Enteral p.o.

(oral) sublingual- effective sublingual vein lingual internal jugular with subclavian braciocephalic SVC can bypass liver preventing first pass metabolism rectal- not common lower rectum bypass portal venous systems parenteral IV dorsal veins of hand ( any vein will do) Intramuscular Subcutaneous Intraperitoneal Transdermal-patch (price is high) Intrathecal- in the brain under arachnoid space Intraosseous- Israeli gun Intrapulmonary (never naco3 for acidosis by lung) Bid (2x a day) more are now slower release allow for qd (1x a day) Absorption- from ingestion to circulation (arterial) Passive for the most part Food usually slows down absorption (but can increase, decrease, no effect on quantity absorbed) In stomach weak base ( becomes ionized) poor absobtion, weak acid becomes unionized and absorbed Aspirin and barbituates (weak acids) Gastro protection coat so aspirin is absorbed in duodenum instead of stomach But it affects stomach by inhibiting prostaglandin and cyclooxygenase system (preventing damage prevention) Intestines weak bases less acidic so they are unionized and absorbed Some first pass effects are much more important Lidocaine makes no sense orally (caine =local anesthetic) No swallow morphine Meperidine (dont give with antidepressants, ny ice skater died) High oral vs low iv is indication of first pass effect Lower distribution more likely it stays in circulation Higher distribution could appear to be dilution but could just be the body has absorbed (fat soluble) Ends in ol (beta blocker) Lidocaine Na channel blocker (pain and heart inhibitor) Distribution = dose/concentration Metabolism = make more water soluble and kidney actionable Hepatic performance can be judged by child pugh score Bilirubin Albumin International normalization ratio coagulation assessment Ascites- accumulation in peritoneal cavity

Encephalopathy- brain disorder Liver has two types of reactions Phase II conjugation ( add things) dont need liver strength Phase I oxidation (structural changes) need liver strength (drugs that are phase II are preferred) P450 enzymes (cytochrome) Number, letter,Number 1a2 metabolizes xanthine (coffee/tea)- 10% hepatic metabolism Phase 1 more complex need more functionality of liver Strong Coffee used to be medication for asthma Relax smooth muscle (today we use telopholin) 3A4 most abundant and does the most metabolism Erythromycin (antibiotic) first identified metabolized drugs Inducers of 3a4 amount and activity: Barbituates (affect almost all liver enzymes, not used as much), carbamazepine (seizure control), glucocorticoids, phenytoin (neuro function sodium channel blocker, but not anesthetic), rifampin (TB, orange discoloration) , st johns wart (European anti-depressant) Renal patient on cyclosporine (immune suppressant) starts taking st johns wort for depression. Starts 3a4 metabolism eliminating cyclosporine 3a4 inhibitors: azole antifungals, cimetidine (suppress acidic secretion in stomach; dine indicates antihistamine acid suppressor), ciprofloxacin (antibiotic), erythromycin, nefazadone (antidepressant), grapefruit juice (will increase blood levels of drugs metabolized by 3a4) CAD patients on high dose statins starts a grapefruit diet: statin levels go through roof, muscle pain/destruction releasing myoglobin which blocks kidney filtration rd 2c9- 3 most abundant Phenytoin metabolized (anticonvulsant anti arythmic )NA channel blocker Phase 1 gingival hyperplasia 2c19 Mephenytoin 2d6 Debrisoquine (blood pressure by inhibiting NE release) Elimination By gut or renal Renal Filtration (non protein bound drugs) Reabsorption Secretion (weak acids) Clearance ratio = clearance drug/clearance creatine Only filteration then CR = 1

<1 then reabsorption >1 then secretion as well Transporters move drugs Anion transporters Endogenous (proximal tubules): cAMP, pg, bile salt, oxalate, hippurate, urate, thyroid hormone Exogenous (proximate tubules): penicillin, probenecid (boost penicillin levels by competing for transporter spot) Cation Endogenous (proximal tubules): dopamine, epinephrine, norepinephrine, creatine Exogenous (proximal tubules): cimetidine, morphine Cockcroft & gault scale (24 urine collection with calculation of creatine clearance Double the administration or half the dose for high clearance Zero order = per unit of time and is constant No half life Ethanol ( constant metabolism), asa (high concentration, aspirin), heparin (anticoagulants), theophylline, phenytoin. Last 4 are zero order at high concentration First order= constant fraction Have a half life Clearance = distribution * proportionality constant Proportionality constant = .7/ half life C= dose/distribution