front
- Back
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Action of tryciclic antidepressants |
inhibit reuptake of norepinephrine & serotonin |
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Amine hypothesis |
depression = caused by reduction of monoamine mediated neurotransmitters 1950’s: reserpine induced depression and depleted stores of amineneurotransmitters. Thus it was reasoned that depression = associated withdecreased amine-dependent neurotransmission. |
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Neurotrophic hypothesis |
reduced neurotrophic support (= reduced growth & interconnectivity of neurons) Suggests thatantidepressants stimulate neurogenesis and synaptic connectivity in brain Brain-derived neurotrophicfactor (BDNF) (= a protein necessary for neural growth) is reduced indepression but antidepressants reverse process. |
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ANS |
voluntary a) sympathetic (fight & flight) b) parasympathetic (rest & relax) |
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Glutamate |
= major excitatory neurotransmitter foundin almost all neurons involvedwith learning |
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GABA |
= major inhibitory neurotransmitter many receptors in cerebral cortex, hippocampus, cerebellum 2classes of receptors: A (fast acting) and B (slow acting). CNS depressants enhance receptor A function. |
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Parkinson's Alzheimer's |
loss of dopaminergic neurons in substantia nigra loss of cholinergic neurons from cortex |
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1) What causes tolerance, dependence & addiction? 2) What causes only tolerance & addiction? |
1) Opiates, CNS depressants (ethanol, benzodiazpines) & stimulants (amphetamines, cocaine) & cannabis 2) Hallucinogens |
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1) Parasympathetic 2) Sympathetic |
1) preganglionic --> acetylcholine postganglionic --> acetylcholine 2) preganglionic --> acetylcholine postganglionic --> norepinephrine |
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Basic functions of the nervous system |
The nervous system controls all bodily functions 1) Recognize (identify changes ininternal/external environment)
2) Process & Integrate(perceive such changes)
3) React |
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1) central part of the nervous system consists of? 2) peripheral part of the nervous system consists of? |
1) brain & spinal cord 2) nerve fibres |
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1) ____________ nerves carry messages from tissues to brain 2) ____________ nerves carry messages from brain to the tissues |
1) sensory nerves 2) motor nerves |
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Spinal cord functions |
1) Carries sensory info from skin/muscles/joints/internal organs tobrain 2) Control motor outflow to muscles 3) Controls sensory input (e.g. pain sensations)4) Controls reflex activity (e.g. breathing) |
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Brain functions |
1) Receives and processes information 2) Initiates a response 3) Stores memory 4) Generates thoughts and emotions |
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3 parts of the brain |
1) Forebrain: 2) Midbrain: 3) Hindbrain: |
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Forebrain |
a) Cerebral cortex (celebrum) b) Thalamus c) Hypothalamus d) Limbic system e) Pituitary gland |
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Cerebral cortex (celebrum) |
occipital (vision), temporal (hearing), parietal (sensory perception), frontal (high level cognitive functions). Functions = sensory & motor coordination, mental processes, intelligence, memory, vision, judgement, thought, speech, emotions, consciousness. |
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Thalamus |
Thalamus: = relay centre from which impulses are relayed to cerebral cortex. Functions = coordinate & filter incoming signals & pain sensation |
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Hypothalamus |
Functions = controls involuntary bodily processes (heart beat, blood pressure, body temperature etc.), controls feeding/drinking/sexual/emotional responses. Neurons in hypothalamus produce “releasing factors” which can modify pituitary gland. |
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Limbic system |
Closely associated with hypothalamus. It integrates memory, emotion and reward. Together with hypothalamus it controls emotion and behaviour. Contains dopaminergic reward centers, which are targets for drugs of abuse. |
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Pituitary |
= small gland, located at base of brain that secretes hormones (e.g. follicle stimulating hormone), which then act on peripheral tissues. These hormones are involved with growth, behaviour and metabolism. |
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Midbrain |
links forebrain tohindbrain. = Relay centre for visual and auditory signals |
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Hindbrain |
1) Pons 2) Medulla (the bulb) 3) Cerebellum |
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Brain stem |
midbrain, pons & medulla |
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Pons |
Connects midbrain tomedulla/cerebellum. Conducts signals from cerebral cortex down tomedulla/cerebellum. |
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Medulla (the bulb) |
= site oforigin of many cranial nerves. Regulation of respiration, heart rate, bloodpressure occurs here. It also controls some involuntary activity (autonomousnervous system). Barbiturates depress respiration & blood pressure bydepressing the medulla. |
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Cerebellum |
= connected tobrainstem by large fibre tracts. Responsible for coordination & posture. Doesn’t initiate movement but organizes voluntary activity that imitatedelsewhere. Drugs which effect the cerebellum (alcohol) will cause ataxia (drunkenness). |
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neuron |
= brain nerve cell = Functional unit of brain Generates & transmits electrical signals |
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neuroplasticity. |
The continuous remodelling that occurs when neurons are generated continuously(neurogenesis), and connections between them are constantly being reshaped. |
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3 main parts of a neuron |
1) Cell body (soma): largest part,contains nucleus 2) Dendrites: like a receivingantenna for incoming info, via receptor on dendritic membrane. When a signal isreceived an electric current is generated and directed down the neuron. 3) Axon: carries this signal awayfrom dendrites/cell body via electrical pulses. |
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1) Synapse 2) Synaptic cleft
3) Synaptic transmission |
1) junction between 2 neurons 2) space between them 3) passage of a signal from neuron to another (= usually chemical) |
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chemical transmission |
The release of a substance is required in order to activate the other neuron or pass on the message |
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neurotransmitters |
= endogenous (normally found in body) chemicals |
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synaptic transmission: |
1) The nerve impulse (electrical activity) passes down axonand causes vesicles (containing the neurotransmitter) to fuse with themembrane. 2) The vesicles release theneurotransmitter into the synaptic cleft (=exocytosis) and the neurotransmitter diffusesacross the synaptic cleft to the postsynaptic membrane. 3) The neurotransmitter binds to the receptors on the postsynaptic membrane, changing the permeability of the membrane. 4) Ions (e.g. calcium) then move across the postsynaptic membrane,causing a change in electrical activity of the membrane and thus passing theelectrical activity along to the next neuron. |
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Terminationof synaptic transmission: 3 major mechanisms |
1) Broken down by enzymes (e.g.Acetylcholine is broken down into Acetate + Choline by Acetylcholinesterase(AChE)) 2) Taken back up into presynaptic neuron(e.g. dopamine, norepinephrine, serotonin) 3) Taken up into adjacent glial cells (e.g.glutamate) |
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Acetylcholine |
= a neurotransmitter called "cholinergic" synapses & receptors Found in peripheral & central NS. 2types of receptors: Nicotinic receptors & Muscarinic receptors. |
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Drugs which block or antagonize the action of acetylcholine produce __________? |
Amnesia |
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Nicotinic receptors |
= cholinergic (involving acetylcholine) receptors, stimulated by nicotine Found in all autonomic ganglia, at the neuromuscular junction, and in certain regions of the brain. Loss of these cholinergic neurons = associated with Alzheimer's disease. Respone: impulse conducted to postganglionic neuron |
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Muscarinic receptors |
stimulated by the alkaloid "muscarine" Found in many regions of the brain, heart, smooth muscle, glands. Involved in learning, memory, and cognitive function. Response: 1) decreased heart rate and force of contraction 2) smooth muscle contraction and gland secretion |
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Catecholamines |
= the neurotransmitters dopamine and norepinephrine |
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Dopamine |
= a neurotransmitter. Pathways found in hypothalamus, basalganglia and brain stem. Involved in motivation, rewards, hormonal systems, andmotor coordination. à Associated with Parkinson’s, Schizophrenia. Most important receptors = D1 (excitatory) and D2 (inhibitory) |
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Norepinephrine |
= a neurotransmitter. Pathways originate in brain stemand project to cerebral cortex, hypothalamus, limbic system, and cerebellum. 2main classes of receptors: alpha (α)and beta (β) (both usually excitatory) |
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Serotonin |
= a neurotransmitter. Receptors found in brain stem, medulla, hypothalamus and cerebral cortex. Hyperactivity of this system = involved in anxiety, hypo-activity = involved in depression. 4 types of receptors. |
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Opioidpeptides |
= neurotransmitters. 3 classes:enkephalins, endorphins, dynorphins. They have varying degrees of selectivityfor the 3 receptor types: mu (μ),delta (δ) and kappa (κ) Severaltypes of a particular receptor, each with differing functions, and specifically distributed throughout the brain. This allows for integration of functions in the CNS. |
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SubstanceP |
= 11amino acid peptide = a neurotransmitter. Plays an important role as a sensoryneurotransmitter à paintransmission in spinal cord & brain. Opioids and other drugs owe someof their analgesic action to the inhibition of the release of substance P. |
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2 maintypes of nerve fibres in peripheral NS: |
1) Afferent (sensory) fibres = carry messagesto brain (not targeted by drugs) 2) Efferent (motor) fibres = carry messagesfrom brain to tissues a) Somatic nervous system (innervatesskeletal muscle) b) Autonomic nervous system (controlsinvoluntary movement) |
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Somaticnervous system (peripheral NS) |
Longmotor nerves release neurotransmitter acetylcholine when innervating skeletal muscles Acetylcholinebinds to nicotinic receptors on muscle called NM Synapse= called neuromuscular junction, which is where drugs would interfere with neurotransmission
Notmany drugs target skeletal muscle. Usuallyduring surgery and to reduce spasticity. Example= curare |
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Autonomicnervous system (peripheral NS) |
2parts: 1) Sympathetic nervous system:“fight and flight”, activated when under stress 2) Parasympathetic nervous system: “rest and relax”, activated under non stressful conditions Controlsinvoluntary responses by influencing organs, glands and smooth muscle (governs unconscious bodily functions like heart rate, blood pressure, bowelmovement etc.) Here, 2 neurons are needed to reach target organ. First neuron’s cell body = inCNS (“preganglionic nerve”), second neuron’s cell body = in ganglia(“postganglionic nerve”) |
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Parasympatheticnervous system |
increases thevegetative functions of the body its neurons originate in the cranial(top) and sacral (bottom) parts of the spinal cord. All parasympathetic nerves release the neurotransmitteracetylcholine To terminate response, acetylcholinesterase breaks downacetylcholine into acetate and choline |
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Organizationof parasympathetic NS |
Longpreganglionic fibres release acetylcholine, which binds to nicotinicreceptors of ganglia Activationof these receptors transmits signal to postganglionic neuron Shortpostganglionic fibres release acetylcholine, which binds tomuscarinic receptors on target organ |
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Drugs thattarget parasympathetic NS |
Drugseither target the receptors (direct acting agents) OR block metabolism ofacetylcholine, thus increasing amount of acetylcholine in synaptic cleft(indirect acting agents) Drugsthat stimulate parasympathetic NS = notwidely used as they may slow heart rate & constrict respiration Drugsthat inhibit parasympathetic NS byblocking M receptors (= anticholinergic drugs) = more common. But: adverse sideeffects limits clinical use |
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Sympathetic nervous system |
(Stress-->)Stimulation of sympathetic NS--> mobilization of resources for emergency --> increased activity of body functions --> permitsphysical performances otherwise impossible (“sympathetic alarm reaction”) Preganglionicneurons originate in middle of spinal cordand release acetylcholine, which binds to NN receptors of ganglia. Postganglionic neuronsrelease the norepinephrine which binds to “adrenergic”receptors |
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3types of adrenergic (norepinephrine) receptors |
Alpha-receptors Beta-receptors: β1 receptors & β2 receptors: |
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Alpha-receptors (adrenergic) |
on smooth muscle (e.g.blood vessels, gastrointestinal muscle, uterus). Activation leads to contraction of muscle. Multiple subtypes that allow for drug selectivity. |
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Beta-receptors (adrenergic) |
β1 receptors: found in heart. Activation leads to increased force & rateof heart contractions. β2 receptors:found in lungs, blood vessels, gastrointestinal muscle, and uterus. Activation leads to smooth muscle relaxation. |
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Organizationof sympathetic NS: |
Shortpreganglionic neurons that release acetylcholine and bind to NN receptors on ganglia. Activationof these receptors transmits signal to postganglionic neuron Longpostganglionic fibres release norepinephrine, which binds adrenergicreceptors on target organ |
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Drugsthat stimulate sympathetic NS |
used for heart, bronchial tree & nasal passages Effects= similar to anticholinergics, but more specific & dependable due toreceptor subtypes Examples:phenylephrine (activatesα receptors) for nasal congestion; salbutamol (activates β2 receptors) for asthma. Manydrugs activate more than 1 receptor subtype |
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Drugs that inhibit sympathetic NS |
“rest& relaxation” --> wide therapeutic application! Most widely prescribed drugs that targetautonomic NS = drugs that block sympathetic NS. Example: β1-blockers slow heart rate & lower bloodpressure. |
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Summary ofdrugs that target autonomic NS |
1) Drugs that MIMIC the effects of the sympathetic system. Example: norepinephrine (α and β1 receptors) 2) Drugs that BLOCK the effects of the sympathetic system. Example: propranolol (β receptors in the heart) 3) Drugs that MIMIC the effects of the parasympathetic system. Example: acetylcholine (N and M receptors) 4) Drugs that BLOCK the effects of the parasympathetic system. Example: atropine (M receptors) |
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Drugs affecting the ANS via the brain |
Central stimulants canincrease sympathetic and parasympathetic activity (excitation) Central depressants can decrease the activity ofthese two systems (inhibition). |
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Level ofaddiction/dependency depends on |
a) Genetic factors b) Co-existing disorders c) Environmental risk factors d) Developmentalaspect |
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Dopamine hypothesis: |
motivational reward systems Predominant hypothesis toexplain addiction Suggests that drugs ofabuse increase dopamine in reward systems of brain (+ nucleus accumbens &ventral tegmental area) |
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Substance Abuse |
1) The use of prohibited drugs. 2) The use of any therapeutic drugs for other than its intended use. 3) The intentional ingestion of any therapeutic drug in amountsgreater than that prescribed, or taking the drug by routes other than thosemedically approved. 4) Taking drugs in combination in order to obtain a greaterpleasurable effect. 5) The excessive use of licit (legal) social drugs (alcohol,caffeine, tobacco). |
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Abuse potential of a drug |
1) Dependence liability: tendency of drug to cause addiction/dependence
2) Availability: example: alcohol = most highly abused psychoactive substancebecause it is readily available 3) Inherent harmfulness = potential of drug to cause harm. |
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Substance dependence |
= State of periodic orchronic intoxication produced by repeated consumption of the drug 3 important aspects: - tolerance, - dependence & withdrawal, - addiction |
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Drug tolerance |
state in which repeatedadministration of drug has less and less effect OR a state in which dose ofdrug must be increased to obtain same magnitude of effect as original dose. |
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Drug dependence & withdrawal |
= abnormal physiologicalstate produced by repeated administration of a drug that leads tocharacteristic symptoms when dose is decreased or drug use discontinued. A withdrawal symptom = the characteristicfeature that defines dependence. |
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Drug addiction |
= state in whichstopping/reducing dose produces non-physicalsymptoms. It is characterized by emotional & mental preoccupation withdrug & persistent cravings. Harder to treat than dependence. |
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Compulsive substance use |
When the individual takes the substance in larger doses and for longerperiods of time than intended. |
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Reactive (secondary depression) |
= most common (60% of all depression cases). Occurs in response toreal stimuli like grief or illness. Resolves spontaneously or variety of treatments |
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Major depression (endogenous) |
= a genetically determined biochemicaldisorder, which causes an inability to cope with ordinary stress. Characteristic disturbances of major body rhythms (sleep, hunger, appetite). Accounts for 25% of all depressions. Treated with antidepressants |
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Depression associated with manic-depressive (bipolar) disorder |
accounts for 10-15% of all depressions. Treated with mood stabilizers & antidepressants |
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Possible sites of antidepressant drug action |
1) Re-uptakeinhibitors (neurotransmitter stays in synaptic cleft longer) 2) MAOinhibitors (MAO destroys neurotransmitter (serotonin, norepinephrine, dopamine)after re-uptake so more available neurotransmitter) 3) Blockthe auto receptors where the released norepinephrine/serotonin feedback tocontrol their release from the presynaptic neuron |
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Tricyclic antidepressants (TCA’s) |
Allshare a 3 ring nucleus. Example: imipramine Firstantidepressants. Overdosecan be lethal Inhibit the reuptake of serotonin and norepinephrine Manyadverse effect, thus not used no unless alternative:a) Anticholinergic effects (dry mouth,constipation, urinary retention, blurred vision)b) Antiadrenergic (alpha) effects (hypotensionwhen standing)c) Antihistaminic actions (sedation)d) Weight gaine) Sexual dysfunctionf) May disturb heart rythm |
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Second-generation (atypical) antidepressants |
Structurallyunrelated to tricyclic antidepressants. Introducedafter 1980 Inhibitsserotonin & norepinephrine re-uptake Fewerside effects Examples:bupropion, amoxapine |
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Selective Serotonin Reuptake Inhibitors (SSRI’s) |
- Introducedbetween 1980-90. Example: fluoxetine (Prozac) - Mostcommonly used drug for depression - Selectivefor inhibiting serotonin re-uptake (much less effect on norepinephrinere-uptake) - Nausea, headache, nervousness, insomnia happen more frequently than with TCAS’s(however: they do not cause hypotension, weight gain or anticholinergiceffects) - Biggestadvantage over TCA’s: much safer in over-dosage |
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Monoamine Oxidase (MAO) inhibitors |
Twotypes of enzymes: MAO-A and MAO-Bo MAO-A= responsible for metabolism of norepinephrine, serotonin, tyramine àtargeting this system = better for treating depression MAO-B= more selective for metabolism of dopamine Byblocking a major pathway for the monoamine neurotransmitters, more aminesaccumulate in presynaptic stores and more will be released into the cleft Usedonly when other drugs have failed Inhibition persists for several weeks even after drug is no longer detectable. Interacts with other drugs & tyramine containing foods. |
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1) Example of a non-selective inhibitor of MAO-A and MAO-B. 2) Example of a short-acting reversible inhibitor of MAO-A |
1) phenelzine 2) moclobemide (selective & drugis rapidly cleared from system) |
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5 Common features of neurodegenerative diseases |
1) The brain area where the neuronal lossoccurs = selective for that diseases (other areas = unaffected) 2) Each disease has distinct genetic formsof the condition. 3) Presence of inappropriate protein ordeposition of a protein in a specific brain region. 4) Primarily disorders of age, althoughchildhood forms exist 5) Currently available treatments controlsymptoms but do not alter disease process. |
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Parkinson’s 4main clinical features: |
4main clinical features:1) Bradykinesia (slow/poor movement)2) Muscle rigidity 3) Tremor at rest4) Poor postural balance as well as ashuffling and impaired gait |
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Parkinson’s |
Characterizedby loss of dopaminergic neurons in the substantia nigra pars. They project tostriatum (--> motor coordination & movement) Lossof dopaminergic function = normal aging process, but in Parkinson’s 70-80% ofdopaminergic function is lost Asthe disease progresses, other brain structures are affected (--> sleep and memory loss) |
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idiopathic Parkinson’s |
= no known cause Most common form of Parkinson’s (other forms can result from stroke or drugs) |
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Parkinson’s Treatment aims at |
enhancing function of remaining dopaminergic neurons by increasingamount of dopamine, inhibiting breakdown of dopamine or administering dopamineagonists. |
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Drugs for Parkinson’s |
o Dopamine o Levodopa o SelectiveMAO-B inhibitors o Catechol-o-methyltransferase(COMT) inhibitors o Dopaminereceptor agonists |
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Dopamine (Drugs for Parkinson’s) |
Dietary phenylalanine gets converted totyrosine Tyrosine = taken up into neuron, whereenzyme tyrosine hydroxylase converts it into DOPA, which is converted intodopamine (DA)
The enzymes "monoamine oxidase" and "catechol-o-methyltransferase" inactivate dopamine |
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Levodopa (Drugs for Parkinson’s) |
Dopamine does not cross blood brainbarrier --> administering dopamine has no effect But levodopa (manufactured form of DOPA)can cross it. However it is rapidly metabolized to dopamine in peripheraltissues Then, an inhibitor of the enzyme thatconverts levodopa to dopamine (carbidopa) is added The combination allows 10% of a dose oflevodopa to reach brain Adverseeffects of levodopa = nausea & hallucinations |
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The most effective drug treatment for Parkinson’s |
= Combination of levodopa & carbidopa Dramatic improvement in tremor, rigidity, andmovement. Effect is reduced with long-term use & motor symptoms beginto fluctuate “Wearing off” phenomenon, whereeach dose of the drugs improves walking and balance for one to two hours, andthen the symptoms return. |
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SelectiveMAO-B inhibitors (Drugs for Parkinson’s) |
he enzymes MAO-A and MAO-B metabolisemonoamines, including dopamine MAO-B = predominant in striatum &responsible for most metabolism of dopamine in brain Inhibitors (like "selegiline") inhibitbreakdown from dopamine to DOPAC Selegline does not interact with tyramine in cheeses likenon-selective MAO inhibitors |
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Catechol-o-methyltransferase(COMT) inhibitors (Drugs for Parkinson’s) |
= Another enzyme that breaks downdopamine Administration of levodopa &carbidopa decreases amount that gets converted into dopamine, BUT increasesamount converted to another metabolite Inhibitors (like tolcapone) reducemetabolism of levodopa & increase levels of levodopa reaching the brain Adverse effects: nausea, vivid dreams, confusion, hallucinations |
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Dopaminereceptor agonists (Drugs for Parkinson’s) |
Useful for patients who are notadequately controlled with levodopa Adverse effects: hallucinations, confusion & reward-seeking behaviour Example: ropinirole (= dopamine agonistfor D2 dopamine receptors) |
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Alzheimer’s |
1) Progressiveloss of memory & cognitive function 2) Patientsbecome anxious, depressed, irritable. Can result in vegetative state 3) Presenceof proteins (β-amyloid)into cerebral cortex --> development of neurofibrillary tangles --> progressive neuronal loss (esp. cholinergic neurons) |
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Alzheimer’s Treatment aims at |
modifyingcholinergic transmission, or to enhance transmission in remaining cholinergicneurons |
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Drugs for Alzheimer’s |
1) Cholinesteraseinhibitors 2) Memantine 3) Others (antipsychotics& mood stabilizers) (tocontrol behavioural symptoms) |
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Cholinesteraseinhibitors (Drugs for Alzheimer’s) |
Reduce rate of breakdown ofacetylcholine in brain, enhancing activity of acetylcholine àimproving memory & cognition Leads to modest symptom improvement· Adverse effects --> gastrointestinal effects, muscle cramps, and abnormal dreams. Examples: donepezil, rivastigmine,galantamine |
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Memantine (Drugs for Alzheimer’s) |
An antagonist for a glutamate receptorcalled NMDA receptor. It slows rate of destruction of neuronsby inhibiting excitatory responses to glutamate, preventing glutamate-inducedexcitatory neuronal death This is mediated by NMDAreceptors. By inhibiting glutamate from binding to NMDA receptors, neurons canbe protected |
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Huntington’s |
Inherited. Gradual onset of motor incoordination, impairment of balance & decline of cognitive functions (usually in midlfe) Memory is impaired but patients don’t lose memory of friends/family; and depression often co-occurs Loss of neurons in striatum, specifically loss of nerve projections from the striatum --> decrease in GABA |
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Treatment for Huntington’s |
Currently only symptom control Antidepressants for depression, antipsychotics for paranoia, psychosis, delusional states, BUT no effective treatment for primary disorder Depletion of catecholamines using resperpine or tetrabenazine (inhibits storage of catecholamines into vesicles) may help with motor symptoms |
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Amyotrophic Lateral Sclerosis (ALS) (LouGehrig’s disease) |
Disorder(loss) of motor neurons in spinal cord, brain stem and brain. Theseneurons control voluntary muscles Messagesfrom motor neurons in brain (upper motor neurons) = transmitted to motorneurons in spinal cord (lower motor neurons) and then to muscles Firstsymptoms = mild (muscle twitching, cramps), but rapid progression. Death canresult from compromised respiration or complications due to loss of motorfunction |
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Treatment for Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig’s disease) |
No cure Riluzole (= glutamate receptor blocker) thought to decrease rate of cell death, increases survival by several months Other treatments focus on control of spasticity and respiratory assistance |
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Amphetamines |
CNS stimulants Dextroamphetamine, methamphetamine & designer drugs (like MDA) Structurally similar to norepinephrine, epinephrine, dopamine Act primarily by releasing neurotransmitters norepinephrine & dopamine from nerve terminals = substrates for dopamine transporter (DAT) and taken into nerve terminal where it blocks packaging of dopamine into vesicles --> more dopamine |
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Illicit metamphetamine |
Meth, Crystal, Speed |
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3 common amphetamine compounds, in order of magnitude of CNS effects they cause |
1) methamphetamin 2) dextroamphetamine 3) amphetamine |
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How does methamphetamin differ from amphetamine? |
methamphetamin: more central & less sympathetic stimulation than amphetamine |
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Cardiovascular effects of amphetamine |
1) fight & flight response 2) Increased blood pressure 3) Increased heart rate |
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CNS effects of amphetamine |
1) alterness, hyperactivity, insomnia 2) Anorexia 3) Hyperthermia (increase in body temp) 4) Respiratory centre stimulation 5) Neurotransmission in spinal cord 6) Convulsions (with high doses) |
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Brain areas amphetamines act on |
1) reticular activating system (RAS) (sensory info) 2) Medial forebrain bundle (reward) 3) Hypothalamus (temperature, food) 4) Limbic system (emotion) |
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Therapeutic uses of amphetamine-like drugs |
1) Narcolepsy (drug: methylphenidate) 2) ADHD (drug: methylphenidate) methylphenidate --> lowers incidence of cardiovascular effects |
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Effects of long term amphetamine use |
1) chronic sleep problems 2) anxious & tense 3) poor appetite 4) elevated blood pressure & abnormal heart rhythm 5) suspicious, paranoid 6) repetitive behaviour |
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Effects of long term amphetamine use |
1) CNS: alertness, restlessness, dizziness, euphoria, feeling of well being & enhance performance 2) Cardiovascular: increased BP, irregular heartbeat 3) Increased respiratory rate |
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Tolerance to amphetamines |
tolerance develops rapidly to euphoria & mood elevating effects. also develops to the anorectic, lethal, cardiovascular & respiratory effects tolerance does not develop to psychosis. |
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Dependence on amphetamines Addiction to amphetamines |
Cessation of drug use results in - mood depression - prolonged sleep - huge appetite - lassitude and fatigue Addiction develops: users will crave drug intensely when unavailable |
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Potential for abuse: amphetamines |
= extremely high (powerful euphoria) large doses can easily be injected (drug = water soluble) Inherent harmfulness resides in the long-term toxicities. There is also a substantial risk with the "user-lifestyle" (contaminated needles, poor nutrition) |
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Cocaine |
= naturally occurring alkaloid found in leaves of cocoa bush = local anaesthetic = CNS stimulant = narcotic (law) Freud studied it. Karl Koller introduced it as anaesthetic. It inhibits re-uptake of dopamine (CNS) & norepinephrine (periphery) |
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Differences/similarities between amphetamines & cocaine |
behavioural effects & pattern of toxicity = similar differences - shorter duration - less complications associated with intravenous use (cocaine = ususally snorted) - tolerance develops slower |
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Only legitimate use of cocaine? |
Local anaesthetic for mouth, throat & in the eye. Rarely used. |
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Metabolism of cocaine |
Cocaine is metabolized to inactive form "benzoylecgonine", which is excreted in urine. Benzoylecgonine can be detected up to 48hrs after a single dose and up to 2 weeks in a chronic user. |
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Alcohol & cocaine |
Alcohol potentitaes the effects of cocaine. It reacts with cocaine to form the active metabolite "cocaethylene" |
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1) Streetnames for cocaine 2) Streetnames for freebase of cocaine |
1) coke, flake, snow, stardust 2) crack, rock, freebase |
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Short-term cocaine effects |
1) CNS: dilated pupils, euphoria, well being, reduced appetite, increased self-confidence, feeling of superiority 2) cardiovascular: increased BP, increased heart rate (after it initially slows), vasoconstriction 3) increased respiratory rate With high doses: tremor & muscle twitches, seizures, acute renal failure |
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Effects of long-term cocaine use |
1) mood swings, nervous, agitated, excitable 2) paranoia 3) hallucinations or sensations of insects crawling under skin 4) sleep & eating disorders 5) Impaired sexual function 6) perhaps brain damage 7) high BP & irregular heart rhythm 8) changes to nasal mucosa (from snorting) 9) social problems |
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Cocaine: Tolerance |
Tolerance develops to mood elevating effects Does not develop to psychotic effect |
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Cocaine: Dependance |
Develops. Withdrawal symptoms = similar to amphetamines |
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Cocaine: Addiction |
Develops. because effects are so pleasurable & rewarding |
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Cocaine: Potential for abuse |
abuse liability & inherent harmfulness = one of the highest among al drugs of abuse. Due its rapid, powerful euphoria. |
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Caffeine effects |
Cerebral cortex: increased mental performance & enhanced motor activity, decreased fatigue Medulla: increased respiration & heart rate Cardiovascular: increased heart rate & BP (high doses --> disturbance in heart rhythm) |
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Caffeine |
- rapidly absorbed - blood levels peak 2 hrs after ingestion - freely crosses to brain & placenta - half-life = 2.5-10 hourse - rate of metabolization depends on genetics |
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Caffeine mechanism of action |
In striatum, adenosine receptors stimulate GABA neurons that inhibit dopamine release Blocking adenosine receptors --> increased dopamine Adenosine has inhibitory effect. Blocking it leads to increased neuronal activity. |
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Caffeine: effects of short term use |
CNS: - mild mood elevation & reduced fatigue - small increase in performance (?) - more clear & rapid flow of thought - nervousness & jitters Cardiovascular: constriction of cerebral blood vessels Mild increase in respiratory rate |
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Caffeine: effects of long term use |
restlessness, nervousness, insomnia, increases urination, gastric upset, rambling speech & thought. |
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Caffeine: tolerance |
Some evidence that it develops for some people. But its placebo effect = very strong. |
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Caffeine: dependance & addiction |
both develop. Abrupt cessation will lead to: headache, fatigue, drowsiness |
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1) Caffeine: potential for abuse 2) Caffeine: inherent harmfulness |
1) = low. The "high" is mild in intensity. 2) = very low. Low to moderate intake (3 cups/day) = not associated with adverse events |
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Nicotine |
= naturally occurring substance, found in tobacco. 1 of the 3 most used psychoactive drugs (next to caffeine & alcohol) Leading cause of preventable disease/death in Canada Stimulates nicotinic receptors in the CNS and ganglia in peripheral/sympathetic NS (cardiovascular effects) It readily penetrates the brain and crosses into placenta. Half-life: 2 hours |
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Nicotine: absorption & metabolism |
rapidly absorbed (when inhaled) 20% of nicotine in a cigarette is absorbed occurs in GI tract, oral mucosa and across skin (patches). rapidly metabolized in the liver, and excreted with urine. |
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Medical us of nicotine |
Only in smoking cessation programs Administered as chewing gum or transdermal patch, which allows tapering off of the nicotine dose. Aim = to satisfy cravings |
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Short term effects of nicotine use |
Non-smoker: dizziness, headache, nausea, , coughing, vomiting. Regular smoker: mild euphoria, enhanced arousal, increased concentration, sense of relaxation. May depress appetite. |
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Tobacco smoke contains |
nicotine, carbon monoxide, and other compounds (including carcinogens). Nicotine & carbon monoxide cause cardiovascular disease, by reducing capacity of red blood cells to carry oxygen. |
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Long term effects of nicotine use |
Nicotine & carbon monoxide cause cardiovascular disease, by reducing capacity of red blood cells to carry oxygen. Lung disease Cancer: strong association. 30% of all cancers are caused by cigarette smoke. Esp. lung, oral cavity, throat, bladder, uterus |
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Effects of "passive smoke" |
increased risk of cardiovascular disease & cancer In children: increased risk of bronchitis, pneumonia, asthma and sudden infant death syndrome. |
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1) Nicotine: tolerance 2) Nicotine: dependance & addiction |
1) does not develop. Most smokers smoke to keep their nicotine levels at a certain range. 2) both develop. Withdrawal symptoms: irirtability, restkessness, anxiety, insomnia, fatigure, inability to concentrate & extreme urge to smoke (which may persist for 2 months). |
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Nicotine: Potential for abuse |
= high powerful reinforcer cessation programs involve counselling & pharmacological support. Attempts to quit often fail. |
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Nicotine & pregnancy |
1) adverse effects on fetus (even with passive smoke) 2) mechanism: decreased oxygen flow to fetus 3) if mother stops smoking early in pregnancy the effect of 2) is reversed 4) 2-3 x increase in fetus being born small or preterm |
