non-ester cholinomimetics

pilo/nico- well absorbed

cevi- m3, increases salivation- sjogrens, post-radiation

direct acting cholinomimetic

b-methyl- selective for muscarinic

carbamic acid- resistance to hydrolysis

cholinesterase inhibitors

neostigmine- carbamates: pyrido/phyo- carbomoylated enzyme takes much longer to release

edro/donepazil- no covalent bond- dock with quat ammonium and transiently inhibit

donepazil- crosses BBB

organophosphate cholinesterase inhibitors- phopshorylate the enzyme

phosphorylated enzyme - takes essentially forever to come off

 soman- nerve gas

echo- glaucoma, 100 h

pilocarpine, phyostigmine, echothiophate - contraction of ciliary mucle and papillary sphincter leads to drainage.

b blockers, a agonists

edrophonium- (ileus too)- 5-15 m

neostigmine- .5-2 h

pyridostigmine- 3-6 h

give atropine for muscarine poisoning

give PAM (praldoxime) too for organophosphates

salivation, lacrimation, urination, defecation, gi distress, emesis

competitive muscarinic receptor inhibitor - non-selective

scop-differs by one oxygen

inhibit nicotinic ach receptor (Nn)- ganglionic blocker

used as anti-hypertensive- decrease in arteriolar and venomotor tone

curare amazon poison- non-depolarizing NMJ blocker

paralysis

30-60 m

miva-derivative, shorter acting

superagonist of NMJ- depolarizing blocker, slowly metabolized and binds more tightly than Ach, causes paralysis

2- Ach joined together

5-10 m

A: degrades SNAP-25 - involved in Ach vesicle fusion, prevents release

wrinkles, achalasia- abn esoph. contractions, strabismus, oromandibular dystonia,

formation of ip3 and dag, increased Ca

3: bladder contraction, peristalsis(1), pupillary constriction, salivation, vasodilation(1), bronchoconstriction

inhibit Phospholipase A2-> no prostaglandins

inhibits cytokines-> prevent induction of COX-2

inhibits il1 and tnf release?

se: n/v headaches, rashes, leucopenia

antifolate, but AICAR inhibitor, thymidylate synth inh, secondary effects on poly chemotaxis

t: hepatotoxicity, stomatitis

oral prodrug, inhibits DHODH, pyridimine synth

t: diarr, hepat

mouse/human hybrid IgG1 against TNFa

ad- fully human, same effect as etanercept, 2/month dosing

psoriasis

inhibits leukocyte migration, used for gout

t: n/v, inhibition of GI proliferation, neuorpathy, blood dyscrasias

uricosuric agents, compete with urate in renal tubule,

t: gi, can lead to acute gouty arthritis, reduced secretion of weak acids like penicillin

inhibits xanthin oxidase competetively

febuxostate- non comp inhibitor in trials

tertiary amines- peripheral antimuscarinics

di- peptic, hypermotility

trop-mydriasis, cyclopegic-paralysis of ciliary

tolt-urinary incont

antimuscarinic quaternary amines- asthma

tio-longer lasting

b2 agonist

terb:relax uterine SM

a1 agonist

also postural hypotension

dopa-prodrug

a2 agonist- decrease sympathetic tone-->used to treat hypertens, shock, withdrawal

NTS

indirect NE release, CNS stimulation, increased BP/HR

NE is not from vesicles

tachyphylaxis- acute tolerance, use up NE stores

d1, b1, a1 ne release- vasodilation, incr gfr, incr hr/bp

low-d1: vasodilation, renal, mesenteric, cerebral

medium, d1 and b1, some indirect->NE release

high- d1,b1,a1-vasoconcstriction

nonselective a antagonists-> vasodilation, decr resistance, decr bp

phenoxybenzamine-covalent bond

used in Raynauds, pheochromocytoma, frostbite

propran, tim- nonselective 1, 4hr, variable bioav-first pass and plasma protein binding

metopr, ateno- b1 2nd, 4 better bioav, a:6-8, poor BBB

additional actions: a antagonism

carved, labeta- nonselective 3rd- no sex dysf

betax- b1 3rd

vine:oxtoxic- pp bleeding a agonist

amine:migrane, acute a-agonist

cript: used in hyperprolactinema-da2 agonist adn parksonism da agonist.

alkalosis increase secretion

aldo increases secretion

competes with aldo in binding intracell receptor

only work in high aldo concentrations (low na diet)

canrenonate- more active form, can admin IM

also theophylline, prox tubule

phosphodiesterase inh->incr cAMP->PKA->inh Na/H atpase

used clinically in asthma

monitoring reqd, gi, cns, tachyc

phenytoin and smoking-->decr blood levels

CAIs

opth to decr intraocular vol, acute mountain sickness

hypokalemia, metabolic acidosis, hepatic encephalopathy from ammonia

kidney is refractory in metabolic acidosis, eye is not

loop diuretics

ecf contraction->alkalosis, hyperuricemia, inc BUN,

decr filtration->creatinine inc

acute- correct edema, increase veous compliance (kidney pg release, NSAID interaction?), increase ca excretion

chronic->hypoNa (corrected by water restriction), hypoK, hypoMg, destab diabetes, ototoxic (w.Ag's)

thiazide like

all: less Ca in urine, balance re-achieved without regain

transient hyponatremia in beginning (restrict water)

contraction alkalosis, hyperuricemia, hypoMg, increased BUN maybe inc creat, hypoK->diabetes?, hypercalcemia, incr LDL/cholesterol?

used to decr GFR in nephrogenic insipidus, Li therapy- can cause toxicity but helps the polyuria

metolazone- still used in renal failure

interactions:digitalis, quinidine, corticosteroids, amphoB

decreased eff: NSAIDs, bile sequesterants

eNac antagonists, k-sparing

amiloride: helps hypercalciuria, useful in Li

risk of hyperK

b2 agonists

inh mediator release from mast cells/basophils

suppress microvasc perm

decr basal bronch sm tone

antimuscarinic

inhalation-->low side effects

preventer, given on regular basis, not acute

inh of gf secretion, inh of arach acid metabolits and platelet activating factor, inh of leuk aggregation and edema, inh of mucous glyco release

se:thrush, cough, low systemic se

oral se:cataracts, striae, muscle weakn,

bone necro, glauc, hyperCa/gly/tens, hypogonad, osteoporosis, pancr, PUD, psych

leuk antagonists

zileuton- 5LO inh--blocks synth

still experimental-ish

psoralens + UVA

furocoumarin-limes, lemons, figs, parsnips

ind: atopic dermatitis, lichen planus, psoriasis

phenothiazines, sulfas, NSAIDs, tertracycline, benzodiazepine

psoriasis,

po, im, 1/wk

toxicity from displacement from plasma proteins

sulfonamides, salicylates, phyenytoin, tetracycline

pulmonary toxicity, sometimes small doses

rxr and rar, when activated-->transcriptional activators

retinol, tretinoin, isoretinoin

etretinate, acitretin

arotinoids (tazarotene)

only as adjunctive