Bolded Drugs Flashcards
Sodium thiopental
Barbituates
Therapeutic use: Induce anesthesia, anxiety (less common)
Delivery: Long half-life, parenteral
Side effects:
CNS - Reduce cerebral O2, blood flow, intracranial pressure
CV - Produces vasodilation (venous), severe BP drop
Respiratory depression
Propofol
Parenteral anesthesia Therapeutic use: Induce and maintain anesthesia, antiemetic Delivery: Shorter half-life Side effects: Elicits pain on injection Produce excitation during induction CNS - Same as barbituates CV - Bigger BP drop than thiopental Respiratory depression more than thiopental Potential for abuse
Etomidate
Parenteral anaesthesia
Therapeutic use: Induce anesthesia in patients at risk for hypotension
Delivery: Parenteral
Side effects:
CNS - Like thopental
CV - Less than thiopental and propofol
Respiratory depression less than thiopental
More nausea and vomiting than thiopental
Increased post-surgical mortality due to suppression of the adrenocortical stress response
Ketamine
Parenteral anesthesia
Therapeutic use: Induce dissociative anesthesia
Primarily patients with bronchospasm, children undergoing short, painful procedures
Midazolam
Parenteral anesthesia - Benzodiazepine
Therapeutic use: Conscious sedation, anxiolysis and amnesia duringminor surgical procedures, induction agent, adjunct during regional anesthesia, anti-anxiety effects pre-op
Delivery: Parenteral, half-life of 1.5 hrs
Side-effects:
Has been associated with respiratory depression and respiratory arrest
Caution with neuromuscular disease, Parkinson’s, bipolar
CV - Like thiopental
Isoflurane
Oral anesthetic
Therapeutic use: Induce and maintain anesthesia, co-administration of nitrous oxide allows for a reduction in isoflurane
Delivery: Oral delivery, moderate blood:gas partition coefficient, 99% excreted unchanged from the lungs
Side-effects:
Respiratory - Airway irritant, reduces tidal volume, increase RR, increase PaCO2
CV - Myocardial depression leading to a decrease in BP, arrhythmia, dilates cerebral BV increasing intracranial pressure
Desflurane
Oral anesthetic
Therapeutic use: Outpatient surgeries, direct skeletal muscle relaxation
Delivery: Oral delivery, special equipment due to volatility, very low blood:gas partition coefficient
Side-effects:
CV - Similar to isoflurane
Respratory - Similar to isoflurane, irritant
Sevoflurane
Oral anesthetic
Therapeutic use: Inpatient and outpatient; induction and maintenance; children and adults
Delivery: Oral, Very low blood:gas partition coefficient, metabolized to flouride ion in liver, ex vivo degradation by CO2, absorbents in the anesthesia circuit forms “compound A” nephrotoxic in rats
Side effects:
CV - Similar to isoflurane
Respiratory - Similar to isoflurane, less respiratory depression, not an irritant
Nitrous oxide
Oral anesthetic
Therapeutic use: Weak anesthetic, produce sedation and analgesia in outpatient dentistry, adjunct with other inhalation anesthetics allows for a reduction in their dose
Delivery: Oral, very insoluble in blood and other tissues
Side effects:
Contraindicated in pneumothorax, negative inotrope but also sympatho-stimulant
Respiratory effects - Minimal except for the oxygen dilution issue
Abuse liability
Cocaine (Anesthetic)
Ester local anesthetics
Therapeutic use: Upper respiratory tract vasoconstrictor and anesthetic
Delivery: Topical
Side effects: Toxicity and potential for abuse
Procaine
Ester local anesthetic
Therapeutic use: Synthetic local anesthetic, infiltration anesthesia
Low potency, slow onset, short duration of action
Tetracaine
Ester local anesthetics
Therapeutic use: Widely used in spinal anesthesia
Delivery: Long acting, spinal, topical, opthalmic
Side-effects: Used for peripheral nerve block because large doses are necessary increasing potential for toxicity
Benzocaine
Ester local anesthetics
Therapeutic use: Applied to wounds and ulcerated surfaces where it provides relief for long periods of time
Delivery: Anesthetic with low solubility in water, therefore too slowly absorbed when applied topically to be toxic
Lidocaine
Amide local anesthetics
Therapeutic use: Almost any application where a local anesthetic of intermediate duration of action is needed
Delivery: Intermediate duration, use with epinephrine decreases the rate of absorption decreasing toxicity
Metabolized in the liver
Side-effects: Standard toxicity associated with local anesthetics
Bupivacaine
Amide local anesthetics
Therapeutic use: Prolonged analgesia
Side-effects: More cardiotoxic than lidocaine (ventricular arrhythmias and myocardial depression)
More sensory than motor block
Ropivacaine
Amide local anesthetics
Therapeutic use: Similar to bupivacaine
Delivery: Epidural and regional, long-lasting
Side-effects: Less cardiotoxic and more motor-sparing than bupivacaine
Fluoxetine
SSRI
Therapeutic: Major depressive disorder, OCD, panic disorder, socialphobia, PTSD, Generalized Anxiety Disorder, PMS
Delivery: Effects on drug metabolism, long half-life active metabolite, sustained release product
Side-effects: Nausea, vomiting, insomnia, nervousness, sexual dysfunction
Sertaline
SSRI
Therapeutic: Major depressive disorder, OCD, panic disorder, socialphobia, PTSD, Generalized Anxiety Disorder, PMS
Delivery: Less drug metabolism effects, shorter half-life
Side-effects: Nausea, vomiting, insomnia, nervousness, sexual dysfunction, SSRI discontinuation syndrome
Duloxetine
SNRI
Therapeutic: Typical uses and fibromyalgia, diabetic neuropathy, back pain, osteoarthritis pain
Delivery: 12-18 hr half-life
Side-effects: SSRI-like, caution with liver disease
Bupropion
Atypical antidepressant
Therapeutic: Depression, nicotine withdrawal, seasonal affective disorder
Mechanism: Norepi and dopamine uptake blocker
Mirtazapine
Atypical antidepressant
Mechanism: Blocks presynaptic alpha-2 receptors in brain
Side-effects: Increase appetite
Amitriptyline
Tricyclic Antidepressants
Therapeutic use: Depression, secondarily to SSRIs, Chronic pain
Delivery: Parenteral or oral administration, high concentrations in brain and heart, long plasma half-life: 8 to 100 hours
Side effects: Anticholinergic effects, sedation, cardiac abnormalities, decreases REM and increase stage 4 sleep
Clomipramine
Tricyclic Antidepressants
Therapeutic use: Depression, secondarily to SSRIs, OCD
Delivery: Parenteral or oral administration, high concentrations in brain and heart, long plasma half-life: 8 to 100 hours
Side effects: Anticholinergic effects, sedation, cardiac abnormalities, decreases REM and increase stage 4 sleep
Phenelzine
Irreversible MAO Inhibitor
Therapeutic use: Major depression, not drug of first choice
Delivery: Antidepressant action takes about 2 weeks
Side effects: Food and drug interaction with tyramine from food results in hypertensive crisis
Chlorpromazine
Phenothiazine Antipsychotic Alipathic side chain Therapeutic use: Antipsychotic Delivery: Low to medium potency Side effects: Sedative, anticholinergic
Thioridazine
Phenothiazine Antispychotic
Piperidine side chain
Delivery: Low potency
Side effects: Sedative, less extrapyramidal actions, anticholinergic
Fluphenazine
Phenothiazine Antipsychotic
Piperazine side chain
Delivery: High potency
Side effects: Less sedative, less anticholinergic, more extrapyramidal reactions
Haloperidol
Butyropheone Derivative Antipsychotic
Similar to high-potency piperazine derivatives
Clozapine
Atypical Antipsychotic
Side effect: Less extrapyramidal symptoms, serious agranulocytosis, blood dyscrasias, weight gain, effects on negative symptoms
Olanzapine
Atypical Antipsychotic
Related to clozapine
Delivery: More potent as 5-HT2 antagonist
Side effects: Few extra pyramidal symptoms, no agranulocytosis, weight gain and diabetes risk
Risperidone
Atypical Antipsychotic
Combined dopamine and serotonin receptor antagonist
Side effects: Low incidence of extrapyramidal side effects
Quetiapine
Atypical Antipsychotic
Structural related to clozapine on D2 and 5-HT2 receptors
Potential abuse
Arpiprazole
Atypical Antipsychotic
D2 partial agonist
Adjunct in treatment of depression
Lithium
Bipolar disease
Therapeutic use: Blocks manic behavior, depletes PIP2
Delivery: Oral administration, eliminated in urine (affected by sodium), interactions with ACE inhibitors and AT-II receptor blockers
Side effects: Fatigue and muscular weakness, tremor, GI symptoms, Goiter, slurred speech and ataxia, serious toxicity at plasma levels > 2 mEq/liter
Carbamazepine
Antiseizure drug
Therapeutic use: Seizure, Bipolar I disorder, acute manic/mixed episodes
Delivery: Unpredictable absorption, hepatic enzyme induction, dose-related toxicity
Side-effects (from toxicity): Diplopia, ataxia, GI upset, drowsiness, rare blood dyscrasias, teratogen (Spinal Bifida)
Valproic Acid
Therapeutic use: Antiseizure
Mechanism: Block repetitive neuronal firing, may reduce T-type Ca2+ currents, GABA concentration
Delivery: Oral, bound to plasma protein, extracellular fluid, inhibits metabolism of phenobarbital, phenytoin and carbamazepine
Side-effects: GI upset, weight gain, hair loss, idiosyncratic hepatotoxicity, teratogenicity - spinal bifida
Divalproex
Therapeutic use: Antiseizure
Mechanism: Block repetitive neuronal firing, may reduce T-type Ca2+ currents, GABA concentration
Delivery: Oral, bound to plasma protein, extracellular fluid, inhibits metabolism of phenobarbital, phenytoin and carbamazepine
Side-effects: GI upset, weight gain, hair loss, idiosyncratic hepatotoxicity, teratogenicity - spinal bifida
Buspirone
Partial agonist at 5-HT1A
Also binds to dopamine-D2 receptors
Therapeutic use: Treatment of generalized anxiety
Delivery: Elimination half-life 2-11
Flumazenil
Pure antagonist of benzodiazepine receptor
Treatment of anxiety
Flurazepam
Benzodiazepines
Therapeutic Use: Generalized anxiety disorder, sleep disorders, seizure treatment
Effects: Decrease of anxiety, sedation, hypnosis, anterograde amnesia (IV), anticonvulsant
Delivery: Pharmacokinetics are related to relative lipophilicity, metabolized to active metabolites
Abuse potential: Chance for tolerance, dependence and withdrawl, treatment of abuse
Alprazolam
Benzodiazepines
Therapeutic Use: Generalized anxiety disorder, sleep disorders, seizure treatment, panic disorders
Effects: Decrease of anxiety, sedation, hypnosis, anterograde amnesia (IV), anticonvulsant
Delivery: Pharmacokinetics are related to relative lipophilicity, metabolized to active metabolites
Abuse potential: Chance for tolerance, dependence and withdrawl, treatment of abuse
Diazepam
Benzodiazepines
Therapeutic Use: Generalized anxiety disorder, sleep disorders, seizure treatment, muscle relaxant, IV sedation and anesthesia
Effects: Decrease of anxiety, sedation, hypnosis, anterograde amnesia (IV), anticonvulsant
Delivery: Pharmacokinetics are related to relative lipophilicity, metabolized to active metabolites
Abuse potential: Chance for tolerance, dependence and withdrawl, treatment of abuse
Zolpidem
Hypnotic
Mechanism: Omega-1 BDZ receptors
Delivery: Antagonized by Flumazenil, long acting controlled release form
Therapeutic effect: Less disruption of sleep architecture –> Stage 3 and 4 sleep preserved
Side-effects: Relative lack of muscle relaxant or anxiolytic effects
Pentobarbital
Hypnotic barbiturate
Rarely used today
Chloral Hydrate
Therapeutic use: Sedative hypnotic
Delivery: Metabolized to trichloroethanol (active form), similar to barbituates
Side-effects: Less on stages of sleep than benzodiazepines and barbituates
Baclofen
Therapeutic use: Treatment of muscle spasticity
Mechanism: Mimetic agent at GABA B receptors, decreased release of excitatory transmitters such as glutamate
Side effects - Less sedation than diazepam
Tizanidine
Therapeutic use: Treatment of muscle spasticity
Mechanism: Alpha-2 adrenergic agonist related to clonidine
Delivery: Similar efficacy to diazepam
Side effects: Include drowsiness, hypotension, dry mouth and asthenia
Ethanol
Alcohol (Review lecture notecards for specifics)
Delivery: Non-potent, GI tract post oral
Short-term effects based on dosage (BAC):
50-100 - Sedation, subjective “high”, increased reaction times
100-200 - Impaired motor function, slurred speech, ataxia
200-300 - Emesis, stupor
300-400 - Coma
>500 - Respiratory depresssion, death
Chronic effects: Alcoholic liver disease, GI pathologies, nervous system tolerance and physical dependence, neurotoxicity, teratogenic effects/FAS, CYP2E1 drug interactions
Disulfiram
Pharmacotherapy of Alcoholism
Mechanism of action: Inhibition of aldehyde dehydrogenase
Pharmacologic effects: Acetaldehyde syndrome
Not very effective, ethical issues
Diazepam
Benzodiazepines
Therapeutic use: Prevention of seizures, delirium, arrhythmias from Alcohol Withdrawl Syndrome
Delivery: Gradual reduction of dose “tapering off”
Chlordiazepoxide
Benzodiazepines
Therapeutic use: Prevention of seizures, delirium, arrhythmias from Alcohol Withdrawl Syndrome
Delivery: Gradual reduction of dose “tapering off”
Naltrexone
Pharmacotherapy of Alcoholism
Therapeutic use: Reduces “urge to drink”; increases control
Mechanism of action: Opioid receptor antagonist
Best together with psychosocial therapy
Acamprosate
Pharmacotherapy of Alcoholism
Therapeutic use: Decreases drinking frequency and reduces
Mechanism of action: GABA mimetic
Side Effects: Well tolerated; Primary side effect is diarrhea
Caffeine
CNS Stimulant
Mechanism: Block adenosine receptor
Therapeutic use: Stay awake, headache
Toxicity: Excessive CNS stimulation, nervousness, insomnia, excitement
Chronic use: Physical dependence at 2 cups of coffee a day, withdrawal of fatigue/sleepiness, nausea, headaches, vomiting (rare)
Cocaine (Stimulant)
Therapeutic: Local anesthesia in URT
Effects: Peripheral sympathomimetic, increased alertness; vigilance, euphoria, elation, well being, competency
Delivery: Well absorbed through most mucous membranes, peak effect dependent on delivery route, metabolized primarily by serum and liver esterases, short half-life, metabolites in urine (for testing)
Mechanism: Potent inhibitor of the reuptake of NE, epi, dopamine
Toxicity and chronic use: Tolerance and physical dependence occurs with heavy use, mild withdrawal, neurotoxic, overdose cause seizures or cardiovascular effects, fetal effects, high abuse potential
Amphetamine
Therapeutic use: Narcolepsy, ADD
Delivery: Absorbed orally, longer action than cocaine 4-6 hrs orally, deamination to benzoic acid
Pharmacological effects: Wakefulness, alertness, decreased fatigue, enhances athletic and intellectual performance, elevation of mood; increased self-confidence
Side effects: Insomnia, abdominal pain, anorexia, suppression of growth, fever
Toxicity: Acute toxicity (sympathomimetic effects, restlessness, dizziness, tremor), psychosis, neurotoxicity, abuse liability
Methamphetamine
Amphetamine-like drug
Therapeutic use: ADD
Delivery: Absorbed orally, longer action than cocaine 4-6 hrs orally, deamination to benzoic acid, highest CNS effect
Pharmacological effects: Wakefulness, alertness, decreased fatigue, enhances athletic and intellectual performance, elevation of mood; increased self-confidence
Side effects: Insomnia, abdominal pain, anorexia, suppression of growth, fever
Toxicity: Acute toxicity (sympathomimetic effects, restlessness, dizziness, tremor), psychosis, neurotoxicity, abuse liability (particularly high)
Methylphenidate
Therapeutic use: Narcolepsy, ADD
Delivery: Absorbed orally, longer action than cocaine 4-6 hrs orally, deamination to benzoic acid
Pharmacological effects: Wakefulness, alertness, decreased fatigue, enhances athletic and intellectual performance, elevation of mood; increased self-confidence
Side effects: Insomnia, abdominal pain, anorexia, suppression of growth, fever
Toxicity: Acute toxicity (sympathomimetic effects, restlessness, dizziness, tremor), psychosis, neurotoxicity, abuse liability
Nicotine
Mechanism: Agonist of nicotinic cholinergic receptors (Not NMJ)
Pharmacological effect: CNS stimulant (increased alertness), activates dopamine signaling in nucleus accumbens; Muscle relaxant
Delivery: Absorbed readily through mucous membranes, lungs to brain in 7 seconds
Withdrawal symptoms: Irritability, impatience, hostility, anxiety, depression, difficulty concentration, increased appetite, weight gain
Bupropion
Nicotine dependence treatment
Mechanism: Unknown, seems to enhance noradrenergic and dopaminergic signaling
Adverse effects: Dry mouth, insomnia
Moderately effective: reduces craving and nicotine withdrawal symptoms
Varenicline
Nicotine dependence treatment
Mechanism: Partial agonist of CNS nicotinic receptors, only enough activation to reduce craving and withdrawal
Adverse effects: Nausea, insomnia, headache, constipation, increased thoughts of suicide; depression
Produces significant increase in abstinence compared to placebo
Beta-Endorphin
Mu receptor endogenous agonist
Dynorphins
Kappa receptor endogenous agonist
Enkephalins
Mu and delta receptor endogenous agonist
Morphine
Opioid agonist
Prototype strong analgesic
Mechanism: Mu agonist
Delivery: Low oral to parenteral potency ratio: 3-4 to 1, IV, oral, oral sustained release, suppository forms, analgesia - 4-5 hours
Heroin
Opioid agonist
Delivery: More lipophilic than morphine, converted to 6-mono-acetyl morphine and morphine
High abuse potential
Codeine
Opioid agonist
Therapeutic use: Mild to moderate pain, never morphine-like
Delivery: Some codeine is metabolized to morphine, in combination with NSAIDS or acetaminophen
Hydrocodone
Opioid agonist
Therapeutic use: Moderate to severe pain
Delivery: Sustained oral release preparation (major abuse problem), in combination with NSAIDS or acetaminophen
Oxycodone
Opioid agonist
Therapeutic use: Moderate to severe pain
Delivery: Sustained oral release preparation (major abuse problem), in combination with NSAIDS or acetaminophen
Methadone
Opioid agonist
Mechanism: Mu agonist
Therapeutic use: Opioid abuse and chronic pain
Delivery: Equipotent with morphine, good oral bioavailability
Meperidine
Opioid agonist
Therapeutic use: Analgesic, shorter duration than morphine
Delivery: Toxic metabolite, normeperidine, MAO inhibitor interaction
Fentanyl
Opioid agonist
Therapeutic use: Mu opioid agonist
Delivery: 100X as potent as morphine, short-acting 1 to 1.5 hours
Available in injectable form and as transdermal patches, buccal soluble film for breakthrough pain
Hydromorphone
Opioid agonist
Delivery: 2-3x as potent as morphine
Nalbuphine
Mixed-action agonist/antagonist
Mechanism: Mu antagonist, kappa agonist
Delivery: Similar in efficacy and potency to morphine, injectable form
Lower abuse potential, precipitate withdrawal in opioid dependent patients
Buprenorphine
Mixed-action agonist/antagonist
Therapeutic use: Treat moderate to severe pain (patch), opioid dependence treatment (oral)
Mechanism: Partial mu agonist
Delivery: Patch or oral
Naloxone
Opioid Antagonist
Therapeutic use: Treat opioid ODs, combined with opioids to decrease parenteral abuse liability
Mechanism: High affinity for mu receptors, significantly less for kappa and delta
Delivery: Much greater activity parenterally than orally, short duration of 1 to 2 hours
Naltrexone
Opioid Antagonists
Therapeutic use: Tratment of alcoholism and opiate addiction
Delivery: Orally active with long half-life
Dextromethorphan
Dextro isomer of levorphanol
Antitussive but not analgesic
NMDA antagonist
Tramadol
Weak mu opioid agonist
Therapeutic use: Mild to moderate pain
Delivery: Oral use, sustained release preparation
Suboxone
Treatment of opioid abuse
Penicillin G and V
Route: Oral (V) vs IV/IM (G)
Spectrum: Anaerobes (G+ in particular)
Gram-pos (Non-Beta-lactamase-producing, 1st line Streptococcus in particular)
Very limited gram-neg (Non-beta-lactamase-producing, Neisseria meningitidis)
Spirochetes (Syphilis)
Dosing: 1600U/mg
Notes: Slow releasing dose of penicillin G are pen G procaine & benzathine (pen G benzathine for syphilis)
General Pencillin Properties (Pharmacokinetics, allergy, side effects)
Pharmacokinetics: Well-distributed but low penetration into CSF, increases during meningitis Renal elimination: Anion transport, competes with anionic drugs (probenecid) for elimination Short half-lives Allergies: Not frequent (<25%) Enetrocolitis (1%) Elevated liver enzymes (1-4%) Hemolytic anemia (1-2%) Seizures
Oxacillin
Pencillin for beta-lactamase-positive staph
Methicillin-type
Delivery: IV/IM
Note: Staph. aureus sensitive to it is designated methicillin-sensitive Staph. aureus (MSSA)
Ampicillin, Amoxicillin
Spectrum: Maintain reasonable gram-pos. spectrum (Incl. Enterococcus), Expanded gram-neg. spectrum
Delivery: Oral better for amoxicillin, IV or oral for ampicillin
Notes: High dose amoxicillin is the drug of choice for otitis media
Amoxicillin is an alternate choice for Lyme disease
Ampicillin only for meningitis (Neisseria, Listeria) and GI infections (esp. Shigella)
Ticarcillin
Penicillin with extended gram-negative spectrum
Delivery: Injection
Spectrum: Retain some gram-pos.
Some anaerobes incl. gram-neg.
Gram-neg. spectrum extended (incl. Pseudomonas a.)
Notes: Susceptible to beta-lactamases
Piperacillin
Penicillin with extended gram-negative spectrum Delivery: Injection Spectrum: Gram-neg. like ticarcillin Pseudomonas and klebsiella Ticarcillin-resistant bacteria
Beta-Lactamase inhibitors
Bolded examples: Clavulanic acid, Tazobactam
Mechanism: Beta-lactam analogs that irreversibly bind to beta-lactamase
Use: Inhibition of some types of beta-lactamases to restore utility of some beta-lactams
Cephalosporin common properties (Pharmacokinetics, mechanism, resistance, allergy, side effects)
Pharmacokinetics: Well-distributed, only some reach the CSF (3rd gen, and one 2nd gen)
Majority require injection
Short half-lives in general
Renal excretion
Mechanism: Same as penicillins
Resistance: Similar mechanisms as penicillins
Allergy: Cross-reaction with penicillins, no reliable skin test
Side effects: Nausea, vomiting, diarrhea, enterocolitis, hepatocellular damage
1st Gen Cephalosporins
Examples: Cefazolin, Cephalexin
Spectrum: Mostly gram-pos. (good alternative for Staph. & Strep.)
Uses: Uncomplicated outpatient skin infections, surgical prophylaxis especially skin flora
Specific notes:
Cefazolin: Best gram-pos. activity of 1st gen
Cephalexin: Oral
Cefuroxime
2nd Gen Cephalosporin
Pharmacokinetics: Only 2nd gen to penetrate CSF
Best 2nd Gen for haemophilus
Not the best against enterics
Good tolerance to many gram-neg beta-lactamases
Cefoxitin
2nd Gen Cephalosporin
Spectrum: Similar to other 2nd gen but also good for anaerobes, incl. some B. fragilis
Good tolerance to many gram-neg beta-lactamases
Ceftriaxone
3rd Gen Cephalosporin
Spectrum: Many gram-negs., stable against many gram-neg beta-lactamases
Usage: Common meningitis, gonorrhea
Long half-life (6-9 hrs)
Ceftazidime
3rd Gen Cephalosporin
Spectrum: Many gram-negs., stable against many gram-neg beta-lactamases
Poorest 3rd gen for gram-pos.
Usage: Best 3rd gen against Pseudomonas a.
Shorter half-life (90 min)
Cefepime
Spectrum: Similar to ceftazidime
More resistant to type I beta-lactamases
Usage: Empirical treatment of serious inpatient infections where both gram-pos. and gram-neg etiologies are possible
Imipenem
Carbapenem
Spectrum: Broad, resistant to many beta-lactamases incl. ESBL
Not for: Clostridium difficile, MRSA, Enterococcus faecium, some Pseudomonas, Stenotrophomonas
Therapeutic use: Mixed infections, ill-defined infections, non-responsive or resistant to other drugs
Clinical note: Imipenem with cilastatin to prevent hydrolysis by renal dipeptidases
Side-effects: Allergic reactions (cross allergies with penicillins and cephalosporins), seizures, dizziness, confusion, nausea, vomiting, diarrhea, pseudomembranous colitis, superinfection
Aztreonam
Spectrum: Gram-neg. aerobic rods, resistant to many beta-lactamases
Allergy: No cross-reactions with beta-lactams
Delivery: IM or IV, not labeled for meningitis
Side effects: Seizures, anaphylaxis, transient EKG changes, cramps, nausea, vomiting, enterocolitis
Vancomycin
Glycopeptide, not-beta-lactam
Mechanism: Bactericidal, cell-wall synthesis inhibitor by binding to free carboxy end of D-ala-D-ala to interfere with crosslinking
Spectrum: Gram-pos only
Staph., MRSA, Strep. pneumoniae (incl. penicillin-resistant), hemolytic Strep., Enterococcus (20-30% are resistant: VRE), Clostridium difficile enterocolitis (2nd choice)
Delivery: IV for systemic infections, oral for Clostridium difficile enterocolitis
Therapeutic use: Primarily in serious infections
Empirically for bacterial meningitis with 3rd gen cephalosporin
Side effects: “Red man” or “red neck”, nephrotoxicity, ototoxicity, phlebitis, possible hypersensitivity
Fosfomycin
Mechanism: Block enolpyruvyl transferase in peptidoglycan synthesis
Spectrum: E. coli, enterococcus
Delivery: Single oral dose for 3 days effective urinary concentration
Therapeutic use: Uncomplicated UTIs
Side effects: Headache, diarrhea, nausea, vaginitis
Note: Costly
Bacitracin
Polypeptide, not a beta-lactam Mechanism: Interferes with cell wall synthesis by interfering with carrier that moves early wall components through cell membrane Spectrum: Gram-positive Delivery: Topical use only Side effects: Allergic dermatitis
Polymyxin B
Mechanism: Cationic detergents that bind LPS in the outer membrane of gram-negatives
Spectrum: Gram-neg. (incl. Pseudomonas)
Delivery: Topical
Side effects: Topical - few problems, allergies
Systemic - Potential for serious nephrotoxicity, neurotoxicity
Daptomycin
Mechanism: Bind to bacterial cytoplasmic membrane causing rapid membrane depolarization, bactericidal
Spectrum: Gram-pos.
Staph. aureus (MSSA and MRSA)
Various Strep (pyogenes, agalactiae)
Enterococcus (non-VRE)
Therapeutic use: Complicated skin and skin structure infections, bacteremia, not pneumonia
Side effects: Nausea, diarrhea, GI flora alteration, muscle pain and weakness
Quinolone general properties (Mechanism, Pharmacokinetics, Side Effects)
Mechanism: Inhibits DNA gyrase, affecting DNA winding, replication, and repair, is bactericidal
Pharmacokinetics: Oral, some also IV
Well-distributed for many fluorinated incl. CSF
Some fluorinated (e.g. norfloxacin) and nonfluorinated are UT-specific
Side effects: Nausea, vomiting, ab pain, enterocolitis, dizziness, headache, restlessness, depression, seizures, rashes
EKG irregularities, arrhythmias
Peripheral neuropathy
Precautions: Seizure disorders, Category C in pregnancy, children (cartilage damage, only 2nd line in certain serious infections, avoid in less serious)
Arthropathy (10-15%), tendon rupture
Norfloxacin - Use
Use: Prototype quinolone for UTI
Ciprofloxacin - Uses
UTI Infectious diarrhea Bone and joint infections Skin infections Chlamydia Ciprofloxacin is not best choice for gram-pos.
Moxifloxacin - Uses
Better gram-pos. than many quinolones
Respiratory infections, community-acquired pneumonia
Bacterial bronchitis
Not approved for Strep. throat
Nitrofurantoin
Mechanism: Nitroreductase enzyme converts these drugs to reactive compounds (incl. free radicals) to damage DNA
Use: Lower UTI: E. coli, Enterococcus, Staph
Side effects: Nausea, vomiting, diarrhea
Hypersensitivity, fever, chills
Peripheral neuropathy
Acute & chronic pulmonary reactions
Acute and chronic liver damage
Granulocytopenia, leukopenia, megaloblastic anemia
Acute hemolytic anemia
Rifampin
Mechanism: Bind to and inhibits bacterial RNA pol B, bactericidal
Therapeutic use: TB, meningitis prophylaxis (Neisseria meningitidis, HIB), leprosy combo therapy
Side effects: Serious hepatotoxicity, many CYP inductions (3A, 2C9, 2C19, 1A, 2A, 2B) which inactivate other drugs
Orange color to urine, saliva, sweat, tears
A lot of the usual suspects (headache, fatigue, nausea, etc.)
Fidaxomicin
Mechanism: Non-competitive RNA pol inhibitor, Bactericidal
Spectrum: Narrow gram-pos. spectrum, mainly Clostridium
Use: C. difficile infection
Delivery: Oral administration, poorly absorbed
Side-effects: GI upset (4-10%), GI bleeding (4%), neutropenia (2%)
Fun fact: $2800/10 day therapy.
Metronidazole
Mechanism: Anaerobes reduce it to damage and disrupt DNA, bactericidal
Spectrum and uses: Anaerobes, C. difficile enterocolitis, H. pylori combo therapy, Gardenella vaginalis (bacterial vaginosis)
Side effects: Nausea, vomiting, anorexia, diarrhea
Transient leukopenia, neutropenia
Thrombophlebitis after IV infusion
Bacterial and fungal superinfections (esp. Candida)
Aminoglycosides (Mechanism, Pharmacokinetics, Spectrum, Specific Examples, Side Effects)
Mechanism: Transported into bacteria via active process
Bind to several ribosomal sites during 30S/50S interface: stop initiation, premature release of ribosome from mRNA, cause misreads
Bactericidal
Pharmacokinetics: IV, IM, topical
Limited penetration into CSF
Concentration-dependent killers (toxicity is dose-related)
Post-antibiotic effect: Sustained activity for several hours after dropping below effective levels
Narrow therapeutic window
Spectrum: Gram-neg aerobic bacilli often in combination with cell wall inhibitors, poor activity against anaerobes
Therapeutic use: Restricted to serious infections
Specifics: Gentamicin, tobramycin, amikacin
50% gentamicin-resistant Pseudomonas is tobramycin-sensitive
Amikacin used for tobramycin and gentamicin resistant strains
Side effects: Nephrotoxicity (rev.), ototoxicity (irrev.), neuromuscular blockade (less common)
Tetracycline
Mechanism: Transported into cell by protein-carrier system, prevent attachment of aminoacyl-tRNA to 30S ribosomal subunits
Bacteriostatic
Resistance: Most common is drug efflux pump, resistance to one tet implies resistance to them all
Spectrum: Originally broad-spectrum, now preferred for “unusual” bugs
Rickettsia, Lyme disease, chlamydia, Mycoplasma, Ureplasma
Delivery: Oral, parenteral,
Bind calcium, inhibits tet absorption
Side effects: GI disturbances, enterocolitis
Candida superinfection in colon
Photosensitization with rash
Teeth discoloration: Avoid use in children, esp. < 8 yo; contraindication in pregnancy
Doxycycline
Tetracycline
Usage: Alternative for Pen-G-sen. syphilis
Uncomplicated N. gonorrhoeae
Pharmacokinetics: Least affinity for calcium
Minocycline
Usage: Alternative for Pen-G-sen. syphilis, uncomplicated gonorrhea
Pharmacokinetics: More affinity than dox, gonorrhoeaeless than tet for calcium
Tigecycline
Glycylcyclines
Mechanism: Bacteriostatic, Like Tet but binds to other unique sites
Resistance: no cross-resistance with other antibacterials
Spectrum: Gram-negs: E. coli, Citrobacter, Klebsiella, Enterobacter, Not pseudomonas
Gram-pos: Staph (MSSA/MRSA), Strep
Anaerobes: Bacteriodes, Clostridium perfringens
Use: Skin/skin structure infections, complicated intra-abdominal infections, community-acquired pneumonia (CAP)
Delivery: IV only, not metabolized, no P450 inhibi
Adverse reactions: Nausea, vomiting, enterocolitis
Other side effects similar to tetracyclines including calcium binding
Increased risk of death (FDA Alert 2010)
Chloramphenicol
Mechanism: Interferes with binding of aminoacyl-tRNA to 50S ribosomal subunit and inhibits peptide bond formation, generally bacteriostatic
Spectrum: Broad
Therapeutic use: Meningitis alternative for cephalosporin allergy
Brain abscesses (often anaerobic)
Side effects: Severe
Bone marrow depression - Fatal aplastic anemia (1 in 30,000)
Grey baby syndrome
Optic neuritis and blindness
GI effects incl. enterocolitis
And many more
Erythromycin
Macrolide
Mechanism binds to 50S subunit, blocks translocation along ribosomes, bacteriostatic
Spectrum and uses: Primarily against gram-pos (recommended for Strep. in penicillin-allergic patients)
Unusual or atypical bugs: Chlamydia, mycoplasma
Legionella (azithromycin now preferred)
Bordetella
Side-effects: Nausea, vomiting (GI motility)
Inhibits CYP3A metabolism/excretion of many drugs
Increases risk of arryhtmias and cardiac arrest
Clarithromycin
Macrolide
Mechanism binds to 50S subunit, blocks translocation along ribosomes, bacteriostatic
Spectrum: Wider than erythromycin
Uses: Additional include Haemophilus influenzae, Moraxella, penicillin-resistant S. pneumoniae, atypical mycobacteria, H. pylori (3 drug combo of 2 antibacterials and an acid blocker)
Kinetics: Less frequent dosing
Side-effects: Less GI motility, some CV risk (long QT)
Azithromycin
Macrolide
Mechanism binds to 50S subunit, blocks translocation along ribosomes, bacteriostatic
Uses: Outpatient respiratory tract infections
Genital infections: Chlamydia, 2nd line gonorrhea
NOT Heliobacter
Side effects: Least of macrolides
Few effects on 3A4
Chance of long QT but lower than erythromycin
Clindamycin
Mechanism: Binds to 50S ribosomal subunit, blocks translocation along ribosomes
Spectrum and uses: Gram-pos cocci (Strep. and MSSA), suppresses Strep. and Staph.
Many anarobes incl. Bacteroides fragilis but not C. difficile
Side effects: GI irritation, diarrhea (20%)
Antibiotic-associated enterocolitis (3-5%)
Hepatotoxicity
Linezolid
Mechanism: Inhibits protein synthesis
Binds to 50S ribosomal subunit, interfering with 70S formation
Bacteriostatic
Delivery: IV or oral, high bioavailability
Spectrum: Gram-positive
Use: Skin/skin structure infections (VRE, MSSA/MRSA, Strerp grps A and B)
Nosocomial pneumonia (Strep pneumoniae (including MDR) and Staph)
Side-effects: Non-selective MAO inhibitor (drug interactions, avoid foods with tyramine)
Diarrhea, superinfection, enterocolitis
Headache, nausea/vomiting
Bone marrow suppression
Sulfonamides
Anti-folate
Mechanism: Competitive analog of p-aminobenzoic acid, bacteriostatic
Spectrum: Broad
Use: Combined with other antibacterials
Side effects: Hypersensitivity (2-10%)
Rashes, serum sickness (sunlight makes rash worse)
GI disturbances
Renal damage (cyrstalluria)
Potentiate action of other drugs (Inhibit CYP2C9, effect on warfarin)
Sulfamethoxazole
Sulfonamide
Used with trimethoprim for synergy
Best pharmacokinetic match to trimethoprim
Silver sulfadiazine
Used topically for infection prevention in burn patients
Trimethoprim
Anti-folate
Mechanism: DHF analog, competive inhibitor of DHF reducatase, bacteriostatic
Uses: In combination with sulfamethoxazole, together result in bacteriocidal synergy
TMX/SMX combination used for:
Empiric therapy for uncomplicated UTIs (cystitis) - Enterobacteriaceae (E. coli), coagulase-negative Staph
URT/ear infections: H. influenzae, Moraxella, Strep. pneumoniae
GI infections: Salmonella, shigella
PNneumocystis jiroveci: 1st choice for treatment & prophylaxis
Side effects: All of sulfonamide
Trimethoprim adds: Nausea, vomiting, diarrhea, rashes
Bone marrow suppression
Trimethoprim side-effects especially pronounced with long-term use (AIDS patients)
Isoniazid
Nicotinic acid derivative - Anti-mycobacterial
Bacteriocidal for activiely growing bacilli
Mechanism: Inhibits synthesis of mycolic acids
Activated by the catalase-peroxidase (KatG protein)
Targets the enoyl-acyl carrier protein reductase (InhA protein)
Therapeutic use: Primary TB drug, all patients infected with INH-sensitive strains should receive INH if possible, in combination with other drugs for TB treatment
Resistance: Mutations in KatG, InhA
Adverse Side Effects:
Neurotoxicity, esp. peripheral neuritis - Significantly improved with pyridoxine (vitamin B6) administration
Hepatotoxicity (10-20%)
Rifampin
Anti-mycobacterial
Mechanism: Inhibits DNA-dep RNA pol
Cidal
Use: Combo, never used alone
Delivery: Readily absorbed, well-distributed, only limited penetration into CSF
CYP Metabolism
Side-effects: Hepatotoxicity, potent inducer of multiple CYPs, orange-red color (urine, feces, saliva, sputum, tears, sweat)
Ethambutol
Mechanism: Interferes with arabinosl transferase, blocking cell wall synthesis
Tuberculostatic
Use: Combo
Delivery: Well-absorbed & distributed, adequate levels in CSF
Side-effects: Well tolerated, optic neuritis, not hepatotoxic
Pyrazinamide
Mechanism: Blocks mycolic acid synthesis by inhibiting fatty acid synthase I
Tuberculocidal
Resistance: Spontaneous
Use: Combo, important component of short-term therapy
Delivery: Well-absorbed, widely distributed
Particularly useful for CNS involvement
Side-effects: Hepatic damage, esp. with rifampin
Streptomycin
Aminoglycoside
Mechanism: Binds to several ribosomal sites, stops initiation of translation, causes mRNA misreading
Resistance: Spontaneous
Use: Usually reserved for the most serious forms of TB
Side effects: Ototoxicity, nephrotoxicity
Rifabutin
Lipophilic rifampin analog
Use: Single-agent prophylaxis of MAC in AIDS patients
Alternate to rifampin for multi-drug treatment of MAC
Side-effects: Similar to rifampin but less frequent, drug interactions similar to rifampin, but to a lesser extent
Clarithromycin (Mycobacterial use)
Therapeutic use: Multi-drug regimen for treatment for M. avium-intracellulare in AIDS patients, MAC prophylaxis
Mechanism: Bactericidal
Dapsone
Anti-mycobacterial
Mechanism: Structural analog of para-aminobenzoic acid (PABA); inhibits synthesis of folic acid
Bacteriostatic
Therapeutic use: Combo with other drugs for leprosy
Alternative for prophylaxis & treatment of Pneumocystis jiroveci (carinii) in AIDS patients
Pharmacokinetics: Similar metabolism to isoniazid, slow & fast acetylators
Side effects: Hemolytic anemia, methemoglobinemia
Other lessers (allergic rxn, drug fever, otoxic effects, blurretced vision, peripheral neuropathy, hepatitis)
Clofazimine
Anti-mycobacterial
Mechanism: Poorly understood, involves DNA binding and interference
Use: Leprosy combo therapy (eff. for dapsone-resistant)
Delivery: Highly lipophilic, serum half-life is about 2 months
Side-effects: Red-brown pigmentation of the skin (also sputum, urine, sweat, eyes)
Generally well-tolerated
Amphotericin
Systemic anti-fungal
Gold standard for anti-fungal effectiveness by which other drugs are judged
Therapeutic use: Effective (broad-spectrum agent) for most serious (immediately life-threatening) systemic mycoses
Mechanism: Pore-formation
Pharmacokinetics: Prolonged therapy (6-12 weeks)
IV, intrathecally or intraperitoneally (not GI tract)
Total cumulative dose is important for permanent renal toxicity
Difficulty to administer due to high lipophilicity
Side Effects: Fever, nausea, vomiting, headache chills
Hypotension, hypokalemia, tachypnea
90% will show nonpermanent nephrotoxicity (but permanent renal damage can occur)
Reversible hypochromic, normocytic anemia
Flucytosine (5-FC)
Anti-fungal
Therapeutic use: Serious infections of candida, cryptococcus
Synergistic conjunction with AmpB
Fungistatic
Mechanism: Antimetabolite that inhibits thymidylate synthetase and is incorporated in RNA in place of uracil
Side Effects: Nausea, vomiting, diarrhea, enterocolitis, leukopenia, thrmbocytopenia, reversible elevated hepatic enzymes, use extreme caution in those with renal insufficiency or bone marrow depression
Fluconazole
Triazole
Therapeutic use: Crypto
Candida: Many sites including CNS and urinary, some albicans & glabrata, not krusei
Delivery: Oral (or IV)
CNS and urine activity
90% renal elimination unchanged
Side effects: Nauesea, vomiting, rash, diarrhea, headache
Mild hepatotoxicity: Discontinue with onset of liver dysfunction (least of the azoles)
Inhibit metabolism of other drugs: CYP3A, 2C
Itraconazole
Triazole
Therapeutic use: Blastomyces, Histoplasma
Candida (not CNS & urinary): More albicans and glabrata
Delivery: Oral or IV, hepatic elimination
Side effects: Nauesea, vomiting, rash, diarrhea, headache
Mild hepatotoxicity: Discontinue with onset of liver dysfunction
Inhibit metabolism of other drugs: CYP3A, 2C
Voriconazole
Triazole
Therapeutic use: Aspegillus (better than AmpB), Scedosporium, Fusarium
Candida (non-urinary): Many species including glabrata & krusei
Delivery: IV or oral
Hepatic, inactive metabolites in urine
Side effects: Nauesea, vomiting, rash, diarrhea, headache
Mild hepatotoxicity: Discontinue with onset of liver dysfunction
Inhibit metabolism of other drugs: CYP3A, 2C
Voriconazole specific: Visual disturbances (30%), photosensitive component to rash
Caspofungin
Cell wall anti-fungal
Mechanism: Non-competitively blocking synthesis of B(1,3)-D-glucan in filamentous fungi
No cross-resistance with imidazole and triazole
Therapeutic use: Invasive Aspergillus, Candia (esophageal and systemic)
Delivery: IV infusion
Slow metabolism, spontaneous degradation
Side-effects: Generally well-tolerated
Fever, nausea/vomiting, flushing, phlebitis at injection site
Pulmonary edema
Fluconazole - Superficial usage
Superficial Azole
Therapeutic use: Superficial Candida infections (vaginal, UT, oropharynx)
Side-effects: Possibly less than systemic
Miconazole
Superficial Azole
Therapeutic use: Creams/suppositories for vaginal Candida
Side effects with topical use (burning, itching, irritation)
Clotrimazole
Superficial Azole
Therapeutic use: Topical Candida, not ophthalmic
Side effects: Topical use - Allergic/irritation reactions
Oral Troches - Abnormal liver function tests (15%)
Itraconazole - Superficial usage
Superficial Azole
Therapeutic use: Oropharyngeal and esophageal Candida
Nystatin
Superficial Anti-fungal
Mechanism: Similar to AmpB, should be effective against -azole resistant strains
Therapeutic use: Topical use for Candida:
Skin, mucous membranes, vaginal infections, GI tract (NOT ophthalmic)
Oral use: GI Candida
Side-effects: Topical - well tolerated, Oral - GI distress
Natamycin
Superficial Anti-fungal
Mechanism: Similar to amphotericin B
Therapeutic use: Ophthalmic infections
In conjunction with appropriate surgical measures
Side-effects: Toxicity - Conjunctival chemosis and hyperemia
Ciclopirox
Topical dermatophyte treatment
Mechanism: Possibly inhibits metal-dep. fungal enzymes by metal chelation
Therapeutic use: Only FDA-approved topical Rx for mild-to-moderate fungal nail infections
Terbinafine
Oral dermatophyte treatment
Mechanism: Blocks ergosterol synthesis at squalene epoxidase, fungicidal
Therapeutic use: 12-week therapy for nail infection
Pharmacokinetics: Oral, well-absorbed
Remains in skin 12 weeks after therapy stopped
Side-effects: Diarrhea, dyspepsia, ab pain (<5%)
Others: Rash, urticaria, elevated hepatic enzymes, inhibition of CYP2D6
Griseofulvin
Oral dermatophyte treatment
Mechanism: Interferes with microtubule function/mitotic spindle/mitosis
Can be static or cidal
Therapeutic use: Recalcitrant dermatophytic infections of skin, hair, nails
Childhood therapy for tinea capitis
Pharmacokinetics: Oral, aided absorption by high-fat foods
Hepatic metabolism
Side-effects: Nausea, vomiting, rash, diarrhea, headache, edema
Inhibits metabolism of many drugs
Caution with penicillin allergies
Itraconazole (Oral dermatophyte)
Therapeutic use: Fungal toenail infections
Side effects: Nausea, vomiting, rash, diarrhea, headache, edema, inhibits metabolism of many drugs
Mebendazole
Anti-parasitic
Therapeutic use: Intestinal roundworms, kills some ova
Pharmacokinetics: Poorly absorbed, low systemic toxicity
Albendazole
Anti-parasitic
Therapeutic use: Echinococcus, cutaneous larval migrans (unlabeled)
Treat neurocysticercosis
Pharmacokinetics: Well distributed
Side-effects: Elevated hepatic enzymes, abdominal pain, nausea, vomiting headache
Thiabendazole
Anti-parasitic
Therapeutic use: Strongyloides, cutaneous larva migrans (“disseminated” dog or cat hookworm) (oral or topical if limited)
Delivery: Oral form rapidly absorbbed
Side-effects: Nausea vomiting dizziness
Pyrantel pamoate
Anti-parasitic Therapeutic use: Hookworm, pinworm, and roundworm OTC as Pin-x for pinworm Not for whipworm (Tricharis) Delivery: poorly absorbed Side-effects: GI symptoms
Praziquantel
Anti-parasitic
Therapeutic use: Schistosoma, some activity against other trematodes
Taenia solium eggs
Side Effects: Ab discomfort, nausea
Paromomycin sulfate
Anti-parasitic
Therapeutic use: 3rd choice for cestodes
Luminal amebicide; aminoglycoside that inhibits protein synthesis
Delivery: oral dose is very poorly absorbed = low incidence of systemic side effects
Side-effects: Diarrhea, nausea, vomiting, epigsastric pain
Chloroquine
Anti-malarial
Mechanism: Blood schizonticide, parasitizied erythrocytes concentrate the drug (> 25-fold) by pH-dependent mechanism into acidic vacuoles
Inhibits heme polymerization
Therapeutic use: Prevents attacks of all 4 species of malaria provided they are chloroquine-sensitivie (P. falciparum and P. vivax is chloroquine-resistant strains)
Eradicate P. malariae and chlorquine-sensitive P. falciparum, target blood schizonts of P. vivax or ovale (not liver hypnozoites)
Administration: Oral or parenteral
Side-effects: Visual impairment with extended use
Mefloquine
Anti-malarial
Mechanism: Similar to chloroquine
Blood schizonticide
Therapeutic use: Treatment of chloroquine-resistant P. falciparum, prophylaxis in chloroquine-resistant areas
Side-effects: Contraindicated in those with epilepsy or psychiatric disorders
Psychiatric effects: Anxiety, paranoia, depression
Vestibular effects: Dizziness, vertigo
Atovaquone + Proguanil
Anti-malarial
Mechanism: Atovaquone - Selectively inhibits malarial mitochondrial transport, disrupting pyrimidine synthesis
Proguanil - Inhibits malarial DHF reductase, disrupting pyrimidine pynthesis
Therapeutic use: Synergistic combo for prevention and treatment of chloroquine-resistant P. falciparum
Side effects: Nausea, diarrhea, vomiting, rash
Quinine
Anti-malarial
Mechanism: Similar to chloroquine
Use: Blood schizonticide, all four malarial parasites
Severe malarial acute attacks (quick action)
Alternative for chloroquine-resistant P. falciparum
Side-effects: Cinchoism (headache, visual disturbance, dizziness, tinnitus)
Gastric irritation, nausea, vomiting
Cardiac effects similar to quinidine
Doxycycline (Anti-malarial)
Mechanism: Decreases malarial protein synthesis
Depresses dihydrofolate dehydrogenase activity, interfering with pyrimidine synthesis
Therapeutic use: Treatment of multi-drug resistant P. falciparum
Prophylaxis of chloroquine-resistant P. falciparum
Primaquine
Anti-malarial
Mechanism: Poorly understand
Uses: Kill liver hypnozoites, radical cure/terminal prophylaxis of P. vivax and P. ovale (in conjunction with blood schizonticide)
Pneumocystis jiroveci (carinii) pneumonia in AIDS patients, in combination with clindamycin
Side-effects: Hemolytic reactions in those with G6P-dehydrogenase deficiency
Metronidazole (Anti-parasitic)
Therapeutic use: Tissue amebicide with luminal amebicide for symptomatic infections
Giardia lambia
Trichomonas vaginallis
Iodoquinol
Anti-parasitic
Therapeutic use: Luminal amebicide
Side effects: Diarrhea, other GI symptoms
Contraindications: Iodine hypersensitivity
Nitazoxanide
Anti-parasitic
Therapeutic use: Giardia lambila, cryptosporidium pavrum
Side-effects: Diarrhea, nausea, ab pain
Avotaquone (protozoa)
Anti-parasitic
Therapeutic use: Pneumocystis jiroveci prophylaxis or treatment
Toxoplasma gondilI (Avotaquone + Ribautin)
Amantadine
Anti-viral
Mechanism: Blocks viral uncoating by interfering with influenza A M2 protein (ion channel)
Resistance is common
Therapeutic use: Prophylaxis against influenza A, not B
Therapy for A: Reduces fever in 50% of patients and illness duration by 1-2 days if given within 2 days of illness
Side effects: CNS effects - slurred speech, anxiety, confusion, depression, headache, hallucinations
Oseltamivir
Anti-viral
Mechanism: Inactive prodrug, metabolized by hepatic esterases
Competitively inhibits influenza NA, interfering with release and penetration
Therapeutic use: Treatment of uncomplicated influenza A and B in patients > 1 yo
Only effective if given within 48 hrs of symptom onset
Effectiveness even better if given in first 24 hr
Shortens duration of symptoms by 1-2 days
Less effective against B than A
Influenza prophylaxis in patients > 1yo
Trifluridine
Anti-viral
Mechanism: Thymidine analog, interferes with DNA synthesis
Therapeutic use:
Herpes simplex types 1 and 2
Also primary kerato-conjunctivitis, recurrent epithelial keratitis
Delivery: Ophthalmic use
Side effects: Burning, stinging, hypersensitivity
Acyclovir
Anti-viral
Mechanism: Phosphorylated form is produced 40-100x fasted in infected cells
Inhibits herpes DNA pol. 10-30x more effectively than host cell DNA pol.
Competes with deoxy-GTP for DNA pol
Terminates DNA chain elongation
Therapeutic use: IV use for serious systemic herpes simplex virus (HSV), HSV encephalitis, disseminated neonatal HSV
Oral use for primary genital herpes (initial episode), primary herpetic gingivostomatitis (limited use for recurrent orolabial herpes)
Topical uses: Primary gentle herpes (may shorten healing time and pain when applied early, limited benefit)
Side effects: Generally well-tolerated; rash, itching; nausea, vomiting, headache, fatigue
Famciclovir
Anti-viral
Mechanism:
Prodrug activation: Complex with multiple intermediates to penciclovir-triP
Similar to acyclovir
Therapeutic use: Acute herpes zoster (shingles/latent chicken pox)
Treatment and suppression of recurrent genital herpes
Delivery: Oral administration, better absorbed than acyclovir
Valacyclovir (an analog): Reduce genital herpes transmission
Side-effects: Similar to acyclovir
Penciclovir
Anti-viral
Mechanism: Very similar to acyclovir
Therapeutic use: Recurrent herpes of the lips and face, topical administration
Side effects: Skin irritation, rash
Ganciclovir
Anti-viral
Mechanism: Similar to acyclovir, except mono-phos. By CMV protein kinase
Therapeutic use: CMV retinitis - in AIDS patients, only slows progression
CMV prophylaxis for transplant recipients
Side Effects: Bone marrow suppression (Leukopenia, thrombocytopenia, anemia, may enhance bone marrow suppression of Zidovudine (AZT))
Foscarnet
Anti-viral
Mechanism: Selectively inhibits CMV DNA pol by binding to its pyrophosphate-binding site
Does not require conversion to triphosphate form to be active
Therapeutic use: CMV retinitis, acyclovir-resistant herpes simplex
Side-effects: Renal damage, electrolyte imbalances, seizures
Compared to ganciclovir, higher % of patients on foscarnet must be taken off due to side effects
Lamivudine (3TC)
Anti-viral
Mechanism: Nucleoside analog, inhibits the reverse transcriptase domain of the hepatitis B DNA pol
Therapeutic use: Approved for hepatitis B, Synergistic with AZT against HIV
Side effects: Nausea, diarrhea
Tenofovir
Anti-viral
Mechanism: Adenosine monophosphate analog, Inhibits the reverse transcriptase domain of the hepatitis B DNA pol
Therapeutic use: Approved for hepatitis B, HIV
Delivery: Oral, 25%
Side effects: GI upset, Well-tolerated for HIV patients
Ribavirin
Anti-viral
Mechanism: Interferes with viral mRNA synthesis
Mono-P form inhibits insosine-5’-P dehydrogenase and thus GMP (and GTP) synthesis
Tri-P form inhibits GTP-dependent capping of viral mRNA
Therapeutic use:
Aerosol - Infants and young children with documented severe RSV infections (no longer commonly used)
Oral capsules: Hepatitis C
Side-effects: Aerosol use - Drug may precipitate in and clog respiratory equipment; pulmonary function deterioration
IV/Oral - Anemia, bone marrow suppression
Alpha-intreferons
Anti-viral
Therapeutic use: Condyloma acuminata
Hepatitis B and C: Interferons in combination with ribavirin and boceprevir for HCV
Side-effects: Flu-like syndrome, leukopenia, bone marrow suppression, neurotoxicity, myalgia
Greatest limit to long-term use
Boceprevir
Anti-viral
Mechanism: Reversible inhibitor of NS3 protease of HCV, blocks formation of infectious virus
Therapeutic use: Approved for HCV genotype I
Side-effects: Anemia, neutropenia, contraindicated with CYP3A substrates or inducers (Strong 3A inhibitor)
Zidovudine
Anti-viral
Mechanism: Thymidine nucleoside analog, phosphorylated by cellular kinase, AZT-triP inhibits RT & acts as a chain terminator
Therapeutic Use: Anti-HIV Drugs
Delivery: Drugs that inhibit glucuronidation of AZT increase the hematologic toxicity of AZT
Side-Effects: Bone marrow suppression, neutropenia, anemia; Avoid drugs which inhibit glucuronyl transferases; Myopathy
Emtrictabine (FTC)
Anti-viral
Mechanism: Fluorinated analog of lamivudine, same mechanism & resistance as 3TC
Therapeutic Use: Anti-HIV, Off-label Hep B
Abacavir
Anti-viral
Mechanism: Nucleoside analog inhibitor of RT
Therapeutic use: Anti-HIV
Side effects: Hypersensitivity, Assoc. with HLA-B*5701, If occurs need to stop drug immediately and never restart
Lactic acidosis, hepatic steatosis
Efavirenz
Anti-virals
Mechanism: Non-nucleoside inhibitor of RT
Binds at different site than NRTIs, disrupts active site at RT
Therapeutic Use: Multi-drug therapy for HIV, #1 anti-HIV drug in USA in 2005
Side-effects: Rash, CNS/Psychiatric symptoms, nightmares, vivid dreams, 50% of patients especially early in Tx
Lopinavir
Anti-viral
Mechanism: Protease Inhibitor
Therapeutic use: Anti-HIV
Side-effects: Diabetes, alterations in lipid metabolism increased triglycerides and cholesterol, fat distribution, alters metabolism of many other drugs (CYP3A)
Ritonavir
Anti-viral
Mechanism: Protease inhibitor
Therapeutic use: Used to boost levels of other protease inhibitors, blocks their metabolism by CYP3A
Too toxic for PI only use
Enfuvirtide
Anti-viral
Mechanism: Binds to gp41 subunit of HIV glycoprotein, blocks membrane fusion to CD4+
Therapeutic use: For HIV-1 only, treatment-experienced patients who have failed multiple regimens
Side effects: Local injection reactions (98%), Diarrhea, Nausea, Fatigue
Mainly used as a later option when other regimens have failed
Maraviroc
Anti-viral
Mechanism: Antagonist of chemokine co-receptor CCR5, blocks entry of HIV into cells
Therapeutic use: Treatment of CCR5-tropic HIV-1, effective in strains resistant to other drugs (CCR5-tropic strains tend to predominate early in infection)
Side-effects: Hepatotoxicity, CV events
Raltegravir
Anti-viral
Mechanism: Inhibits HIV-1 integrase activity, preventing integration of HIV-1 DNA into the genome
Therapeutic use: Treatment of HIV-1, new and treatment experienced patients
Works on virus that is resistant to other drugs
Side-effects: Generally well-tolerated
