Glaucoma drugs
- Decrease IOP via decreased amount of aqueous humor
- Inhibit synthesis/secretion or increase drainage
Epinephrine
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drug: α-agonist
- Mechanism
- Decreases aqueous humor synthesis via vasoconstriction
- Side effects
- Mydriasis
- Do not use in closed-angle glaucoma
Brimonidine
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drug: α-agonist
- Mechanism
- Decreases aqueous humor synthesis
- Side effects
- Blurry vision
- Ocular hyperemia
- Foreign body sensation
- Ocular allergic reactions
- Ocular pruritus
Timolol, betaxolol, carteolol
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drugs: β-blockers
- Mechanism
- Decrease aqueous humor synthesis
- Side effects
- No pupillary or vision changes
Acetazolamide
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drug: Diuretic
- Mechanism
- Decreases aqueous humor synthesis via inhibition of carbonic anhydrase
- Side effects
- No pupillary or vision changes
Pilocarpine, carbachol
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drugs: Direct cholinomimetics
- Mechanism
- Increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
- Side effects
- Miosis and cyclospasm (contraction of ciliary muscle)
Physostigmine, echothiophate
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drugs: Indirect cholinomimetics
- Mechanism
- Use pilocarpine in emergencies
- Very effective at opening meshwork into canal of Schlemm
- Side effects
- Miosis and cyclospasm (contraction of ciliary muscle)
Latanoprost
- Type of drug
- Mechanism
- Side effects
- Type of drug
- Glaucoma drug: Prostaglandin (PGF2α)
- Mechanism
- Increases outflow of aqueous humor
- Side effects
- Darkens color of iris (browning)
Opioid analgesics
- Examples
- Mechanism
- Clinical use
- Toxicity
- Examples
- Morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate.
- Mechanism
- Act as agonists at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission
- Open K+ channels, close Ca2+ channels –> decreased synaptic transmission.
- Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.
- Clinical use
- Pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts (methadone).
- Toxicity
- Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs.
- Tolerance does not develop to miosis and constipation.
- Toxicity treated with naloxone or naltrexone (opioid receptor antagonist).
Butorphanol
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- Mu-opioid receptor partial agonist and kappa-opioid receptor agonist; produces analgesia.
- Clinical use
- Severe pain (migraine, labor, etc.).
- Causes less respiratory depression than full opioid agonists.
- Toxicity
- Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors).
- Overdose not easily reversed with naloxone.
Tramadol
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- Very weak opioid agonist
- Also inhibits serotonin and norepinephrine reuptake
- Works on multiple neurotransmitters
- “Tram it all” in with tramadol
- Clinical use
- Chronic pain.
- Toxicity
- Similar to opioids.
- Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs.
- Tolerance does not develop to miosis and constipation.
- Toxicity treated with naloxone or naltrexone (opioid receptor antagonist).
- Decreases seizure threshold.
- Serotonin syndrome.
- Similar to opioids.
Ethosuximide
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? N
- Complex? N
- Generalized
- Tonic-clonic? N
- Absence? Y (1st line)
- Status Epileptics? N
- Mechanism
- Blocks thalamic T-type Ca2+ channels
- Side effects
- GI, fatigue, headache, urticaria, Steven-Johnson syndrome.
- EFGHIJ—Ethosuximide causes Fatigue, GI distress, Headache, Itching, and Stevens-Johnson syndrome
- Notes
- Sucks to have Silent (absence) Seizures
Benzodiazepines (diazepam, lorazepam)
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? N
- Complex? N
- Generalized
- Tonic-clonic? N
- Absence? N
- Status Epileptics? Y (1st line for acute)
- Mechanism
- Increases GABAA action
- Side effects
- Sedation, tolerance, dependence, respiratory depression
- Notes
- Also for eclampsia seizures (1st line is MgSO4)
Phenytoin
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y (1st line)
- Absence? N
- Status Epileptics? Y (1st line for prophylaxis)
- Mechanism
- Increases Na+ channel inactivation
- Zero-order kinetics
- Side effects
- Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia, teratogenesis (fetal hydantoin syndrome) SLE-like syndrome, induction of cytochrome P-450, lymphadenopathy, Stevens-Johnson syndrome, osteopenia
- Notes
- Fosphenytoin for parenteral use
Carbamazepine
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y (1st line)
- Complex? Y (1st line)
- Generalized
- Tonic-clonic? Y (1st line)
- Absence? N
- Status Epileptics? N
- Mechanism
- Increases Na+ channel inactivation
- Side effects
- Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P-450, SIADH, Stevens-Johnson syndrome
- Notes
- 1st line for trigeminal neuralgia
Valproic acid
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y (1st line)
- Absence? Y
- Status Epileptics? N
- Mechanism
- Increases Na+ channel inactivation
- Increases GABA concentration by inhibiting GABA transaminase
- Side effects
- GI, distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain, contraindicated in pregnancy
- Notes
- Also used for myoclonic seizures, bipolar disorder
Gabapentin
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y
- Absence? N
- Status Epileptics? N
- Mechanism
- Primarily inhibits high-voltage-activated Ca2+ channels
- Designed as GABA analog
- Side effects
- Sedation, ataxia
- Notes
- Also used for peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder
Phenobarbital
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y
- Absence? N
- Status Epileptics? N
- Mechanism
- Increases GABAA action
- Side effects
- Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression
- Notes
- 1st line in neonates
Topiramate
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Notes
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y
- Absence? N
- Status Epileptics? N
- Mechanism
- Blocks Na+ channels
- Increases GABA action
- Side effects
- Sedation, mental dulling, kidney stones, weight loss
- Notes
- Also used for migraine prevention
Lamotrigine
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Side effects
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y
- Absence? Y
- Status Epileptics? N
- Mechanism
- Blocks voltage-gated Na+ channels
- Side effects
- Stevens-Johnson syndrome (must be titrated slowly)
Levetiracetam
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? Y
- Absence? N
- Status Epileptics? N
- Mechanism
- Unknown
- May modulate GABA and glutamate release
Tiagabine
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? N
- Absence? N
- Status Epileptics? N
- Mechanism
- Increases GABA by inhibiting re-uptake
Vigabatrin
- Type of drug
- Partial (focal)
- Simple?
- Complex?
- Generalized
- Tonic-clonic?
- Absence?
- Status Epileptics?
- Mechanism
- Type of drug
- Epilepsy drug
- Partial (focal)
- Simple? Y
- Complex? Y
- Generalized
- Tonic-clonic? N
- Absence? N
- Status Epileptics? N
- Mechanism
- Increases GABA by irreversibly inhibiting GABA transaminase
Stevens-Johnson syndrome
- Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital).
- Skin lesions progress to epidermal necrosis and sloughing.
Barbiturates
- Examples
- Mechanism
- Clinical use
- Toxicity
- Examples
- Phenobarbital, pentobarbital, thiopental, secobarbital.
- Mechanism
- Facilitate GABAA action by increasing duration of Cl- channel opening, thus decreasing neuron firing
- Barbidurates increase duration
- Contraindicated in porphyria.
- Facilitate GABAA action by increasing duration of Cl- channel opening, thus decreasing neuron firing
- Clinical use
- Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
- Toxicity
- Respiratory and cardiovascular depression (can be fatal)
- CNS depression (can be exacerbated by EtOH use)
- Dependence
- Drug interactions (induces cytochrome P-450).
- Overdose treatment is supportive (assist respiration and maintain BP).
- Respiratory and cardiovascular depression (can be fatal)
Benzodiazepines
- Examples
- Mechanism
- Clinical use
- Toxicity
- Examples
- Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam.
- Mechanism
- Facilitate GABAA action by increasing frequency of Cl- channel opening.
- “Frenzodiazepines” increase frequency
- Decrease REM sleep.
- Most have long half-lives and active metabolites
- Exceptions: triazolam, oxazepam, and midazolam are short acting –> higher addictive potential
- Benzos, barbs, and EtOH all bind the GABAA receptor, which is a ligand-gated Cl- channel.
- Facilitate GABAA action by increasing frequency of Cl- channel opening.
- Clinical use
- Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal–DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia).
- Toxicity
- Dependence, additive CNS depression effects with alcohol.
- Less risk of respiratory depression and coma than with barbiturates.
- Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor).
Nonbenzodiazepine hypnotics
- Examples
- Mechanism
- Clinical use
- Toxicity
- Examples
- Zolpidem (Ambien), Zaleplon, esZopiclone.
- “All ZZZs put you to sleep.”
- Mechanism
- Act via the BZ1 subtype of the GABA receptor.
- Effects reversed by flumazenil.
- Clinical use
- Insomnia.
- Toxicity
- Ataxia, headaches, confusion.
- Short duration because of rapid metabolism by liver enzymes.
- Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects.
- Decrease dependence risk than benzodiazepines.
Anesthetics—general principles
- CNS drug solubility
- MAC
- Examples
- N2O
- Halothane
- CNS drug solubility
- CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported.
- Drugs with decreased solubility in blood = rapid induction and recovery times.
- Drugs with increased solubility in lipids = increased potency = 1 / MAC
- MAC
- MAC = Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (e.g., skin incision).
- Examples
- N2O has decreased blood and lipid solubility, and thus fast induction and low potency.
- Halothane, in contrast, has increased lipid and blood solubility, and thus high potency and slow induction.
Inhaled anesthetics
- Examples
- Mechanism
- Clinical use
- Toxicity
- Examples
- Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.
- Mechanism
- Mechanism unknown.
- Clinical use
- Myocardial depression, respiratory depression, nausea/emesis, increased cerebral blood flow (decreased cerebral metabolic demand).
- Toxicity
- Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (nitrous oxide).
- Can cause malignant hyperthermia—rare, life-threatening hereditary condition in which inhaled anesthetics (except nitrous oxide) and succinylcholine induce fever and severe muscle contractions.
- Treatment: dantrolene.
Intravenous anesthetics
- B. B. King on OPIOIDS PROPOses FOOLishly.
- Barbiturates
- Benzodiazepines
- Arylcyclohexylamines (Ketamine)
- Opioids
- Propofol
Barbiturates
- Intravenous anesthetics
- Thiopental—high potency, high lipid solubility, rapid entry into brain.
- Used for induction of anesthesia and short surgical procedures.
- Effect terminated by rapid redistribution into tissue (i.e., skeletal muscle) and fat.
- Decreased cerebral blood flow.
Benzodiazepines
- Intravenous anesthetics
- Midazolam most common drug used for endoscopy
- Used adjunctively with gaseous anesthetics and narcotics.
- May cause severe postoperative respiratory depression, decreased BP (treat overdose with flumazenil), and anterograde amnesia.
Arylcyclohexylamines (Ketamine)
- Intravenous anesthetics
- PCP analogs that act as dissociative anesthetics.
- Block NMDA receptors.
- Cardiovascular stimulants.
- Cause disorientation, hallucination, and bad dreams.
- Increased cerebral blood flow.
Opioids
- Intravenous anesthetics
- Morphine, fentanyl used with other CNS depressants during general anesthesia.
Propofol
- Intravenous anesthetic
- Used for sedation in ICU, rapid anesthesia induction, and short procedures.
- Less postoperative nausea than thiopental.
- Potentiates GABAA.
Local anesthetics
- Examples
- Mechanism
- Principle
- Clinical use
- Toxicity
- Examples
- Esters—procaine, cocaine, tetracaine.
- Amides—lIdocaIne, mepIvacaIne, bupIvacaIne
- AmIdes have 2 I’s in name
- Mechanism
- Block Na+ channels by binding to specific receptors on inner portion of channel.
- Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons.
- 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
- Principle
- Can be given with vasoconstrictors (usually epinephrine) to enhance local action
- Decrease bleeding, increase anesthesia by decreasing systemic concentration.
- In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively –> need more anesthetic.
- Order of nerve blockade: small-diameter fibers > large diameter.
- Myelinated fibers > unmyelinated fibers.
- Overall, size factor predominates over myelination such that small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers.
- Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure.
- Can be given with vasoconstrictors (usually epinephrine) to enhance local action
- Clinical use
- Minor surgical procedures, spinal anesthesia.
- If allergic to esters, give amides.
- Toxicity
- CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).
Neuromuscular blocking drugs
- Clinical use
- Depolarizing
- Succinylcholine
- Reversal of blockade
- Phase I
- Phase II
- Complications
- Nondepolarizing
- Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium
- Reversal of blockade
- Clinical use
- Used for muscle paralysis in surgery or mechanical ventilation.
- Selective for motor (vs. autonomic) nicotinic receptor.
- Depolarizing
- Succinylcholine
- Strong ACh receptor agonist
- Produces sustained depolarization and prevents muscle contraction.
- Reversal of blockade
- Phase I
- Prolonged depolarization
- No antidote.
- Block potentiated by cholinesterase inhibitors.
- Phase II
- Repolarized but blocked
- ACh receptors are available, but desensitized
- Antidote consists of cholinesterase inhibitors.
- Phase I
- Complications include hypercalcemia, hyperkalemia, and malignant hyperthermia.
- Succinylcholine
- Nondepolarizing
- Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium
- Competitive antagonists
- Compete with ACh for receptors.
- Reversal of blockade
- Neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors.
- Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium
Dantrolene
- Mechanism
- Clinical use
- Mechanism
- Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle.
- Clinical use
- Used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
Parkinson disease drugs
- Parkinsonism is due to…
- Strategies
- Dopamine agonists
- Increase dopamine
- Prevent dopamine breakdown
- Curb excess cholinergic activity
- Parkinsonism is due to…
- Loss of dopaminergic neurons and excess cholinergic activity.
- Strategies
- Dopamine agonists
- Bromocriptine (ergot), pramipexole, ropinirole (non-ergot)
- Non-ergots are preferred
- Increase dopamine
-
Amantadine
- May increase dopamine release
- Also used as an antiviral against influenza A and rubella
- Toxicity = ataxia
-
L-dopa/carbidopa
- Converted to dopamine in CNS
-
Amantadine
- Prevent dopamine breakdown
-
Selegiline
- Selective MAO type B inhibitor
- Entacapone, tolcapone
- COMT inhibitors
- Prevent l-dopa degradation –> increased dopamine availability
-
Selegiline
- Curb excess cholinergic activity
-
Benztropine
- Antimuscarinic
- Improves tremor and rigidity but has little effect on bradykinesia
-
Benztropine
- Dopamine agonists
- Mnemonics
-
BALSA:
- Bromocriptine
- Amantadine
- Levodopa (with carbidopa)
- Selegiline (and COMT inhibitors)
- Antimuscarinics
- For essential or familial tremors, use a β-blocker (e.g., propranolol).
- Park your Mercedes-_Benz_.
-
BALSA:
L-dopa (levodopa)/carbidopa
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- Increased level of dopamine in brain.
- Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine.
- Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to increase the bioavailability of L-dopa in the brain and to limit peripheral
side effects.
- Clinical use
- Parkinson disease.
- Toxicity
- Arrhythmias from increased peripheral formation of catecholamines.
- Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia between doses.
Selegiline
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby increasing the availability of dopamine.
- Clinical use
- Adjunctive agent to l-dopa in treatment of Parkinson disease.
- Toxicity
- May enhance adverse effects of L-dopa.
Memantine
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- NMDA receptor antagonist
- Helps prevent excitotoxicity (mediated by Ca2+).
- Clinical use
- Alzheimer’s
- Toxicity
- Dizziness, confusion, hallucinations.
Donepezil, galantamine, rivastigmine
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- AChE inhibitors.
- Clinical use
- Alzheimer’s
- Toxicity
- Nausea, dizziness, insomnia.
Huntington drugs
- Neurotransmitter changes in Huntington disease
- Treatments
- Neurotransmitter changes in Huntington disease
- Decreased GABA
- Decreased ACh
- Increased dopamine.
- Treatments
- Tetrabenazine and reserpine
- Inhibit vesicular monoamine transporter (VMAT)
- Limit dopamine vesicle packaging and release.
- Haloperidol
- Dopamine receptor antagonist.
- Tetrabenazine and reserpine
Sumatriptan
- Mechanism
- Clinical use
- Toxicity
- Mechanism
- 5-HT1B/1D agonist.
- Inhibits trigeminal nerve activation
- Prevents vasoactive peptide release
- Induces vasoconstriction.
- Half-life < 2 hours.
- Clinical use
- Acute migraine, cluster headache attacks.
- A SUMo wrestler TRIPs ANd falls on your head.
- Toxicity
- Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling.