Neuro-pharmacology Flashcards
Phenytoin
For simple partial and complex partial1st line for tonic clonic1st line prophylaxis for status epilepticusMechanism: Increase Na+ channel inactivationNotes: Fosphenytoin for parenteral use
Carbamazepine
For both simple and complex partial.1st line for tonic-clonicMechanims: increases Na+ channel inactivationNotes: 1st line for trigeminal neuralgia
Lamotrigine
For both Simple and complex partial.Used in Tonic clonic.Blocks voltage-gated Na+ channel.
Gabapentin
For both simple and complex partialTonic clonicDesigned as GABA analog, but primarily inhibits HVA Ca2+ channelsNotes: Also used for peripheral neuropathy; bipolar disorder
Topiramate
For simple and complex partialFor tonic-clonicMechanism: Blocks Na+ channels and increases GABA action
Phenobarbital
For simple and complex partial For Tonic-clonicIncreases GABA action1st line in CHILDREN AND PREGNANT WOMEN
Valproic acid
For simple and complex partial1st line for tonic-clonic generalizedUseful for AbsenceIncrease Na+ channel inactivation and increases GABA concentrationUsed for myoclonic seizures
Ethusuximide
2st line for Absence seizuresBlocks thalamic T-type Ca2+ channels
Benzodiazepines (diazepam or lorazepam)
1st line for acute status epilepticusIncreases GABAa actionAlso used for seizures of eclampsia, though first line is MgSO4
Tiagabine
For simple and complex partial.Inhibits GABA uptake
Vigabatrin
For simple and complex partial.Irreversibly inhibits GABA transaminase - increases GABA
Levetiracetam
For simple and complex partial.For generalized tonic-clonic.Unknown mechanism - may modulate GABA and glutamate release
What are the 1st line therapies for tonic-clonic
Phenytoin, Carbamazepine, and valproic acid
Benzodiazepines toxicities
Sedation, tolerance, dependenceAlprazolam, Triazolam, Oxazepam, Midazolam (ATOM) (short-acting): high risk of dependence/withdrawalLorazepam, Estazolam, Temazepam (LET) (medium-acting): moderately severe side effectsDrazepam, Flurazepam, Clorazepate, Chlordiazepoxide (DFCC) (long-acting): daytime drowsiness/falls
Carbamazepine toxicity
Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P-450 system, SIADH, Stevens-Johnson syndrome
Ethosuximide toxicity
GI distress, fatigue, headache, urticaria, Stevens-Johnson syndromeEFGH - ehtosuximide, fatigue, GI, headache
Phenytoin toxicity
Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, megaloblastic anemia, teratogenesis *fetal hydantoin syndrome), SLE-like syndrome, induction of cytochrome P-450
Valproic acid toxicity
GI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain. Contraindicated in pregnancy.
Lamotrigine toxicity
Steven-Johnson syndrome
Gabapentin toxicity
Sedation, ataxia
Topiramate toxicity
SEdation, mental dulling, kidney stones, weight loss
Phenytoin: mechanism, clinical use, toxicity
Mechanism: Use-dependent block of Na+ channels; increases refractory period; inhibition of glutamate release from excitatory presynaptic neuron.Clinical use: Tonic-clonic seizures. Also a class IB antiarrhythmic.Toxicity: Nystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome P-450. Chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia (decreased folate absrption). Teratogenic (fetal hydantoin syndrome)
Barbituates (phenobarbital, pentobarbital, thiopental, secobarbital) are contraindicated in?
porphyria
Barbiturates (phenobarbital, pentobarbital, thiopental, secobarbital) Mechanism, Clinical use, toxicity
Mechanism: Facilitate GABAa action by increasing the duration of Cl- channel opening, thus decreasing neuron firing.Clinical use: sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)Toxicity: Dependence, additive CNS depression effects with alcohol, respiratory or cardiovascular depression (can lead to death), drug interactions owing to induction of liver microsomal enzymes (cytochrome p-450).Treat overdose with symptom management (assist repiration, increase BP), induces enzymes involved in heme synthesis –> acute intermittant porphyria exacerbation.
Benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
Short acting benzodiazepines.
TOM: Triazolam, oxazepam, midazolam.Highest addictive potential
Mechanism of benzodiazepines (diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam)
Facilitate GABAa action by increased frequency of Cl- channel opening. Decreased REM sleep.Most have long half-lives and active metabolites.
Clinical use of benzodiazepines (diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam)
Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal - DTs), night terrors, sleepwalking, general anesthetic (amnes, muscle relaxation), hypnotic (insomnia)
Benzos, Barbs, and EtOh all bind to?
GABA(A)-R, which is a ligand-gated chloride channel (increase frequency of channel opening)
Toxicity of benzodiazepines
Dependence, additive CNS depression effects with alcohol.less risk of respiratory depression and coma than with barbituates.Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Nonbenzodiazepine hypnotics
Zolpidem (ambien), zaleplon, eszopiclone
Mechanism, clinical use, and toxicities of nonbenzodiazepine hyponotics (Zolpidem (ambien), zaleplon, eszopiclone)
Mechanism: Act via BZ1 receptor subtype and is reversed by flumazenilClinical use: insomniaToxicity: Ataxia, headaches, confusion. short duration because of rapid metabolism by liver enzymes.Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects.Lower dependence risk than benzodiazepines.
Inhaled anesthetics
halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
Inhaled anesthetics (halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide) effects, toxicity
mechanism is unknown. (HST150: Isoflurane potentiates GABAa, whereas nitrous oxide xenon, and cyclopropane do not.)Effects: Myocardial depression, respiratory depression, nausea/emesis, increases cerebral blood flow and decreases cerebral metabolic demandToxicity: hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), malignant hyperthermia (rare), expansion of trapped gas (NO)
Which inhaled anesthetic is hepatotoxic?
halothane
Which inhaled anesthetic is nephrotoxic?
methoxyflurane
Which inhaled anesthetic is a proconvulsant?
enflurne
Intravenous anesthetics - Barbiturates
Thiopental - high potency (because lipid solubility), high lipid solubility, rapid entry into brain.Used for induction of anesthesia and short surgical procedures.Effect terminated by rapid redistribution into tissue and fat.Decreased cerebral blood flow.
intravenous anesthetics - benzodiazepines
Midazolam most common drugs used for endoscopy; used adjunctively with gaseous anesthetics and narcotics.May cause severe postoperative respiratory depression, decreased BP (treat overdose with flumazenil), and amnesia.
Intravenous anesthetics - Arlcyclohexylamines
Ketamine - PCP analogs that act as dissociative anesthetics.Block NMDA receptors.Cardiovascular stimulants. Cause disorientation, hallucination, and bd dreams.Increased cerebral blood flow.
Intravenous anesthetics - opiates
Morphine, fentanyl used with other CNS depressants during general anesthesia
Intravenous anesthetics - Propofol
Used for rapid anesthesia induction and short procedures.Less postoperative nausea than thiopental. Potentiates GABAa.
Local anesthetics: esters and amides
Esters - procaine, cocaine, tetracaine.Amides (two I’s) = lidocaine, mepivacaine, bupivacaine
Mechanism of local anesthetics - procaine, benzocaine, cocaine, tetracaine, lidocaine, mepivacaine, bupivacaine
Block Na+ channels by binding to specific receptors on inner portion of channel.Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons.Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.Often norepinephrine is coinjected in order to prolong time to removal from circulation. This has its own problems, as NE is packaged in neurotoxant antioxidants and at a low pH, which impairs anesthetic penetration (many local anesthetics are bases).Sensations from more proximal regions are blocked earlier and recover later than those from more distal segments. This reflects the diffusion of anesthetic through the somatotopically organized peripheral nerve.
Local anesthetics - procaine, cocaine, tetracaine, lidocaine, mepivacaine, bupivacaine principles
Principles:1) In infected (acidic tissue), alkaline anesthetics are charged and cannot penetrate membrane effectively.More anesthetic needed.2) Order of nerve blockade: small-diameter fibers>large diameter. Myelinated fibers> unmyelinated.Overall, size factor predominates over myelination such that small myelinated fibers > small unmyelinated fibers>large myelinated fibers>large unmyelinated fibers. Order of loss - pain (lost first), > temperature > touch > pressure (lose last)3. Except for cocaine, given with vasoconstrictors (usually epinephrine) to enhance local action (decreases bleeding, increases anesthesia by decreased systemic concentration)
Local anesthetics - procaine, cocaine, tetracaine, lidocaine, mepivacaine, bupivacaine clinical use and toxicities
Clinical use: minor surgical procedures, spinal anesthesia.if allergic to esters, give amides.Toxicity: CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine)
Neuromuscular blocking drugs- use
Used for muscle paralysis in surgery or mechanical ventilation.Selective for motor (vs. autonomic) nicotinic receptor
Neuromuscular drugs - depolarizing
Succinylcholine (complications include hypercalcemia and hyperkalemia). Reversal of blockade:Phase I (prolonged depolarization) - no antidote.Block potentiated by cholinesterase inhibitors.Phase II (repolarized but blocked) - antidote consists of cholinesterase inhibitors (e.g. neostigmine)
Neuromuscular blocking drugs-nondepolarizing
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuroniumCompetitive blockage - compete with nicotonic Ach for receptors (nAChRs). Reversal of blockage - neostigmine, edrophonium, and other cholinesterase inhibitors
Depolarizing effects - organophosphate - inhibit AchE.Treatment?
Common cause of poisoning - treat with atropine, pralidoxime
Dantrolene
Used in the treatment of malignant hyperthermia, which is caused by inhalation anesthetics (except nitric oxide) and succinylcholine.Also used to treat neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).Mechanism: prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
Dopamine receptor agonists for Parkinson’s
Bromocriptine, pramipexole, ropinirole (non-ergot); non-ergots are preferred
Drugs for increasing dopamine in Parkinson’s
Amantadine (may incrase dopamine relase); also used as an antiviral against influenza A and rubella.Toxicity = ataxiaLevo-dopa with carbidopa (converted to dopamine in CNS. Carbidopa inhibits peripheral conversion to dopamine)
Drugs for parkinson’s: preventing dopamine breakdown
Selegiline (selective MAO type B inhibitor); entacapone, tolcapone *COMT inhibitors - prevents L-dopa degradation, thereby increasing dopamine availability)
Parkinson’s drugs: curb excess cholinergic activity
Benztropine (antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia)
How to treat essential or familial tremors?
Beta-blocker (e.g. propranolol)
L-dopa can cross the blood-brain barrier and is changed into dopamine by?
dopa decarboxylasecarbidopa keeps this from happening peripherally
Toxicity of Levodopa
Arrhythmias from peripheral conversion to dopamine.Long-term use can lead to dyskinesia following administration, akinesia between doses.Carbidopa, a peripheral decarboxylase inhibitor, is giving with L-dopa to increase bioavailbility of L-dopa in the brain and decrease peripheral effects
Selegiline - Mechanism, Clinical use, toxicity
Mechanism: Selectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5-HT, thereby increasing the availability of dopamine.Clinical use: Adjunctive agent to L-dopa in treatment of Parkinson’s diseaseToxicity: May enhance effects of L-dopa
Alzheimer’s drugs
MemantineMechanism - NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)Toxicity - Dizziness, confusion, hallucinationsDonepezil, galantamine, rivastigmineMechanism: Acetylcholinesterase inhibitorsToxicity: Nausea, dizziness, insomnia
Huntington’s drugs
Disease: Increase dopamine, decreased GABA + AChReserpine + tetrabenazine = amine depletingHaloperidol = dopamine receptor antagonist
Sumatriptan
Mechanism: 5-HT agonist.Causes vasoconstriction, inhibition of trigeminal activation and vasoactive peptide release.Half-life < 2 hours. Clinical use: Acute migraine, cluster headache attacksToxicity: Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal’s angina), mild tingling
Treatment for ADHD
methylphenidate (Ritalin), amphetamines (Dexedrine), atomoxetine (nonstimulate SNRI)
Treatment for Tourette’s syndrome
antipsychotics (e.g., haloperidol)
Treatment for bipolar disorder
Lithium, valproic acid, carbamazepine, atypical antipsychotics (use of antidepressants lead to increased mania)
Depressants - Intoxication and withdrawal
Intoxication - nonspecific: mood elevation, decreased anxiety, sedation, behavioral disinhibition, respiratory depressionWithdrawal - nonspecific: anxiety, tremor, seizures, insomnia
Alcohol (depressant)
Intoxication: Emotional lability, slurred speech, ataxia, coma, blackouts. Serum gamma-glutamyltransferase (GGT) - sensitive indiator of alcohol use.Lab AST is twice ALT value.Treatment: NaltrexoneWithdrawal: Symptoms similar to other depressants.Severe alcohol withdrawal: Delerium tremens- delirium, tremors, autonomic instability.Treatment: Benzodiazepines
Opioids (e.g. morphine, heroin, methadone) (depressant)
Intoxication: CNS depression, nausea, vomiting, constipation, pupillary constriction (pinpoint pupils), seizures (overdose is life-threatening).Treatment: Naloxone, naltrexoneWithdrawal: Sweating, dilated pupils, piloerection (cold turkey), fever, rhinorrhea, nausea, stomach cramps, diarrhea (fluelike symptoms). Treat symptomatically
Barbiturates (depressant)
Intoxication: Low safety margin, marked respiratory depression. Treatment: symptom management (assist respiration, increase BP)Withdrawal: Delirium, life-threatening cardiovascular collapse
Benzodiazepines (depressant)
Intoxication:Greater safety margine. Ataxia, minor respiratory depression.Treatment: Flumazenil (competitive GABA antagonist)
Stimulants: Intoxication and withdrawal
Intoxication: Nonspecific: mood elevation, psychomotor agitation, insomnia, cardiac arrythmias, tachycardia, anxietyWithdrawal: Nonspecific: post-use “crash”, including depression, lethargy, weight gain, headache
Amphetamines (stimulants)
Intoxication: Impaired judgment, pupillary dilation, prolonged wakefulness and attention, delusions, hallucinations, fever Withdrawal: Stomach cramps, hunger, hypersomnolence
Cocaine (stimulant)
Intoxication: Impaired judgment, pupillary dilationf, hallucinations (including tactile), paranoid ideations, angina, sudden cardiac death.Treatment: benzodiazepines.Withdrawal: Suicidality, hypersomnolence, malaise, severe psychological craving
Caffeine (stimulants)
Intoxication: Restlessness, increased diuresis, muscle twitching
Nicotine (stimulant)
Intoxication: RestlessnessWithdrawal: irritability, anxiety, craving.Treatment: nicotine patch, gum, lozenges.Bupropion/varenicline
PCP (Hallucinogen)
Intoxication: Belligerence, impulsiveness, fever, psychomotor agitation, vertical and horizontal nystagmus, tachycardia, homicidality, psychosis, deliriumWithdrawal: Depression, anxiety, irritability, restlessness, anergia, disturbances of thought and sleep
LSD (hallucinogens)
Intoxication: Marked anxiety or depression, delusions, visual hallucinations, flashbacks, pupillary dilation
Marijuana (hallucinogen)
Intoxication: Euphoria, anxiety, paranoid delusions, perception of slowed time, impaired judgment, social withdrawal, increased appetite, dry mouth, hallucinationsWithdrawal: Irritability, depression, insomnia, nausea, anorexia.Most symptoms peak in 48 hours and last for 5-7 days.Can detected in urine for up to 1 month after use.
Heroin addiction
Users at increased risk for hepatitis, abscesses, overdose, hemorrhoids, AIDS, and right-sided endocarditis.Look for track marks (needlesticks in veins). Methadone - long-acting oral opiate; used for heroin detoxification or long-term maintenance (prevent withdrawal symptoms)Suboxone - naloxone + buprenorphine (partial agonist); long acting with fewer withdrawal symptoms than methaodone. naloxone is inactive when administered orally, but will induce withdrawal when injected.Pentazocine - partial agonist; can parcipitate withdrawal
What is given to condition patients not to abuse alcohol
disulfiram
Treatment for alcohol withdrawal
Benzodiazepines
Treatment for Anorexia/Bulimia
SSRIs
Treatment for Anxiety Disorder
Benzodiazepines, buspirone, SSRIs
Treatments for ADHD
Methylphenidate (Ritalin)Amphetamines (Dexedrine)
Treatment for atypical depression
MAO inhibitors SSRIs
Treatments for Bipolar disorder
Mood stabilizers: Lithium, Valproic acid, Carbamazepine
Two drugs that work in absence seizures
Ethosuximide (1st line), valproic acid
Treatment for depression
SSRIs, SNRIs, TCAs
Treatment for depression with insomnia
Mirtazapine
Treatment for OCD
SSRIs, Clomipramine
Treatment for Panic disorder
SSRIs, TCAs, Benzodiazepines
Treatment for PTSD
SSRI
Schizophrenia treatment
Antipsychotics
Treatment for Tourette’s
Antipsychotics (haloperidol)
Treatment for social phobias
SSRIs
CNS stimulants
Methylphenidate, dextroamphetamine, mixed amphetamine salts.Mechanism: Increased catecholamines at the synaptic cleft, especially NE and dopamineClinical use: ADHD, narcolepsy, appetite control
Antipsychotics (neuroleptics)
Haloperidol, trifluoperazine, fluphenazine, thioridazine, chlorpromazine (haloperidol + -azine’s)
Mechanism of antipsychotics (Haloperidol, trifluoperazine, fluphenazine, thioridazine, chlorpromazine)
All typical antipsychotics block dopamine D2 receptors (increase cAMP1)
High potency antipsychotics
Neurologic side effects (extrapyramidal effects are greater)Haloperidol, trifluoperazine, fluphenazineEPS symptoms:4h acute dystonia (muscle spasm, stiffness, oculogyric crisis)4 d akinesia (parkinsonian symptoms)4 wk akathisia (restlessness)4 mo tardive dyskinesia
Low potency antipsychotics
Thioridazine, chlorpromazineNon-neurologic side efects (anticholinergic, antihistamine, alpha blockade effects)Thioridazine - reTinal depositsChlorpromazine - Corneal depositsblock Muscarinic - dry mouth, constipationblock alpha - hypotensionblock histamine - sedation
Which low potency antipsychotic can lead to corneal deposits?
Chlorpromazine
Which low-potency antipsychotic can lead to retinal deposits?
Thioridazine
Toxicity of antipsychotics
Other than EPS of high potency and anti muscarinic, anti alpha, anti-histamine of low potency-Highly lipid soluble and stored in body fat - slowly removed from body-Endocrine effects - dopamine receptor antagonism - hyperprolactinemia leading to galactorrhea-Neuroleptic malignant syndrome (NMS) - rigidity, myoglobinuria, autonomic instability, hyperpyrexia. Treatment: dantrolene, agonists (bromocriptine)-Tardive dyskinesia
Neuroleptic malignant syndrome, an adverse effect of antipsychotics, can be treated how (has ridigity, myoglobinuria, autonomic instability, hyperpyrexia)
Dantrolene, agonists (bromocriptine)
Atypical antipsychotics
Olanzapine, colzapine, quetiapine, risperidone, aripiprazole, ziprasidone
Clinical use of antipsychotics
Schizophrenia (primarily positive symptoms, psychosis, acute mania, Tourette’s syndrome)
Atypical antipsychotics (olanzapine, clozapine, quetiapine, risperidone) mechanism
Block 5-HT2, dopamine, alpha, and H1 receptors
Clinical use for atypical antipsychotics: olanzapine, clozapine, quetiapine, risperidone, aripiprazole, ziprasidoneMechanism: Block 5-HT2, dopamine, alpha, and H1
Schizophrenia - both positive and negative symptoms. Olanzapine is also used for OCD, anxiety disorder, depression, mania, Tourette’s syndrome
Toxicities of atypical antipsychotics
Fewer extrapyramidal and anticholinergic side effects than traditional antipsychotics.Olanzapine/zclozapine may cause significant weight gain.Clozapine may cause agranulocytosis (requires weekly WBC monitoring)
Which of the atypical antipsychotics cause weight gain?
Olanzapine/clozapine
Which atypical antipsychotic may cause agranulocytosis (WBC monitoring)
clozapineWatch clozapine clozely
Lithium
Mechanism: Not established, possibly inhibition of phosphoinositol cascadeClinical use: Mood stabilizer for bipolar disorder; blocks relapse and acute manic events.Also SIADHToxicity: Tremor, sedation, edema, heartblock, hypothyroidism, polyuria (ADH antagonist causing nephorgenic diabetes insipidus), teratogenesis.Fetal cardiac defects include Ebstein anomaly and malformation of great vessel.Narrow therapeutic window requires close monitoring of serum levels.Almost exclusively excreted by the kidneys; most is reabsorbed at the proximal convoluted tubules following Na+ reabsorption
Lithium side effects
MNOPMovement (tremor)Nephrogenic diabetes insipidusHypOthyroidismPregnancy problems
Buspirone
Mechanism: Stimulates 5-HT1A receptorsClinical Use: Generalized anxiety disorder. Does not cause sedation, addiction, or tolerance. Does not interact with alcohol (vs. barbituarates, benzodiazepines)I’m always anxious if the BUS will be ON time, so I take BUSpirONe.
Tricyclic antidepressants
Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin, amoxapine Mechanism: Block reuptake of NE and serotonin
Mechanism and clinical use, toxcity of TCAs (Imipramine, amitriptyline, desipramine, nortriptyline, comipramine, doxepin, amoxapine)
Mechanism: Block reuptake of NE and serotoninClinical use: Major depression, bedwetting (imipramine), OCD (clomipramine), fibromyalgiaSide effects: Sedation, alpha-blocking effects, atropine-like (anticholinergic) side effects (Tachycardia, urinary retention).Tertiary TCAs (Amitriptyline) have more anticholinergic effects than do secondary TCAs (nortriptyline). Desipramine is least sedating and has lower seizure threshold.Toxicity: Tri-C’s: Convulsions, Coma, Cardiotoxicity (arrythmias); also respiratory depression, hyperpyrexia, confusion, hasslucinations in elderly due to anticholinergic effects (use nortriptyline).Treatment: NaHCO3 for CV toxicity.
Which TCA (blocks reuptake of NE and serotonin) can be used to treat bedwetting?
imipramine
Which TCA (blocks reuptake of NE and serotonin) can be used to treat OCD?
clomipramine
What TCA should be used in the elderly (because they encounter confusion and lassucination due to anticholinergic)
nortriptyline - less cholinergic effects
SSRIs
Fluoxetine, paroxetine, sertraline, citalopramTakes 2-4 weeks to work. Mechanism: Serotonin-specific reuptake inhibitors Clinical use: Depression, OCD, bulimia, social phobiasToxicities: Fewer than TCAs. GI distress, sexual dysfunction (anogasmia). “Serotonin syndrome” with any drug that increases serotonin (e.g. MAO inhibitors) - hyperthermia, muscle rigidity, cardiovascular collapse, flushing, diarrhea, seizures.Treat with cyproheptadine
Serontonin syndrome and treatment
Caused by SSRIs, MAO inhibitors : any drug that increases serotoninHyperthermia, muscle rigidity, cardiovascular collapse, flushing, diarrhea, seizuresTreat: Cyproheptadine (5-HT2 receptor antagonist)
SNRIs
Venlafaxine, duloxetineMechanism: Inhibit serotonin and NE reuptakeClinical use: Depression. Venlafaxine is also used in GAD; duloxetine is also indicated for diabetic peripheral neuropathy. Duloxetine has greater effet on NE.Toxicity: Increased BP most common, stimulant effects, sedation, nausea
SNRI’s (Venlafaxine, duloxetine) work how?
Inhibit serotonin and NE reuptake
Which SNRI is used in GAD?
Venlafaxine
Which SNRI is used in diabetic neuropathy?
Duloxetine (greater effect on NE)
Monoamine oxidase inhibitors (MAO)
Phenelzine, tranylcypromine, isocarboxazid, selegiline (selective MAO-B inhibitor)Mechanism: Nonselctive MAO inhibition, increase levels of amine neurotransmitters (NE, serotonin, dopamine)
MAO inhibitors - phenelzine, tranylcypromine, isocarboxazid, selegiline (MAO-B selective) used in? Toxicity?
Atypical depression, anxiety, hypochondriasisToxicity: Interact with indirect sympathomimetics, e.g. hypertensive crisis with tyramine ingestion (in many foods such as wine and cheese) and Beta-agonists; CNS stimulation. Contraindicated with SSRIs or meperidine to prevent serotonin syndrome
Atypical antidepressants - Bupropion
Also used for smoking cessation.Increased NE and dopamine via unknown mechanisms. Toxicity: stimulant effects (tachycardia, insomnia), headache, seizure in bulimic patients. No sexual side effects
Atypical antidepressants - Mirtazapine
Alpha-2 antagonist (Increase release of NE and serotonin) and potent 5-HT2 and 5-HT3 receptor antagonist.Toxicity: Sedation, increased appetite, weight gain, dry mouth
Atypical antidepressant - Maprotiline
Blocks NE reuptake. Toxicity: sedation, orthostatic hypotension
Atypical antidepressant - Trazodone
Primarily inhibits serotonin reuptake. Used for insomnia, as high doses are needed for antidepressant effects.Toxicity: sedation, nausea, priapism (continuous erection), postural hypotension.
What is scopolamine used for?
Muscarinic cholinergic antagonist.Used in motion sickness.
What is phenoxybenzamine used for?
Non-selective alpha-adrenergic antagonist used to treat pheochromacytoma
Carbachol and pilocarpine
cholinergic agonists used to lower intraocular pressure in glaucoma.Cholinergic-associated miosis causes the iris to move further from the cornea, widening the anterior chamber angle and allowing better outflow of the aqueous humor.
Drugs whose co-administration increase risk of lithium toxicity.
Thiazide diuretics, ACE inhibitors, NSAIDs
Treatment of acute lead and mercury poisoning.
CaNa2EDTA - chelating agent; forms complexes with mono, di- and trivalent ions
Carbamazepine - what is it used for, how does it work?
Blocks voltage-taged Na channels in cortical neurons-Used for the management of generalized tonic-clonic seizures, as a mood stabilizer in bipolar disorder, and to treat trigemanl neuralgia Side effects: Bone marrow suppression, hepatoxicity, and increase in ADH
Hemicholinium
Blocks the entry of choline into the neuron to make it into acetylcholine.
Vesamicol
Blocks uptake of AcH into vesicles (anticholinergic).
Botulinum
Blocks release of Ach on presynaptic terminal
Metyrosine
Blocks conversion of tyrosine to dopa (blocks synthesis of dopamine and NE)
Guathedine
Blocks relesae of Ne at presynaptic nerve terminal
Cocaine, Amphetamines, TCAs
Block NE reuptake
Bethanechol
Ach action. Postoperative and neurogenic ileus and urinary retention. Activates bowel adn bladder smooth muscle.Resistant to AChE.
Carbachol
Ach action. Glaucoma, pupillary contraction, and relief of intraocular pressureCarbon copy of Ach
Pilocarpine
Ach agent.Potent stimulator of sweat, tears, salivaContracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle); resistant to AchE. PILE on the sweat and tears.
Methacholine
Muscarinic ACh agonistChallenge test for diagnoises of asthma - Muscarnic receptors in airway when inhaled.
Neostigmine
Anti-AchEPostoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockage (postoperative).Increases endogenous ACh, no CNS penetration
Pyridostimine
Myasthenia gravis (long acting); does not penetrate CNS). Endogenous Ach, increases strength.
Edrophonium
Diagnosis of myasthenia gravis (extremely short acting)Also helps to distinguish overdose vs underdose of acetylcholinesterase inhibitors.
Physostigmine
AchE inhibitorGluacoma (crosses blood-brain barrier–> CNS) and atropine overdose Increases AchPHYS is for the eyes
Echothiophate
AchE inhibitor for glaucoma(HST150: noncompetitive)Increases endogenous Ach
Cholinesterase inhibitor poisoning
Often due to organophosphates, such as parathion & malathion (insectisides) and soman (nerve agent used in chemical warfare, more potent), that irreversibly bind AchE. Causes DUMBBELSS.Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle adn CNS, Lacrimation, Sweating, and Salivation. Antidote: Atropine + Prolidoxime (regenerates active AchE)
Benzotropine
Muscarinic antagonist used in Parkinson’s disease
Scopolamine
Muscarinic antagonist used for CNS - motion sickness
Oxybutynin, glycopyrrolate
Muscarinic antagonist used for the genitourinary system.Reduce urgency in mild cystitis and reduce bladder spasms.
Methscopolamine, pirenzepine, propantheline
Muscarinic antagonist used in the GI system.Peptic ulcer treatment.
Atropine
Muscarinic antagonistHot as a hare, Dry as a bone, red as a beet, blind as a bat, mad as a hatter.increases pupil dilation, cycloplegia, decreases airway secretion, decreases acid secretion and intestine mobility, decreases urgency in cystitis.Toxicity: Increased body temperature due to decrease in sweating, rapid pusle, dry mouth, dry, flushed skin, cycloplegia, constipation, disorientation.Acute angle-closure in glaucome, urinary retention in prostatic hyperplasia, and hyperthermia in infants.
Hexamethonium
Nicotinic antagonistPut a Hex on smokers to help them quit. Clinical use: Ganglionic blocker (preganglionic sympathetic & parasympathetic neurons release ACh to bind to postganglionic nAChRs). Used in experimental models to prevent vagal reflex responses to changes in blood pressure: prevents reflex bradycardia caused by NE.Toxicity: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction
Epinephrine
Alpha1, Alpha2, Beta1, Beta2 (low dose selects for Beta1). Alpha2 receptors are presynaptic (feedback inhibition).Applications: Anaphylaxis, glaucoma (open angle), asthma, hypotension
NE
alpha1, alpha2> Beta1. Used in hypotension, but decreases renal perfusion.
Isoproterenol
Beta-adrenergic agonist. Beta1 = Beta2.Used in AV block (rare).
Dopamine
D1 = D2 > Beta adrenergic > alpha adrenergic (BP goes up, then down with higher doses), positive ionotropic and chronotropic. Used in shock (to increase renal perfusion), heart failureHypotension is a side effect of L-dopa.
Phenylephrine action
Alpha-1 adrenergic agonist.Alpha1 > Alpha2Pupillary dilation, vasoconstriction, nasal congestion
Metaproterenol, albuterol, salmeterol, terbutaline
Selective Beta2 agonists Beta2 > Beta1.
Amphetamine
Indirect sympathomimetic, releases stored catecholamines Narcolepsy, obesity, ADD
Ephedrine
Indirect sympathomimetic, releases stored catecholamines. Nasal decongestion, urinary incontinence, hypotension
Cocaine
Indirect general agonist, reuptake inhibitor. Causes vasoconstriction and local anesthesia
Clonidine, alpha methyldopa
Centrally acting alpha2-agonists, decrease central adrenergic outflow.alpha2 receptors are presynaptic (negative feedback)used in hypertension, espeically with renal disease (no decrease in blood flow to the kidney)
Phenoxybenzamine (irreversible)Phentolamine (reversible)
Alpha-blockers. Used for pheochromacytoma (use phenoxybenzamine before surgery).Toxicity: Orthostatic hypotension, reflex tachycardia
-zosin endingPrazosin, terazosin, doxazosin
Alpha1 blocker. Used in hypertension, urinary retention of BPH (relax smooth muscle around bladder neck).Toxicity: 1st dose orthostatic hypotension, dizziness, headaches
Mirtazapine
Alpha2 selective blockerused in depression.Toxicity: Sedation, increase in serum cholesterol, increase in appetite
Opioids toxicity treatment
Naloxone/naltrexone
Benzodiazepines toxicity treatment
Flumazenil
TCAs toxicity treatment
NaHCO3(Plasma alkalinization)
Drugs that cause cinchonism (headache, tinitus)
quinidine, quinine
Drugs that cause diabetes inspidus
Lithium, demeclocycline
Drugs that cause parkinson-like syndrome
Haloperidol, chlorpromazine, reserpine, metoclopramide
Drugs that cause seizures
Bupropion, imipenem/cilastatin, isoniazid
Drugs that cause tardive dyskinesia
antipsychotics
Guanethidine
Guanethidine, prevents the release of NE – another kind of chemical sympathectomy. Its side effects, especially postural hypotension and diarrhea, can be severe.
Acetylcholine receptors
nicotinic acetylcholine (ACh) receptors in muscle, neurons, and glia are strongly activated (agonized) by acetylcholine and nicotine (an alkaloid from tobacco), and less so by muscarine (an alkaloid from Amanita muscaria mushrooms), whereas muscarinic ACh receptors in smooth and cardiac muscle are strongly activated by acetylcholine and muscarine, but weakly by nicotine. nAChRs are released by motor neurons and by preganglionic sympathetic and parasympathetic nerve terminals.
alpha-Bungarotoxin
One class of very slowly reversible (days to unbind) antagonists of nAChR are small proteins (6-8000 mol wt) in venoms of certain snakes (Formosan Krait, cobra). These molecules called bungarotoxins bind to the a subunits of the receptor from the extracellular surface and were essentially for the original isolation and purification of the receptor
Latrotoxin (Black Widow venom)
Causes release of acetylcholine from presynaptic terminal, leading to cholergic stimulation followed by block. Symptoms include hypertension, generalized muscle pain, abdominal cramps, extreme sweating and tachycardia. Also works on many other kinds of presynaptic terminals.
Carbon Monoxide Toxicity (Mechanism, Symptoms,Treatment)
Mechanism: CO displaces O2 from hemoglobin and binds to cytochrome oxidase (electron transport inhibitor).Symptoms: Headache, seizures, ventilatory depression, deathTreatment: 100% (possibly hyperbaric) oxygen, and possibly barbituate-induced coma to decrease Oxygen utilization.
Methanol Toxicity (Mechanism, Symptoms, Treatment)
Mechanism: methanol is converted to formic acid by alcohol dehydrogenase, which is toxic to the retina. Symptoms: blindnessTreatment: fomepizole, which inhibits alcohol dehydrogenase
Cyanide Toxicity (Mechanism, Symptoms, Source, Treatment)
Mechanism: binds tightly to Fe3+ in hemoglobin and also inhibits cytochrome oxidase (preventing electron transport). Symptoms: lactic acidosisSource: pesticide (for infestation), gold mining –> artificial lakes, fruit pitsTreatment: nitrites (intentional methemoglobinemia b/c cyanide binds better to methemoglobin than hemoglobin), sodium thiosulfate, 100% oxygen
Lead Toxicity (Mechanism, Symptoms, Source, Treatment)
Mechanism: after GI absorption, circulates bound to hemoglobin and redistributes to bone (remains there chronically until treated)Symptoms: anorexia, constipation, metallic taste, proteinuria, hematuria, anemia, peripheral neuropathySource: old paint, batteries, acidic fruitsTreatment: CaEDTA, dimercaprol, succimer, penicillamine
Codeine
Codeine is O-demethylated by CYP2D6 to morphine in the liver. There are mutations that make patients poor metabolizers, or conversely, extensive metabolizers.Morphine is also metabolized to a more active metabolite.
Latanoprost
Topical medication used to control glaucoma or ocular hypertension by reducing intraocular pressure. It’s a prostaglandin analog that works by increasing the outflow of acqueous fluid from the eyes.
Leflunomide
Inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, which plays a role in de novo pyrimidine synthesis. Lymphocyte expansion is inhibited. Used treat rheumatoid arthritis and psoriatic arthritis.
Potassium Iodide
-For hyperthyroidism; high amounts suppress secretion of thyroxine from the thyroid gland-Topical treatment for sporotrichosis
Remifentanil
An opioid analgesic which undergoes rapid esterase breakdown in the blood, allowing quick dissipation even after very long infusions.
slow acetylator mutation (pertinent drugs)
Inability to detoxify sulfapyridine from sulfasalazine. Inability to metabolize procainamide to active N-acetylprocainamide. Decreased clearance of isoniazid and hydralazine.
Palivizumab
Monoclonal antibody used against paramyxoviruses (parainfluenza, RSV, measles, mumps). Binds to surface F (fusion) protein.
Nimodipine
Calcium channel blocker used to treat vasospasm, a complication of blood breakdown products after subarachnoid hemorrhage.
Beta blockers (glaucoma)
Work by decreasing aqueous humor production by ciliary epithelium.
Primidone
Antiepileptic that is metabolized to phenobarbitol and phenylethylmalonamide (PEMA)
Which TCA has strong anti-cholinergic properties?
Amitriptyline
How do you distinguish between amides and esters for local anesthetics?
Amides have two i
Esters have one i
