Carbamazepine (Classic Car)

• Generally used to treat focal seizures (waitress with shaking arm). Note that narrow spectrum prescriptions may be used to treat generalized tonic-clonic seizures, but should be avoided in other generalized disorders, including JME, as may cause exacerbation. • Carbamazepine (classic car) o Ineffective against absence seizures and should be avoided in other generalized disorders o Binds VG dependent Na channels, probably after closure of inactivation gate (closed bags of chips). preventing sustained high-frequency firing and sustaining inactivation phase of neurons. o First line for treatment of trigeminal neuralgia (three gems on seize the night sign). Reduces pain in 80% of patients o Adverse effects ▪ Dose related diplopia (cross car headlights). Often occurs first ▪ Dose related ataxia (toppling stack of burgers) ▪ Rare: SIADH (inappropriately wet head). Due in part to increased responsiveness of collecting tubules to ADH causing dose related hyponatremia that develops over the first few months of therapy. ▪ Idiosyncratic blood dyscrasias • Leukopenia (12% children, 7% adults). May be transient or persistent. Doesn’t usually require immediate discontinuation • Fatal aplastic anemia, Fatal agranulocytosis (hourglass; falling level of granulocytes in anemia). Usually within 3-4 months of initiating therapy. WBC < 3000 or neutrophil < 1000 are indications for lowering dose or cessation. ▪ CYP450 inducer; drug interactions (license plate) ▪ Rare, potentially life-threatening DRESS syndrome (=drug reaction with eosinophilia & systemic symptoms). Can occur 2-8 weeks after exposure; px with fever, generalized lymphadenopathy, diffuse morbilliform rash, facial edema (waitress wearing spotted dress) ▪ Teratogenic (greaser’s spider jacket) Neural tube defects, esp. spinal bifida. May be implicated in fetal malformation of nails, distal phalanges, hypertelorism, characteristic facial features. ▪ Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) (mask). Much more common with HLA-B15 allele, which occurs almost exclusively in people of Asian ancestry; screening for this allele prior to initiating treatment recommended. ▪ Drug induced lupus (lupus wolf) • Phenytoin (classic tow truck) o Ineffective against absence seizures and should be avoided in other generalized disorders o Binds VG dependent Na channels, probably after closure of inactivation gate (closed bags of chips). preventing sustained high-frequency firing and sustaining inactivation phase of neurons. o Treat status epilepticus with benzos or phenytoin (Order Status at Ben’s Diner). Maintenance therapy is usually with IV phenytoin or fosphenytoin (tow truck under Order Status sign) ▪ If patient doesn’t respond, start IV phenobarbital (barbershop) o Adverse effects ▪ Dose related ataxia (toppling stack of burgers) ▪ Diplopia, nystagmus ▪ Low folate & megaloblastic anemia have been reported; clinical significance unknown (spilled salad) ▪ Gingival hyperplasia (bubble gum) ▪ Hirsutism & coarsening of facial features (especially rugged man) ▪ Drug induced lupus (lupus wolf) ▪ Rare, potentially life-threatening DRESS syndrome (=drug reaction with eosinophilia & systemic symptoms). Can occur 2-8 weeks after exposure; px with fever, generalized lymphadenopathy, diffuse morbilliform rash, facial edema (waitress wearing spotted dress) ▪ Rash. Patients who have rash to phenytoin are more likely to have with carbamazepine too ▪ SJS/TEN (mask). Much more common with HLA-B15 allele, which occurs almost exclusively in people of Asian ancestry; screening for this allele prior to initiating treatment recommended. ▪ Teratogenic (greaser’s spider jacket) Orofacial clefts, genitourinary defects, cardiac malformations (cleft trucker hat). ▪ CYP450 inducer; drug interactions (license plate) ▪ Altered bone and mineral metabolism & decreased bone density (osteoporotic axel). Related to increased induction of CYP450 combined with decreased Vitamin D catabolism. Suggest supplementation • Gabapentin, pregabalin (grab a pint) o Sometimes used as addon therapy for refractory focal seizures o Binds avidly to VG calcium channels; may inhibit inward calcium currents and attenuate NT release (calci-yum ice cream door blocked). No binding to GABA o Used more often to treat neuropathic pain (Frayed wire), including post herpetic neuralgia (Zeus’s Ice Cream), fibromyalgia (fiber bars), & painful diabetic neuropathy (diasweeties candy). o Adverse effects ▪ Dose dependent dizziness, sedation, ataxia (tall falling ice cream cone) • Vigabatrin o Irreversible inhibitor of GABA transaminase (transmission), which is normally responsible to GABA degradation. Results in sustained elevation of GABA levels in the CNS (elevated Cab-A), resulting in tonic inhibition of the CNS o Used as adjunctive treatment for partial seizures • Tiagabine o Inhibits GABA uptake, prolonging inhibitory action of GABA in the synaptic cleft (cab driver stuck outside of cab) o Used as adjunctive treatment for partial seizures • Used to treat absence seizures (absences clipboard). Generalized seizures that occur most often in children, characterized by sudden momentary lapse in awareness accompanied by staring, blinking, or clonic jerks (kid gazing out window). Behavior returns to normal and patients will not typically remember anything. Usually last ~10s. Will typically present with 3 Hz spike wave complexes on EEG (kid in EEG/dunce cap sitting under “3 spikes” sign) • Ethosuximide (ethos) o Blocks t-type calcium channels in thalamic neurons, preventing sustained rhymical burst discharges occurring in that region (closed bottle of calci-yum chocolate milk; T- thermos for thalamic T-type neurons o Adverse effects ▪ Dose related GI distress (kid getting beat up) ▪ Lethargy, fatigue (sleeping student) ▪ Ethosuximide can cause fatigue, GI distress, headache, itching, SJS (“EFGHIJ” – per First Aid) • Valproate (Festival) o Highly effective in management of absence seizures. Used especially if there is also a h/o tonic-clonic seizures. • Lamotrigine (llamas) o Not quite as effective as valproate, but generally effective. Historical aside: Vincent van Gogh was a Dutch post-impressionist painter whose work is characterized by bold colors, expressive brushwork, and a variety of subjects, including landscapes, still life, portraits, and self-portraits. While highly influential on 20th century modern art, van Gogh was considered a madman and a failure during his lifetime, and only achieved fame & recognition after his death by suicide in 1890 at 37 yo. He suffered from psychotic episodes, depression, and delusions, and spent a period of his life in a psychiatric hospital in Saint-Rémy in southern France. In 1880s Paris, van Gogh ran in avant-garde art circles, where he apparently befriended Paul Gauguin; their friendship fell apart when van Gogh, angry at Gauguin following a fight, cut off his own ear. Van Gogh apparently had no recollection of this event afterward, suggesting an acute psychotic episode. Now on to the medical stuff. Physiology • Several NTs are involved in psychosis, including dopamine and serotonin. o FGAs target dopamine transmission, specifically bock D2 receptors in the mesolimbic & striatofrontal system (snapping double rope with D-rings) o 5HT-2A receptors are key in modulating release of both excitatory and inhibitory NTs, and are a main target of 2nd generation antipsychotics. • Antipsychotics are highly lipophilic, highly protein & tissue bound, and consequently have a large Vd, leading to long half-lives (long tapering flag). Typically have half-lives of 20-40 hours, and many have active metabolites as well. Indications • Antipsychotics are used in many condition with characteristics of psychosis. While schizophrenia is the primary indication, may also be used in psychotic mania in bipolar, MDD with psychotic features, delirium, psychosis associated with Alzheimer’s or Parkinson’s, and drug induced psychosis • Schizophrenia is the primary indication for antipsychotic drugs. o FGA are generally effective at treating positive symptoms (hallucination, delusions, disorganized thoughts, or behavior) (positive angel sitting on van Gogh’s shoulder next to his dead ear – i.e. angel is “blocked”) o Not so effective at treating negative symptoms (apathy, flat affect, lack of energy) (negative devil on opposite shoulder is still audible) • Acute psychotic episodes, regardless of etiology, are generally managed with antipsychotics (patient running up angled roof). • Can be used to treat acute aggression or anxiety. In particular, psychosis is often associated with increased motor activity, heightened emotional arousal, anxiety (angry patient not wanting to share roof). • Manage motor tics of Tourette’s (marionette), although has fallen out of favor for other dopamine depleting agents Rx • Can be classified as high- or low-potency drugs. • Note the -azine ending of many names (starry gazing) • High potency include trifluoperazine, fluphenazine (person on roof trying to fly), haloperidol (halo around moon in painting) o High clinical potency = greater dopamine receptor binding. o Associated with less sedation, weight gain and anticholinergic activity o Higher risk of extrapyramidal adverse effects • Low potency include thioridazine (color theory wheel) & chlorpromazine (Color-pro paints) o higher histaminic & muscarinic activity with corresponding sedation & antimuscarinic effects o Lower incidence of extrapyramidal effects • Adverse effects (for all antipsychotics) result from effects on multiple receptors and NTs. Most of these effects are more prominent with FGAs than SGAs, or in high- or low-potency drugs; however, any adverse effects may be seen in any antipsychotics o QT prolongation, increasing risk for torsades des pointes (twisted streamers) o Can lower seizure threshold (shaking escapee). Should be used with caution in patients on other seizure exacerbating meds. More prominent with high potency rx (characters high up on roof): o Extrapyramidal symptoms are the major limiting factor in FGA use, and the incidence of such symptoms is the defining difference between FGA & SGA (patient trying to fly is wearing pyramid shaped newspaper hat with “Extra”) . Occur d/t D2 dopamine blockade in the nigrostriatal tract, which is normally involved in the control of muscle movement. Will most often present with initiation of treatment or changes in dosing; may include: ▪ Acute dystonia (i.e. sudden onset sustained muscle contractions); may occur within hours of treatment (observer with cocked head & rigid back). More common in young men on high-potency FGAs. Depending on muscle group may involve • Spasmodic torticollis • Oculogyric crisis with forced sustained elevation of the eyes • Arching of back and neck ▪ Akathisia (subjective restlessness with inability to is still) (critic knocking over chair); may occur within days. ▪ Drug induced parkinsonism with cogwheel rigidity, bradykinesia, masked facies, tremor (cogged wheels). Usually occur within weeks. Cannot be managed with levodopa, which may precipitate psychosis; instead, ▪ Tardive dyskinesia; abnormal choreoathetoid movements following months to years of use (escapee in carriage with newspaper hat sticking out tongue). Advanced cases may be irreversible, so want to catch early and decrease dose or change to SGA. ▪ Tuberoinfundibular blockade → hyperprolactinemia (person laughing milk out nose). More common with high-potency. Downstream effects include inhibition of GnRH release, resulting in central hypogonadism (galactorrhea, amenorrhea, impotence, ↓libido) ▪ Neuroleptic malignant syndrome (“Now More Spicy” chicken bucket). Occurs in patients extra sensitive to dopaminergic effects (patient is sensitive to friend’s antics & is laughing). • Treatment: Dantrolene (mm relaxant) (trampoline). Blocks RyR and prevents further release of calcium into muscle fibers (adult blocking Ryan from getting on trampoline). ▪ More common with high-potency FGAs, but can be seen with any antipsychotic meds. • Lead pipe rigidity (person holding onto pipe) • Altered mental status, fever, autonomic instability (crazy, sweating, and tachycardic) • Rhabdomyolysis (eating chicken). Watch for elevated CK. ▪ Note D2 dopamine blockade in the nigrostriatal tract is often accompanied by excess cholinergic activity. So may coadminister with rx with M1 antagonism effects (e.g. benztropine, diphenhydramine) to reestablish dopaminergic/cholinergic balance. More prominent with low potency rx o Systemic effects are most prominent with low-potency rx (painting with Color-Pro paints) o Antimuscarinic action (tea party in Café Terrace at Night): dry mouth & constipation common; blurred vision, urinary retention less common. Results from inhibition of central and peripheral muscarinic blockade. Symptoms significantly less or entirely absent with higher potency drugs. o Orthostatic hypotension d/t blockade of α-1 receptors (Siesta painting; extinguished α candle). Often accompanied by tachycardia, especially in the first days of treatment or with increased dosing. o Block H1 activity (bees around Sunflowers); can be highly sedating (may be utilized clinically with aggressive or agitated patients) (Bedroom in Arles painting) o Chlorpromazine: gray deposits in cornea and lens (corn yellow paint) o Thioridazine: retinal deposits (deposits on retinal palette). May cause browning of vision; advanced cases may look like retinitis pigmentosa. Historical note: surrealism was a cultural movement developed in the aftermath of World War I, best known for juxtaposing uncommon imagery to create scenes to unnerving or illogical effect. These works drew on dreams and the unconscious as means of expressing a surrealist philosophy. Salvador Dalí was a Spanish Surrealist renowned for technical skill, precision, and striking and bizarre imagery in a variety of visual art forms. Themes prevalent in his work include dreams, the subconscious, sexuality, religion, science, and his personal relationships. Now on to the medical stuff. Atypical an antipsychotics tipsychotics • Clozapine is the prototype (closet). Quetiapine, olanzapine, risperidone, aripiprazole, ziprasidone (“Quiet please, only whispering appropriate”; zippered dress). • MOA o SGAs block 5HT-2A receptors, which are key in modulating release of both excitatory and inhibitory NTs including dopamine, glutamate, GABA, NE, ACh release in the CNS (block cut out of serotonin cake). Serotonin signaling is also often involved in psychoactive substance use, e.g. LSD – a serotonin agonist (these paintings are pretty trippy) o Like FGA, block postsynaptic D2 receptors in the mesolimbic & striatofrontal system, although effect is less than in the FGAs (snapping double rope with D-rings). MOA is not completely understood; the degree of blockade of D2 receptors does not necessarily correlate to effects at other receptors throughout the body. • Indications o As with FGAs, primary indication is schizophrenia. SGAs are more effective in treating negative symptoms (devil and angel can both be heard; and that mustache – no flat affect here). o Adjunctive treatment for treatment resistant depression (difficulty opening wine bottle with masks) o risperidone can be combined with SSRIs for refractory OCD (person fixing crooked panel of Millet’s The Angelus; Dali was obsessed with this painting) o Motor tics of Tourette’s (funky marionette). • Adverse effects o Cause fewer of the “typical” extrapyramidal effects seen with FGAs, hence “atypicals” (newspaper hat patron). Of the SGAs, risperidone highest risk (person whispering, asking disruptive patron to leave) ▪ Elevated prolactin d/t Tuberoinfundibular D2 blockade (laughing milk out nose). Much more of a problem than with FGAs. Downstream effects include inhibition of GnRH release, resulting in central hypogonadism (galactorrhea, amenorrhea, impotence, ↓libido) ▪ Neuroleptic malignant syndrome (“Now More Spicy” chicken). More common FGAs but can be seen with any antipsychotic meds. • Lead pipe rigidity • Altered mental status, fever, autonomic instability (patron being intrusive, may have altered mental state) • Rhabdomyolysis (eating chicken). Watched for elevated CK. • Treatment: Dantrolene (mm relaxant). Blocks RyR and prevents further release of calcium into muscle fibers o H1 antagonists → sedation (bee swatter); especially clozapine & quetiapine o Orthostatic hypotension d/t α 1 antagonism (extinguished α candle); accompanied by tachycardia, especially in the first days of treatment or with increased doses. May be severe enough to warrant changing medication. o Antimuscarinic action (tea party painting): dry mouth, constipation common; blurred vision, urinary retention less common. Result from inhibition of central and peripheral muscarinic receptors. Clozapine has highest affinity (painting behind closet). Less antimuscarinic affinity than FGAs (partly obscured painting) o Unlike FGAs, can have significant metabolic syndrome: ▪ Weight gain (fat face). Mechanism not totally clear; evidence for ↑appetite & altered metabolism ▪ Dyslipidemia (elevated melting butter) ▪ Hyperglycemia (candy filled landscape) ▪ All SGAs cause to varying degrees (clozapine & olanzapine most, ziprasidone) (gal in zippered dress looking pretty slim) o QT prolongation, increasing risk for torsades des pointes (twisted streamers). Hypothesized to be d/t direct inhibition of cardiac potassium channels. o Clozapine specifically is infamous for the following, although others may cause as well (The Persistence of Memory inspired painting on closet) ▪ Agranulocytosis (hourglass). Absolute neutrophil counts must be routinely monitored. If ANC < 1500, change agents (has been reported in other SGAs as well) ▪ Fatal myocarditis or cardiomyopathy (surrealist heart) ▪ Lowered seizure threshold (shaking alarm clock). Also seen to lesser degree with other SGAs. • Parkinsonism (Park & Sons bank) characterized by “pill-rolling” tremor, bradykinesia, cogwheel rigidity (cogwheel safe door), and postural instability. Most common causes is Parkinson’s disease d/t degenerative loss of dopaminergic nn in the nigrostriatal pathway. Parkinson’s disease also has non-motor abnormalities, but most medical management is focused on motor symptoms. • Note that dopamine therapies are generally contraindicated in psychotic patients, d/t central dopamine control with these conditions (crossed out painting of Van Gogh) • Levodopa (coiled rope) o Most effective treatment for treatment of Parkinson’s motor symptoms. o Dopamine doesn’t cross the BBB (bank vault threshold). Levodopa (L-DOPA) is the immediate metabolic precursor to dopamine, and does cross the BBB (rope coiled, waiting to be used, on spool with L-shaped handle; can enter the vault). Decarboxylated to form dopamine by DOPA decarboxylase. Normally, 97% of L-DOPA converted to dopamine peripherally by intestinal DOPA decarboxylase. o Dopamine is also peripherally methylated to 3-O-methyldopa by catechol-O-methyltransferase (COMT). Central COMT metabolizes L-DOPA to 3-methoxy-tyrosine. o Adverse effects: ▪ Some consequences of peripheral conversion (hostages held in lobby = peripheral effects) • Cause GI distress (bound & nauseated hostage). Results in emetic effect d/t stimulation of the chemoreceptor trigger zone; tolerance usually develops after initiating therapy. • Peripheral conversion can also cause arrhythmias – tachycardia, ventricular extrasystole, postural hypotension, a-fib (unconscious bound woman) ▪ High doses can cause behavioral changes – anxiety, agitation, insomnia, confusion, hallucinations (central effects) (confused hostage). Reducing dose can be helpful in alleviating these effects. May also co-administer with atypical antipsychotic to block central dopaminergic effects. ▪ Long-term administration characterized by • Fluctuations in clinical response occur with increasing frequency with disease progression; this “wearing off” effect may result in parkinsonian symptoms nearing the end of a dosing period (e.g. akinesia, dyskinesia) (worn out end of rope inside vault) • Fluctuations may be unrelated to dosing; can cause on-off phenomenon: periods of akinesia alternating with periods of improved mobility, with timing unrelate to dosing (light flashing on and off; robber pointing to watch for chronic use) • With disease progression, therapeutic window narrows, causing motor fluctuations with even small changes in dose. Fluctuations become unpredictable (narrowing window to make escape). • Fluctuations will often be marked by significant dyskinesias in up to 80% of patients who are on levodopa for 10+ years. May include choreoathetosis of the face & distal extremities is the most common presentation (robber twisting to sneeze) • Carbidopa o Peripheral DOPA decarboxylase inhibitor (police car on periphery). Increases central bioavailability of levodopa (L-DOPA crooks with cranks escaping from lobby into vault). ▪ Does nothing to inhibit COMT, so only about 10% of L-Dopa crosses BBB (guard on intercom shooting L-crank). o Significantly decreases peripheral Adverse effects of levodopa (freeing hostages), but exacerbates neuropsychiatric effects (not releasing delirious hostage) • Entacapone, tolcapone (entrance guy & tall guy are Al Capone bandits) o COMT inhibitors (inhibiting clerk from using intercom) o Increases plasma half-life of levodopa. Used especially as patients begin to experience motor fluctuations with levodopa/carbidopa. ▪ Entacapone only active peripherally (Al Capone gangster at entrance to vault) ▪ Tolcapone active peripherally and centrally (tall Al Capone gangster entering vault and impeding guard with intercom). o Only effective combined with levodopa; ineffective as monotherapy. o Adverse effects ▪ Tolcapone: hepatotoxicity (liver-shaped clip on gun) • Selegiline (sledgehammer) o MAO-B inhibitor. Recall MAO-B selectively metabolizes dopamine (black mouse eating dope rope in vault). Selegiline enhances levodopa availability centrally; used in conjunction with levodopa – has little effect on parkinsonism alone. • Direct dopaminergic receptor agonists o Ropinirole (double ropes in a roll) is a D2 receptor agonist; pramipexole (Robber with big pecs) Preferentially agonizes D3 receptors. Ergot alkaloids (e.g. bromocriptine) are the originals, but are rarely used nowadays d/t Adverse effects o Important role as first line monotherapy for Parkinson’s. Associated with fewer long-term response fluctuations and dyskinesias from levodopa. ▪ May also be added with a dopaminergic agonist to delay inevitable end-of-dose akathisia o Also used to treat restless leg syndrome (escapee climbing ladder and shaking legs) o May have more severe psychiatric Adverse effects than; particularly impulse control disorders (e.g. gambling, compulsive shopping, hypersexuality) (“rock and roll” tattoo) o Contraindicated with h/o psychotic illness • Amantadine (manatee) o Enhances effect of endogenous dopamine by increasing synthesis and release & inhibiting reuptake (extra dope rope crate broken open) • Benztropine & trihexyphenidyl (tri-hexagon logo on Benz outside) o Centrally acting antimuscarinics. Help restore balance of dopaminergic & cholinergic effects on basal ganglia. Can help improve tremor & rigidity of Parkinson’s, with no effect on bradykinesia (car is trembling). • R- -lactam ring (ringed planet). Include penicillins, cephalosporins, carbapenems, and all share similar MOAs & pharmacologic properties. • Bacterial peptidoglycan cell wall is synthesized by repeating D-alanyl-D-alanine oligopeptides (coccoid Death Star with D-ALA scaffolding). Penicillin binding proteins (PBPs) remove the terminal alanine in the process of forming crosslinks between peptides (Planetary Building Project workers). R-lactams inhibit this transpeptidation reaction by covalently binding PBPs, preventing bacterial cell wall synthesis. Effective in actively growing cells. • Bactericidal. • Work particularly well against G+ cell wall (e.g. staph & strep) (purple coccoid spaceships behind Death Star) • Penicillin (Princess Ellen holding purple pencil, fighting off the agalactiae empire.) o Penicillin V is the oral, acid stable form (V-ship in front of acid yellow nebula). Indicated in minor infections. Poor bioavailability, narrow spectrum, 4 qid dosing ▪ Oral form is acid. ▪ First line for streptococcal pharyngitis (red throat) and other infections caused by Group A strep ▪ Both V and G can treat post-strep rheumatic fever (Heart shaped planet Sydenham is very inflamed) o Penicillin G is the IV form (ivy rope distracting Princess Ellen). Benzathine salts of Penicillin G may be given via IM injection ▪ Left sided endocarditis caused by S. bovis, S. viridans (green emperor with miter hat) ▪ Group B strep infection for neonates of infected mothers; given intrapartum for group B strep prophylaxis for fetus (GBS galactic baby) ▪ Actinomyces israelii (Israeli flags on hyphae-like transport vehicles) ▪ C. perfringens (transport driver with road rash) ▪ Pasteurella multocida ˚ B: 5< G8F B9GGE84G87 J < G; R-lactams, as well as more broad-spectrum antibiotics like ampicillin, piperacillin (space dog) ▪ Single dose of benzathine treats primary, secondary, & early latent syphilis (running soldier with characteristic red boots & gloves on palms & soles) ▪ N. meningitidis, if isolate is penicillin sensitive (soldier wearing red mohawk helmet – recurrent symbol for meningitis; Gred, with diplococci-like booster packs) o ' BFG6B@@BA @86; 4A F< @ B9 E8F< FG4A 6 8 < F C B E7 HG6 < BA B9 R-lactamases, often expressed by plasmid genes (Ray gun has a plasmid-like ring around it). May also have PBP or porin mutations. o Generally well tolerated. Adverse reactions: ▪ Type 1 hypersensitivity (IgE mediated) (Rebel ship shooting what look like IgE missiles) • Up to 10% of people claim hypersensitivity, but 90% of those are skin test negative • 10% of those with a true hypersensitivity have cross reactivity with cephalosporins. More likely to cause a reaction if patient has had ⊕ skin test reaction and had definite IgE mediated reaction. ▪ Drug induced autoimmune hemolytic anemia. Will have ⊕ direct coombs test (IgG missiles attacking RBC shaped asteroids) ▪ Interstitial nephritis d/t mononuclear cells entering interstitium of the kidney. Blue cells on histology (kidney shaped nebula with blue stars) • Nafcillin, oxacillin, & dicloxacillin are narrow-spectrum β-lactams of the penicillin class (β lactam planet). Indicated to treat methicillin-sensitive staphylococcus. • MOA: Bind PBPs and halt peptidoglycan synthesis. • Extended activity against β-lactamase-producing bacteria, as bulky R-groups prevent β-lactamase binding (bulked up rebel fighters are protected from plasmid-ring β-lactamase guns) • Narrow spectrum against staph (purple coccoid space station). Drug of choice for methicillin sensitive, penicillin resistant staph (even though methicillin isn’t used clinically anymore). Nafcillin & oxacillin for staph (pencil-shaped staff; ox horns) • Indications: o Mild to moderate localized staphylococcal infections when given orally. Given empirically for skin & soft tissue infections, e.g. folliculitis, abscesses (Red ox hump). o Given IV for systemic staph infection, e.g. staph endocarditis (tricuspid pyramids) & osteomyelitis (fish skeletons) • MRSA (merciless pharaoh): produces PBPs with low affinity for binding β-lactam drugs. This renders β-lactams ineffective (altered wall builders who continue wall synthesis with protective gear, despite rebel missiles)