Block 5 Drugs Flashcards

Question

rivastigmine

Answer 1

Treatment for Alzheimer Inhibits both AChE and BuChE Causes more gastrointestinal problems and cause muscle weakness than other cholinesterase inhibitors

Answer 2

Treatment for Alzheimer ``` Short half-life Needs to be given multiple times per day Poor compliance Many drug interactions Especially NSAIDs May cause liver damage Second-line therapy for AD ```

Answer 3

Treatment for Alzheimer Useful in patients with moderate to severe AD Mechanism of action Antagonist at the NMDA subtype of glutamate (GLU) receptor Found to help patients in the later stages of the disease maintain additional independence Most common adverse effects of memantine are dizziness, headache, constipation and confusion

Answer 4

May have a modest benefit for AD patients Serious side effects (bleeding, seizures, coma) have been reported with commercial pharmaceutical-grade ginko biloba preparations

Answer 5

Derived from the Greek words nous, or “mind,” and trepein meaning “to bend/turn” AKA: smart drugs, memory enhancers, cognitive enhancers, and intelligence enhancers

Answer 6

``` "Wakefulness Enhancers” Examples Modafinil (Provigil) Armodafinil (Nuvigil) Mechanism of action ? Increased release of norepinephrine and dopamine Elevates hypothalamic histamine levels Lower abuse potential as compared to traditional stimulant drugs DEA Schedule IV ``` FDA approved for Narcolepsy Shift work sleep disorder Excessive daytime sleepiness associated with obstructive sleep apnea

Answer 7

Halogenated Hydrocarbon Inhalation Anesthetic Advantages Potent (MAC ranges from 0.7 - 0.9) Rapid induction and recovery Among the least expensive volatile anesthetic Does not irritate larynx - no laryngospasm Disadvantages Inadequate analgesia and muscle relaxation Depresses myocardium and baroreceptor reflexes ↓ Cardiac output ↓ Blood pressure Sensitizes myocardium to catecholamines ↑ automaticity Particularly in the presence of adrenergic agonists (e.g., epinephrine) which might be used to raise blood pressure Increases cerebral blood flow and intracranial pressure Respiratory depression Potential for acute or chronic hepatic toxicity 1:35,000 patients develop “halothane hepatitis” Symptoms include hepatic necrosis, fever, nausea and vomiting, biochemical abnormalities as seen in hepatitis May progress to complete hepatic failure and death May be due to significant liver metabolism (~20%) Malignant hyperthermia

Answer 8

Halogenated Hydrocarbon Inhalation Anesthetic Advantages Potent Induction in less than 10 minutes Doesn’t sensitize the myocardium to catecholamines Less hepatotoxicity and renal toxicity than halothane (may be related to lower rate of metabolism) Disadvantages Rarely arrhythmias Pungent odor Potential for malignant hyperthermia

Answer 9

Halogenated Hydrocarbon Inhalation Anesthetic

Answer 10

Halogenated Hydrocarbon Inhalation Anesthetic ``` Newest approved inhalation agent for use in North America (1996) High potency (low % of inspired gas) Low blood solubility Rapid onset – 5-10 min Rapid recovery – same day surgery Almost perfect inhalation anesthetic ```

Answer 11

Halogenated Hydrocarbon Inhalation Anesthetic Advantages Low blood solubility (rapid onset) Little effect on overall cardiovascular function Second gas effect Hastens anesthesia produced by more potent but more soluble inhalation anesthetics Lowers MAC of other inhalation anesthetics Mild to moderate analgesic activity Disadvantages MAC = 104% - can't use as sole anesthetic agent No muscle relaxing effect Diffusion hypoxia if rapidly discontinued During recovery, rapid transfer from blood to alveoli, displaces air Lack of oxygen uptake – hypoxia

Answer 12

Short-intermediate acting barb Injectable Anesthetics Unlike Phenobarbitol, increasing urinary pH with sodium bicarbonate is ineffective in treating toxicity, since this requires metabolism before renal excretion

Answer 13

Injectable Anesthetics Barbiturate Mechanism of action Facilitates GABA induced Cl- entry into neurons, leading to CNS depression Rapid onset (sec) after iv administration and short action (min) allows quick recovery Toxicity anesthetic dose is between 50 and 75% of the LD50

Answer 14

Injectable Anesthetics Rapid induction (50 seconds) and recovery (4-8 minutes) from anesthesia May be given alone to maintain anesthesia or used for induction as part of balanced anesthesia technique May result in injection site pain

Answer 15

Injectable Anesthetic - best suited for induction of anesthesia, useful for short operative procedures, unsuitable as a single drug anesthetic

Answer 16

Benzodiazepines Mechanism of action Facilitates GABA induced Cl- entry into neurons, leading to CNS depression Characteristics Less cardiovascular and respiratory depression than barbiturates Most important characteristic is amnestic action Insufficient for anesthesia when given alone Used as induction agent prior to anesthesia

Answer 17

Injectable Anesthetics Dissociative anesthetic Patient appears to be awake - eyes open Unaware of environment and doesn't feel pain Pharm. Effects: Principal drawback is the occurrence of emergence reactions (delirium and hallucinations) Relatively high therapeutic index Abuse - currently abused in the US Single dose of ketamine significantly improved symptoms of depression in treatment resistant depressed patients in less than 2 hours and lasts at least one week

Answer 18

Opioid High dose opioids Analgesia Anesthesia Hemodynamic stability - good for patients with compromised myocardial function Respiration must be maintained artificially and may be depressed into the postoperative period Usually supplemented with inhalation anesthetic, benzodiazepine or propofol

Answer 19

Opioid High dose opioids Analgesia Anesthesia Hemodynamic stability - good for patients with compromised myocardial function Respiration must be maintained artificially and may be depressed into the postoperative period Usually supplemented with inhalation anesthetic, benzodiazepine or propofol

Answer 20

Examples - halothane, isoflurane, methoxyflurane (vet), sevoflurane CNS effects Decrease brain metabolic rate Increase cerebral blood flow Increase intracranial pressure CV effects Decreased myocardial contractility and stroke volume leading to lower arterial blood pressure Sensitizes myocardium to catecholamines ↑ automaticity Particularly in the presence of adrenergic agonists Halothane > isoflurane, desflurane, sevoflurane > nitrous oxide

Answer 21

Injectable anesthetics Act faster Best suited for induction of anesthesia Useful for short operative procedures Inhalation anesthetics Maintain anesthesia for longer procedures Muscle relaxation after IV anesthetics is poor Unsuitable as a single drug anesthetic for many surgical procedures

Answer 22

TCA Block the reuptake of NE by nerve terminals

Answer 23

TCA Block the reuptake of NE and 5-HT by nerve terminals

Answer 24

MAO INHIBITOR

Answer 25

``` Selective serotonin and norepinephrine reuptake inhibitor (SNRI) Blocks serotonin reuptake like SSRIs Also blocks NE reuptake So, why isn’t this the same as TCAs? Venlafaxine does NOT affect Adrenergic receptors Histaminergic receptors Cholinergic receptors Action of the TCAs on these receptors trigger majority of adverse effects ``` Raising the dose of venlafaxine improves efficacy due to secondary mechanisms of action

Answer 26

Active metabolite of venlafaxine Approved by the FDA in a once-daily formulation for the treatment of adults with major depressive disorder No evidence that it is any more effective than venlafaxine Patent for venlafaxine expired in 2010

Answer 27

``` Effect in normal subjects - none Effect in manic subjects Clinical use for over 50 years (30 years in US) Therapeutic effect seen in 5-21 days Effective in 60-80 % of treated patients ``` Most likely involves effect on postsynaptic rather than presynaptic neuron Interferes with the production and release of IP3 (phosphatdylinositol-4,5-bisphosphate) and DAG (diacyl glycerol) May uncouple receptor recognition site from GTP-binding protein (G-protein) by competing with Mg++ May affect several cell or nuclear regulatory factors ``` Competes with sodium for reabsorption Sodium deficiency (low sodium diet, diuretics) increases lithium toxicity ``` TOXICITY No tolerance to excessive urination and thirst (must regulate H2O intake to prevent washout) Fatigue, muscular weakness, slurred speech, ataxia, fine tremor of the hands

Answer 28

Anticonvulsant Good for non-rapid cycling bipolar disorder Superior to lithium for rapid-cycling bipolar disorder Anticonvulsants work better for acute manic episodes than for long-term management of bipolar disorder

Answer 29

Anticonvulsant approved by the FDA for prophylaxis of bipolar disorder

Answer 30

``` Atypical Antipsychotic Mechanism of action Blocks 5-HT2A subtype DA antagonist action ???? Antimanic properties Stabilizes mood ```

Answer 31

Atypical antipsychotic – 2010 Approved to treat bipolar depression – 2013 Mechanism of action Central dopamine (D2) and serotonin (5-HT2A) receptor antagonism seem to be involved Precise mechanism is unknown

Answer 32

Effect in normal subjects: No stimulating or mood elevating effect Sleepiness and light headedness Effect in depressed subjects: Elevation in mood only after 2-3 weeks Block the reuptake of NE and/or 5-HT by nerve terminals Orthostatic hypotension Weight gain Tachycardia and increased tendency for arrhythmias with high doses ``` Therapeutic index (TI = LD50 ÷ ED50) between 5-10 Depressed patients should not be given more than one week supply of TCAs ``` ``` Drug Interactions Potentiates central depressants Alcohol Anxiolytic-sedative-hypnotics Opioids Antimuscarinic effect may delay gastric emptying time ↑ Inactivation of levodopa Decreases effectiveness when used to treat Parkinsonism ```

Answer 33

Irreversibly blocks the oxidative deamination of monoamines (e.g., NE and 5-HT) Changes in neurotransmitters Occur within 24-48 hr Clinical improvement usually takes 3+ weeks to begin Low therapeutic index (less than 5) Treat: Symptomatically Hospitalize 1 week (Why?) (IRREVERSIBLY blocks, needs time to make more) Potentiates sympathomimetic amines Particularly indirect acting amines such as tyramine Dietary tyramine is completely metabolized by hepatic MAO If patient has taken MAO inhibitor, tyramine enters systemic circulation Combined effect of tyramine and MAO inhibitor: Massive adrenergic stimulation May result in a hypertensive crisis

Answer 34

WARNING: SSRIs should not be used alone in bipolar disorder Need to include a mood stabilizer to prevent rapid mood switch May cause rapid onset of mania Patients should be receiving prophylactic mood stabilizer therapy to prevent this from occurring Depression Other anxiety disorders Nausea, diarrhea and weight loss Stimulation - anxiety, nervousness, insomnia, sufficient to discontinue treatment SSRIs are not sedating like TCAs or atypical antidepressants 33-50% of those that experience symptoms cannot continue treatment Sexual dysfunction MAY CAUSE SUICIDE! MOA: Selective inhibition of serotonin reuptake by CNS neurons Serotonin receptor actions are much more complex than that of other neurotransmitters 5-HT2A – may contribute to clinical improvement seen with SSRIs 5-HT is released and can act… Postsynaptically to trigger actions in an effector cell Presynaptically on 5-HT1D autoreceptors to inhibit additional 5-HT release NE from neighboring neurons act on a2 receptors to inhibit release of 5-HT (heteroreceptors)

Answer 35

Long acting Barb (slow and partial metabolism) Phenobarbital is selectively anticonvulsant The remainder of the barbiturates are relatively unselective in their depression of the CNS Less lipid soluble (phenobarbital) - 20 min to sleep onset An overdose of a phenobarbital can be treated by administering sodium bicarbonate intravenously to elevate urinary pH

Answer 36

Benzo | plasma half-life = 2 -3 hr.; half-life of active metabolite is >50 hr

Answer 37

benzo | Preanesthetic medication

Answer 38

Benzodiazepine receptor antagonist Administered intravenously Antagonizes sedation, impaired recall, impaired psychomotor function, and respiratory depression Reverses effects of benzodiazepines, zolpidem, zapelon (see below) but not barbiturates or ethanol

Answer 39

Non-Benzodiazepine Benzodiazepine-Receptor Agonists Mechanism of action New drugs interact with benzodiazepine binding site on GABAA receptor Benzodiazepines bind to all GABAA receptor subtypes Selectively bind to certain subtypes of the receptor Advantages Rapid onset Short duration of action (no residual effects upon wakening) Slow tolerance development

Answer 40

``` Mechanism of action Suprachiasmatic nucleus (SCN) Body's "master clock" Regulates 24-hour, or circadian, rhythms Includes sleep-wake cycle ``` Ramelton is an agonist at the melatonin MT1 and MT2 receptors located in the brain's SCN Adverse effects Overall adverse events occur at rates generally comparable to placebo NO evidence of formation of physical dependence or abuse potential, and the drug is not a controlled substance Approved for long term use in adults

Answer 41

Useful in treating chronic anxiety, panic attacks and debilitating anxiety Blocks autonomic signs Less effective than BZs for anxiety and antidepressants for panic attacks

Answer 42

Classified as a "dietary supplement" rather than as a drug Not regulated by FDA Significant variation in dosages (2-3 mg vs endogenous levels of 0.1 - 0.3 mg) depending on brand Clinical effectiveness is unclear - doses above 1 mg may disturb sleep

Answer 43

Mechanism of action New drugs interact with benzodiazepine binding site on GABAA receptor Benzodiazepines bind to all GABAA receptor subtypes Selectively bind to certain subtypes of the receptor Advantages Rapid onset Short duration of action (no residual effects upon wakening) Slow tolerance development

Block 5 Drugs Flashcards

(74 cards)