All Block Drugs (Final Exam)

Methylphenidate

MOA:

• Block DA and NE transports from recycling neurotransmitters → increase DA and NE release in the synapse

• Immediate-release form: Ritalin

• Extended-release form: Concerta

Indication: ADHD

SE: anxiety, irritability, insomnia, increase BP and HR

Amphetamine

MOA:

• Block DA and NE transports from recycling neurotransmitters → increase DA and NE release in the synapse

• Increase dopamine availability by giving more dopamine back into the vesicles

• Immediate-release form: Adderall

• Extended-release form: Vyvanse

  • D-form of amphetamine w/ a lysine attached

  • Is a “pro-drug” so when broken down, you get D-amphetamine, which is slowly released based on metabolism

  • Inactive until it is metabolized → long-acting form limits abuse potential b/c taking short-acting form doesn’t produce immediate effects

Indication: ADHD

SE: anxiety, irritability, insomnia, increase BP and HR

Botulism Toxin (Botox)

MOA: Disrupts neurotransmission of ACh (preventing vesicle fusion with membrane of the presynaptic vesicle)

• Decrease release of ACh at the NMJ → muscles cannot contract → weakness and paralysis

• ANS actions at PNS (recall ACh is the neurotransmitter at parasymapathetic post-ganglionic receptors!) → reduce salivation and GI motility

• Has actions at sympathetic pathways to reduce ACh dependent sweat production

Indication:

• Spasticity (Local injections)

• Overactive bladder (Bladder botox)

• Excessive drooling (sialorrhea) in conditions like Parkinson’s or ALS

• Migraine prophylaxis

SE:

• Delivered by injection; lasts weeks-months

Diltiazem

MOA: CCB

Indication: HTN

Disulfiram

MOA: inhibit acetaldehyde dehydrogenase

• Taken with alcohol → build-up of acetaldehyde → flushing, vomiting, nausea

Indication: alcohol use disorder

SE: may not want to be taken daily as a preventative medication

Acamprosate

MOA: interacts w/ glutamate and GABA transmission centrally to reduce cravings for alcohol

Indication: alcohol use disorders

SE: Renally excreted; contraindicated in low GFR

Naltrexone

MOA: opioid antagonist

• Directly blocks opioid receptors and prevents euphoria associated w/ opioid abuse

• Also used in alcohol dependence (opioid system plays a role in reinforcement behavior of alcohol use disorder)

Indication: Alcohol use disorder/opioid use disorder

SE:

• Metabolized in the liver → need to check LFTs before starting

• oral or injectable form

Varenicline (Chantix)

MOA:

• Partial agonist at the a4, b2 nicotinic AChRs → dopamine release → rewarding properties of nicotine

  • Mimic nicotine’s actions and blocks nicotine from binding fully

    • Analogous to Buprenorphine binding strongly to opioid receptors and preventing heroin from binding

Indication: Nicotine dependence

SE: monitor for neuropsychiatric SEs

Guanfacine

MOA:

• Alpha 2A adrenoreceptor agonist

  • Decrease sympathetic nerve impulses via reduction in release of NE

• Preferentially binds postsynaptic alpha 2A adrenoreceptors in the prefrontal cortex → increase connectivity in the dorsolateral prefrontal cortex (which has fewer connections in ADHD, given people have less “top-down” control of behavior)

Indication: ADHD

SE: reduces sympathetic transmission → mild sedative properties that can be useful with insomnia

Modafinil

MOA:

• NDRI (NE + DA reuptake inhibitor)

• Histamine stimulator

Indication:

• Narcolepsy (primary)

• off label treatment of ADHD

Ethanol

MOA:

• CNS depressant

• Potentiates action of GABA

• Inhibit release of ADH

Sx of intoxication: euphoria, impaired attention

Intoxication Tx: none

Withdrawal Tx: benzodiazepine

Amphetamine/Methamphetamine

MOA: increase synaptic concentration of NE and dopamine (increases amount of catecholamine packaged into vesicles)

Sx of intoxication: euphoria, decreased fatigue, hypervigilance, paranoia

Intoxication Tx: Lorazepam for agitation; Haldol for psychosis

Withdrawal Tx: Supportive care

MDMA (Ecstasy)

MOA: increase dopamine and serotonin in the brain (can have psychostimulant and psychotomimetic effects)

Sx of intoxication: depersonalization, derealizaton, hallucination, illusions

Intoxicaton & Withdrawal Tx: supportive care

Cocaine

MOA: inhibit neuronal reuptake of NE and dopamine

Sx of intoxication: euphoria, decreased fatigue, hypervigilance, paranoia

Intoxication Tx: Lorazepam for agitation or seizures

Withdrawal Tx: supportive care

Caffiene

MOA: produces mild stimulation by blocking adenosine receptors in neurons throughout the CNS

Sx of intoxication: decreased fatigue, increased concentration

Intoxication & Withdrawal Tx: supportive care

Nicotine

MOA:

• Activates cholinergic nicotinic receptors in the CNS and PNS

• MAOI → activate dopaminergic neurotransmission and dependent properties

Sx of intoxication: tachycardia, increased concentration

Intoxicaton & Withdrawal Tx: supportive care

Marijuana

MOA: THC (primary cannabinoid); binds to cannabinoid receptors in neurons

Sx of intoxication: mild stimulation followed by depressive stage; can lead to impaired short-term memory

Intoxicaton & Withdrawal Tx: supportive care

Lysergic acid diethylamide (LSD)

MOA: selectively activates subtypes of serotonin (5-HT) receptors in the neocortex, limbic system, and brainstem

Sx of intoxication: visual hallucinations, synesthesia, little effect on cognitive function or arousal

Intoxicaton & Withdrawal Tx: supportive care

Phencyclidine (PCP)

MOA: dissociative anesthetic; blocks NMDA receptors

Sx of intoxication: anxiety, delusions, emotional lability

Intoxication Tx: Lorazepam for agitation, Haldol for psychosis

Withdrawal Tx: supportive care

Benzodiazepines

MOA: facilitates activity of GABA
Sx of intoxication: euphoria, impaired attention

Intoxication Tx: Flumazeinl for overdose

Withdrawal Tx: supportive care

Alprazolam (Xanax)

MOA: Benzodiazepine; facilitates activity of GABA

• works only in the presence of GABA (therefore exhibits a ceiling effect)

Indication: acute anxiety

SE:

• can lead to dependence

• caution in elderly

• can lead to CNS depression; avoid w/ alcohol and other CNS depressants

Chlordiazepoxide (Librium)

MOA: Benzodiazepine; facilitates activity of GABA

Indication: alcohol detoxification given longer duration of action

SE:

• can lead to dependence

• caution in elderly

• can lead to CNS depression; avoid w/ alcohol and other CNS depressants

Phenobarbital

MOA: Barbiturate

• Facilitates activity of GABA; Enhances GABA-mediated chloride flux that causes membrane depolarization

  • Works independent of GABA, and do not exhibit ceiling effect (more prone to severe respiratory depression)

Indication: 2nd line drug for seizure disorders

SE:

• respiratory depression

• induces CYP450 enzymes

Zolpidem (Ambien)

MOA: selectivity at targeting only GABA (A) receptors

Indication: insomnia

SE: shorter duration of action; fewer SEs and less dependence than Benzodiazepines

Buspirone (Buspar)

MOA:

• 5HT-1A partial agonist

  • Agonism inhibits serotonin release in short term. Overtime, chronic stimulation desensitizes auto-receptors, allowing increased serotonin levels in synapse and downstream

• Antagonistic properties at dopamine D2 receptors (lesser action)

  • Can decrease irritability

Indication: anxiety, depression

• Non-sedating anxiolytic drug

• Caution w/ SSRIs

Carbamazepine

Indication:

• Alternative to lithium in tx of bipolar disease

SE: potent inducer of CYP450 enzymes

Phenytoin

SE:

• Inducer of CYP3A4 isoenzyme

• Stevens-Johnsons Syndrome

Lamotrigine

Indication: partial seizures; manic phase of bipolar disorder

SE: Stevens-Johnson Syndrome

Topiramate

Indication: seizure disorders; weight loss

Haloperidol (Haldol)

MOA: FGA; D2 antagonist

• D2 antagonism in the mesolimbic pathway represses positive symptoms of schizophrenia

• D2 antagonism in nigrostriatal pathway responsible for EPS symptoms

Indication: schizophrenia, severely agitated patients

SEs: EPS symptoms, which is managed by

• Benztropine (anti-cholinergic)

• Diphenhydramine (anti-histamine)

• Amantadine (increases dopamine release in basal ganglia)

Clozapine (Clozaril)

MOA: SGA; D2 and 5HT-2 antagonist

• 5HT-2 antagonist blocks negative feedback → increase dopamine → relieve negative sx of schizophrenia

  • normally serotonin leads to negative feedback on dopamine release in mesocortical pathway

Indication: schizophrenia/psychosis

SEs:

• “HAM” SEs

• Risk of agranulocytosis; need frequent WBC monitoring

Olanzapine (Zyprexa)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication: schizophrenia/psychosis

SEs:

• “HAM” SEs

• Fewer autonomic SE than Clozapine

• High risk of weight gain

Quetiapine (Seroquel)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication

• Low dose (50mg) → hypnotic (mainly histamine receptors)

• Medium dose (300mg) → antidepressant (mainly serotonin receptors)

• High dose (800mg) → antipsychotic (mainly dopamine receptors)

SE: “HAM” SEs

Risperidone (Risperdal)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication: Schizophrenia/psychosis

SE:

• Can increase Prolactin

• Most likely atypical to cause EPS

• Can also be used as injection (Invega)

Aripiprazole (Abilify)

MOA: Dopamine partial agonist

Indication: depression

SE: akathisia; overall not a great antipsychotic

Amitryptyline

MOA: TCA; blocks reuptake of NE and serotonin

Indication: depression

SE: can cause sedation (sometimes used to augment sleep)

Fluoxetine (Prozac)

MOA: SSRI (blocks reuptake of serotonin)

Indication: depression, OCD, anorexia, bulimia

SE: fewer autonomic effects than TCAs

Sertraline (Zoloft)

MOA: SSRI (blocks reuptake of serotonin)

Indication: depression

SE: preferred in elderly patients (elimination not impacted by aging)

Venlafaxine

MOA: SNRI; blocks reuptake of NE and serotonin

Indication: depression

SE: similar to SSRIs, withdrawal can be severe/cause brain zaps

Bupropion (Wellbutrin)

MOA:

• MOA in depression: NDRI (Blocks reuptake of NE and dopamine → increase in transmission)

• MOA in smoking cessation: Non-competitive antagonist of nicotinic AChRs at allosteric sites on receptor (changes conformation of receptor to prevent the nicotinic receptor from being fully activated)

Indication: depression; nicotine dependence

SE:

• Lower sexual SEs than SSRI or SNRI d/t minimal or no activity on serotonin receptors

• Increase concentration of drug (ex. nicotine via smoking) → nothing happens d/t change in the conformation of the receptor from non-competitive antagonism

• Can be “activating” and lead to weight loss

Mirtazapine (Remeron)

MOA:

• Blocks presynaptic a-2 autoreceptors → increase neuronal release of NE and serotonin

• 5HT-2A and 5-HT-3 receptor antagonist

  • Prevents overstimulation of serotonin pathways

  • Blockage of both leaves more serotonin around to bind at 5HT-1 receptors, which act to improve mood

• Antihistamine

• Peripheral a-1 adrenergic receptor antagonist

  • Can lead to hypotension

Indication: depression/insomnia

SE:

• Orthostatic hypotension

• Antihistamine SEs

Lithium

MOA: Overall reduces neuronal response to serotonin and NE

Indication: bipolar disorder (best tx to control acute mania)

SE: low therapeutic index, need to monitor lithium levels

L-DOPA

MOA: taken up by dopamine neurons and converted to dopamine

Intervention: Parkinson’s disease

SE: Movement disorders from excess dopamine

Carbidopa

MOA:

• Structural analog to Levodopa

  • reduces conversion of levodopa to dopamine in peripheral tissues → increases amount of Levodopa that enters the brain

• Sinemet (Carbidopa/Levodopa) allows Carbidopa to inhibit conversion of Levodopa to dopamine in the periphery, allowing more Levodopa to cross BBB

Intervention: adjunct to Levodopa in tx of Parkinson’s disease

SE: Reduces GI and cardiovascular effects of Levodopa when added in formulation of Sinemet (peripheral dopamine is responsible for nausea/vomiting, orthostatic hypotension)

Bromocriptine

MOA: D2 receptor agonist; D1 receptor antagonist

Intervention: adjunct to Levodopa in patients w/ advanced Parkinson’s disease

Ropinirole

MOA: D2 receptor agonist

Intervention:

• Early stages of Parkinson’s disease

• Restless leg syndrome

Benztropine

MOA:

• Helps restore the balance of too little dopamine and too much ACh in the brain from EPS caused by antipsychotics

  • Anti-muscarinic: block muscarinic ACh receptors in the striatum (CNS)

  • Inhibit reuptake of dopamine

Intervention: Adjunctive tx to control EPS SEs

SE: anticholinergic (sympathetic) SEs

Donepezil

MOA: reversible cholinesterase inhibitor, which increases ACh in the CNS

Intervention: Alzheimer’s

Penicillin G

MOA: narrow-spectrum penicillin; activity against strep and enterococcus

Indication: syphilis, meningitis, erysipelas

Nafcillin

MOA: penicillinase-resistant penicillin

Indication: osteomyelitis

Amoxicillin

MOA: narrow-spectrum penicillin; activity against Strep species and enterococcus

• “aminopenicillin” which has additional side chain to inhibit penicillin-binding protein

Indication:

• Upper respiratory tract infections

• Otitis media

Augmentin (Amoxicillin/Clavulanate)

MOA: extended-spectrum penicillin / beta-lactamase inhibitor combination

• Beta-lactamase inhibitor destroys beta-lactamase enzyme produced by bacteria

Indication: upper respiratory tract infections caused by Haemophilus influenzae and Moraxella catarrhalis

Cephalexin

MOA: first-generation cephalosporin

Indication: skin and soft tissue infections

SE: NO MRSA coverage

Ceftriaxone

MOA: third-generation cephalosporin

Indication: gonorrhea, UTI, pneumonia

SE: only available as IV therapy

Cefepime

MOA: fourth-generation cephalosporin

Indication:

• Drug-resistant Gram-negative infections (UTI, pneumonia)

• Has coverage for pseudomonas

• NO MRSA coverage

• “broad-spectrum”

SE: only available as IV therapy

Imipenem

MOA: carbapenem

Indication: multi-drug resistant advanced infections

• No MRSA coverage

• “broad-spectrum”

Bacitracin

MOA: bacterial cell wall synthesis inhibitor

Indication:

• Skin and eye infections

• Activity against strep and staph

SE: topical treatment

Fosfomycin

MOA: bacterial cell wall synthesis inhibitor

Indication:

• Lower UTI

• Activity against E.coli and enterococcus

SE:

• Does not achieve concentrations anywhere else except the bladder

  • Only use for mild UTI

• Long half-life allows for one time dose

• Common treatment w/ one pill for UTIs

Vancomycin

MOA: bacterial cell wall synthesis inhibitor

Indication:

• Bone and joint infections

• Activity against MRSA

SE: IV tx needs blood monitoring w/ Vancomycin drug troughs

Gentamycin

MOA: Aminoglycoside

Indication:

• Aerobic GN bacilli

• Pseudomonas coverage

SE:

• Combo w/ Penicillin to treat Endocarditis

• Nephrotoxicity and ototoxicity

Doxycycline

MOA: tetracycline

Indication: GP and GN bacterial that cause respiratory tract infections and pneumonia

SE:

• MRSA coverage

  • Can be used to treat MRSA cellultiis

• Teeth discoloration

• Nephrotoxicity, Hepatotoxicity, Phototoxicity

Azithromycin

MOA: macrolide

Indication:

• Sinusitis, otitis media, bronchitis

• Effective single treatment for Chlamydia

SE: prolonged QTc

Erythromycin

MOA: macrolide

Indication: topical tx of conjunctivitis

Clindamycin

MOA: macrolide

Indication:

• Activity against gram-positives and anaerobic organisms

• MRSA coverage

SE:

• Associated w/ superinfections cause by C.diff

• multiple day dosing to mitigate SEs

Mupirocin (Bactroban)

MOA: inhibits bacterial protein synthesis

Indication: topical tx of superficial infections (impetigo, folliculitis)

Neomycin

MOA: aminoglycoside

• used in triple therapy alongside Bacitracin and Polymyxin

Indication: topical tx of superficial infections

SE: most nephrotoxic aminoglycoside

TMP-SMX (Bactrim)

MOA: anti-folate drugs w/ synergistic activity

Indication:

• UTI

• Pulmonary infections caused by Pneumocystis jiroveci

• MRSA coverage

SE:

• Check renal function for dose-adjustment

• monitor potassium for hyperkalemia

Ciprofloxacin

MOA: fluoroquinolone

Indication:

• Bacterial diarrhea

• UTI

• bone and joint infections

• Strong pseudomonas coverage

SE:

• Black box warning from FDA causing tendonopathies

• increased in elderly and young children

• can cause delirium in elderly (caution use in those w/ dementia)

• QTc prolongation

• Decreases seizure threshold (caution use in those w/ epilepsy)

Levofloxacin

MOA: fluoroquinolone

Indication:

• Bronchitis/Community acquired pneumonia

• UTI

• Moderate pseudomonas coverage

SE:

• Black box warning from FDA causing tendonopathies

• increased in elderly and young children

• can cause delirium in elderly (caution use in those w/ dementia)

• QTc prolongation

• Decreases seizure threshold (caution use in those w/ epilespy)

Nitrofurantoin (Macrobid)

MOA: inhibition of bacterial enzymes

Indication: lower urinary tract (bladder) infections

SE:

• Only use for cystitis, does not have good tissue penetration

• Dependent on renal function to get to the bladder (avoid use in CrCl <50mL/hr)

Rifaximin

MOA: Decreases colonic bacteria and ammonia production in tx of hepatitis encephalopathy

Indication:

• Traveler’s diarrhea

• Hepatic encephalopathy

Metronidazole (Flagyl)

MOA: inhibits DNA synthesis by causing strand breakage

Indication:

• C.diff (primary)

  • First-line tx for C.diff is typically PO Vancomycin or another drug first

• GP and GN organisms and anaerobes

SE: given PO or IV

Amphotericin B

MOA: polyene antibiotic; binds to fungal cell membrane and increases membrane permeability

Indication: PO and IV tx of systemic and subcutaneous fungal infections

SE: “Ampho-terrible”; renal and other organ system toxicities

Nystatin

MOA: polyene antibiotic; binds to fungal cell membrane and increases membrane permeability

Indication: Candida infections

SE: oral or topical

Clotrimazole

MOA: inhibits ergosterol synthesis

Indication:

• Candida infections of mouth, throat, vagina, and vulva

• Dermatophyte infections

SE: oral and topical formulation

Fluconazole

MOA: inhibits ergosterol synthesis

Indication:

• Cryptococcal meningitis

• AIDS

• Vaginal candidiasis

SE: excellent penetration of the CSF

Ketoconazole

MOA: inhibits ergosterol synthesis

Indication: Seborrheic dermatitis

SE: oral and topical formulations

Terbinafine

MOA: inhibits ergosterol synthesis

Indication: Onychomycosis

SE: used orally when topical therapy has not been effective

Morphine

MOA: opioid agonist

Indication: severe pain associated w/ trauma, MI, and cancer

SE:

• Undergoes considerable first-pass metabolism

• Metabolites can accumulate in renal failure

Methadone

MOA: opioid agonist; NMDA antagonist

Indication: opioid dependence or chronic pain

SE: need to monitor QTc

Meperidone

MOA: opioid agonist

Indication: obstetrics or post-surgical analgesia

SE: does not prolong labor as much as morphine

Oxycodone

MOA: opioid agonist

Indication: moderate or severe pain

SE: long acting form of Oxycontin

Tramadol

MOA: opioid agonist; SNRI

Indication: moderate pain

SE: increased risk of suicidal thoughts and behaviors

Codeine

MOA: opioid agonist

Indication: mild to moderate pain

SE:

• Greater bioavailability than morphine

• Converted to morphine by CYP2D6 isoenzyme

Buprenorphine

MOA: partial opioid agonist

Indication: opioid dependence or chronic pain

SE: frequently combined w/ Naloxone (Suboxone is combination Buprenorphine + Naloxone)

Fentanyl

MOA: opioid agonist

Indication: chronic pain

SE:

• Fast onset

• Transdermal for chronic pain

• No active metabolites

Naloxone

MOA: opioid antagonist

Indication: reversal for opioid overdose

SE: frequently combined w/ Buprenorphine (Suboxone is combination Buprenorphine + Naloxone)

Acetaminophen

MOA:

• selective COX-2 inhibitor (no effect on platelet function)

• inhibits synthesis of prostaglandins

• weak anti-inflammatory activity

• inhibition of hypothalamic heat-regulation center

Indication: acute pain

SE:

• low doses can be safely used in pregnancy

• caution in severe hepatic dysfunction

• max dose 4g/day

Aspirin (Bayer)

MOA:

• Non-selective COX inhibitor

• Irreversibly acetylates platelet COX

• COX-1 inhibition leads to anti-platelet effects

Indication: acute pain, acute migraine

SE:

• Anti-platelet effect lasts for 14 days

• used in secondary prevention (post-stroke and MI) for anti-platelet effects

Ibuprofen (Motrin)

MOA:

• non-selective COX inhibitor

• reversibly inhibits COX

• ***Not cardioprotective b/c of short half-life and reversible inhibition of COX-1

Indication: acute pain

SE:

• GI bleeding, peptic ulcers

• caution in renal disease

• ceiling effect on analgesia

Celecoxib

MOA:

• Selective COX-2 inhibitor

• reversibly inhibits COX-2

• does not effect COX-1 (no anti-platelet effects)

Indication: acute pain

SE:

• GI bleeding, peptic ulcers

• caution in renal disease

• ceiling effect on analgesia

Diphenhydramine (Benadryl)

MOA: 1st gen antihistamine, high affinity for central H1 receptors

Indications:

• allergies

• prevent motion sickness

• mild insomnia

• severe pruritus

• anxiety disorders

SE: sedation

Hydroxyzine (Atarax)

MOA: 1st gen antihistamine, high affinity for central H1 receptors

Indications:

• allergies

• prevent motion sickness

• mild insomnia

• severe pruritus

• anxiety disorders

SE:

• Less sedating than diphenhydramine

• Anticholinergic (sympathetic) SEs

Cetirizine (Zyrtec)

MOA: 2nd gen antihistamine

Indication: allergies

SE: lack antiemetic activity

Ondansetron (Zofran)

MOA: 5HT-3 antagonist

Indication: nausea, vomiting

• Often used in chemotherapy-induced nausea

SE: Higher levels are associated with increase in QTc

Alprostadil (Alptrostadil)

MOA: naturally occurring PGE1

Indication:

• Continuous infusion to maintain patency of ductus arteriosus in neonates awaiting surgery

• Tx of erectile dysfunction d/t vasodilatory properties

SE: priapism (painful erection)

Fluticasone (Flovent)

MOA: Inhaled corticosteroid

Indication: Prevention of asthma

SE:

• Administered twice daily

• Oral candidiasis (thrush)

Prednisone (Deltasone)

MOA: oral corticosteroid

Indication: Long-term tx of COPD

SE: Weight gain, hyperglycemia

Fluticasone/Salmeterol (Advair)

MOA: ICS + Beta-2 agonist

Indication: Asthma and COPD maintenance therapy

SE:

• Fluticasone:

  • administered twice daily

  • oral candidiasis (thrush)

• Salmeterol:

  • tachycardia, HTN, hyperglycemia

  • decreased systemic SEs by use of inhaled formulations

  • duration of action up to 24hrs

  • should only be used in combination w/ an ICS in asthma

Cromolyn Sodium (Intal)

MOA: Mast cell stabilizer

• Prevent degranulation and release of histamine, leukotrienes and other substances that cause airway inflammation

Indication: asthma, allergic rhinitis

SE: minimal SEs