CNS Flashcards
(80 cards)
1
Q
Sedative-Hypnotic-Anxiolytic Drugs
A
Barbiturates, Benzodiazepines, Alcohol
2
Q
Effects of SHA Drugs
A
Cause dose dependent CNS depression that extends from sedation to anesthesia to repiratory depression and death
3
Q
Mechanisms of SHA drugs
A
bind to GABAa receptor complex (5 subunits types)
Benzo bind to gamma subunit
Barbiturates bind to beta subunit
Result in increase Cl- infulx -> hyperpolarization
4
Q
Benzodiazepines
A
Potentiate GABA
has no GABA mimetic activity
BZ1 mediates sedation
BZ2 mediates antianxiety and impairment of cognitive functions
Use to treat anxiety and sleep disorders
Can be reversed by FLUMAZENIL
Pharmacokinetics: liver metabolized to active compounds (except oxazepam, tenazepam, Iorazepam)
Withdrawal signs: Rebound insomnia, anxiety, Seizures (rare, only in high doses)
5
Q
Barbiturates
A
Prolong GABA activity
increase duration of Cl- channel opening
Have GABA mimetic activity as high doses
also inhibit complex I of electron transport chain
Pharmacokinetics: Liver metabolized, sometimes to active compounds
inducing drugs metabolizing enzymes (P450) Use as: Seizure (Phenobarbital) induction of anesthesia (thiopental, IV)
Withdrawal signs: anxiety, agitation, life threatening SEIZURES!!!!
Contraindicated in Porphyrias (stimulate heme synthesis)
6
Q
Benzodiazepine compounds
A
Alprazolam, Diazepam, Lorazepam, Midazolam, Temazepam, Oxazepam
7
Q
Drug interations of SHA drugs (BZ)
A
additive with other CNS depressants such as anesthetics, antihistamines, opiates, beta blockers
Barbiturates induce metabolism of most lipid-soluble drugs (oral contraceptive, carbarmazepine, phenytoin, warfarin…)
8
Q
Non-BZ drugs
A
Zolpidem, zaleplon, Buspirone
9
Q
Z drugs
A
Zolpidem and zaleplon BZ1 receptor agonist less effect on cognitive function overdose reversed by FLUMAZENIL Used in sleep disorders Less tolerance and abuse liability
10
Q
Buspirone
A
NO EFFECT on GABA!!! 5-HT (1A) partial agonist used for generalized anxiety disorders Nonsedative Takes 1 to 2 weeks for effects
11
Q
Alcohols
A
Cause CNS depression, through GABA mimetic activity
Cause metabolic acidosis
12
Q
Ethylene glycol
A
Acute intoxication ( testing in case of car accident and suicide) Liquid (sweet, bright color) so kids may want to drink it intoxication sign: CNS depression, severe metabolic acidosis, nephrotoxicity (crystal of oxalic acid)
13
Q
Methanol
A
Wood alcohol Toxic metabolites: Formaldehyde Formaldehyde can cause: Respiratory failure, Severe metabolic acidosis Blindness (ocular damage)
14
Q
Alcohol dehydrogenase inhibitors:
A
Treatment for overdose of alcohol
IV Ethanol
Fomepizole (long acting)
15
Q
Ethanol
A
Caused CNS depression, metabolic acidosis (ketones) and acetaldehyde toxicity (metabolite product of ethanol)
16
Q
Acetaldehyde
A
Hang over effects:
Nausea and vomitting
Headache
Hypotension
17
Q
Disulfiram
A
Alcetaldehyde dehydrogenase inhibitor
Cause negative effect when drinking alcohol
18
Q
Drugs have disulfiram-like effects
A
Metronidazole, Cefoperazone, Cefotetan, Chlorpropamide, Griseofulvin
19
Q
Anticonvulsants
A
Use in treatment of epileptic seizures
20
Q
Mechanism of actions of anticonvulsants
A
- decrease axonal conduction by preventing Na+ influx through fast Na+ channels (carbamazepine, phenytoin)
- Increase inhibitory tone by facilitation of GABA mediated hyperpolarization (benzodiazepines, barbiturates)
- Decrease excitatory effects of glutamic acid (not the 1st choice drug) (lamotrigine, topiramate, felbamate
- Decrease presynaptic Ca++ influx type T channels in thalamic neurons (Valproic acid, ethosuximide)
21
Q
Phenytoin
A
blocks axonal Na+ channels in their INACTIVATE state !!
Prevent seizure propagation
Uses: seizure states (in any seizure states except absence seizure)
Pharmacokinetics:
Variable absorption
Nolinear kinetics
Induction of cytochrome P450s
Zero-order kinetic of elimination
Side effects: CNS depression
Gingival hyperplasia (specific for Phenytoin)
Hirsutism!! (specific for Phenytoin)
Osteomalacia (decrease vitamin D)
Megablastic anemia (decrease folate)
Aplastic anemia (hypersensitivity reaction-> drop in WBC)
Teratogenicity: cleft lip and palate in baby
(caution in case of pregnancy woman
22
Q
Carbamazepine
A
Mechanism indentical to phenytoin Use in any seizure states except absence Drug of choice for trigeminal neuralgia Bipolar disorder Pharmacokinetics: induces CyP450 Side effects: CNS depression Osteomalacia Megaloblastic anemia Aplastic anemia Exfoliative dermatitis (specific) Increase ADH secretion (dilutional hyponatremia) (specific) Teratogenicity: cleft lip and palate, spina bifida
23
Q
Valproic Acid
A
Mechanism: Similar to phenytoin Inhibition of GABA transaminase (enzyme which is inactive GABA) Blockade of T-type Ca++ channels Uses: Any seizure states including absence Mania phase of bipolar disorders Migraines Pharmacokinetics: INHIBITS CyP450 !! Side effects: Hepatoxicity Thrombocytopenia Pancreatitis!!!! Alopecia (losing hair) Teratogenicity: Spina bifida
24
Q
Ethosuximide
A
Blockade of T-type Ca++ channels in thalamic neurons
Use only in case of absence seizures!!!
25
Anticonvulsant drug using
Additive with other CNS depressants
Abrupt withdrwal may precipitate seizures
decrease efficacy of oral contraceptive!!!
Phenobarbital is considered safest anticonvulsant drug
26
Inhaled Anesthetics
Lungs->Blood->CNS
but from blood stream anesthetics can go to fat and accumulate there so think about the redistribution of those gases
Fat->Blood->CNS
27
Minimal alveolar anesthetic concentration (MAC)
the concentration of inhaled anesthetics, as a % of inspired air, at which 50% of patients do not respond to a surgical stimulus
MAC is a measure of potency: ED50
the more lipid soluble the anesthetic, the lower the MAC and greater the potency
MAC values are additive
MAC values are lower in elderly and in the presence of opiates or sedative-hypnotics
28
Blood-gas ration
```
Blood: protein bounding
Gas: Free anesthetics
the more soluble the anesthetic in the blood, the slower the anesthesia (need more time to achieve the target concentration in the brain)
high BGR: slow onset, slow recovery
low BGR: fast onset and recovery
```
29
Intravenous Anesthetics
Thiobental, Midazolam, Propofol, Fentanyl, Ketamine
30
Thiobental
Barbiturate used for induction
| high lipid soluble, rapid onset, short acting due to redistribution
31
Midazolam
Benzodiazepine use for preoperative sedation, anterograde amnesia, induction, outpatient surgery
depresses respiratory fuction
32
Propofol
looks like milk
Antiemetic effects (prevent gastric fluid cause damage to the lungs)
Used for induction and maintenance of anesthesia
CNS and cardiac depressant
33
Fentanyl
Opiates used for induction and maintainance of anesthesia due to its central analgesis effects
Respiratory depressant
34
Ketamine
Dissociative anesthetic (brain will not see pain as a negative feeling, it doesnt care!!)
NMDA-receptor antagonist
Induction of anesthesia
Emergent delirium, hallucinations
Cardiovascular stimulation
Increase intracranial pressure (potential for hernia!!)
35
Local anesthetics
provide regional anesthesia
Mechanism:
First it has to be in NONIONIZED form to crossed axonal membrane then from within the IONIZED form blocks the inactivated Na+ channel
Slow recovery and prevents propagation of action potentials
Has 2 types: Esters( no i before cane) and Amides (has i before cane)
36
Nerve fiber sensitivity
most sensitive to blockade are of the smaller diameter and have high firing rates!!
37
Order of sensitivity
```
from type B & C to type A
type C is small, unmyelinated type (dull type of pain)
Type A (gamma) associated with pain sensation (sharp)
```
38
Side effects of local anesthetics
Neurotoxicity
Cardiovascular toxicity
Allergies (PABA)
to prevent those bad effects to heart and kidney -> coadministrate with Alpha 1 agonist
-> vasoconstriction-> can not spread to systemic circulation (Cocaine)
39
Skeletal muscle relaxants
Nondepolarizing (competitive):
Atracurium, Mivacurium
Depolarizing (non competitive)
Succinylcholine
40
Atracurium
Rapid recovery
Safe in hepatic or renal impairment
spontaneous inactivation to laudanosine which can cause SEIZURE!!!
41
Mivacurium
very short duration
| Metabolized by plasma cholinesterases
42
Succinylcholine
Nicotinic agonist
Mechanism: 2 phases
Phase 1: depolarization, fasciculation, prolong depolarization, flaccid paralysis
Phase 2: desensitization
Rapid hydrolyzed by pseudocholinesterase: short duration
Cautions: atypical pseudocholinesterase, hyperkalemia, malignant hyperthermia
43
Opioid Analgesis
Endogenous opiate peptides: endorphins, enkephalins, dysnophins
Receptors family: Mu (endorphins) ; Kappa (dysnophins) ; Delta (enkephalins)
Mechanism: presynaptic and postsynaptic inhibition through Gi coupling
Mu pharmacology most important (Morphine is Mu agonist)
44
Morphine
Effects:
Analgesia: increase pain tolerance, decrease perception and reaction to pain (dissociative type)
Sedation
Respiratory depression: decrease response to PCO2 (do not give O2)
Naloxone is the antidote
Vasodilation (brain hernia)
GI, GU, Biliary (decrease peristalsis, constipation, cramping, urinary retention, urgency to void...) due to smooth muscle effects -> use with antimuscarinic drug (atropine)
Pupil miosis
Cough supression
Nausea and vomitting (chemoreceptor trigger zone)
Increase histamine relasese
Pharmacokinetics: Glucoronidation
Morphine-6-glucoronidation is highly active (caution in renal dysfuction)
45
Meperidine
Also known as Pethidine
Opioid analgesics
Receptor action: Full agonist
Characteristics:
antimuscarinic drug -> no miosis, tachycardia, no spasm of GI/GU/gallbladder
Metabolized by Cyp450 to normeperidine, a serotonin reuptake inhibitor, which can cuase seizure!!!
46
Methadone
```
Opioid analgesic (full agonist)
Used in maintenance of opiate addict
Slow in mechanism than morphine so will not cause a rush in addict
Long half life (2-3 days) so dont have withdrawal issue
```
47
Codein
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Opioid analgesic
Full but weak agonist
Drug of abuse, can cause significant CNS depression!!
Cough supressant
used in combination with NSAIDs
```
48
Buprenophine
Opioid analgesic
Partial agonist
Precipitation of withdrawal (behave as a blocker in the presence of full agonist)
49
Opioid analgesics (mixed agonist-antagonist)
work not only in Mu receptor (as antagonist) but also on kappa receptor (as agonist)
Drugs: Nalbuphine, pentazocine
Precipitation of withdrawal (mu) so use in heroin user!!
Spinal analgesia, dysphoria (kappa)
50
Opioid analgesic (antagonists)
Naloxone: IV, reversal for respiratory depression
Naltrexone; PO, decrease craving for alcohol and used in opiate addiction
Methylnaltrexone: Treatment of opioid-induced constipation!!
51
Side effects of opioid analgesics
Pinpoint pupils
Respiratory depression
Coma
52
Tolerance of opioid analgesics
Pharmacodynamic!! (receptor, signal transduction)
| the cell will increase cAMP in order to against the overdose of drug (decrease cAMP)
53
Signs and management of Opioid withdrawal
Signs:
Yawning, Lacrimation, rhinorhea, salivation, anxiety, sweating, goose bumps, muscle cramps, spasms, CNS-originating pain
Management: supportive, methadone, clonidine
54
Opiate-related drugs with specific indications
Loperamide (known as Imodium): diarrhea
| Dextromethorphan: cough (teenager can get addicted to it because of hallucination effect in high dose)
55
Dopaminergic Neural Pathways
Nigrostriatal tract: Parkinson disease
Mesolimbic-mesocortical tracts: pleasure feeling, reinforcement, cognitive functions, sensory perception-> Psychotic disorders and addiction
Tuberoinfundibular: hypothalamus, pituitary
prolactin
Chemoreceptor trigger zone: emetic (DA agonist); antiemetic (DA antagonist)
56
Dopamine receptors
D1-like Gs coupled
D2-like Gi coupled
-D2a: nigrostriatal
-D2c: mesolimbic
57
Parkinson disease
Signs and symptoms:
Bradykinesia
Muscle rigidity
Resting tremor
Pathology: degeneration of nigrostriatal dopamine tracts (too little of dopamine and too much of Ach)
Strategy: restore normal dopamine and decrease Ach
58
Levodopaa
prodrug, converted to dopamine by aromatic amino acid decarboxylase (AAAD)
Always given with carbidopa
Side effects: dyskinesias, "on/off" effects (fluctuation of dopamine level), psychosis, hypotention, vomitting
59
Tolcapone and entecapone
inhibit COMT_enzyme that convert dopamine to 3-O-methyldopa, a partial agonist (blocker to dopamine)
So tolcapone and entacapone enhance levodopa uptake and efficacy
But Tolcapone is hepatotoxic!!!
60
Selegiline
MAOb selective inhibitor which inhibit Dopamine metabolize
| Side effects: dyskinesias, psychosis, insomnia (selegiline->amphetamine)
61
Bromocriptine
dopamine receptor agonist
Use: hyperprolactinemia, acromegaly
Side effects: dyskinesias and psychosis
62
Drug decreasing Ach function
benztropine, trihexyphynidyl, diphenhydramine
Actions: decrease tremor and rigidity
Side effect: dry mouth,mydriasis, blurred vision, urinary retention
63
Amantadine
antiviral, which block muscarinic receptors, and increase dopamine release
Side effects: atropine like and liverdo reticularis!!! (pale skin and purple meshwork in the skin)
64
Schizophrenia
```
Benh tam than phan liet
Positive symptoms (thought disorder, delusions, hallucinations, paranoia)
Negative symptoms (Amotivation, social withdrawal, flat affect, poverty of speech)
```
65
Dopamine hypothesis
Symptoms arise because of excessive dopaminergic activity in mesolimbic system
66
Mechanism of antipsychotic drugs
Blockade of dopamine and/or 5HT2 receptors
67
Akathisia
characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless which give the name akathisia mean unable to sit!
68
Tardive dyskinesia (TD)
the patient is hyperkinetic (similar to Hungtinton patient) with symptoms:
facial twisting, tongue protruding...
irrevesible!!!
69
Side effects from Dopamine blockade
dyskinesias (Acute EPS, chronic EPS)
dysphoria
endocrine dysfunction (malignant hyperthermia, weight gain, prolactin...)
70
Typical antipsychotic drugs
Chlorpromazine, Thioridazine, Fluphenazine, Haloperidol
71
Thioridazine
```
EPS +
M block +++
Sedation +++
Alpha block +++
Cardiotoxicity (torsades-quinidine like)
Retinal deposits
```
72
Haloperidol
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EPS +++
M block +
Sedation +
Alpha block +
most likely cause of neuroleptic malignant syndrome and tardive dyskinesia
```
73
Atypical antipsychotic drugs
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Clozapine, Olanzapine, Risperidone, Aripiprazole
Block D2c (Clozapine) and 5HT2 receptors (all of them)
```
74
Drugs used in depression
MAO inhibitors, Tricyclic antidepressants (TCAs), Selective Seretonin Reuptake Inhibitors (SSRIs)
75
MAO inhibitors
Phenelzine, Tranylcypromine
Mechanism: inhibition of MAOa and MAOb
Drug interactions:
Increase NE: hypertension crisis
Increase BP, arrhythmias, excitation, hyperthermia
(tyramine, TCA, alpha 1 agonists, levedopa
Increase 5HT: serotonin syndrome
sweating, rigidity, myoclonus, hyperthermia, ANS instability, seizures
(SSRIs, TCAs, Meperidine)
76
TCAs
Amitriptyline, Imipramine, Chlomipramine
Mechanism: nonspecific blockade of 5HT and NE uptake
Use in: major depressions, phobic and panic anxiety states, obsessive compulsive disorders, neuropathic pain, enuresis
Side effects: muscarinic and alpha blockade
Drug interaction: Hypertensive crisis, serotonin syndrome
also prevent antihypertensive action of alpha 2 agonists and guanithidine
77
SSRIs
Fluoxetine, paroxetine, sertraline
Mechanism: selective blockade of 5HT reuptake
Uses: major depression, OCD, bulimia, anxiety disorders, premenstrual dysphoric disorder
Side effects: anxiety, agitation, bruxism, sexual dysfunction, weight loss so use it with benzodiazepine (Alprazolam)
Toxicity: Serotonin syndrome
Drug interactions: serotonin syndrome with MAO inhibitors, meperidine and TCAs
78
Bupropion
dopamine reuptake blocker, used in smoking cessation (but can cause seizure!!)
79
Lithium
Drug of choice for bipolar disorders
Mechanism: prevents recycling of inositol (decrease PIP2)
Decrease cAMP
Side effects: Narrow therapeutic index, requires therapeutic monitoring
Tremor, flu-like symptoms, life-threatening, seizures
hypothyroidism with goiter (decrease TSH effects and inhibition of 5-deiodinase)
Nephrogenic diabetes insipidus (decrease ADH effects) manage with amiloride
Teratogenicity: Ebstein's anomaly (malformed tricuspid valve)
So in pregnancy woman, use gapapentin and clonazepam
Other drugs used in bipolar disorders: valproic acid and carbamazepine
80
Drug used in ADHD
Methylphenidate: amphetamine like
Side effects: agitation, restlessness, insomnia, cardiovascular toxicity
Atomoxetine: selective NE reuptake inhibitor
Side effects: like TCA
