* activates muscarinic receptors in the urinary tract, increases tone of smooth muscles and sphincters

* relieves urinary retention; also for GERD, ileius

* contraindicated with blockages

* Onset: 30-60min.  DOA: 60min.  make sure a bathroom is nearby!

* ADR's: CHOLINERGIC (N/V/D, cramps, urinary frequency, ^ sweating/salivation, blurred vision, brady♥, ↓HTN

* anticholinergic/muscarinic antagonist - BLOCKS ACH receptors!

* Actions: ↑HR, ↓secretions, relaxes bronchi, ↓bladder tone (irritable bladder), ↓GI tone/motility (UC, crohn's), mydriasis, CNS excitation (muscarinic poisoning)

* ADR's: anticholinergic!  xerostomia, urinary retention, constipation, ↑IOP, blurred vision, photophobia, tachy♥/dysrhythmia, anhydrosis, asthma

* contraindicated with glaucoma because of ↑IOP

* antidote: physostigmine (~2mg IM/IV); ipecac syrup followed by activated charcoal

* irreversible cholineresterase inhibitor - only one that is clinically significant!

* allows to have more Ach available → mydrasis (↓IOP!)

myasthenic cholinergic

* d/t inadequate meds * med OD

* poor transmission @ junction * excessive ACH

* continuous stimulation

give edrophonium (Tensilon) - fast-acting ChEI

* will get better * will get worse

  - resp support   - resp support

  - neostigmine (Prostigmin)   - atropine 

* Block Ach from activation Nm receptors on skeletal muscles @ NMJ

* causes motor relaxation commonly used during surgery, ET intubation, mech ventilation or other dx procedures.

* risk for resp arrest d/t possible paralysis of resp muscles!

* can't cross BBB → no effect on CNS, therefore:

   - need sedation, need analgesia and need respiratory support!

* caution use with myasthenia gravis patients bc they already have extreme muscle weakness!

* non-depol. NMB

* contraindicated in cardiac/renal patients or those with significant ↑K+ (major burns, multiple skeletal m. or UMN injury)

* ADR's: ↓HTN, ↑K+, brady♥, dysrhythmias, ♥arrest

* does not cross BBB, no effect on CNS (need sedation, need analgesia and need resp support!)

* Abx - aminoglycosides, tetracycline, some non-PCN's - inhibitors (intensify response!)

* ChEI's decrease effect d/t competition with Ach receptors!

* depolarizing NMB  (constant state of depolarization - no repolarization!)

* no effect on CNS

* abx intensify response

* Anticholinergics potentiates effects

* risk of malignant hyperthermia - temp up to 43°C/109.4°F with succinylcholine + inhaled anesth.

  - hyperpyrexia d/t ↑ metabolic activity of muscle (constant) and ↑ release of Ca+2 (uncontrolled!)

  - d/c succs, cooling blanket, iced IV NS, dantrolene (stops muscle activity!) 

1:100 PO inhalation

1:1000 SQ, IM, intraspinal

1:10,000 IV, intracardiac

1:100,000 in combo with local anesthesia

these concentrations CANNOT be used interchangeably!

* widespread ↓HTN

* glottal edema

* bronchoconstriction

* treat with epinephrine

* β1: ↑ CO therefore ↑BP!

* β2: bronchodilation

* α1: also helps ↑BP d/t vasoconstriction (also helps with edema!)

* drug of choice for anaphylactic shock

* nasal decongestant d/t α1 stimulation

* all adrenergic receptors (minus DA...only DA can stimulate DA!)

* MAOi's and TCA's prolong and intensify effects!

* ADR's: HTN crisis (d/t excessive α1 stimulation), dysrhythmias (β1), angina, extravasation (IV), hyperglycemia (β2 = glycogenolysis!)

*like epi, but does not activate β2; only α1, 2 & β1

*hypotensive states and cardiac arrest

* improves CO in HF

* + inotropic effect

* adjusted based on BP

* MAOi's and TCA's prolong and intensify the effects

* specific for β1

* β2-specific

* indicated for asthma; delay preterm labor (Ritrodine)

* ADR's: tremors; can cause tachy♥ with large doses that effect B1 (loses selectivity!)

* stimulates all adrenergic receptors (except DA) - like epi!

* nasal decongestion

* narcolepsy

* prevent necrosis d/t extravasation of vasoconstrictors (DA, Levophed/NE)

* if OD, can't give epinephrine because B activation will dominate over A....tx with NE!

* essential HTN - causes dilation to ↓P

* pheochromocytoma

* Raynaud's disease (peripheral vasoconstriction) - dilates these vessels; however α blockers are contraindicated in all other types of PVD!

* OD of α1 agonist, such as epinephrine - HTN secondary to excessive α1 stimulation → blockade causes vasodilation therefore ↓P!

* orthostatic hypotension - Δ position slowly!!!

* reflex tachy♥ d/t baroreceptor reflex

* nasal congestion d/t vasodilation

* inhibition of ejaculation

* Na+ retention (α blockers ↓P, which ↓kidney perfusion which holds onto Na+ and H2O → ↑P!

* ↓HR, force of contraction & velocity of conduction

* ↓ renin release

* AP, HTN, dysrhythmias, MI, HF (carvedilol, bisoprolol, metoprolol), migraine, hyperthyroidism, stage fright, glaucoma (↓ production of aqueous humor), pheochromocytoma 

* brady♥

* reduced CO

* precipitation of heart failure - except with Coreg and Copressor

* AV heart block

* bronchoconstriction*

* peripheral vasocon

* inhibition of glycogenolysis

* rebound cardiac excitation

* carvedilol (Coreg) - best

* bisoprolol (Zebeta) - not as common

* metoprolol (Lopressor) - very common

β-blocker use in HF used to be contraindicated but these 3 drugs have been proven effective!

* indirect α2-adrenergic blocking agent

* centrally-acting, SELECTIVE - acts w/in CNS in areas assoc. with autonomic regulation of CV systems

* primary indication: HTN

   - also used for menopausal flushing, w/d from opioids/narcotics, Tourette's and severe cancer pain (Duraclon)

* ADR's: drowsiness, rebound HTN (d/t baroreceptors), anxiety, depression; constipation!

* Levodopa is metabolized to DA and used in the periphery but only 2% is usable in the brain.

* Combined with carbidopa to prevent breakdown of levodopa → DA in the periphery, allowing more to be used by the brain

* effects in weeks to months - depends on the patient!

* ADR's: darker-colored urine, N/V, dyskinesias, dysrhythmias, orthostat hypotension

* on-off phenomenon: abrupt loss of effect at ANY time; might be r/t too much protein in the diet (spread intake t/o the day!!)

* contraindicated with malignant melanoma (can activate neoplasm) and MAOi's - can lead to HTN crisis.  If on MAOi's, w/d from hem at least 2 weeks before giving Sinemet.  Avoid B6 (pyridoxine) with only levodopa (okay with Sinemet)

* take food with stomach upset but avoid meals high in protein

* MOA: Suppresses Na+ and Ca++ influx, potentiation of GABA (neuronal inhibitor)
  - supp. of Na+ influx: phenytoin (Dilantin), carbamazepine (Tegretol), valporic acid (Depakote), lamotrigine (Lamictal)
  - supp. of Ca+ influx: valporic acid (Depakote), ethosuximide (Zarotin)

  - antagonism of glutamate (excitatory transmitter): felbamate (Felbatol), topiramate (Topamax)

  - potentiation of GABA: benzos, barbs, gabapentin (Neurotin), tiagabine (Gabatril), vigabatrin (Gabril)

* monitor plasma levels with ALL AED's
* majority are teratogenic - women of childbearing age need to use contraception!
* need to be GRADUALLY withdrawn!  Abrupt withdrawal can lead to status epilepticus
     - 20-30 min duration
     - ↑HR, BP, Temp & ↓BS and pH (acidosis!)

* withdrawal needs to be done over a period of MONTHS.  if on multiple AED's, need to d/c ONE AT A TIME

* drugs are matched based on seizure type.  EXCEPTION: valporic acid (Depakote) - effective for all types!

* for partial and 1° generalized tonic-clonic seizures

* PO, IV

   - IV: mix with NS only - it is incompatible with everything!!  Cannot be PB'ed - need its own primary line!
   - give slowly - too fast, and BP can bottom out!!
* ADR's: dysrhythmias, hypotension (IV), skin rashes → D/C! (SJS)...interferes with Vitamin D metabolism (rickets, osteomalacia), gingival hyperplasia, sedation, ataxia, hirsutism, ↓Vit K synth, teratogenic, diplopia, tremors
* phenytoin metabolism INHIBITORS = diazepam, eimetadine, ETOH, valporic acid (need ↓dose!)
* phenytoin metabolism INDUCERS = BCP's, warfarin, glucocorticoids (need ↑dose!)

* Therapeutic range: 10-20mcg/dL!

* Encourage frequent dental check-ups d/t gingival hyperplasia

* prodrug for phenytoin (Dilantin) → immediately converts to phenytoin in blood
* for SE (continuous seizure, 20-30 min)
*non-irritating to veins
* prepared in 5% dextrose

* preferred over phenytoin and phenobarbitol
* 1st choice for partial & tonic-clonic seizures (NOT absence); for bipolar disorder refractory to lithium; trigeminal & glossopharyngeal neuralgias
* ADR's: ataxia, vertigo, visual problems, H/A, myelosuppression, teratogenic (assoc. with NTD's), skin problems (SJS!)

* grapefruit juice is an inhib
* inducer of enzyme for BCP's (tell them to use another form) & warfarin
* oxcarbazepine (Trileptal) - derivative with fewer ADR's

* potentiates GABA
* well-absorbed with a long T1/2 (~4 days)
* ADR's: dependence, depression, agitation, confusion, ↓Vit K&D, paradoxical hyperactivity/irritability w/ kids, drowsiness (but they build a tolerance to it!)
* OD: nystagmus, ataxia, general CNS depression, death

* abrupt w/d → SE!
* primidone (Mysoline) - nearly identical, so don't 'combo'

* 1st line treatment for all major seizure types; also for bipolar disorder and migraines (prophylactic)
* ADR's: (rare) hepatotoxicity, pancreatitis, teratogenic (NTD's)...cognitive impairment, N/V, indigestion (take w/ food or use enteric-coated preparation)
* contraindicated in patients with hx of liver problems, pancreatitis

* maintain blood levels: 60-100ug/dL

* drug of choice for absence seizures (suppresses neurons in the thalamus responsible for absence seizures)
* No signifcant ADR's aside from drowsiness, dizziness and lethargy; but pt will build a tolerance to this!!
* with N/V, tell them to take with food

* risk of SJS

* for localized muscle spasm
   - 2° to epilepsy, hypocalcemia, acute & chronic pain syndromes, trauma (=localized muscle injury)
* diazepam (Valium) - enhances action of GABA

   - only med appropriate for BOTH spasms  & spasicity!
* tizanidine (Zanaflex)
* ADR's for all centrally-acting relaxants (all except dantrolene): CNS depression, hepatotoxicity & physical dependence

* spasicity: state of increased muscle tone with exaggerated tendon reflexes (stiff, awkward movements d/t MS, CP, SC injury)
* 3 drugs used, 2 @ CNS, 1 @ skeletal muscle

     - baclofen (Lioresal) - CNS.  NOT for CVA, PD, HD chorea!  suppresses hyperactive reflexes in the SC
          - suppresses resistance to passive movement.  no direct effect on skeletal muscle.
          - ADR's: drowsiness, dizziness, weakness, fatigue, nausea, constip, urinary retention

     - diazepam (Valium) - CNS.  Mimics GABA
          - ADR's: sedation, dependence (MUST do slow w/d)
     - dantrolene (Dantrium) - acts directly on skeletal muscle.  does not work in CNS.  stops Ca++ release from sarcoplasmic reticulum

          - antidote for malignant hyperthermia caused by anesth and/or succinylcholine.  N2O does not cause this.
          - ADR's: weakness, diminished strength, drowsiness, hepatotoxicity, diarrhea, acne rash

* suppresses pain by blocking impulse conduction along axons (Na+ channels)
* perception of pain lost first, then cold, warmth and finally deep pressure (goes backwards when the med wears off)

* used with a vasoconstrictor (usually epinephrine) to decrease local blood flow which delays systemic absorption (prolongs anesthesia)
* procaine, lidocaine, cocaine

combo of drugs to accomplish analgesia, unconciousness, muscle relaxation, amnesia.
* Combo used: SA barb (induction), NMB, opioids + NO (analgesia) - combo induces a deeper state of anesthesia
* GABA is inhibited; blocks NMDA (excitatory)

* ADR's: (inhaled) resp/♥depression, sensitization of ♥ to catecholamines, malignant hyperthermia (risk with ALL inhaled anesthetics), aspiration, toxic to OR personnel, hepatotoxic

* narcotics: MSO4, codeine, oxycodone, prophyxphene
* endogenous opioid receptors: enkephalins, endorphins, dynorphins
* M (mu) most important from a pharmacological prespective; K (kappa) weak activity; Δ none
* pentazocine (Talwin) = partial agonist/agonist-antagonist
     - ADR's: analgesia, resp depression, sedation, euphoria, constipation, urinary retention, vasodilation, ↑ICP, dependence, tolerance, orthostatic hypotension
* narcosis: OD of opioid
     - naloxone (Narcan) and nalmefene (Revex) = antidotes!  (w/ Narcan, changes are INSTANT; Revex is long-acting with a LONG w/d off med!)
* contraindicated with IBD (r/t constipation)
* with acute exacerbation of COPD - give morphine!  it relieves their discomfort & anxiety and relaxes bronchospasm w/ COPD!

anti-inflammatory (glucocorticoids, cromolyn) → fixed doses, CHRONIC
bronchodilators - β2 agonists → chronic or acute; fixed or PRN

* β2 agonists → bronchodilation!

* inhaled: immediate treatment and prevention
* short-acting: QUICK.  Used for exercise-induced asthma, break through symptoms (albuterol [Proventil])

     - instant effect, lasts 3-5hr, Q4-6h

* long-acting: PROPHYLACTIC.  NOT USED FOR AN ACUTE ATTACK. (salmeterol [Serevent diskus] & moterol [Foradil aerolizer])

     - in 30min, lasts 12h, Q12h.  Fixed dosing, NOT PRN.

* inhaled preps have fewer ADR's, however OD'ing will cause the drug to lose selectivity and stimulate β1: tachy♥/dysrhythmias, angina.  Most common ADR are tremors.

* most effective antiasthmatic drug available.

* prophylaxis for chronic asthma (suppress inflammation)

* decreases bronchial hyperactivity, airway mucous production

* increases # of bronchial β2 receptors and their responsiveness to their agonists

* decreases inflammation! → decreased airway edema

* ADR's: minor w/ acute use.  inhaled: Bone loss (ensure lowest dose, ensure adequate Ca+2/Vit D. intake, wt.-bearing exercises), inahled oropharyngeal candidiasis & dysphonia (gargle after each administration and use a spacer).  Oral: adrenal suppression (Addison's!), bone loss.  LT: cataracts, glaucoma, PUD, hyperglycemia.  Can decrease growth in children.

* fluticasone (inhaled glucocorticoid) + salmeterol (LA inhaled β2 agonist) - chronic prophylaxis
* ADR's/salmeterol: HA, tremor, dizziness, tachy♥, palpitations, HTN, difficulty breathing, bronchospasm(risk higher in african-american population)
* Interactions/salmeterol: ensure cardioselective β-blocker (metoprolol/Lopressor) to ↓ risk of bronchospasm.  Diuretics: worsening hypoK+ & EKG abn.  Potentiated by MAOi's, TCA's, or w/in 2 weeks of d/cing either.

* anti-allergic, anti-inflammatory properties.  mast cell stabilizer, not a bronchodilator!  stabilizes mast cell membrane, decreasing the release of histamine & other mediators

     - inhibits eosinophils, macrophages and other inflammatory cells

* do not use to abort an acute attack

* safest antiasthmatic med!
* especially effective for seasonal allergy attacks; e.g. 15min before mowing the lawn!
* ADR's: cough, bronchospasm (low incidence)

* works in 15min; 1-2 weeks to get maximum benefits!

* allergic rhinnitis: Nasalcrom (intranasally)

* CNS stimulation, bronchodilation, cardiac stimulation, vasodilation, diuresis
* theophylline - PO, IV (not affective by inhalation)
     - narrow therapeutic range: 10-20ug/mL.  best: 5-15ug/mL
          ≥20-25ug/mL: NVD, insomnia, irritability
          ≥30ug/mLvery toxic.  severe dysrhythmias (VFIB), convulsions that are very hard to tx!  Can lead to death by CV/Resp collapse!

     - MOA: adenosine blockade → sm muscle relaxation

- cimetidine & fluoroquinolones increase levels, phenobarb ↓ levels,  Smoking ↓T1/2 by 50%

* Atrovent - an atropine derivative

* approved for COPD bronchospasm

* ADR's: + charge → not really absorbed from the lungs (but systemic effects are rare!); GI tract, xerostomia, pharyngeal irritation.  very high dose → ↑IOP

* PO

* suppresses leukotrienes  (↓infammation, bronchoconstriction, airway edema, mucous secretion, recruitment of eosinophils and other inflammatory mediators to the area)

* ADR's: liver injury (zileuton, zafirlukast), Chrug-Strauss syndrome when glucocorticoid is withdrawan (zafilukast, monelukast)

     - Chrug-Strauss: wt. loss, flu-like sx, pulmonary vascularitis

* zileuton (Zyflo), zafirlukast (Accolate), montelukast (Singulair)

* leukotriene modifier

* not to be used for an actue attack

* stops production of leukotrienes

* ADR's: hepatotoxicity (↑ALT's).  Metabolized by CYP 450.

* effective in 1-2 hours.

* ADR's: myalgia, P450 inhib

* increases levels of theophylline, warfarin

* ADR's: equivalent to placebo.  In combo w/ phenytoin: decreases montelukast levels

* effective w/in 24h.

* MOA: antagonism of IgE → decreases release of inflammatory mediators

* after d/c it takes 1 year for IgE to return to pre-treatment levels

* 2nd line for allergy-related asthma > age 12 and ONLY when preferred options have failed

* SQ

* hay fever, rose fever: outdoor allergens

* PO antihistamines (H1-receptor antagonists)

     - most effective when taking prophylactically for sneezing, rhinorrhea & nasal itching; less effective after sx appear

     - no relief of congestion! - sedating!

     - diphenhydramine (Benadryl), fexofenadine (Allegra), azelastine (Astellin)

* intranasal glucocorticoids - prophylactic.  anti-inflammatory and suppresses all major symtpoms

     - beclomethasone (Beconase), budesonide (Rhinocort), fluticasone (Flonase), mometasone (Nasonex), triamcinolone (nasalcort AQ HFA) - watch for epistaxis!

* Nasalcrom - intranasal cromolyn sodium.  

     - works in 1-2 weeks.

* sympathomimetrics (PO and intranasal decongestants used adjunctively)

     - relieves stuffiness, not sneezing, runny nose or itching

     - limit use to 3-5 days or else will REBOUND (all symptoms will reappear!)

          - phenylephrine (Neo-synephrine), Sudafed PE, Afrin

     - potential for abuse (like amphetamines) - pseudoephedrine, ephedrine

     - ADR's: CNS excitation (irritability anxiety, insomnia)

* dextromethorphan

* diphenhydramine

* codeine - opioid

antitussives do not suppress the productive cough of chronic lung disease (emphysema, asthma, bronchitis) - don't use them!

* act in the CNS to increase cough threshold

* codeine, hydrocodone

* Schedule II controlled substance/Rx alone

* Schedule V when used in an antitussive mixture

↓ respiratory reserve in the elderly and those with COPD.  avoid these drugs!

antidote: Narcan!

* dextromethorphan

* most effective, used in a lot of OTC preparations

* not as effective as codeine for acute, severe cough

* blocks receptors for NMDA in CNS → decreases pain.  also doubles the effect of opioids when used in combo.

* taken Q4-6h with normal therapeutic doses while coughing.

* diphenhydramine - can suppress cough @ high doses only

* benzonatate (Tessalon) - structural analog of tetracaine.  don't chew or else will anesthetize the mouth/pharynx!

* stimulates flow of respiratory secretions

* guaifenesin (Mucinex) - works well in high doses

* reacts directly with mucous to thin secretions

* acetylcysteine (Mucomyst) - sulfur content (also the antidote for Tylenol OD!)

* Hypertonic Na+

* vascular permeability

* chemotaxis - leukocyte

* works with PGE to produce pain**

* bronchoconstriction**

* smooth muscle contraction**

.....inducing HTN!

* synth & stored in mast cells (tissues) and basophils (blood)

* plays a role in allergic reactions and GI acid secretion!

* present in skin, lungs, GI tract

* vasodilation of small vessels

* ↑capillary permeability → tissue edema!

* bronchoconstriction

* CNS effects - sedation, itching, pain, seizure suppression

H₁ antagonists

(classic antihistamines)

* Tx MILD allergic reactions!

* selectively blocks H₁ receptors from histamines but DOES NOT block histamine from mast cells & basophils

* also antagonizes muscarainic receptors - anticholinergic effect (drying out!)

* diphenhydramine (Benadryl) - 1st generation

     - ADR's: highly sedating, pupil dilation, tachy♥, hyperpyrexia

* loratidine (Claritin) - 2nd generation

     - less sedating (does not cross BBB), longer-acting

* fexofenadine (Allegra), cetirizine HCl (Zyrtec) - also 2nd gens

* safety w/ pregnancy unknown

* H₁ and muscarinic receptors blocked in neuronal pathway from vestibular apparatus of inner ear to the vomiting center of the medulla

* promethazine (Phenergan)

* dimenhydrinate (Dramamine)

* meclizine (Antivert) - vertigo

with the common cold: only antimuscarinic activity and moderate decrease in rhinorrhea activity

* enzyme that converts arachidonic acid into prostaglandins (PGE₂, PGI₂) which promote inflammation and sensitize receptors to painful stimuli.

* COX₁ = GOOD! =)

     - found in all tissues.  promotes plt aggregation, protects GI mucosa and supports renal fx

          - inhibit: gastric erosion & ulceration, bleeding tendencies, renal impairment, protection against MI/CVA 2º to ↓plt aggregation!

* COX₂ = BAD! =(

     - produced @ site of injury.  mediates inflammation, sensitizes pain receptors

          - inhibit: supp. of inflamm, alleviates pain, dec. fever, renal impairment

* non-selective - both COX₁ and COX₂

* NSAIDS, including ASA

* ADR's: gastric ulceration/bleeding, renal impairment, MI & CVA (but not with ASA)

* LT use: 12% ↑risk of MI/CVA (except for ASA) and 200-300% ↑ risk with LT use & smoking!

* non-selective COX inhibitor (1, 2)

* irreversible (all other NSAIDS are reversible)

* ADR's: GIB, RI, Reye's, salicylism (tinnitus is one of the first signs!)

* ♥ protective 2° to ↓ platelet aggregation (↓risk of MI/CVA!) - 81mg/day

* acetaminophen, diclofenac (Voltaren), celecoxib (Celebrex) do not interfere with ASA's cardioprotection.  ibuprofen blocks ASA's access to COX, so don't use!

* contraindicated (ALL NSAIDS) in kids <18 y.o. with the chicken pox/flu d/t risk of Reye's.  Tyelnol is best to use! 

* 1st generation - non-selective

* ibuprofen (Motrin), naproxen (Naprosyn), indomethacin (Indocin), sulindac (Clinoril), meloxicam (Mobic)

* mild-moderate pain relief, including OA & RA, bursitis, pain relief, antipyretic, relieve dysmenorrhea

* ketorolak (Toradol) - IV, IM (30-60mg), PO

     - ST use only 

     - relieves pain as well as opioids

     - minimal anti-inflammatory properities

     - ADR's: GI ulceration, GIB, RI, ↑risk thrombosis, SJS

* 2nd generation - COX₂ inhibitors only = -coxibs

* analgesia, antiypyretic, anti-inflamm W/O the bleeding, RF and GI problems with COX₁.

* celecoxib (Celebrex)

     - contains sulfa.  contraindicated with sulfa allergies.

     - ↑ risk of MI and thrombotic events

* antipyretic, analgesic - no anti-inflamm. properties

* inhibits PG synth in CNS only

* no platelet aggregation suppression

* inhibits metabolism of warfarin

* antidote: acetylcysteine (Mucomyst) mixed w/ water or juice (w/in 8-10h OD, there is good protection against the liver)

* do not exceed 4000mg (4g) day. 

* cortisone, prednisone

* ADR's: hyperglycemia, suppresses protein synth, breaks down fat (redistribution w/ LT use) → iatrogenic cushing's (potbelly abd, buffalo hump, moonshaped face), thinning of the skin; promotes vascular stability, increases circulating RBCs & PNMs, decreases immunity, delayed wound healing

* more stress, more glucocorticoids!

     - severe stress → glucocorticoid insuff → circulatory failure → death!

     - Na+ retention, K+ and Ca++ loss (watch with digoxin!!)

* low doses tx adrenocorticol insuff (Addison's)

     - give @ 9am to mimic normal burst @ dawn (cortisol is NORMALLY released in the morning!)

* higher doses: inflammatory supression

     - RA, asthma, certain cancers, prevent donor rejection

* LT: pituitary loses ability to manufacture ACTH → endogenous cortisol

     - SLOW D/C, gradually with NSAIDs so D/C sx not interpreted as return of underlying disease

* reduce joint destruction and retards disease progression in RA

* efficacy in 3wks-6mos depending on the drug

* concurrent use with NSAIDs while waiting for effects

* multiple DMARDs with persistent joint injury progression 

* efficacy in 3-6 weeks

* ADR's: hepatic fibrosis, myelosuppression, GI ulcers, pneumonitis, immunosuppressive

* pregnancy category X

* usually used in combo with methotrexate, NSAIDs

* MOA unknown

* most serious ADR: retinal damage (dose-related) - eye exams Q6mos!

* take w/ milk or food w/ GI upset

* retards joint deterioration w/in 1 month

* contraindicated with allergy to sulfa

* mAb, DMARD II

* TNF blocker

* ADR's: immunosupp/risk of infection, HR, demylenization disorders (MS)

* inflixamab (Remicade), adalimumab (Humira), anakira (Kineret) (an IL1 blocker)

* these drugs are very expensive!

* newer small molecule, less $$

* leflunomide (Avara) - contraindicated with pregnancy!

* cyclosporine (Sandimmune)

* older, limited use

* gold salts - PO, IM...frequent pruritis, stomatitis, renal toxicity

* penicillamine [Cuprimine, Depen] - myelosupp, autoimmune sx

* azathioprine (Imuran) - rarely used; hepatotox, blood dyscrasias

ST - acute (< 3 yrs) → NSAIDs (1st choice), glucocorticoids

LT (≥ 3 years) → to decrease uric acid levels (make sure to look @ these lab values!!)

* for chronic tophaceous gout

* ↓ blood levels of uric acid by decreasing production

* inhibits tubular reabsorption of uric acid and ↑ uric acid excretion

* prevents excretion of penicillin and cephalosporin!!! - can lead to toxic levels, don't combo these drugs together!

* CONTROL VALVES that regulate LOCAL blood flow (everything to do with afterload!)

* the pool - pressure stretching the ventricle of the heart (usually refers to the L ventricle)

* the more a ventricle stretches, the more force that needs to be used to eject the blood out!

* tension produced by a chamber of the heart in order to contract ("load" the heart must eject blood against!)

* ↑ afterload = ↓ SV

* ↓ afterload = ↑ SV

* maintain a pre-set BP

* aortic arch, carotid arteries, vena cava (Bainbridge reflex), atria

* aortic arch & carotids are the ones that primary sense the Δ in pressure!

* ↓ (renal) BP - kidneys secrete renin

* converts angiotensinogen to angiotensin I

* angiotensin I is converted to angiotensin II via ACE (angiotensin converting enzyme) from the lungs

* angiotensin II → strong vasoconstrictor!  Stimulates the release of aldosterone (saves Na+ and water (and secretes K+) which in the end ↑ blood volume, which ↑BP!

* + inotrope (↑ contractility) while ↓HR (hold med if HR <60bpm)

* HF, dysrhythmias

* Monitor kidney fx for renal insufficiency (expect a reduced dose!)

* need blood levels.  Therapeutic range: 0.5-2.0.  0.2-0.8 = BEST

* watch K+!  hold med with hypokalemia (digoxin inhibits the Na+K+ATPase pump.  Dig & K+ compete with each other.  No K+ = no competition with receptors which leads to toxicity!)

* 

s/s of impending digoxin toxicity

s/s of actual digoxin toxicity

*impending: anorexia, N/V (usually appear first), fatigue, visual Δ's (yellow tinge, halos around dark objects, blurring)

*actual: dysrhythmias!!!

* increases with activity, emotions, large meal or cold

* stops with rest

* underlying cause: CAD

* tx with NTG, beta blockers, CCBs *AND* an anti-platelet drug (such as ASA) to reduce the incidence of MI/CVA.

* coronary vasospasm

* you can wake up in the middle of the night with this one!

* treatment is symptomatic only: nitrates and CCBs

* aka acute coronary syndrome (ACS)

* medical emergency - might lead to an MI!

* occurs at rest with new onset or intensification of existing stable angina

* acute management: anti-ischemic therapy: NTG (SL→IVT), BB (if contraind, use a non-dihydropyridine), O₂, morphine sulfate

* dilation of veins

* ↓ preload and (slightly) afterload

* T1/2 5-7min

* ADR's: orthostatic hypotension, reflex tachy♥, HA (pretx with Tylenol)

* can build up tolerance

* PDE₅ inhibitors: Levitra, Viagra, Revadio - can cause severe ↓HTN!  contraind!

* subdue reflex tachy with β blockers

* 0.4mg NTG Q5min x3 if you're stilly having pain after the first pill, take the second pill and call 911 because you might be having an MI!

* all dilate arteries

* for stable angina only

* DO NOT ABRUPTLY D/C (risk of reflex tachy with nifedipine, ↑angina, MI)

* can mask hypoglycemic signs, so use caution with diabetics

* ADR's: will initially c/o fatigue, but  eventually patients will build up a tolerance!

VII, IX, X, prothrombin

* IV, SQ

* inactivates thrombin and factor Xa

* from bovine lungs and porcine intestines (allergies, religious regions!)

* For PE, embolic CVA, MI, DIC, prophylaxis for venous clots/DVTs

* effective in minutes, T1/2 is 1.5 hours

* monitor aPTT (nl=40 sec) 1.5-2x (60-80sec) = therapeutic

* antidote: protamine sulfate

* ADR's: hypersensitivity d/t animal origin, OP w/ LT, high dose therapy, vasospasm; bruising, petechiae, look @ stool, urine...

* contraindicated with eye surgery or CNS (risk of neurological injury!)

* enoxaparin (Lovenox), dalteparin (Fragmin)

* antidote: protamine sulfate (except for fondaparinux (Arixtra)

* inhibits only Factor Xa (not thrombin)

* as effective as heparin

* fixed dose scheduling, no aPTT monitoring, greatly reduced risk of thrombocytopenia

* Vitamin K antagonist (antidote = Vitamin K_1, Aquamephyton)

* Avoid mayo, cannola oil, soybean oil, green leafy veg = good sources of Vit K

* category X

* Monitor PT (therapeutic: 18-24sec) and INR (therapeutic: 2-3; 3-4.5 w/ mech valves, recurrent emboli)