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135 FINAL
| Question | Answer |
|---|---|
| which nt is primarily associated with addiction? | dopamine |
| define tolerance | decreased effect of drug with continued use |
| define physical dependence | neurological adaptation to the continued presence of the drug, req continued use of the drug, l/t withdrawal synd |
| define addiction | obsessive desire for continued adminof a drug, even wh consequences may be deleterious |
| what are the effects of nicotine? | alerting w/ anxiolytic effects |
| what sx are assoc with nicotine withdrawal synd? | irritability, impatience, hostility anxiety dysphoria, depressed mood difficulty concentrating restlessness decreased HR increased appetite and weight gain |
| what are the initial sx of opioid abstinence synd? | within 6-12hr: craving, pupillary dilation, restlessness, irritability, sweating, piloerection, increased pain sensitivity, nnv, muscle cramps and hyperreflexia, increased BP, dysphoria, insomnia |
| what are the long-term sx of opioid abstinence synd? | anx, insomnia, craving |
| name 4 agents used for management of opioid abstinence synd | methadone buprenorphine naltrexone clonidine |
| what is the danger in treating mixed dependency w/ opioids and CNS depressants? | using antagonists of either type (naloxone for opioids or flumazenil for CNS depressants) can increase the risk of seizures |
| what is the MOA of cocaine's effects? | reuptake inhibitor of DA, NE, 5HT, and Na+ channel blocker |
| what are the effects of cocaine? | intense euphoria, cardiac stimulation, tolerance, and addiction |
| what CNS stimulant is the closest pharmacological mimic to cocaine? | modafinil |
| what is the MOA of methamphetamine? | DA releaser, moderate reuptake inhibition |
| what are the cannabinoid receptors and where are they located? | CB-1 CNS CB-2 peripheral |
| what is the endogenous cannabinoid ligand? | anandamide |
| name three psychomimetics | MDMA LSD PCP |
| what is MDMA and what does it do? | methylenedioxymethamphetamine, "ecstasy" synthetic amphetamine-like agent, px perceptual distortions |
| what is LSD and what does it do? | lysergic acid diethylamide typical "hallucinogen" px by fermentation, px perceptual distortions, bizarre sensory anomalies and elation |
| what is PCP and what does it do? what is its MOA? | phencyclidine, px muscular rigidity, aggression, abnl sensory processing, decreased pain sensation MOA: NMDA antagonist w/ sig anticholinergic activity |
| what serious side effects can PCP induce? | high doses induce rhabdomyolysis, seizures, coma |
| what is flunitrazepam? | Rohypnol, a potent anesthetic, hypnotic, muscle relaxant, and anticonvulsant which px anterograde amnesia |
| what is GHB? | gamma-hydroxybutyrate: GABA metabolite and GABA-B agonist, px profound disinhibition, and anterograde amnesia |
| what is the MOA of caffeine? | adenosine antagonism in the CNS |
| what are the effects of caffeine? | increased wakefulness and alertness |
| what are amphetamines used for? | used in management of ADD, narcolepsy, and weight loss |
| what is the MOA of amphetamines? | enhanced release of NE, DA, 5HT in the mesolimbic system and other areas of the brain |
| what are the effects of amphetamines? | alertness and decreased sense of fatigue, increased concentration and focus, euphoria, decreased appetite, decreased sensitivity to pain |
| name 4 amphetamines | metamphetamine (Desoxyn) methylphenidate (Ritalin) dexmethylphenidate (Focalin) pemoline (Cylert) |
| which drugs are used for work-shift d/o and narcolepsy? | modafinil (Provigil) and armodafinil (Nuvigil) |
| how does modafinil work? | facilitates multiple nt activities in the brain, incl NE, DA, 5HT; without direct effects on receptor function |
| what are the side effects of modafinil? | rash, Stevens-Johnson synd, and psychiatric disturbances |
| name 5 CNS stimulants used as appetite suppresants | phentermine (Adipex-P, Fastin) diethylpropion (Tenuate) sibutramine (Meridia) phendimetrazine (Bontril) benzphetamine (Didrex) |
| why can't sibutramine be used with glaucoma? | increases IOP |
| how long can appetite suppressants be used? | 1-2 wks use |
| what are the side effects of appetite suppressants? | similar to amphetamines: HTN, psych disturbances, increased risk of seizure in pts w/ hx of seizure d/o |
| which spasmolytic agent is used for spasticity assoc/ neurodegeneration? | baclofen (Lioresal) |
| how does baclofen work? | analog of GABA, inhibits GABA-B receptors also inhibits glutaminergic activity |
| what alpha2 adrenergic agonist treats spasticity and how does it work? | tizanidine (Zanaflex) inhibits corticospinal stimulation of motor neurons assoc/ spasticity |
| what are the side effects of tizanidine? | drowsiness, hypotension, dry mouth, asthenia (weakness/tiredness) |
| which anticonvulsant is used in spasticity d/o's? | gabapentin (Neurontin) |
| which agent affects calcium release and by interacting with which receptor? | dantrolene (Dantrium) inhibits RyR1-mediated calcium release in the SR |
| why is dantrolene rarely used? | causes liver damage |
| how does botulinum toxin work? | inhibits vesicular release of ACh, can tx group muscle spasticity by direct injection |
| name 6 centrally acting muscle relaxants | carisoprodol (Soma) cyclobenzaprine (Flexeril) chlorzoxazone (Paraflex) metaxalone (Skelaxin) methocarbamol (Robaxin) orphenadrine (Norflex) |
| what is the major side effect of centrally acting muscle relaxants? | sedation is strong |
| what is Alzheimer's Dz char by? | impairment of memory and cognitive function, involving hippocampal region loss of cholinergic neurons and excessive glutaminergic activity (NMDA) amyloid plaques in the brain |
| what agents are used to treat Alzheimer's Dz? | ChE inhibitors donepezil (Aricept) rivastigmine (Exelon) galantamine (Razadyne) tacrine (Cognex) NMDA antagonists memantine (Namenda) |
| what is ALS? | amyotrophic lateral sclerosis, a progressive and fatal spasticity d/o resulting fr degeneration of ventral horn spinal motor neurons and assoc cortical neurons |
| what drug is used to treat ALS and how does it work? | riluzole (Rilutek) inhibits glu activity, incl glu release inhibits voltage-gated Na+ channels |
| what are the adverse effects of riluzole? | GI adverse effects and hepatoxicity |
| what is MS? | multiple sclerosis, c/b monocyte infiltration and T-cell rxns to myelin antigens; autoimmune |
| what drugs are used to treat MS? | glucocorticoids interferon beta-1a (Avonex) - reduces T-cell activity glatiramer (Copaxone) - induces T-cells to secrete cytokines which reduce lesion px |
| what is Huntington's Dz char by? | loss of GABAergic neurons in the striatum loss of fine motor mov't, causes tremor, progressing to abrupt intermitting and involuntary mov't |
| what is Parkinson's Dz char by? | bradykinesia (difficulty initiating mov't) muscular rigidity (struggle to move) resting tremor (subsides w/ intent/mov't) abnl posture and gait, facial exp micrographia |
| what is Parkinson's Dz caused by? | degeneration of DA neurons in the SN, l/t decreased innervation of basal ganglia and increased cholinergic influence; can be induced by drugs |
| what are the goals of pharmacological tx of PD? | pharm support of DA funct in the SN reduction of cholinergic influence |
| what are the four classes of drugs which enhance DA function? | precursors to DA modification of DA transport inhibition of DA metabolism DA agonists |
| which drug is a DA precursor? | L-DOPA/carbidopa (Sinemet) carbidopa is a DOPA decarboxylase inhibitor |
| what are the side effects of L-DOPA? | nnv, psych disturbances, dystonias and involuntary muscle mov't, orthostatic hypotension and arrhythmias; may l/t malignant melanoma, may lower seizure threshold |
| what is neuroleptic malignant synd? | increased body temp, muscular rigidity, tachycardia, sweating |
| which PD agent may cause cancer? | L-DOPA may stimulate malignant melanoma should screen for lesions prior to initiation of therapy |
| which agent modifies DA transport? | amatadine (Symmetrel) |
| how does amatadine work? | increases DA release and inhibits reuptake |
| what are the side effects of amantadine? | nausea, psychiatric disturbances, livedo reticularis, orthostatic hypotension and arrhythmias, may lower seizure threshold |
| which agents inhibit DA metabolism? | entacapone (Comtan), tolcapone (Tasmar), selegiline (Eldepryl), rasagiline (Azilect) |
| how does entacapone work? | inhibits COMT |
| which agent is entacapone used with? | L-DOPA/carbidopa |
| how is entacapone eliminated? | biliary excretion |
| what are the side effects of entacapone? | diarrhea, dyskinesia, orthostatic hypotension, hallucinations |
| how does tolcapone differ from entacapone? | tolcapone is older is metabolized by 2A6 and 3A4 w/ sig renal excretion can l/t fulminant liver failure interferes w/ warfarin metabolism |
| how does selegiline work? | inhibits MAO-B |
| what are the side effects of selegiline? | insomnia, HA, dizziness, nausea, euphoria, increased ADEs of L-DOPA |
| which agents are DA agonists? | bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex), and ropinirole (Requip) |
| what are bromocripting and pergolide? | ergot alkaloid DA aognists |
| what are pramipexole and ropinirole? | non-ergot derivative DA agonists |
| what is the advantage of non-ergot derivative over ergot alkaloid DA agonists? | non-ergot derivative DA agonists have: fewer pulm effects lower incidence of seizure and HTN easier to titrate more prominent narcoleptic synd (drawback) |
| what agents can be added to PD therapy to control tremors? | anticholinergics: benztropine (Cogentin), trihexyphenidyl (Artane), diphenhydramine (Benadryl) |
| what are the effects of EtOH? | enhancement of inhibitory pathways (disinhibition): loss of social inhibitions, memory loss, intellectual deficit, mood swings, emotional outbursts; loss of motor/sensory control; hypnosis and respiratory depression |
| what is the mechanism of EtOH's CNS effects? | enhanced GABAergic effect on Cl- channels (enhancement of inhibitory pathways) inhibited glutamine activation of NMDA channels (loss of excitatory pathways) |
| what order is EtOH metabolism? | zero-order at 120mg/kg/hr |
| what is special about EtOH metabolism? | it has caloric value because it is metabolized to acetate which can enter the TCA cycle |
| what genetic predisposition will increase CNS effects of EtOH? | less active acetaldehyde DH isoform decreases conversion of aldehyde to acetate |
| describe the breakdown of EtOH to entrance in the TCA cycle | EtOH converted by ADH to formaldehyde formaldehyde converted by acetaldehyde DH to acetate acetate converted by thiokinase to acetyl-CoA acetyl-CoA can enter the TCA cycle |
| what are the CV effects of EtOH? | cutaneous vasodilation (flush) l/t enhanced heat loss increased oxygen consumption and myocardial ischemia increased intracranial pressure arrhythmias cardiomyopathy inhibition of platelet aggregation |
| what are the GI effects of EtOH? | increased GI secretions increased gastric damage increased ulcerations of the GI tract and d/o of the colon increased incidence of pancreatitis |
| what are the hepatic effects of EtOH? | EtOH reduces fatty acid oxidation and promotes hepatic fat accumulation acetaldehyde is directly hepatotoxic |
| what are the teratogenic effects of EtOH? | Fetal Alcohol Syndrome: reduces intellectual ability and causes facial abnl increased spontaneous abortion low birth weight |
| what effects does EtOH have on sexual function? | inhibition of erection and ejaculation in males testicular atrophy and infertility chronically |
| what hematological effects does EtOH have? | depressed leukocyte infiltration marrow suppression anemia |
| how do you treat acute EtOH intoxication? | treat respiratory depression and hypothermia hemodialysis if necessary |
| what agent is used for EtOH aversion therapy? | disulfiram (Antabuse) |
| what sx does acetaldehyde synd produce? | vasodilation, cramping, abd pain, nnv, blurred vision, vertigo, confusion, hypotension, CP, syncope |
| how is the median lethal dose of EtOH affected by development of tolerance? | median lethal does d/n change |
| what sx are produced by EtOH abstinence/withdrawal synd? | anx, tremors, sleep in 3-72hr cramps, hyperreflexia, HTN hallucination, confusion, disorientation delirium, CV collapse, death in 24-72hr |
| how do you treat acute EtOH abstinence synd? | readministration of EtOH or use of another CNS depressant like a long-acting benzodiazepine |
| how do you treat chronic EtOH abuse? | correction of fluid and electrolyte disturbances, nutrition deficits thiamine benzodiazepine clonidine, naltrexone, acamprosate |
| why is thiamine used to treat chronic EtOH abuse? | to reverse or prevent Wernicke-Korshakoff synd (ataxia, memory loss, neuromuscular degeneration) |
| what drugs are used to reduce cravings and autonomic manifestations of EtOH dependence? | clonidine, naltrexone, acamprosate |
| what sx does MeOH toxicity cause? | CNS depression and visual field disturbances blindness d/t formate px |
| what agent is used to treat MeOH toxicity? | fomepizole (Antizol) |
| how does fomepizol work? | inhibits conversion of alcohol to aldehyde |
| what are the sx of ethylene glycol toxicity? | CNS depression, acidosis (hyperventilation), oxalate-induced renal failure |
| what does "sedative" mean? | anxiolytic |
| what does "hypnotic" mean? | sleep-inducing |
| what is the progression of pharmacological effects for sedative-hypnotics? | anxiolytic hypnosis/sleep respiratory depression CV collapse w/ or w/o seizures death |
| how do barbiturates work? | activation of inhibitory GABA Cl- channels |
| name 3 barbiturate drugs | phenobarbital (long onset, anticonvulsant) thiopental (ultrashort onset, used for anesthesia) secobarbital (used in migraines) |
| what effects to barbiturates produce? | respiratory depression, sensory/motor impairment, tolerance/physical dependence; may intensify pain; px a barbiturate hangover |
| what is the most common sedative-hypnotic? (class) | benzodiazepines |
| how do benzodiazepines work? | enhancement of inhibitory GABA Cl- channels |
| what are the effects of benzodiazepines? | anxiolytic, tolerance/physical dependence; benzodiazepine hangover; anterograde amnesia ("conscious sedation"); respiratory depression generally not seen in outpatient dosing |
| which benzodiazepines do not have active metabolites? | lorazepam (Ativan) oxazepam |
| what drug is a benzodiazepine antagonist? | flumazenil (Romazicon) |
| what is the danger in using flumazenil? | if pt is physically dependent on benzodiazepines then flumazenil can induce seizures/withdrawal synd |
| which benzodiazepine class only has a hypnotic effect? | benzodiazepine alpha1 agonists |
| name 3 benzodiazepine-alpha1 agonists | zolpidem (Ambien) zaleplon (Sonata) eszopiclone (Lunesta) |
| name a melatonin agonist | ramelteon (Rozerem) |
| what are the side effects of melatonin agonists? | HA and hangover |
| which sedative-hypnotic is a 5HT1A/D2 agonist? | buspirone |
| what are the effects of buspirone? (sedative, hypnotic, or both) | anxiolytic only, no hypnotic effect |
| what is tolerance? | increase in dose is necessary to px equivalent effect upon continuous admin of the drug, d/t down-regulation of receptors (PD tolerance) or increased metabolism (metabolic tolerance) |
| what are the sx of sedative-hypnotic withdrawal/abstinence synd? | anx/delirium, seizures, CV collapse, death |
| what are the predominant actions of antiseizure drugs? | enhancement of GABAergic inhibitory nt, inhibition of glutaminergic excitatory nt, modification of ion channel activity |
| which antiseizure drugs work on voltage-gated Na+ channels? | phenytoin carbamazepine lamotrigine lacosamide |
| which antiseizure drugs work on voltage-gated Ca2+ channels? | ethosuximide lamotrigine gabapentin pregabalin |
| which antiseizure drug works on K+ channels? | retigabine/ezogabine |
| which antiseizure drug affects synaptic vesicle proteins? | levetiracetam |
| which antiseizure drug interacts with CRMP-2? | lacosamide |
| which antiseizure drugs act on AMPA receptors? | phenobarbital topiramate lamotrigine |
| which antiseizure drug acts on NMDA receptors? | felbamate |
| which antiseizure drug acts on GAT-1 (GABA transporters)? | tiagabine |
| which antiseizure drugs acts on GABA-T (GABA transaminase)? | vigabatrin |
| which antiseizure drugs act by enhancing GABA-A activity? | benzodiazepines phenobarbital |
| which antiseizure drug is used for absence seizures? (generic and brand) | ethosuximide (Zarontin) |
| which antiseizure drug is used for mixed seizure types? (generic and brand) | valproate (Depakene) |
| which side effect of antiseizure drugs should immediately be reported to the pt's MD? | any appearance of unexplained rash or mucosal lesions - exfoliative dermatitis |
| what are the general side effects of most antiseizure drugs? | drowsiness, sensory and/or cognitive impairment, changes in behavior |
| which nt are antipsychotics assoc with? | dopamine |
| what is the rate limiting step in DA synthesis? | tyrosine --> L-DOPA by tyrosine hydroxylase |
| how does L-DOPA become DA? | decarboxylation by AAAD |
| what three substances can be px from metabolism of DA and by which enzymes? | 3-methoxy-tyrosine by COMT 3,4-dihydroxyphenyl acetate (DOPAC) by MAO NE by DbetaH |
| what are the major receptors implicated in psychosis and what are their actions? | D1 excitatory D2 inhibitory |
| which DA tract is important in psychosis? | mesolimbic-mesocortical pathway |
| what is schizophrenia caused by? | overactivity of the mesolimbic-mesocortical DA tract |
| how do we know that the D2 receptor is implicated in psychosis? | efficacy of drugs linearly correlates to affinity for D2 receptors |
| which serotonin receptor is also implicated in psychosis? | 5HT2A, many antipsych drugs have strong 5HT2A antagonism |
| what is the difference between "typical" and "atypical" antipsychotics? give an example drug for each | typical APs l/t EPS and treat positive sx; e.g., Haldol atypical APs have less EPS and treat both positive and negative sx; e.g., clozapine |
| what action is thought to make atypical APs different than typical APs? | 5HT2A antagonism |
| which receptor are typical APs mostly associated with? | D2 receptors |
| which antipsychotic has high affinity for D2 and high antimuscarinic activity? | thioridazine |
| describe the metabolism of risperidone | 2D6 metabolism to active metabolite 9-hydroxyrisperidone caution with 2D6 poor metabolizers, allows inactive metabolites to dominate |
| describe the metabolism of quetiapine | 3A4 metabolises to inactive metabolites |
| describe the major and minor paths of olanzapine metabolism | 1A2 major path 2D6 minor path |
| which antipsychotic must be monitored for hematological and hepatotoxic effects? | clozapine |
| which clozapine metabolite is active? | norclozapine |
| what is the active metabolite of aripiprazole? | dehydroaripiprazole via 3A4 and 2D6 caution in 2D6 poor metabolizers |
| what CV side effect can ziprasidone cause? | lots of 3A4 metabolism, if blocked, drug builds up and can l/t QT prolongation |
| describe migraine initiation and propagation | trigger initiates CSD; trigeminal nerve depol l/t release of VAPs; sterile neurogenic infl starts migraine sx with orthodromic conduction; antidromic conduction; reflex activation of cholinergic neurons; more pain; cycles |
| list 5 VAPs and what do VAPs do | neurokinin A, substance P, histamine, NO, CGRP, prostaglandins l/t vasodilation, edema, infl at/around dural/pial arteries |
| what is CSD? | cortical spreading depression: widespread depolarization of brain neurons stim 5HT neurons in Raphe Nucleus and/or NE neurons in locus coeruleus, sends signals out to trigeminal nerve |
| what is sterile neurogenic inflammation? | vasodilation and inflammation d/t VAPs at dural/pial arteries sensitizes pain receptors and sends pain signals to brain |
| what is orthodromic conduction? | the pain impulse to the brain which triggers migraine sx of pain, photophobia, nnv |
| what is antidromic conduction? | after orthodromic conduction, the brain sends signals back to the inflamed area l/t additional release of VAPs and l/t increased infl, pain, etc and infl spreads |
| which neurons are involved in reflex activation? | cholinergic neurons |
| what is an example of a 5HT1B/D agonist? | sumatriptan |
| what is an example of a non-selective 5HT1 agonist? | ergotamine |
| what agent will block reflex activation of cholinergic neurons? | botulinum toxin |
| what drugs can be used for prophylaxis of migraines? | anticonvulsants (valproate) |
| what endogenous substance is the triptan structure similar to? | serotonin |
| what is a CV side effect of triptans? | constriction of coronary arteries d/t 5HT1B agonism, l/t myocardial ischemia; d/n use in pts w/ CAD |
| which triptan has a low incidence of DDIs and why? | sumatriptan b/c it is metabolized v fast |
| which triptan has the lowest BA? | sumatriptan, d/t rapid first pass metabolism and low lipophilicity |
| which triptans have active N-desmethyl metabolites? | zolmitriptan and rizatriptan |
| which triptan is affected by renal clearance? | naratriptan is excreted 50% unchanged in urine so t1/2 is affected by renal clearance |
| triptan metabolism is affected by which two drugs? | propranolol and MAOIs |
| what makes 5HT3 antagonists different than agonists? | no 5' sub bulky N-sub N-Me in ring |
| list 4 5HT3 antagonists | ondansetron granisetron dolasetron alosetron |
| which ergot alkaloid is a 5HT agonist and of what receptor? | ergotamine is a 5HT1 agonist |
| which ergot alkaloid is an antagonist and of which receptor? | ergonovine is a 5HT2 antagonist |
| 5HT is synthesized from what precursor? | tryptophan |
| what is the rate-limiting step of 5HT synthesis? | hydroxylation at 5-benzene by tryptophan hydroxylase |
| what is the step which makes 5HT? | decarboxylation to 5-hydroxytryptamine by AAAD |
| what triggers 5HT release? | AP firing l/t Ca2+ entering synapse and triggers 5HT exocytosis |
| what is the major termination method of 5HT? | reuptake by SERT |
| what is the major metabolite of 5HT and which enzyme creates it? | MAO and aldehyde dehydrogenase acts on excess 5HT in the terminal to create 5HIAA (5-hydroxyindole acetic acid) |
| how is 5HT converted to melatonin? | 5HT N-acetylase converts 5HT to N-Ac-5HT; hydroxyindole O-methyltransferase converts to melatonin |
| what is the 5HT1 receptor? (location, effect, action) | post-synaptic, Gi linked (inhibitory); inhibits AC l/t decreased cAMP |
| is the 5HT2 receptor inhibitor or excitatory? | 5HT2R is excitatory |
| what channel is 5HT3 linked to? | ligand-gated Na+ channels in gut and CTZ |
| where does 5HT4 act? | acts in the gut |
| how does PCPA affect 5HT? | inhibits tryptophan hydroxylase (and 5HT synthesis) |
| how does reserpine affect 5HT? | reserpine is a releaser; inhibits VMAT and depletes pre-synaptic 5HT; severe side effects and rarely used |
| where do MAOIs work? | in the mitochondria |
| what does buspirone do? | partial agonist of pre-synaptic 5HT1A receptors |
| what does ondansetron do? | 5HT3 antagonist of receptors in gut and CTZ |
| which 5HT receptor is generally involved in antipsychotics? | 5HT2A |
| what are the CV effects of 5HT? | plt aggregation releases 5HT stores in plts; 5HT2A changes shape of plts and accel. aggregation and stim contraction of smooth muscle; 5HT1 stim NO px; OVERALL: promotes thrombus formation and hemostasis |
| what are the GI effects of 5HT? | affects ACh release and motility, affects nausea and vomiting; most drugs have GI side effects but resistance/tolerance builds up |
| what CNS functions are affected by 5HT? | sleep, cognition, sensory perception, motor activity, temperature regulation, nociception, mood, appetite, sexual behavior, hormone secretion; emetic effects in CTZ |
| define NRI and give an example | selective NE reuptake inhibitor desipramine |
| define SSRI and give an example | selective 5HT reuptake inhibitors paroxetine |
| define SNRI and give an example | nonselective amine reuptake inhibitor (5HT/NE/DA) venlafaxine |
| define MAOI and give an example | monoamine oxidase inhibitor tranylcypromine |
| give an example of an alpha2 adrenergic antagonist | mirtazapine |
| give an example of a 5HT1A/D partial agonist | buspirone |
| give an example of a DA reuptake inhibitor | bupropion |
| give an example of a 5HT2/1C antagonist | trazodone |
| what is the amine hypothesis of depression? | depression is d/t too little 5HT (also NE) activity in hippocampus which l/t upregulated receptors and abnl responses |
| describe rapid desensitization | rapid phosphorylation of the receptor so that the G protein cannot reassociate, but phosphorylase can remove the phosphate group. there is also phosphorylation at a second site which allows arrestins to bind and blocks G protein coupling |
| describe downregulation of receptors | continued activation of receptors l/t the cell decreasing the number of those receptors by sequestering them in the membrane and pinching off; reversible at first, longer term process |
| describe the MOA of SSRIs | inhibit 5HT reuptake; stim of pre-syn receptors l/t decreased synth/release; cont stim l/t desensitization; increase of synaptic 5HT, post-syn receptors stim; constant stim l/t downregulation; CREB increases, BDNF activated; neuron grows; takes 2-3 wks |
| describe the alpha2 antagonist MOA | blocks pre-synaptic inhibition of nt synth/release; l/t increased stim of beta- receptors, l/t downregulation of beta-receptors, l/t increased cAMP, increased CREB, increased BDNF; **faster onset than SSRIs b/c skips first desensitization step |
| describe the MOA of MAOIs | inhibits metabolism of nt so immediately increases release of nt |
| what is the difference between the enantiomers of tranylcypromine? | the + enantiomer is a more effective MAOI but the - enantiomer is a better inhibitor of NE/DA reuptake - mechanisms work together to make an effective antidep |
| what CV problem can MAOIs cause? (hint = related to food) | HTN crisis d/t foods high in tyramine; w/o MAO in the gut to break down tyramine it is absorbed and l/t releaser effects |
| what where the first antideps developed from? | anti-muscarinics and anti-histamines |
| describe the SAR of TCAs | tricyclic structure e- withdrawing benzene sub = antipsychotic 3C chain b/w amine and cycles best 3' amine = 5HT/NE block; 2' amine = NE block only looks similar to antihistamines and antimuscarinics |
| what is the issue with paroxetine metabolism? | paroxetine is a sub/inhibitor of 2D6 caution in 2D6 poor metabolizers |
| what is venlafaxine metabolized by and to? | venlafaxine is metabolized by 2D6 and 3A4 2D6 converts to desvenlafaxine which is equiactive can use desvenlafaxine to avoid 2D6 interactions |
| what is the problem with trazodone metabolism? | 3A4 converts trazodone to a reactive iminoquinone which l/t liver tox |
| which antidepressant is hepatotoxic? | trazodone |
| what is imipramine converted to and what are the actions of parent and metabolite? | imipramine --> despiramine imipramine = SERT inhibitor desipramine = NERT inhibitor |
| which SSRI is least likely to inhibit 2D6? | citalopram |
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aerummel
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