Pharm Flashcards
drug elimination
0 order: PEA
- phenytoin, ethanol, ASA (high dose)
- straight-line graph
first order - curved line
Vd = drug mg/plasma concentration
Cl = rate of elimination/plasma drug concentration
t1/2 = 0.693*Vd/Cl in first order elimination, 3.3 half-lives to reach 90% of SS level
urine pH
- weak acids - phenobarb, methotrexate, ASA, trapped in basic environments
- weak base - amphetamines, TCA, acidify urine with ammonium Cl
pulmonary fibrosis
my nose cant breathe bad air methotrexate nitrofurantoin carmustine bleomycin - lymphomas and gyn/testicular cancers busulfan amiodarone
sulfa drugs
…probenecid, furosemide, acetazolamide, celecoxib, thiazides
CV drug reactions
coronary vasospasm - …ergots, sumatriptan
cutaneous flushing - niacin, vanc, echinocandins
- adenosine, nitrates, CCBs = vasodilators
dilated CM - anthracyclines (doxorubicin), prevent with dexrazoxane
b-blockers
reduce mortality in MI and HF
angina, SVTach (decreased AV conduction - class 2 anti-arr), HTN (+ b1 blockade on JGA cells)
glaucoma - decreased aq humor production
variceal bleeds - decreases pressure gradient from liver
ADRs: erectile dysfunction, CV/CNS adrs, dyslipidemia (metoprolol), asthma/COPD exacerbations
b1 selective - A-M names
non-selective b - N-Z
a and b- carvedilol, labetalol (dont have classic olol)
nebivolol - super drug, b1 blocker and b3 agonist (activates NO synthase)
drug metabolism
phase 1 - water-soluble, geriatrics lose phase 1 first
phase 2 - conjugation (methylation, glucuronidation, acetylation, sulfation)
- POLAR and inactive
drug interactions
additive (ASA and acetaminophen), permissive (cortisol and catecholamine), synergistic (clopidogrel and ASA), tachyphylactic (need more drug with repeated admins, nitrates, niacin, phenylepi, LSD, MDMA)
dosing
loading dose = CpVd/F
Md = CpCl*tau/F where tau is dosing interval
renal/liver disease - decrease Md, Ld unchanged
therapeutic index = median toxic dose/ median effective dose
- safer drugs have high TI
- drugs with low TI = warfarin, theophylline, digoxin, lithum
enzyme kinetics
Km inversely related to enzyme-substrate affinity
Vm - prop to enzyme concentration
inhibitors
- Km - competitive inhibitors decrease Km, other inhibitors dont change Km
G proteins
q = phospholipase C --> IP3, DAG --> Ca2+ and PKC a = adenyl cyclase ... PKA --> increases Ca2+ in heart, inhibits myosin light chain kinase (smooth muscle)
a1 - q
a2 - inhibitory (…decreases aq humor production, insulin release, and lipolysis), but increases platelet aggregation
b1 - …increases renin release and lipolysis
b2 - opp of a2 in many ways, tocolysis
b3 - increased lipolysis, thermogenic in skeletal muscle, increased bladder relaxation
M_odd - q M_even - i M1 - higher functions, enteric NS M2 - decreased HR and contractility of atria M3 - cholinergic, increased sweat
D1 - s - relaxes renal VSMC, activates direct pathway
D2 - i - inhibits indirect pathway
H1 - q - nasal/bronchial mucus production, contraction of bronchioles, increased vasc perm, pruritis, pain
H2 - s - gastric acid
V1 - q - VSMC
V2 - s - kidney
CNS, SNS, PSNS
NAch used in autonomic ganglia and adrenal medulla
PSNS - pre is long
SNS - pre is short
- sweat glands but they have Ach-M receptors
somatic - NAch - motor endplate
autonomic drugs
- NE feedback regulates itself - via a2 receptors on presynaptic terminals
- amphetamines use NET to enter presynaptic terminal –> VMAT to enter vesicles –> NE displaced
- once NE reaches a certain conc in the presynaptic terminal –> NET is reversed and NE is expelled into the synaptic cleft
cholinomimetics
Bethanechol - Bowel + Bladder, resistant to ACHe
carbachol - Ach analog, resistant to ACHe
- constricts pupil, relieves open-angle glaucoma
methacholine
pilocarpine - contracts ciliary muscle of eye (open angle glaucoma), pupillary sphincter (closed angle), resistant to AchE
- potent stimulator of sweat, tears, saliva (think sjogrens)
acetylcholinesterases
galantamine, donepezil, rivastigmine - Alzheimers
edrophonium - used to ddx myasthenia gravis
neostigmine - NO CNS penetration
physostigmine - phyxes atropine OD, crosses BBB
pyridostigmine - long acting, doesnt penetrate CNS
risk of excess Ach - watch for exacerbation of COPD, asthma, and peptic ulcers
note - organophosphates irr inhibit AchE, give atropine (competitive inhibitor) and pralidoxime (regenerates AchE)
muscarinic antagonists
atropine, -mines (scopolamine), -tropium, etc.
atropine - used to treat bradycardia and for optho applications
- does NOT block excitation of skeletal muscle and CNS (nicotinic Ach receptors)
- side effects are - increased body temp (due to decreased sweating), disorientation, cycloplegia (loss of accommodation, paralysis of ciliary muscle)
- can cause acute angle-closure glaucoma due to mydriasis
Jimson weed = mydriasis due to plant alkaloids
seafood toxins
tetrodotoxin (pufferfish) - binds to Na channel in heart and nerve –> prevents depolarization
- GI upset, etc.
- supportive care
ciguatoxin - eel
- OPENs Na channels –> depolization
- GI upset, perioral numbness, reversal of hot and cold sensations, bradycardia, heart block, hypotension
- supportive care
histamine - spoiled tuna
- histidine carboxylase –> histamine - frequently misddx as fish allergy
- give antihistamines, albuterol, epi
