- no permanent damage to nerve structure

- no irritation to tissue to which it is applied

- low systemic toxicity

- effective with both injection into tissue or applied to mucous membranes

- time of onset as short as possible

-long enough duration of action for procedure without being too long

- weak base with 3 structural elements

1) hydrophilic amino group at one end

2) intermediate alkyl chain

3) aromatic lipophilic (hydrophobic) group at the other end

- are substituted amino groups, making these bases (weak bases)

- important in determining the onset of action

- either an ester or amide type linkage

- linkage determines the route of metabolism, hypersensitivity and chemical stability

- Esters: metabolized by cholinesterases in plasma and liver, more likely to cause hypersensitivity reaction (bc metabolized to PABA), and are ubstable (short shelf life)

- Amides: metabolized by liver enzymes (amidase, oxidase). avoid in liver disease

- require lipophilicity/hydrophobicity to get to  the site of action

- smaller and more lipophilic the molecule, the faster the effect

- also determines potency

- poorly absorbed after oral administration, may be absorbed after topical administration, usually given by injection

- better blood supply = more rapid absorption = shorter duration of action

- distributed throughout body

- plasma levels relate to toxicity

- hydrolyzed to more water soluble metabolites and secreted in urine

- act at the cell membrane to prevent the generation and conduction of nerve impulses

- decreasing or preventing the large transient increase in the permeability of excitable membranes to Na+

- do not affect resting potential

- due to direct interaction with voltage- sensitive Na+ channels

- bind to receptors near intracellular end of channel, blocking it in both time and voltage dependent manner

- threshold for excitation increases, impulse conduction slows, rate of rise of AP declines, AP amplitude decreases, and ability to generate AP is abolished

- resting state channels have a much lower affinity for local anesthetics than activated and inactivated channels

- recovery is 10-1000 times slower than for recovery from normal inactivation

- block small fibers first

- sensory (especially pain) fibers have a higher firing rate and are blocked sooner

- blockade order: autonomic, pain, temp, pressure, proprioception, motor

- the unionized form diffuses across membranes to reach site of action

- drugs with pKa closer to physiologic pH will have more rapid onset of action

- charged cationic species bind with the Na+ and exert effect

- based in the duration of action required

- esters are metabolized to PABA and more likely to cause an allergic reaction

- procaine is the most potent vasodilator, which increases the rate of absorption

- cocaine is the one vasoconstrictor bc it inhibits NE re-uptake

- CNS effects are dose dependent

- apparent stimulation due to depression of inhibitory neurons-- restlessness, tremor, convulsions, followed by depression (resp depression can lead to death)

- CVS effects are seen at high systemic concentrations

- decreased: myocardial excitability, conduction rate, force of contraction

- arteriolar dilatation

- hypersensitivity especially to esters (PABA)

Cocaine

(ester)

- in addition to local anesthetic properties, blocks to reuptake of NE and DA- so it is the only anesthetic with vasoconstrictor effect and strong abuse potential

- available for topical use only in ENT practice

- No opthalmic use bc can cause corneal damage

Procaine

(Novocaine)

ester

- metabolized to PABA, associated with hypersensitivity reactions

- may antagonize sulfonamides, not effective topically in safe concentrations

Tetracaine

ester

- 10x as potent and 10x as toxic as procaine

- active topically

- widely used for spinal anesthesia

- high pKa = slow onset and longer duration of action

Lidocaine

amide

- most used- standard for comparison

- significant vasodilator activity, so usually used with a vasoconstrictor (epi)

- low pKa, faster onset of action

- has cardiac effects and is used as an anti-arrhythmic

- may cause drowsiness, sedation, and headache, and death from cardiac effects

Prilocaine

amide

- less potent and toxic than lidocaine

- slightly longer duration of action than lidocaine

- may cause methemoglobinemia, so be careful in children

- can give without epi

Bupivacaine

amide

- more potent than lidocaine

- prolonged duration of action makes it better for long procedures (with analgesia)

Articaine

amide

- contains an additional ester group-- better able to diffuse through soft tissue and bone

- avoids mydriasis, irritation, and corneal damage produced by cocaine

example: proparacaine

- used for hemorrhoids, endoscopies, intubations, and cytoscopies

examples: pramoxine and dyclonine HCl

- benzocaine

- water solubility is low enough that it can be applied directly to open wound wihout producing high circulating levels

- good for sunburn, poison ivy, and hemorrhoids

EMLA

(Eutectic Mixture of Local Anesthetics)

- a combo of equal portions of lidocaine and prilocaine in free base form (oil at room temp)

- useful for procedures involving skin and superficial subcutaneous structures

- applied topically 45-60 minutes before painful procedure

- decreases rate of absorption, localizing the anesthetic at the site for longer

- also allows the rate at which the local anesthetic is destroyed in the body to keep pace with the rate it is absorbed, reducing systemic toxicity

- also reduce blood loss associated with surgical procedures

- some disadvantages include systemic effects, delayed wound healing, edema, or necrosis

- epinephrine, vasopressin, felypressin

- after injection directly into surgical sites, alpha effects predominated resulting in vasoconstriction and hemostasis

- as levels decrease with time, beta effects predominate causing vasodilation -- bleeding 6 hours after surgery

- increases the work of the heart and O2 consumption- so cardiac efficiency is decreased

- leads to muscle cell necrosis, microscarring of tissue

- causes fear, anxiety, restlessness, tremor, palpitations, etc etc

- sodium bisulfate is usually added to delay deterioration. may be a source of allergy

- increases TPR causing a reflex decrease in CO

- felypressin is a synthetic analogue

- Alpha adrenergic blockers

- epi is unable to bind to alpha 1 receptors, and so binds to beta instead causing vasodilation and hypotension

- Antidepressants (TCA)

- increase cardiovascular effects of vasopressors

- Cimetidine

- inhibits drug metabolizing enzymes and can increase plasma conc and toxicity of drugs such as lidocaine

- Sulphonamides

- ester local anesthetics --> PABA, so can decrease the antimicrobial effects  

- application to mucous membranes and denuded skin and can have systemic toxic effects

- injected directly into tissue to be anesthesized. duration can be doubled by adding a vasoconstrictor

- allows tissue at sites distant from injection site to be anesthesized

Field Block:

- injection that blocks neuronal transmission proximal to the site to be anesthesized. less drug can be used for a greater area

Nerve Block:

- injection in proximity to peripheral nerves or nerve plexuses supplying the area to be anesthesized. allows for use of less

IV regional:

- relies on vasculature to bring anesthetic to nerve trunk and endings. Potential for toxicity. Usely only for limited regions, such as forearm

Spinal:

- into CSF subarachnoid space in lumbar space below termination of spinal cord. Use low amounts so low potential for toxicity.

- Disadvantages: hypotension, respiratory arrest, and headaches

Epidural:

- into epidural space. catheter may be placed for repeat administrations. fentanul added for analgesia and epi for decreased toxicity

1) Lipid affinity or "unitary theory" and membrane perturbation- OLD theory

2) promote hyperpolarization of neurons, affect inhibitory (GABA) or excitatory (glutamate) NT function

- Analgesia

- Delirium (stage II)

- surgical anesthesia (stage III)

- medullary depression (resp paralysis)

- uptake, distribution, and elimination are dependent on partition coefficients (blood:air and blood:brain), steady state must be established

- lower blood:air partition coefficient means more rapid onset and offsent of effect because blood compartment becomes saturated more quickly

MAC

Minimum alveolar concentration

- inspired concentration of anesthetic that will prevent response to a standard stimulus (surgical incision) in 50% of population

- expression of potency, equiv to ED50

- 1.3 x MAC produces anesthesia in 95-99% of patients

- all produce some muscle relaxation, decr BO, and produce some organ toxicity (liver and kidney)

- volatile liquid

- sensitizes myocardium to catecholamines, may induce fatal hepatotoxicity, malignant hyperthermia (treat with dantrolene)

- volatile liquid

- good muscle relaxation

- may increase intracranial pressure

- volatile liquid

- more irritating, more apnea and laryngospasm in children

- otherwise, closest to ideal agent

- volatile liquid

- less laryngospasm, but possible renal toxicity

- volatile liquid

- much longer acting, but has renal toxicity

Ultra short-acting barbituates

- thiopental

- methohexital

- only takes a matter of seconds

- promotes chloride ion channel opening (hyperpolarization of neuron)

- used for induction of anesthesia, reduction of cerebral metabolism and blood flow

- adverse: respiratory depression, laryngospasm, hyperalgesia

- peak brain concentration in 30 seconds - 1 min

- then brain concentration declines (ie clinical duration of action)

- distribution in lean tissues is rapid and longer acting

- after leaving brain it goes into lean and fatty tissues, and accumulates in fat, so plasma half life is 4-8 hours, but only a matter of minutes in brain

- accumulation in fat causes a hangover or sedative effect

- general anesthetic

- like barbiturates but more rapid recovery

- antiemetic effect

- "dissociative" anesthesia with analgesia and amnesia

- antagonist at NMDA glutamate receptor

- does not cause resp or CV depression

- can be problematic with psychic effects (hallucinations) when emerging

- general anesthetic

- has less cardiopulmonary effects than barbiturates, and more pure anesthesia

- adverse: irritation, pain on injection, and myoclonic movements

- part of "balanced" anesthesia regimens include:

- sedatives

- opiate analgesics (especially fentanul analogs)

- antianxiety agents (esp benzos such as midazolam and diazepam, and lorazepam

- NM blockers ( succinylcholine and atrcurium)

- muscarinic blockers to reduce resp tract secretions (atropine)

- alprazolam, lorazepam , oxazepam (intermediate acting)

- diazepam- long acting

- midazolam, triazolam (short acting)

- chlordiazepoxide (note: this is the one that doesn't end in "zolam" or "zepam"

- major group of anxiolytic-sedatives

- safer but less efficacious

- do not induce enzymes and there is less tolerance

- MOA: potentiate effects of GABA on neuronal inhibition - increase the frequency of GABA induced openings of chloride channels, but no effect on these in the absence of GABA

- uses: dec anxiety, sedation, hypnosis, anterograde amnesia, central muscle relaxation, anticonvulsant, withdrawal from sedative drugs

- inc reaction time, drowsiness, confusion, dry mouth, bitter taste, altered sleep

- are dependence producing

- metabolized in liver, where active metabolites are formed, so half life has little relationship to duration of action

- eliminated more slowly in elderly patients

- benzodiazepine antagonist- competitive at benzo receptors

- also works on

zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta)

- does not antagonize CNS effects of depressants that act on other receptors (ie barbiturates)

- short half life so repear admin is required

- adverse effects: agitation, confusion, dizziness, nausea

- can cause seizures and arhythmias in pts taking benzos and TCAs

- potent anxiolytic that does not cause marked sedative effects

- partial agonist at 5HT receptors, and also has affinity for CNS D2 receptors

- no hypnotic, anticonvulsant, or muscle relaxant properties

- no rebound anxiety or withdrawal signs on abrupt discontinuation

- takes days to week to work, so not for acute anxiety states

- not benzos, but act at the benzo site of the GABA-A receptor

- zolpidem: bed-time use only

- zaleplon: use at bedtime and if difficultly falling asleep after bedtime

- eszopiclone: reduces sleep latency and improves sleep maintainance

- been replaced by benzos as sedatives/hypnotics

- Ultrashort acting: used for anesthetic induction- thiopental

- long acting- phenobarbital, used as an anticonvulsant

- facilitate actions of GABA- increase the duration of GABA gated chloride channel openings-- at high doses are GABAmimetic

- act at different sites than benzos, so not inhibited by flumazenil

- adverse: respiratory depression, drug interactions, precipitation of porphyria, ventricular arrhythmias

- tolerance, dependence producing, and may be fatal

- OD treatment is supportive and dialysis

- other sedative/hypnotic

- prodrug reduced to trichoroethanol

- causes unpleasant taste and epigastric distress

- may cause lightheadedness, ataxia, nightmares

- other sedative/ hypnotic

- diphenhydramine- H1 antagonist. also anticholinergic

- non- prescription sleed aid, used as sedative in children  

- causes CNS depression, sedation, ataxia

- activates GABA and inhibits glutamate NMDA receptors

- causes GI irritation, incr secretion, and renal diruesis

- rapidly absorbed from GI tract and distributes throughout total body water

- metabolism is linear (zero-order)

- in liver and stomach and converts ehtanol to acetylaldehyde

- requires NAD

- converts acetylaldehyde to acetate

- lower activity in Asians and Native Americans

- accumulate acetylaldehyde when they drink, so more flushing

- requires NAD

- respiratory depression (leading cause of death)

- hepatic- fatty infiltration, cirrhosis, portal htn, ascites

- CNS- Wernicke's and Korsakoff's (treat or prevent with thiamine)

- CV- cardiomyopathy, HTN, stroke

- GI- gastritis, pancreatitis, esophageal varices, inc risk of cancer

- immune system depressed

- fetal alcohol syndrome

- both psychological and physical

- withdrawal syndrome: agitation, insomnia, tremor, delirium, convulsions, arrhythmias

- treat with sedative such as diazepam and psycho treatment

- inhibits aldehyde dehydrogenase to cause acetylaldehyde accumulation

- long half life

- opiate antagonist which reduces reward and cravings

used in alcohol dependence

- for alcohol dependence

- decrease glutamergic transmission

- reduce relapse rate

- used as fuel, solvent, and denaturant to rubbing alcohol

- metabolized by alcohol dehydrogenase to formaldehyde and formate

- produces blindess, and high anion gap metabolic acidosis

- Tx: bicarb, enthanol

Analeptics

(potent stimulants)

- Strychnine- blocks glycine receptor

- block inhibitory neurotransmittors

- causes skeletal muscle spasm, convulsions, and increases respiration

- Caffeine, Theophylline (aminophylline) and theobromine

- block adenosine receptors, inhibit PDEase

- cause CNS and resp stimulation (Tp the most)

- increase HR, CF, and CO (Tp the most)

- constrict cerebral vessels- use in migrain (caffeine)

- smooth muscle relaxation- Tp the most- use in asthma

- diuresis

- toxicity- excitement, tachycardia, convulsions

- dependence and withdrawal- mild; headache, lethargy

- neurotransmitter mechanisms (DA, NE, and 5HT)

- methylphenidate (Ritalin), amphetamines, modafanil

- effect central and motor stimulation

- uses are for narcolepsy, ADHD

- chronic use/abuse leads to paranoia and dependence

- Sibutramine - serotonergic agent

-used for obesity

- alter perception of sensory stimuli, alter thought processes, produce states similar to psychoses

- mydriasis, ataxia, incr HR and BP

- perceptual distortions, hallucinations, magical and paranoid thought

- LSD, psilocybin- agonist at 5HT receptors

- mescaline and MDMA

- anticholinergics are hallucinogenic only at toxic doses

- THC

- PCP- antagonist at NMDA receptor

- sulfonamides            - Trimethoprim

- choramphenicol         - Isoniazid

- Rifampin                  - Pyrazinamide

- Ethionamide             - Cycloserine

- Metronidazole

- Aminoglycosides         - first gen cephalosporins

- Cefoperazone            - second gen cephalos

- clindamycin               - ketoconazole

- amphotericin B           - itraconazole  

Most likely organisms

Newborn - 1 mo

+

Empiric therapy

- gram negative enterics (e. coli, klebsiella, enterobacter)

- Ampicillin + cefotaxime or ceftriazone or AG

Most likely organisms

1 mo - 4 years

plus

empiric therapy

- H. influenzae, N. meningitidis, S. pneumoniae

- Ceftriaxone or ceoftaxime and vancomycin

Most likely organisms

5- 29 years

plus

empiric therapy

- N. meningitidis, S. pneumoniae, H. influenzae

- ceftriaxone, cefotaxime, or vancomycin

Most likely organisms

30- 60 years

plus empiric therapy

- S. pneumoniae, N. meningitidis

- ceftriaxone, cefotaxime, or vancomycin

most likely organisms

>60 years

plus empiric therapy

- S. pneumoniae, gram negative enterics, L. monocytogenes

- ampicillin + cefotaxime, ceftriaxone or aminoglycosides and vancomycin

Treatment for strep pneumoniae and neisseria meningitidis

bacterial meningitis

- parenteral penicillin G is first choice

- cefotaxime, ceftriaxone, and chloramphenicol are alternatives

- 7-14 days of therapy

Treatment for group B strep

bacterial meningitis

- parenteral penicillin G is first choice

- cefotaxime, ceftriaxone, and chloramphenicol are alternatives

- gentamycin may be added

Treatment for staph

bacterial meningitis

- Nafcillin is first choice

- Vancomycin if nafcillin-resistant

Listeria monocytogenes treatment

bacterial meningitis

- ampicillin IV is first choice

- alternatives are penicillin G + gentamycin, TMP/SMX, vancomycin + gentamicin

- 14-21 days of therapy needed

Gram negative bacilli treatment

bacterial meningitis

- 3rd generation cephalosporin ( cefotaxime, ceftriaxone) EXCEPT:

- ampicillin IV for beta-lactamase negative H. influenzae

- meropenem is alternative

- minimum of 21 days therapy needed

- useful adjunct in h. influenzae and pneumococcus to reduce neurological sequelae

Treatment for TB

bacterial meningitis

- combination therapy with isoniazid, rifampin, pyrazinamide and ethambutol

- cycloserine, ethionamide as alternatives

- minimum 9 mo therapy

Treatment for viral encephalitis

Herpes simplex

- acyclovir IV for 2-3 weeks

- foscarnet is alternative

- supportive treatments for other viruses

- for cryptococcus- amphotericin B +/- flucytosine, and fluconazole as alt

- for aspergillus- amphotericin B, voriconazole as alternative

- Toxoplasmosis- pyrimethamine and sulfadiazine

- cysticercosis- albendazole with corticosteroid as adjunct

- depression is due to a lack of amine NTs, particularly serotonin and/or NE

- 3-4 weeks for full effect

- rapid onset of adverse effects in days to hours

- since all classes have potential for serious interactions with each other, should not be used together

- washout period should be allowed when switching from one class to another

- 2 weeks for most, up to 6 weeks for fluoxetine (Prozac)

- MOA: block reuptake of serotonin

- citalopram, fluoxetine, paroxetine, sertraline

- uses: depression, anxiety, obesity, panic disorder, social anxiety disorder, OCD

- drug of choice for OCD

- Adverse: suicidality, Nausea, diarrhea/constipation, decreased libido, drowsiness, sedation, tremor, dry mouth, sweating, headache, nervousness, anxiety

- SSRI

- also approved for bulimia

- very long acting

- has mild sedative and antimuscarinic effects

- inhibits cytochrome P450 (so does paroxetine)

- combo of SSRIs and MAOIs may be toxic

- hyperthermia, hyperreflexia, rigidity, seizures, and autonomic instability

- wait 5 weeks after fluoxetine to start MAOI

- combo of SSRI with St. John's Wort may also cause serotonin syndrome

- bupropion, duloxetine, trazadone, venlafaxine

- inhibit reuptake of NE and serotonin (and some DA)

- atypical

- used in smoking cessation therapy

- has no sedative or antimuscarinic effects

- inhibits reuptake of DA**

- atypical

- given with tryptophan for aggressive behavior

- used in panic disorder

- used in alcoholics to decrease cravings

- low dose used in treatment of insomnia (has high sedative effects)

- only works on serotonin

- found in large amounts in basal ganglia, especially in caudate nucleus; basal ganglia controls sequential movements

- controls prolactin secretion- inhibits its release

- NT at the CTZ

- 2 receptors have been found: D1 and D2

- D2 inhibits adenylyl cyclase activity, supresses Ca2+ currents, and activates K+ currents

- 4 chemical types: phenothiazines, butyrophenes, thioxanthese, and atypicals

- are all similar in action and efficacy, but different in potency and adverse effects

- all block D2 receptors in CNS, potency correlates to affinity for receptor

- block D2 immediately, but onset of action takes weeks

- dirty drugs because also act at cholinergic, adrenergic, and histaminergic receptors --> adverse effects

- atypicals block 5HT as well

- most are highly lipid soluble- accumulate in fat and brain

- much longer duration than indicated by their half-lives

- metabolized in liver to water-soluble metabolites and excreted by kidneys

- metabolism is slower in elderly

Antipyschotics

Adverse effects

- elderly are more susceptible.

- sedation (antihistamine)

- convulsions

- anticholinergic effects

- antidopaminergic (extra pyramidal syndrome)

- dystonia, tardive dyskinesia, and akathisia

- hyperprolactinemia (gynecomastia/galactorrhea)

- orthostatic hypotension from peripheral alpha block

- impaired temp regulation

- weight gain

- sexual dysfunction

- skin problems

-** adverse effects reduce compliance

- decrease dose of drug

- antiparkinsonian agents such as anticholinergics or amantidine

- beta blockers or benzodiazepines for akathisia

- propanolol

- older patients are moved away from lower potency drugs such as chlorpromazine to higher potency drugs such as haloperidol

- atypicals are useful in refractory patients

- such as clozapine

- also clozapine is used for tardive dyskinesia

- antipsychotics, divided into 3 groups based on structure

1) aliphatic- chlorpromazine

- cause hypotension and endocrine effects

2) piperidul- thioridazine

- cause sedation, antimuscarinic effects

3) piperazine - prochlorperazine

- less sedation and CNS effects, high parkinsonian side effects and dyskinesias

- can also be used as an anti-emetic agent  

Promethazine

(Phenergan)

- is a phenothiazine, but used as an antihistamine to sedate kids

- haloperidol

- potent, selective D2 receptor blockers

- adverse effects profile is similar to pierpazine and phenothiazines

- associated with "neuroleptic malignant syndrome"

- block DA receptors to varying degrees, also block 5HT2 receptors

- much less extrapyramidal effects than classical agents

- clozapine, olanzapine, quetiapine, risperidone

- not first line because of increased risk for agranulocytosis, diabetes, weight gain, high cholesterol, etc

- mood stabilizing drug for treatment of mania

- lithium can substitute for sodium

- may have effects on NE or DA turnover

- possibly enhances some actions of serotonin

- has effects on inositol phosphate second messengers decreasing IP3 and DAG

- avoid diuretics and NSAIDs bc decrease Li excretions --> toxicity

- side effects- thirst, tremor, ataxia, confusion, hypothyroid, nephrogenic diabetes insipidus, edema

Valproic Acid

- as effective as lithium in treatment of mania

- also an anticonvulsant

- elderly

- causes hepatotoxicity and pancreatits  

- carbamazepine

- pregabalin

- haloperidol for acute episodes

- prevent excessive discharge

- prevent spread of discharge (more common effect)

- Agents for tonic-clonic and complex partial seizures: Reduce Na conductance

- Agents for Absence seizures- reduce Ca activity or enhance GABAergic activity

- phenytoin, fosphenytoin

- for GTC, psychomotor, and focal cortical seizures

- phenytoin is also an antiarrhythmic and for some neuralgia

- stabilize the membrane, reduce Na conductance

- adverse effects- CNS (nystagmus and ataxia) and gingival hypertrophy

- induce cytochrome P450

- mechanism similar to phenytoin

- used in psychomotor, GTC, and trigeminal neuralgia

- toxicity- CNS, Stevens-Johnson syndrome

- induces cytochrome P450

- uses and mechanism similar to carbamazepine and phenytoin

- less adverse effects

- not an enzyme inducer

- used in absence and mixed seizure disorders

- causes hepatotoxicity, and spina bifida in fetus

- inhibits cyt P450 (increases levels of other agents)

- ethosoximide

- use in absence seizure- DOC for classic absence

- causes GI effects, dizziness, rashes, and dyscrasias

- phenobarbital and primidone used in grand mal, psychomotor

- phenobarbital in febrile seizure

- most prominent adverse effect is sedation

- prompt absorption

- used for anterior infections or posterior uveitis

- can cause local toxicity

- careful not to cause trauma during administration

- prompt absorption

- used for anterior segment surgery

- careful of corneal toxicity

- only has local effect- little absorption

- used for retinitis

- careful of retinal toxicity

- dacryocystitis

- blepharitis and hordeolum (stye)- staph

- conjunctivitis - more commonly caused by irritants and allergens, but may be neisseria, strep pneumoniae, staph, chlamydia

- keratitis

- endophthalmitis- infxn of intraocular tissues

- Bacitracin ointment

- gentamicin, tobramycin solutions and ointment

- polymyxin B solution and ointment

- also good for some keratitis

- chloramphenicol (may cause blood dyscrasia)

- tetracycline

- ciprofloxacin

- sulfacetamide

- Acyclovir for herpes

- foscarnet or ganciclovir for CMV

- Yeast conjunctivits- Natamycin suspension

- yeast/ fungal endophthamitis- fluconazole or amphotericin B

- concentration of drug in preparation

- partition coefficient btwn formulation and skin

- diffusion coefficient across layers of skin

- thickness of stratum corneum- scrotum is thinnest

- dosing schedule- skin may act as reservoir

- vehicles and occlusion - occlusive dressing promotes penetration and absorption

- topical application

- used for inflammatory skin conditions. start with strongest and taper off to weaker

- Drugs:

- Betametasone (most potent)

- fluocinonide

- traimcinolone

- hydrocortisone valerate

- hydrocortisone (least potent)

- may use intralesional injection for localized conditions (inflamed cysts or discoid lupus)

- can cause thinning and atrophy of skin, overgrowth of fungus or bacteria (don't use on something alive!)

- long term use or short term use depending on skin disease. examples of some skin diseases systemic steroids are used for include bullous diseases, SLE, sarcoidosis, contact and atopic dermatitis, erythema nodosum, etc

- adverse effects are same as always for corticosteroids

- tretinoin (all-trans retinoic acid, Retin-A), isotretinoin (accutane), adapalene (Differin)

- bind to nuclear receptors and affect transcription to cause remodeling of skin

- Uses: Acne- topical (tretinoin or adapalene) or systemic (isotrtinoin), keratinization disorders, skin cancer (BCC and SCC), AK, Psoriasis, Aging (tretinoin)

- Adverse effects: dry skin and mucosa, sucidal tendencies (black box for accutane)

- Pregnancy category X- teratogenic effect

- stays in body for a long time

- topical steroids, oral antihistamines, oral leukotriene antagonists, oral or topical immunosuppressive agents

- there are numerous routes and agents

Topical Therapy:

- steroids for mild/moderate

- calcipotriene (vit D analog)

- tazarotene- retinoid

- coal tar- unknown mechanism

Systemic Therapy

- methotrexate

- acitretin- retinoid but it takes 3-6 mo to work

- immunosuppressive agents such as cyclosporine

- Leukocyte function associated antigens and TNF alpha antagonists

- Photochemotherapy (PUVA)

- Psoralen, methoxsalen

- topical antimicrobial agents vs P. acnes:

- azelaic acid, benzoyl peroxide, erythromycin, clindamycin

- topical retinoids:

- tretinoin and adapalene

- systemic therapy:

- antibacterial agents: tetracycline (doxycycline)

- can cause photosensitivity and vaginal candidiasis

- retinoids- isotretinoin

- androgen antagonists- oral contraceptives, spironolactone

- Topical antimicrobial agents vs P. acnes= azalaic acid

- topical metronidazole

- topical retinoids- tretinoin

- topical treatment- triple antibiotic ointment (neomycin, bacitracin, and polymyxin) for minor infxns

- mupirocin for superficial staph

- systemic treatment for complicated infections  

- acyclovir for herpes simplex and varicella

- podophyllin for condyloma

- imiquimod- induces interferon- used for condyloma, verrucae, etc. can cause flu like illness

- topical and systemic azoles

- systemic only for onychomycosis

- use neurotoxins

- permethrin- opens Na+ channels

- used for protection against diseases carried by mosquitoes, ticks, and fleas

- N,N-Diethytoluamide (DEET)

- duration of protection is concentration-dependent

- Adverse effects- rash, damage to plastics

- insecticide applied to clothing, camping equipment, etc

- more effective than DEET against ticks

- UVB- causes erythema

- UVA- phototoxicity and aging

SPF = dose of UV radiation to produce minimal erythema with sunscreen / dose of UV radiation to produce minimal erythema without sunscreen

- most products are combos to provide protection against UVB and UVA

- PABA analogs- most effective vs UVB

- Oxybenzone effective in 250-360 nm range, which is UVA and some UVB

- zinc oxide and titanium dioxide are physical sunblocks