Pharmacology Flashcards
Catecholamine
precursor to EP
DA, NE
Monoamine
NTs that contain one amino group that is connected to an aromatic ring
Ex) thyroid hormones, Histamine, catecholamines (EP, DA, NE), tryptamines (5-HT)
Where is ACh made?
Nucleus basalis of Meynert
Where is DA made?
substantia nigra and ventral tegmental area
Where is Histamine made?
Ventral Posterior hypothalamus (Tuberomammillary nucleus)
Where is NE made?
locus ceruleus in upper pons
Where is 5-HT made?
raphe nucleus in brain stem
NMJ-blocking Agents: What do they cause?
Used for skeletal muscle relaxation–> ONLY paralysis, NO analgesia or unconsciousness
Depolarizing Agents (mech, ex, use, side effects)
Mech: binds aggressively to AChR–> depolarizes–> resistant to AChE–> stays bound–> Na+ channels remain closed–> cannot depolarize. Cannot be reversed.
Ex) Succinylcholine
short-acting (onset 30sec, last 10min) due to Pseudocholinesterase
temporary muscle paralysis (surgery, intubation)
Non-depolarizing agents
Mech: competitive inhibition
Ex) MivaCURIUM, -curium
elimination depends on renal/hepatic activity
Side effects: resp. failure
How do you reverse Nondepolarizing Agents?
AChE inhibitors
Why can’t you give AChE inhibitor to person w/ Depolarizing Muscle agent?
AChE inhibitors will also block Pseudocholinesterase, which is the main way to eliminate depolarizing agents–> prolong Phase I (aggressive binding)
Cholinesterase Inhibitors
Mech: inactivate AChE
used to reverse nondepolarizing NMJ agents
Ex) neostigmine, physostigmine
Side effects: bradycardia, broncospasm, pupil constriction, increased bladder tone, etc.
Anticholinergic Drugs
Mech: competitive inhibition
used in anesthesiology
Ex) Atropine
Side effects: decreased secretions, urinary retention, CNS stimulation, cutaneous blood vessel dilation
Atropine
first-line tx for organophosphate poisoning, w/ pralidoxime (2-PAM)
Effects: reverses bradycardia, bronchial smooth muscle relaxation, decrease resp. secretions, reverse psychotic effects
What are the 2 biggest concerns with benzodiazepines and barbiturates?
tolerance and withdrawal
Barbituates
Mech: increase DURATION of Cl- channel opening
Uses: anesthesia, anticonvulsants, anxiolytics, insomnia
*withdrawal is dangerous and pts must be hospitalized
What are 3 side effects of barbituates?
induce CYP-450
suppress REM sleep (even though given for insomnia)
Contraindicated in pts w/ Acute Intermittent Poryphyria b/c barbs activate ALA synthase–> heme synthesis
Benzodiazepines
Mech: Increase FREQUENCY of Cl- channel opening
Uses: anxiolytics, muscle relaxants, amnesic agents, anticonvulsants
Benzodiazepines and pregnancy
can cross placental barrier
How to reverse effects of benzodiazepines? How does withdrawal compared to that of barbiturates?
Flumazenil (competitive antagonist)
Withdrawal similar, but NOT as severe as barb withdrawal
How do benzodiazepines and barbituates affect sleep?
Benzo: decrease latency, increase Stage 2 of NREM sleep, decrease REM and slow-wave sleep
Barb: suppress REM sleep
Opiods
Mech: agonist at M-opioid receptors, with varying strengths
Uses: local analgesia, systemic pain relief, chronic pain management, antitussive
Side effects: tolerance, dependence, overdose
Buspirone
Mech: partial agonist of 5-HT-1A receptors
* NO EFFECT on GABA rec, does NOT interact w/ EtOH, NO sedating effects or euphoria (like with benzo, barb). Less potential for abuse!
Use: Generalized Anxiety Disorder (NO muscle relaxant or anticonvulsant properties)
What are endogenous endorphins made from?
POMC (proopiomelanocortin)
Which NTs do Antidepressants target? What can extended treatment lead to?
5-HT, NE, and sometimes DA
Extended treatment can lead to downregulation of postsynaptic NT receptors
Selective Serotonin Reuptake Inhibitors
first-line tx for depressive and anxiety disorders
Increases 5-HT levels
Ex) Citalopram, fluoxetine, paroxetine, sertraline, fluvoxamine
see effects after 3-6wks
Uses: depressive disorders, panic disorder, generalized anxiety disorder, OCD, etc.
Side effects: diarrhea, sexual dysfcn, Discontinuation Syndrome
For whom are SSRI’s better to use? Who should NOT use them? For whom are they ineffective?
Good: Pregnant women, elderly
Bad: patients with Mania
Ineffective: mood is not elevated in non-depressed patients
What is the most common congenital defect with SSRI use?
ventral septum defect
SSRI Discontinuation Syndrome
dizziness, vertigo, nausea, fatigue, HAs, agitation, suicidal ideation, etc.
Monoamine Oxidase Inhibitors (contraindications)
IRREVERSIBLY inhibits MAO–> Increases NE levels
Ex) Phenelzine, tranylcypromine, isocarboxazid
Uses: depressive disorders, anxiety
Contraindications: tyramine-containing foods, SSRIs
What else is MAO responsible for?
breakdown of 5-HT and tyramine
What are some side effects if take MAOIs w/ tyramine-foods? What kinds of food have tyramine?
Side Effects: HTN crisis, diaphoresis, HA, vomiting
Foods: cheese, pepperoni, beer/wine, smoked/pickled meat, liver
What can happen if take MAOIs w/ SSRIs?
“Serotonin Syndrome”: confusion, hyperthermia, myoclonus, hyperreflexia, diaphoresis
Tricyclic Antidepressants
Inhibit reuptake–> Increase levels of NE and 5-HT
ex) amytriptyline, imipramine, amoxaprine
Uses: chronic pain, major depression, anxiety
Side effects: Constipation, cardiac arrhythmia, coma
Noncyclic Heterocyclic Antidepressants (Bupropion)
inhibits reuptake of DA and NE–> Increase levels of DA and NE
Ex) Bupropion
Uses: 2nd and 3rd-line meds for major depression and smoking cessation. God for pts who do not tolerate TCAs.
Side effects: stimulant effects, tachycardia, insomnia
Noncyclic Heterocyclic Antidepressants (Venalfaxine, Duloxetine)
Inhibit reuptake of 5-HT > NE–> increase levels
Uses: major depression, melancholia, anxiety, chronic pain, diabetic peripheral neuropathic pain
Noncyclic Heterocyclic Antidepressants (Nefazodone, trazodone, mirtazapine)
5-HT modultors–> Block 5-HT2 receptors and inhibit 5-HT and NE reuptake
Uses: major depression, anxiety
Noncyclic Heterocyclic Antidepressants (Maprotiline)
inhibits reuptake of NE. ONLY one that does not affect 5-HT levels!
Uses: Major depression
Side effects: orthostatic hypotension, sedation
Neuroleptics
Anti-psychotics
Block Type 2 DA Receptors
Uses: positive symptoms of schizophrenia (hallucinations, delusions)
First-Generation Antipsychotics
Ex) Thioridazine (Low-potency) Haloperidol (High-potency)
Uses: acute psychosis, schizophrenia, bipolar disorder
Side effects: extrapyramidal signs, tardive dyskinesia, dystonia, hyperprolactinemia, prolongation of QT interval, neuroleptic malignant syndrome.
High-potency vs. Low-potency 1st generation antipsychotics
High-potency: greater affinity for D2 receptors
Low-potency: also have affinity for mAChRs, alpha-Adrenergic Rs, Histaminergic Rs
Side effects of Low-potency 1st generation antipsychotics due to blockade of Histamine and mAChRs?
Histamine Rec: weight gain, sedation, orthostatic hypotension, tremor, sexual dysfunction
mAChRs: facial flushing, dry mouth, urine retention, constipation
Neuroleptic Malignant Syndrome
Muscle rigidity, fever, autonomic instability, and cognitive changes such as delirium
Associated with elevated plasma creatine phosphokinase
Second Generation (Atypical) Antipsychotics (advantages)
Ex) clozapine, Risperidone, olanzepine
Advantages: more effective against negative/chronic symptoms (flattened affect, alogia). Less risk for tardive dyskinesia, neuroleptic malignant syndrome, extrapyramidal signs
Side effects: cardiotoxicity, neuroleptic malignant syndrome, hyperprolactinemia, prolongation of QT interval
Anticonvulsants (mechanisms?)
suppress uncontrolled neuronal discharge
epileptic seizures
Mech: 1) increase GABA-ergic activity 2) block VG-Na+ channels 3) block VG-Ca2+ channels
Valporic Acidd
Mech: 1) binds to VG-Na channels–> keep in inactivated state. 2) block VG-Ca2+ channels (Type T channels in Thalamus)
Uses: partial and generalized tonic-clonic seizures, bipolar disorder
Side Effects: GI upset, sedation, increased appetite, weight gain
Ethosuximide
Mech: Block VG-Ca2+ channels (Type T channels in Thalamus)–> stop rhythmic discharge
Uses: First-line for ABSENT seizures
Side Effects: GI upset, lethargy, HA, Stevens-Johnson Syndrome
Phenobarbital
Mech: Barbiturate (increases DURATION of GABA receptor)
Uses: Status epilepticus
Side Effects: sedation, tolerance, dependence, Induce P450 (Barbiturate side effects)
Carbamazepine
Mech: reduces rate of recovery of Na+ channels–> block rapid firing
Use: First-line for partial seizures, tonic-clonic seizures, TRIGEMINAL NEURALGIA, bipolar disorder
Side Effects: hyponatremia, Induces P450
Phenytoin
Mech: reduces rate of recovery of VG-Na+ channels
Uses: First-line PROPHYLAXIS for Status Epilepticus, all types of partial/generalized seizures (EXCEPT Absent seizures)
Side Effects: nystagmus, diplopia, Fetal Hydantoin Syndrome, Induce P450
Lamotrigine
Mech: reduces rate of VG-Na+ channels AND reduces glutamate release
Uses: partial seizures, generalized seizures, focal epilepsy, Lennox-Gastaut syndrome, bipolar disorder
Side Effects: Dizziness, Nausea, HA, Stevens-Johnson Syndrome
Pregabalin
Mech: binds to alpha2-delta subunit of high-VG-Ca2+ channels, increases density of GABA transporter/increases rate of GABA transport, AND decreases glutamate, NE, and substance P release
Uses: Anitnociceptive AND antiseizure. Neuropathic pain (diabetic neuropathy and postherpetic neuralgia, fibromyalgia, partial seizures
Side Effects: dizziness, somnolence, weight gain
Gabapentin
Mech: GABA-analog, BUT does NOT work at GABA receptor. Binds to alpha2-delta high-VG-Ca2+ AND decreases glutamate release
Uses: partial seizures, pain, peripheral neuropathy, bipolar disorder, anxiety
Side Effects: sedation, weight gain
Lithium
Uses: Mood stabilizer. Bipolar disorder, augment antidepressants
Mech: UNKNOWN, may interfere w/ monoamine synthesis, release, reuptake.
Low Therapeutic Index
Side Effects: Can be toxic to thyroid and kidney–> MUST monitor. Hypothyroidism, nephrogenic diabetes insepidus
What happens to NT levels in Alzheimer’s?
Decrease in ACh
Increase in glutamate–> influx of Ca2+ can lead to neuronal cell damage
Memantine
Mech: Non-competitivelyblocks NMDA receptors in CNS
Uses: moderate to severe Alzheimer AND vascular dementia
Side effects: agitation, urinary incontinence, insomnia, diarrhea
Tacrine, Donepezil, Rivastigmine, Galantamine
Mech: Selective AChE in the CNS! Crosses BBB (less peripheral side effects)
Use: Alzheimer
Side effects: nausea, vomiting, diarrhea, insomnia
What are the 3 ways to increase CNS levels of DA?
1) prevent degradation of DA
2) add exogenous precursor
3) give D2 receptor agonists
Bromocriptine (extra effects?), Pergolide, Ropinirole, Pramipexole
Mech: DA receptor agonists. Different effects on different types of receptors. Bromocriptine ALSO antagonizes D1 receptors in hypothalamus.
Uses: Parkinson. Bromocriptine can ALSO be used to reduce growth rate of pituitary adenoma (prolactinoma)
Side Effects: HA, nausea/vomiting, epigastric pain, Hypotension—> HTN
Levodopa (L-dopa) (Contraindications?)
Mech: precursor of DA. Enters brain through L-amino transporter (DA canNOT cross the BBB). In CNS, metabolized to HVA and DOPAC.
Uses: First-line for Parkinson’s tx w/ Carbidopa.
Side effects: nausea/vomiting, tachycardia, dyskinesia, agitation, confusion, depression
Contraindications: psychosis and closed-angle glaucoma
Carbidopa
reduces peripheral conversion of L-Dopa to DA–> increases availability of L-Dopa for CNS
MAO Inhibitors (different Types)
MAO-A: metabolizes NE and 5-HT
MAO-B: metabolizes DA (striatum)
Selegiline and Rasagiline
Mech: IRREVERSIBLE selective inhibitors of MAO-B (striatum).
Uses: Parkinson. Selegiline given in LOW-dose–> no interaction w/ tyramine-containing foods
Side effects: Serotonin syndrome if taken w/ SSRIs, TCAs, merperidine
Tolcapone and Entacapone
Mech: COMT inhibitors–> prolong action of L-Dopa. Tolcapone (peripheral and central). Entacapone (peripheral ONLY)
Uses: Increase L-Dopa levels. Entacapone PREFERRED b/c less hepatotoxic.
Side effects: dyskinesia, nausea, confusion
General Anesthetics
Cause analgesia, amnesia, unconsciousness, muscle relaxation, suppression of reflexes
4 Stages of Anesthesia
1) Analgesia: “Conscious and Conversational”
2) Disinhibition: Autonomic variations (changes in BP, HR, RR)
3) Surgical anesthesia: Unconscious w/ relaxed muscles
4) Medullary depression: Respiratory and vasomotor center depression
Inhaled Anesthetics
Uses: MAINTENANCE of anesthesia b/c depth of anesthesia can be rapidly altered.
Mech: poorly understood.
Ex) Halothane, isoflurane, sevoflurane, desflurane
Side effects: resp. depression, nausea, emesis, hypotension
Toxicity of Inhaled Anesthetics
Hepatotoxicity, nephrotoxicity, convulsions, malignant hyperthermia (EXCEPT Nitrous Oxide)
What determines speed of anesthesia induction?
1) alveolar gas and venous blood partial pressures
2) solubility in blood
3) alveolar blood flow
MAC (Minimum Alveolar Concentration)
Similar to ED50–> Alveolar conc. of inhaled anesthetic that stops movt in 50% patients in response to incision
What is the difference between anesthetics with LOW and HIGH solubility in blood?
LOW solubility: Rapid induction and recovery. Not as potent.
HIGH solubility (in oil/lipid): Slower induction/recovery. Increased potency.
Higher lipid solubility–> higher solubility in blood.
Tradeoff between potency and speed of induction.
How do you treat Malignant Hyperthermia?
Dantrolene: interferes w/ Ca2+ release from SR in muscles by binding to ryanodine receptors
Intravenous Anesthetics (Types)
Rapidly INDUCE anesthesia
1) barbiturates
2) benzodiazepines
3) ketamine
4) opiates
5) propofol (can ALSO maintain anesthesia)
6) Etomidate
Benzodiazepines
Ex) Midazolam
Use: endoscopy
Side effects: severe postoperative respiratory depression and amnesia
Barbiturates
Ex) Thiopental
Highly lipid-soluble–> enters brain rapidly
NOT analgesic–> need supplementary
Side effects: severe Hypotension in hypovolemic/shock patients
Ketamine
Ex) Arylcyclohexylamine)
Dissciative anesthetic (Act via NMDA receptors)
Causes: sedation, amnesia, immobility, disorientation, hallucinations
Opioids
Ex) Morphine, fentanyl, sufentanil
*Used w/ other CNS depressants during anesthesia
Toxicity: hypotension, respiratory depression, muscle ridigity
Propofol
Rapid induction AND maintenance
*Excitatory phase: muscle twitching, hiccups
Uses: resection of spinal tumors. Can be used when assessing spinal cord function b/c less effect on CNS-evoked potentials
How can you reverse opioids?
Naloxone and naltrexone (Mu-opioid receptor antagonists)
