EXAM #3: REVIEW Flashcards
What sedative drug classes are “selective” CNS depressants?
1) Barbiturates
2) Benzodiazepines
3) Ethanol
Outline the progression of dose-dependent effects seen with the sedative hypnotics.
1) Sedation
2) Sleepiness
3) Anesthesia
4) Coma
5) Respiratory depression/ death
List the six clinical indications for the sedative hypnotics.
1) Anxiety
2) Insomnia
3) Amnesia-induction
4) Seizures
5) Ethanol withdrawal
6) Muscle relaxation
What are the two suffixes associated with the Benzodiazepines?
- “zepam”
- “zolam”
What are the two benzodiazepines that undergo metabolism to weakly active, short lived metabolites with intermediate duration of action?
- Alprazolam
- Triazolam
What effects are associated with Alpha-1 GABA receptor agnoism?
1) Sedation
2) Anticonvulsant
3) Anterograde amnesia
What effect is associated with Alpha 2,3, and 5 GABA receptor agonism?
Anxiolysis
What are the five adverse effects associated with benzodiazepines?
1) Respiratory depression
2) Anterograde amnesia
3) Tolerance
4) Dependence
5) Withdrawal
What drug classes will cause additive CNS depression when combined with benzodiazepines?
1) Ethanol
2) Opoids
3) Anticonvulsants
4) Phenothiazine
5) Antihistamines
6) TCAs
List the four indications for Barbiturates.
1) Anticonvulsant
2) Sedative-hypnotic
3) Anesthesia
4) Medically induced coma
List the three common side effects of the MAOIs.
- Orthostatic hypotension
- Weight gain
- Sexual dysfunction
What are TCAs first line therapeutic agents for?
Chronic pain
What are TCAs second line therapeutic agents for?
Major depression
What TCA is used to treat neuropathic pain?
Desipramine
What TCA has the most sedative effects?
Amitriptytline
What is the MAJOR side effect to remember as being associated with the TCAs?
Cardiac toxicity i.e. induction of lethal cardiac arrhythmias
What are all of the side effects of the TCAs?
1) Cardiac toxicity
2) Orthostatic hypotension
3) Delirium in the elderly
4) Sexual dysfunction
What is important to remember about the safety of SSRIs compared to other antidepressants?
SSRIs are much safer than MAOIs or TCAs
What symptoms compose the triad of Serotonin Syndrome?
1) AMS
2) Autonomic hyperactivity
3) Neuromuscular abnormalities
What is the MOA of Venlafaxine?
SNRI
What receptor does Venlafaxine have its major effect on? Minor?
Major= SERT Minor= NET
What is the clinical indication for Venlafaxine?
Severe Depression
What is the MOA of Duloxetine?
SNRI with balance SERT and NET inhibition
What is the primary clinical indication for Duloxetine?
Chronic pain (increasingly prescribed over the TCAs i.e. Desipramine)
What is the MOA of Trazadone?
Antihistamine (H1 antagonist)
What is the primary clinical indication for Trazadone?
Depression + insomnia (unlabeled)
What is the MOA of Buproprion?
1) NE/ DA reuptake inhibitors
2) Increases catecholamine release
What are the clinical indications for Bupropion?
1) Major depression
2) Smoking cessation
What drug class does Mirtazapine fall under?
TCA
What is the MOA of Mirtazapine?
1) TCA (SERT and NET inhibitor)
2) Alpha-2 antagonist
3) Antihistamine (H1)
4) 5-HT2/3 antagonist
List the three antidepressants that are potent CYP2D6 inhibitors.
- Paroxetine
- Fluoxetine
- Fluvoxamine
What two anticonvulsants are prescribed for Bipolar Disorder?
1) Valproate
2) Carbamazepine
What is the MOA of Lithium?
Decreases the post-synaptic response to NE and 5-HT by:
- Decreasing cAMP
- Decreasing IP3
What are the four major side effects associated with Lithium?
1) Tremors
2) Hypothyroid
3) Nephrogenic Diabetes Insipidus
4) Skin reactions
What is the most common type of partial seizures?
Complex partial
What is an absence of Petit Mal seizure?
A seizure that is characterized by:
- Brief LOC
- Some motor signs/ automatisms
*More common in children
What are the three molecular events underlying EPSPs?
1) Na+ influx
2) Ca++ influx
3) Paroxysmal Depolarization
What drugs are best for treating absence/ petite mal seziures?
Ethosiximide
Valproate
What drugs are best for treating myoclonic seizures?
Clonazepam
Valproate
What drugs are best for treating Status Epilepticus?
Diazepam
Lorazepam
Phenytoin
Fos-phenytoin
List the adverse effects associated with anticonvulsant agents.
1) Sedation
2) Diplopia
3) Nystagmus
4) Ataxia
5) GI disturbances
What two things do you need to remember about anticonvulsant therapy in women?
1) Anticonvulsants decrease the efficacy of oral contraceptives
2) Anticonvulsants are teratogenic
What are the three elements of the Phenytoin MOA?
1) Na+ channel blocker
2) Enhanced GABA release
3) Decreased Glutamate release
Generally prevents seizure propagation
What are the clinical indications for Phenytoin?
1) Gran mal seizures
2) Partial seizures
3) Status epilepticus
What is the MOA of Carbamazepine in regards to its anticonvulsant effects? What drug class does Carbamazepine fall into?
Carbamazepine is TCA that also:
- Blocks Na+ channels –anticonvulsant
What is Oxcarbazepine?
Carbamazepine analog that has fewer side effects
List the clinical indications for Carbamazepine.
1) General (tonic-clonic) seizures
2) Partial seizures
3) Manic phase of bipolar phase (acute)
AND
4) TRIGEMINAL NEURALGIA
What unique side effect is associated with Carbamazepine?
SIADH
What are the clinical indications for phenobarital?
1) Neonatal seizures
2) Seizures in pregnancy
3) Status epilepticus
What is the unique side effect associated with Valproate?
Hepatotoxicicty
What is the MOA of Lamotrigine?
Na+ and Ca++ channel antagonist
What is the MOA of Felbamate?
Na+ and Glutamate receptor antagnoist
What are the adverse effects associated with Felbamate?
1) Aplastic anemia
2) Liver failure
What is the MOA of Tiagabine?
Inhibits GABA uptake
What is the difference between GABA-A and GABA-B receptors?
GABA-A= Cl- ion channel
GABA-B= GPCR that increases K+ conductance on stimulation
What are the six characteristics of an ideal anesthetic?
1) Unconsciousness
2) Amnesia
3) Analgesia
4) Skeletal muscle relaxation
5) Areflexia
6) Good minute-to-minute control
What are the four phases of anesthesia?
1) Induction
2) Maintenance
3) Emergence
4) Recovery
What are the stages of anesthesia?
1) Analgesia
2) Excitement
3) Surgical anesthesia
4) Medullary depression
What are the three general mechanisms of action of general anesthetics?
1) Increased GABA-A activity
2) Activation of K+ channels
3) Inhibition of NMDA receptors
What clinical scenario will cause a decreased MAC value?
Presence of CNS depressants
What are the three major drawbacks to NO?
1) Lack of potency (110% MAC value)
2) Diffusion hypoxia
3) Increased risk of spontaneous abortion
List the halogenated anesthetic agents.
1) Halothane
2) Enflurane
3) Isoflurane
4) Desflurane
What major adverse effect is associated with Halothane?
Hepatitis
What major side effect is associated with Enflurane?
CNS stimulant effects
What drug class does Thiopental fall into?
Barbiturate (used for anesthesia induction)
What is the MOA of Ketamine?
NMDA antagonist
What type of local anesthetic, protonated (LAH) or non protonated (LA) is more lipophilic? Which binds the internal portion of Na+ channels with higher affinity?
LA= more lipophilic LAH+= binds Na+ channels with higher affinity (internally)
Which type of LA has a longer half-life, amides or ester?
Amides have a longer half-life
Which type of LA is metabolized in the liver? Blood?
- AmIdes– with 2x i’s–are metabolized in the lIver
- Esters– with 1x i– are metabolized in the blood
What is the Cm?
Minimum anesthetic concentration for standard block in 50% of the population
List the amide type LAs.
Lidocaine
Bupivicaine
Ropivacaine
Articaine
List the ester type LAs.
Cocaine Procaine Tetracaine Benzocaine Chloroprocaine
What is the clinical utility of Benzocaine?
This is an ester-LA that has enhanced lipid solubility–it can be used topically
What is the clinical utility of Chloroprocaine?
This is an ester-LA that is used as an epidural agent in labor b/c:
- Low risk of systemic toxicity
- Low risk of fetal exposure
What is Exparel-Liposome? What is it used for?
- Encased Bupivacaine (amide LA) w/ extended half-life
- Provides up to 72 hours of post-op pain relief
What are the four clinical indications for antipsychotic medications?
1) Schizophrenia
2) Psychotic behavior
3) Severe mania
4) Antiemetic
List the typical antipsychotics.
Chlorpromazine
Thioridazine
Fluphenazine
Haloperiodol
List the atypical antipsychotics.
Clozapine Olanzapine Risperiodone Aripiprazole Quetiapine Zisprasidone
What is the difference between the metabolism of the typical and atypical antipsychotics?
Typical= metabolism into an INACTIVE metabolite
Atypical= metabolism into an ACTIVE metabolite
What receptor/s is primarily antagonized by typical antipsychotics? Atypical?
Typical= D2
Atypical D2 + 5-HT2A
What antipsychotic is associated with high 5-HT2A affinity?
Clozapine
List the subtypes of extrapyramidal symptoms.
1) PD-like Syndrome
2) Akathesia
3) Dystonia
4) Tardive Dyskinesia
List the four most common reasons that patients will stop taking antipsychotics.
1) Lack of efficacy
2) Cannot tolerate side effects in general
3) Weight gain
4) Sexual dysfunction
List the five hallmark cognitive symptoms of AD.
1) Loss of short-term memory
2) Disorientation
3) The A’s
- Aphasia
- Apraxia
- Agnosia
Describe the pathologic changes that underly the development of the AD phenotype specifically in regards to Beta-amyloid.
1) ABPP or Amyloid Precursor Protein is cleaved into Beta-Amyloid
2) There is an IMBALANCE between Beta-Amyloid production and clearance
3) Beta-amyloid accumulates and is TOXIC to neurons
What is the function of “Presenilin?”
Presenilin cleaves Amyloid Precursor Protein
What are the consequences of neurofibrillary tangles in AD?
1) Microtubular disintegration and instability
2) Collapse of the neuronal transport system
3) Altered neurotransmitter release
4) Cell death
List the four drugs that are used as first line agents in AD. What drug class do they belong to?
Cholinesterase inhibitors:
1) Tacrine
2) Donepezil
3) Rivastigmine
4) Galantamine
What adverse effect of Tacrine limits its clinical use today?
Hepatotoxicity
*Also has a v. short half-life and had to be dosed 4x per day
Which first line agent for AD can be given as a transdermal patch? What are the clinical implications?
Rivastigmine can be given transdermally
- Limits the adverse GI disturbances
What is the MOA of Memantine?
Non-competitive NMDA antagonist
What class of antidepressants are contraindicated in the treatment of depression in AD patients?
TCAs–alpha-1 effects have an increased risk for orthostatic hypotension and falls
What are the four cardinal symptoms of PD?
1) Bradykinesia
2) Muscular rigidity
3) Resting tremor
4) Postural instability
What are the adverse effects associated with L-DOPA administration in PD?
1) Dyskinesia
2) Response fluctuations
3) Postural hypotension/tachycardia
4) Behavioral disturbance
5) GI disturbances
What is the drug interaction between L-DOPA and the antipsychotics?
- L-DOPA is aiming to increase DA concentrations
- Antipsychotics are D2 ANTAGONISTS
Thus, the drugs counteract each other.
List three DA receptors agonists that are used to treat PD.
Pramipexole
Ropinirole
Apomorphine
List the two MAO-B receptor antagonists used to treat PD.
Rasagiline
Selegiline
List the two COMT inhibitors used to treat PD.
Entacapone
Tolcapone
What is the MOA of Amantadine to treat PD?
Increased DA release
What adverse effect is associated with Amantadine?
Livedo Reticularis
List the two anticholinergic agents used to treat PD.
Benztropine
Trihexyphenidyl
Name the three endogenous opioids.
Endorphins
Enkephalins
Dynorphins
What is the difference between Mu1 and Mu2 receptors?
Mu1= outside the CNS Mu2= inside the CNS
How does agonism of Mu opioid receptors produce analgeisa?
1) Mu opioid receptors are GPRCs coupled to Gi subunits
2) Activation causes decreased adenylyl cyclase
3) Decreased adenylyl cyclase causes decreased cAMP
The final result is LESS intracellular Ca++ and increased K+ conductance i.e. INHIBITION
List five clinical indications for opioids.
1) Analgesia
2) Anesthesia
3) Anti-tussive
4) Anti-diarrheal
5) Acute pulmonary edema
What class of drugs are contraindicated with opioids?
MAOIs
List the “strong” opioids.
Morphine Hydromorphone Oxymorphone Methadone Fentanyl Sufentanil Meperidine Heroin
List the mixed opioid agonist-antagonists.
Bupreneorphine
Butorphanol
Nalbuphine
Pentazocine
List the “other” opoid agonists.
Dextromethorphan
Diphenoxylate
Loperamide
Tramadol
What effects will CNS stimulants produce?
1) Alterness
2) Productivity and motivation
3) Arousal
4) Euphoria
5) Nervousness and anxiety
What is Methylxanthine?
- CNS/ Respiratory stimulant
- Derivative of xanthine
What are the clinical indications for Theophylline?
- COPD
- Asthma
Note that this drug has bronchodilator properties
List the sympathomimetic amide stimulants.
1) Amphetamine analogs including:
- Methamphetamine
- Dexamphetamine
- Methylphenidate
2) Cocaine
3) Modafinil
4) Atomoxetine
How are the amide psychomotor stimulants metabolized?
1) MAO
2) CYP p450
What classes of drugs will have adverse interactions with CNS stimulants?
MAOIs
SSRIs
List the CNS related side effects seen with the psychomotor stimulants.
Euphoria Dysphoria Insomnia Irritability Tremor Headache Anorexia
List the stimulant drugs that are used to treat ADHD.
Methylphenidate
Amphetamine salts (adderall)
Dextroamphetamine
List the non-stimulant drugs that can be prescribed for ADHD.
1) Atomoxetine
2) Clonidine
3) Modafininl
4) Antidepressants
- TCAs
- MAOIs
- Bupropion
List the psychological manifestations of drug withdrawal.
- Dysphoria
- Depression
- Anxiety
- Craving
- Psychosis
What are the three drugs “targets” of the VTA?
1) Gi GPCRs that inhibit GABA
2) Inonotropic DA receptors
3) DA uptake transporter
What drugs act on ionotropic DA receptors in the VTA?
1) Benzodiazepines
2) Nicotine
3) Alcohol
What is the MOA of GHB?
Disinhibition of GABA-B receptors in the VTA
What are the side effects associated with Methamphetamine use?
Methamphetamine is sympathomimetic, thus:
- Mydriasis
- Tachycardia
- Hypertension
What is the MOA of MDMA?
1) SERT Antagonism
2) Increases the release of 5-HT
Wha toxicity is associated with MDMA?
Acute hyperthermia and dehydration
List the Psychedelcis.
1) LSD
2) Psilocybin
3) Ketamine
4) Phecyclidine
What is the MOA of LSD and Psilocybin?
- Increase glutamate release
- 5-HT2A agonist
What is the MOA of Ketamine and PCP?
NMDA antagonists
What is the RR of opioid addiction?
4
List the four most commonly abused opioids.
1) Codeine
2) Heroin
3) Morphine
4) Oxycodone
What is the MOA of euphoria seen in opioid use?
1) Activation of Mu opioid receptors
2) Inhibition of GABAnergic neurons in the VTA
Result in disinhibition of VTA DA neurons
What is the MOA of THC?
Blocks GABA-A receptors on DA neurons in the VTA
