GABA-ergics
Increase the frequency with which the Cl channel is in the open state.
BENZODIAZEPINES (BZD)
MOA: GABAA
receptor agonists. Increase the frequency with which the Cl channel is in the open state.
Causing CNS Depression.
➢ Low doses = anxiolytic, sedative, dizziness
➢ Higher doses = hypnotic, anesthetic, muscle relaxant
Uses:
Anxiolytic/panic disorders (short term preferably)
Anticonvulsant
Anesthesia - cause anterograde amnesia
Hypnotic
Muscle Relaxant
Prophylaxis for CNS depressant withdrawal (e.g., ethanol)
a hereditary disorder of skeletal muscle is an adverse effect of what type of anesthesia
Malignant hyperthermia
ADVERSE EFFECTS OF INHALED ANESTHESIA
Changes in CNS blood flow
2. Decreased myocardial contractility
3. Malignant hyperthermia
a hereditary disorder of skeletal muscle that classically presents as a hypermetabolic response to halogenated anesthetic gasses succinylcholine.
and/or the depolarizing muscle relaxant
4. BP and HR
Most decrease BP (and renal blood flow)
5. Halothane hepatitis
Stabilizes inactivated Na+ channels and has an Adverse effect include :Stevens-Johnson syndrome in South East Asians
CARBAMAZEPINE (TEGRETOL®)
MOA: Stabilizes inactivated Na+ channels
Also blocks norepinephrine/serotonin reuptake and adenosine receptors
Molecular structure related to tricyclic antidepressants (anticholinergic effects, serotonin reuptake
inhibition, etc)
Used primarily in partial seizures, occasionally in generalized seizures. Used to tx pain, especially
trigeminal neuralgia; and to manage manic phase of bipolar
Side effects:
Aplastic anemia
Stevens-Johnson syndrome in South East Asians
Syndrome of inappropriate antidiuretic hormone secretion (SIADH), nephrotoxicity
Drug Interactions: it’s an enzyme inducer, autoinduction, increased lithium toxicity, don’t combine with
Adverse effects: nausea, dizziness, flushing, tingling, coronary vasoconstriction
Triptans
MOA: 5HT-1DR agonist. Most important: Sumatriptan.
Adverse effects: nausea, dizziness, flushing, tingling, coronary vasoconstriction
Avoid in patients with history of MI, CAD, etc and don’t combine with ergots, SSRI’s or MAO inhibitors
serotonin syndrome!
MOA: directly activate DA receptors
pramipexole,
ropinirole, bromocriptine
Full MOR agonists with few other
actions (no ceiling dose)
Codeine and morphine
Hydrocodone
Oxycodone
Fentanyl,
CYP450 enzyme INDUCERS that are contraindicated in acute intermittent porphyria.
Phenobarbital and Thiopental (barbituates))
MOA: Increase duration of Cl channel in open state – increase affinity of GABA for GABAA receptor
AND have inherent activity in the absence of GABA, causing CNS Depression.
➢ Examples: Phenobarbital, Pentobarbital, Thiopental
➢ VERY SEDATING, VERY ADDICTING, VERY TOXIC: In overdose, death is usually due to suppression of
respiratory drive
➢ Uses:
• Phenobarbital (C IV) is generally used only as anticonvulsant
• Thiopental (CII) for anesthesia induction
➢ Barbiturates are CYP450 enzyme INDUCERS causing a lot of drug interactions
➢ Barbiturates is contraindicated in acute intermittent porphyria
Specific antidote for malignant hyperthermia
Dantrolene
RYR1 (skeletalmuscle) ryanodine receptor antagonist that reduces Ca2+ release
Specific antidote for malignant hyperthermia
Gingival hyperplasia is a side effect of which drug
PHENYTOIN AND FOSPHENYTOIN (D ILANTI N® AND CER EBYX®)
Stabilizes inactivated Na channels
Use: generalized tonic-clonic, partial, prophylaxis post neurosurgery; used in status epilepticus to prevent reemergence of seizure activity
Side Effects:
Gingival hyperplasia
Teratogenic
Induced enzymes
What group of drugs has these adverse effects :Adverse effects: weight gain, sexual dysfunction,
nausea (usually remits), insomnia, anxiety,
suicidality (boxed warning)
Selective Serotonin Reuptake Inhibitors
MOA: DAT/NET blocker and Used to treat depression
DAT/NET blocker:
- Bupropion
Used to treat depression and to facilitate smoking cessation.
Not linked to weight gain (SSRI’s are)
c, causes mydriasis
Meperidine
Do not use in chronic pain, caution in renal failure due to toxic metabolite normeperidine (FYI daily
ceiling dose is 600mg in nl renal function)
Anticholinergic, causes mydriasis
Has serotonin activity at high doses
Review: what parkinson/ antidepressant drug may cause serotonin syndrome when combined with meperidine due to
inhibition of MAOb?
GABAA receptor agonists that No muscle relaxation, No anticonvulsant
Zdrugs
MOA: GABAA receptor agonists.
➢ Examples: Zolpidem, Zaleplon, Eszopiclone
➢ Uses:
• Short term hypnotic (though eszopiclone is indicated by FDA for
use > 7 days)
➢ Different from benzodiazepines (BZD)
• No muscle relaxation
• No anticonvulsant
➢Still produce anterograde amnesia, dependence, etc.
➢Reversed with flumazenil
Adverse effects of Hiccoughs, Inhibits cortisol synthesis
ETOMIDATE (AMIDATE)
MOA: GABAergic
Small ↑HR, no change in BP – good in cardiac
patients
AE:
• Hiccoughs
• Inhibits cortisol synthesis, so not used as long-term infusion
Use: partial seizures and generalized monotherapy
MOA: Stabilizes inactivated Na channels AND GABA augmentation AND blockade of glutamate AMPA and kainate receptors AND inhibits carbonic anhydrase AND blocks HVA Ca++ channels
Use: partial seizures and generalized monotherapy
Also used for migraine prophylaxis, post traumatic stress disorder, bipolar disorder, obesity
Partially renally cleared – encourage fluids
SE:
WEIGHT LOSS
Drug limited to limited to compassionate use
due to toxicity
Cisapride
5-HT4 RECEPTO Agonist, ,
limited to compassionate use
due to toxicity.
Partial agonist, tegaserod, used for IBS and
constipation.
What type of antipsychotyics AD2 receptor antagonists 5-HT2A receptor
antagonists
Atypical antipsychotics MO
a competitive narcotic antagonist to reverse opiate overdose
Naloxone
Two recommended drug to treat insomnia
ramelteon, suvorexant
Treatment:
• BZDs
• Z-drugs
• Antihistamines (H1 receptor): e.g. diphenhydramine
• Melatonin agonists: e.g. ramelteon
• Orexin antagonists: e.g. suvorexant
Adverse side effect of this drug include acidosis, rhabdomyolysis, renal failure limits infusion rate in chronic use
PROPOFOL (DIPRIVAN) & FOSPROPOFOL (LUSEDRA)
MOA: GABAergic
Problem in pancreatitis, egg allergy
Little “hangover”
Marked respiratory depression – monitor SaO2
Propofol infusion syndrome – acidosis, rhabdomyolysis, renal failure limits infusion rate in chronic use (e.g.,
ventilator patients)
Several mechanisms: Ca block (T-type), Na block, ↑GABA levels, NMDA block, inhibition of histone deacetylases
DIVALPROEX AND VALPROIC ACID (
drugs that cause Tyramine toxicity
Selegiline and rasagiline are MAO-B selective
• SSRIs should not be coadministered with MAOIs due to the risk of serotonin syndrome.
Neuroleptic malignant syndrome is caused by what group of drugs?
ANTIDOPAMINERGICS
Haloperidol
Chlorpromazine
MOA: synthetic THC that activates CB1>CB2
DRONABINOL (MARINOL) CIII
Effects:
CNS: euphoria, dysphoria, anxiety, hallucination, confusion, impaired memory
HEENT: red eyes
Cardio: palpitations, flushing
GI: increased appetite, nausea, abdominal pain
MSK: weakness
Withdrawal syndrome
Used for spasticity associated with motor neuron disease and has a side effect of ataxia and sedation
Baclofen
MOA: Agonist at metabotropic GABA-B receptors in spinal cord
➢ Use: Used for spasticity associated with motor neuron disease (post-trauma,
MS, etc.)
➢ Oral, IV, intrathecal
➢ SE: ataxia, sedation
➢ Toxicity: blurred vision, hypotension, respiratory depression, cardiac depression,
coma
➢ Withdrawal: increased spasticity, pruritis, delirium, rhabdomyolysis, fever
Group of anesthetics that block Na+ channel and be can slowed by addition of epinephrine and low pH
LOCAL ANESTHETICS
Don’t inject a local anesthetic containing a vasoconstrictor (eg, epinephrine) into an
area with limited blood supply (fingers, toes, etc.)
exclusively for absence seizures,
ETHOSUXIMIDE
Ethosuximide is used
exclusively for absence
seizures (drug of choice
for school age children)
used in migraine prophylaxis, performance anxiety
Propranolol
Nonselective beta AR antagonist
D4 antagonist & 5HT2
antagonist
Clozapine
– 2nd line after
failure of 2-3 atypicals
ADE: agranulocytosis
Pinpoint pupils, Unconsciousness, Diminished bowel sounds are symptoms of
OPIOID OVERDOSEOPIOID OVERDOSE