5 - CNS DRUGS

Glutamate

Aspartate

Main excitatory neurotransmitters

Brain: GABA

Spinal cord: glycine

Others: taurine, B-alanine

Inhibitory neurotransmitters

Dopamine

Predominant catecholamine in the CNS; Play a role in motivation and reward

Histamine

Mostly located in ventral posterior hypothalamus for arousal, body temperature, and vascular dynamics

Serotonin

(5HT)

Diverse neurotransmitter with roles in mood, depression, anxiety, and phobia

(1)   Antidepressant

Smoking cessation

Uses (2) of the drug Bupropion

NE and Dopamine Reuptake Inhibitor

MOA of Bupropion

Fever

Agitation

Tremor

Clonus

Hyperreflexia

Diaphoresis

Features of Serotonin Syndrome

CLUE: FAT CHD

Selective Serotonin Reuptake Inhibitor (SSRIs)

DOC for Major Depressive Disorder

Fluoxetine

Paroxetine

Citalopram

Escitalopram

Sertraline

Common SSRIs

•  Sedate (with benzodiazepines),

intubate, ventilate

• Block 5-HT2 with cyproheptadine

Treatment for serotonin syndrome

Increased risk of suicidal ideation in those <25

(except with fluoxetine)

Black box warning of SSRI

Citalopram

SSRI with side effect of QT prolongation

Tricyclic

Antidepressants (TCA)

Have more antihistamine, alpha blocking, and anticholinergic effects than SNRIs

Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)

Inhibits neuronal reuptake of serotonin & norepinephrine

Use: chronic pain

Coma, Convulsions, Cardiotoxicity (Cardiomyopathies, Arrhythmias)

3Cs of TCA Overdose

MAO-A

Form of MAO present in both dopamine & norepinephrine neurons

Found in brain, gut, placenta, and liver

Tyramine crisis

Rapid hypertension + sympathetic symptoms when MAO-is are taken with tyramine (aged cheese, red wine, pickled veg)

Selegiline

Rasagiline

used in Parkinson's

Selective MAO-is

(MAO-B)

Hepatotoxicity

Black box warning of Nefazodone (a serotonin antagonist)

Trazodone

Papaverine

Sildenafil

Quetiapine

Alprostadil

Warfarin

Bupropion

Drugs can cause priapism

CLUE: Tigas PeniS Qo, AyaW Bumaba!

“ANTI-HAM”

Antihistamine

Sedation and weight gain

Antiadrenergic

Hypotension, failure of ejaculation

Antimuscarinic

Alice in Wonderland symptoms

Adverse effects of low potency typical antipsychotics: Chlorpromazine, thioridazine

Extrapyramidal symptoms

Adverse effects of high potency typical antipsychotics: Haloperidol, Fluphenazine

(1) Neutropenia/

agranulocytosis

(2) Orthostatic hypotension, bradycardia, syncope

(3) Seizures

(4) Myocarditis

(5) Increased mortality in

dementia-related psychosis in elderly (risk of cardiovascular event)

Five black box warnings of Clozapine (DOC for refractory and suicidal schizophrenia)

Agranulocytosis

Serious side effect of Clozapine, PTU, Methimazole, Tocainide

Chlorpromazine:

Corneal deposits

Thioridazine:

PigmentaryRetinopathy

Eye side effects of low potency typical antipsychotics

CLUE: Color Theory

Atypical/2nd-Generation Antipsychotics

Antipsychotics with greater affinity to 5HT2A > D2 receptors

Clozapine and

Olanzapine

Visualize O = a round person won’t fit in the clozet doors

Antipsychotics with highest weight gain

Quetiapine

SE: Cataracts, Priapism, QT Prolongation

Antipsychotic with the high risk of sedation

Risperidone, Paliperidone

Associated with marked hyperprolactinemia (highest propensity)

Ziprasidone

Lowest risk of weight gain

Black box warning: Increased mortality in elderly with dementia-related psychosis

Aripiprazole

partial D2 agonist

Lowest risk of hyperprolactinemia

Lithium

Has a very narrow therapeutic index

Used for manic phase of bipolar disorder (acute and for prevention)

NSAIDs, ACE-is, diuretics

Drugs that increase lithium levels

Ebstein’s anomaly (atrialization of Right ventricle)

Teratogenic effect of lithium

Clonazepam

Preferred benzodiazepine as anticonvulsant maintenance

Levodopa-carbidopa

Single most effective agent for Parkinson's

MAO-B inhibitor

MOA of Selegiline

Tolcapone, Entacapone

TWOlcapone – tolcapone inhibits both central and peripheral COMT

COMT inhibitors

Inhibits peripheral metabolism of Levodopa via dopa decarboxylase

MOA of Carbidopa

On-off phenomenon

Fluctuations in motor response to drugs;

Apomorphine

DOC for off periods

Wearing off phenomenon

Treat with COMT-I, MAO-I, or DA

Duration of benefit becomes progressively shorter until it

only lasts as long as Levodopa's half-life

Ergot: Bromocriptine, Pergolide, Cabergoline

Non-ergot: Pramipexole (D3, Ropinirole

Examples of Dopamine agonists

Amantadine

Hydroxyurea

Minocycline

Gemcitabine

Quinidine

Drugs can cause livedo reticularis

CLUE: A man reads FHM and GQ

Amantadine

Antiviral for parkinsonism

Benztropine, Trihexyphenidyl, Biperiden

Anticholinergics for extrapyramidal symptoms and parkinsonism

Benzodiazepines

Allosteric modulator of GABA-A resulting to increased frequency of Cl- opening

Temazepam, Oxazepam, Lorazepam

All benzos undergo CYP metabolism, except

CLUE: “They don’t take a TOL on your LIVER”

Triazolam Oxazepam, Midazolam

Short acting (rapidly

inactivated) benzos

CLUE: little TOM

Midazolam

Diazepam

Lorazepam

Acute seizure status epilepticus

Chlordiazepoxide (Librium)

Drug used for alcohol withdrawal

Flumazenil

Tx for benzodiazepine overdose

Phenobarbital

(pheno-BABY-tal)

Status epilepticus, DOC for neonatal seizures, hyperbilirubinemia

Primidone

Derivative of phenobarbital, used for essential tremors

Thiopental

Barbiturate used for induction of anesthesia

Z drugs

Zolpidem, Zaleplon, Eszopiclone

Novel drugs used in insomnia and sleep disorders: faster and safer

Therapy +/- SSRI (sertraline)

First-line tx for GAD

Methanol (wood alcohol)

GIN BULAG

Alcohol that creates toxic formate, which

causesvisual disturbance, coma, seizures

Ethylene glycol (antifreeze)

Alcohol that creates toxic aldehydes and

oxalate, which causes kidney damage and severe acidosis

Fomepizole

Ethanol – no longer the first line!

Tx for methanol and ethylene glycol poisoning

Aldehyde dehydrogenase inhibitor

MOA of disulfiram

Phenytoin

Antiepileptic that is a CYP inducer, SE of gingival hyperplasia, nystagmus, teratogenicity (fetal hydantoin syndrome)

Carbamazepine

Antiepileptic that is a DOC for trigeminal neuralgia

ADR: rash, SJS, diplopia and ataxia

(MC), SIAD, megaloblastic anemia

Valproic acid

Most teratogenic AED, a CYP inhibitor (unlike other AEDs), causes weight gain, hepatotoxicity, pancreatitis

Hemophagocytic lymphohistiocytosis

can also cause SJS/TEN

Black box warning of lamotrigine

Topiramate

Felbamate

can cause angle closure glaucoma

Ion channel modifier AED that is well-tolerated and has the most anti-seizure MOAs, also a weak Carbonic Anhydrase inhibitor

Ethosuximide

Reduce current through T-type Ca channel

DOC for absence seizures

Vigabatrin

AED that causes irreversible inhibition of GABA transaminase

ADR: permanent vision loss

Gabapentin

Pregabalin

DOC for postherpetic neuralgia (2)

block Ca2+ a2d channels

leading to decreased glutamate release

MOA of gabapentinoids

Levetiracetam

AED that selectively binds synaptic vesicular protein (SV2A), favorable AE profile, minimal drug interactions

Propofol

Most commonly used IV anesthetic, first-line

Etomidate

IV Anesthetic reserved for patients at risk of hypotension or MI

Ketamine

IV Anesthetic best suited for asthmatics or for children undergoing short, painful procedures

Propofol, Etomidate

IV Anesthetics (2) with analgesic properties

Minimum Alveolar Anesthetic concentration (MAC)

lower MAC, higher Potency

Best measure of potency of inhaled anesthetics, INDIRECTLY proportional with potency

Lowest: Methoxyflurane

Highest: Nitrous Oxide

Inhaled anesthetic with:

Lowest MAC? Highest MAC?

Nitrous Oxide

Inhaled anesthetic that can cause megaloblastic anemia, can increase ICP

Desflurane,

Enflurane,

Isoflurane

Inhaled anesthetics (3) with Pungent odor, not suitable for induction and asthmatics

Isoflurane

Volatile anesthetic that can cause coronary steal syndrome, leading to myocardial ischemia

Sevoflurane > halothane

Non-pungent inhaled anesthetics (2), best for asthmatics

Desflurane

Isoflurane

Inhaled anesthetics (2), with the highest propensity to cause reflex tachycardia

Halothane (halothane hepatitis)

Inhaled anesthetic associated with fulminant hepatic failure

Sevoflurane

Most commonly used inhaled anesthetic for pediatric patients

Sevoflurane

Inhaled anesthetic associated with Nephrotoxic due to "compound A"

Enflurane

Inhaled anesthetic associated that lowers seizure threshold

ESTERS have only 1 I in their names

Tetracaine, procaine, benzocaine

One-eyed easter bunny

Atracurium

Inhaled anesthetic that undergoes Hoffman elimination yielding laudanosine (seizures)

Fentanyl

ADR: Truncal rigidity

Rapid and potent opioid that can be given transdermally

Lidocaine

Most commonly used amide local anesthetic

Bupivacaine

Most cardiotoxic amide local anesthetic. Ventricular arrhythmias if given IV

• Pancuronium

• Potassium chloride

• Thiopental

Drugs used in lethal injection

CLUE: “PaPoThayin kita!”

Sugammadex

Reversal agent for rocuronium

Baclofen

GABA-B agonist. Facilitates spinal inhibition of motor neurons

Dantrolene

Drug for malignant hyperthermia

• Remifentanil = shortest half-life (3-4 mins)

• Buprenorphine = longest half-life (4-8 hrs)

Which opioids have the shortest and longest half-lives?

Fentanyl

Responsible for the majority of opioid overdose deaths in the US

Naloxone

DOC for Opioid overdose

Cocaine (coke)

Recreational drug that inhibits reuptake of dopamine, norepinephrine, and serotonin

Key features: enhanced self-confidence