3/15 pharm Flashcards
Clearance can be impaired w/defects in which systems?
cardiac, renal, hepatic.
Clearance
-equation:
Cl = (rate of elim of drug)/(plasma drug conc.) Cl = (Vd)*(Ke) Cl = (Q)*(Er)
Q = flow to that organ (ie. liver) Er = extraction ratio
Loading dose
-equation
Loading dose = (Cp)(Vd) / (F)
Cp = target plasma concentration at steady state F = bioavailability
Maintenance dose (MD) -equation
MD = (Cp)(Cl)(t) / F
t = dosage interval (time between doses), if not administered continuously.
*If continuous, leave t out. You will also know its IV so F = 1. B/c only IV is continuous.
In liver or renal disease, does maintenance dose inc. or dec.?
Dec.
-less being cleared, so less dose needed.
Which drugs follow zero-order elimination?
-mnemonic?
-Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations).
-PEA. (A pea is round, shaped like the “0” in
“zero-order.”)
Capacity-limited elimination
-0 or 1st order?
0 order elim.
Flow-dependent elimination
-0 or 1st order?
1st order elim.
Phase I drug metabolism
P450 system
-Reduction, oxidation, hydrolysis.
Phase II drug metabolism
Conjugation (Glucuronidation, Acetylation, Sulfation)
Which is most common P450 enzyme?
CYP3A4 = most common
Name 3 drugs that might cause trouble in a slow acetylator.
-which would also have a bimodal pop. distribution.
- hydralazine, isoniazid, procainamade
* HIP: its not hip to be a slow acetylator.
What kind of antagonist is ketamine?
-ketamine (noncompetitive antagonist) on NMDA receptors.
Therapeutic index:
-equation:
TI = Toxic dose/Effective dose
*high therapeutic index is good b/c that means theres a big difference btwn toxic and effective doses.
Whats good, a high or low therapeutic index?
High.
-Safer drugs have higher TI values.
Is the therapeutic index the same as therapeutic window?
No, b/c the therapeutic window would never extend all the way until the toxic dose.
Some receptors that respond to autonomic neurotrasmitters/drugs receive NO nerve innervation (must get ligand through blood).
-can you name these uninnervated autonomic receptors?
- muscarinic receptors on endothelium of blood vessels
- adrenoreceptors on apocrine sweat glands
- alpha-2 and beta adrenoreceptors in blood vessels.
para/pre, sym/pre: all release what?
ACh
All ganglia have what type of receptor?
Nicotinic: ligand-gated ion channels.
Do all sym/post release NE?
NO
- adrenal medulla releases NE and epi.
- sym/post release ACh that innervate sweat glands & piloerector muscles. These = sympathetic cholinergic.
sympathetic cholinergic
sym/post that releases ACh
-innervate sweat glands & piloerector muscles.
All glands have what receptors on them?
muscarinic
-even sweat glands that have sym/post innervation: these sym/posts dump ACh, not NE (sympathetic cholinergic).
adrenal medulla & sweat glands = part of sym nervous system but are innervated by _______ fibers.
cholinergic
Nicotinic ACh receptors
-what type of receptor is it?
-ligand-gated Na/K channels.
which receptors are more sensitive to activation, alpha or beta?
beta
Epi: acting more on alpha1 or beta2?
- low dose =
- high dose =
- low dose - acts more on beta-2
- high dose - acts more on alpha-1
*remember, beta-receptors are more sensitive.
Ciliary muscle innervation:
- muscarinic
- its NOT dual innervated.
*if there is an effect on accomodation, its a muscarinic (agonist or antagonist) drug
Cycloplega = what is it, what can cause it?
paralysis of ciliary muscles = M-antagonist
Gs => inc. cAMP => PKA => phosphorylates MLC kinase.
-whats the result?
smooth muscle relaxation
-hence beta-2 (Gs) causing smooth muscle relaxation in lungs.
Hemicholinium
- mech:
- use:
- Prevents reuptake of choline so you have less in nerve terminal so you make less ACh and release less ACh.
- NO CLINICAL USE.
NMJ
-what kind of receptor?
nicotinic, ACh.
Reserpine
- inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.
- used in huntingtons.
guanethidine
- like botulinum but for NE.
* not clinically used
Where do you find AChE?
- AChE is only found in the synpatic cleft.
- Not everywhere you find a M or N receptor.
*that means AChE inhibitor can not vasodilate b/c endothelial cell M3 receptors are not innervated = no synaptic cleft.
Can AChE inhibitors vasodilate?
- AChE is only found in the synpatic cleft.
- Not everywhere you find a M or N receptor.
*that means AChE inhibitor can not vasodilate b/c endothelial cell M3 receptors are not innervated = no synaptic cleft.
M agonists
-give pattern of what type of lung disease?
-obstructive, like COPD.
What an effect you can see via cholinomimetic drugs that you dont see w/parasym. nerve stimulation?
sweating
-b/c sweat glands have sym innervation but release ACh at the sweat glands M3 receptor.
Is bethanechol resistant or sensitive to AChE?
- resistant to AChE.
- not the same exact structure as ACh so its not broken down by AChE!
Someone at movie and gets intense pain in their eyes.
-They’re in a dark room, their pupils dilate, the angle gets smaller, and this precipitates their glaucoma
Administer _______ to Cystic Fibrosis pt to get sweat so you can do sweat test
pilocarpine
Pilocarpine is resistant or sensitive to AChE?
resistant, just like bethanechol.
-not exactly the same structure as ACh so AChE doesn’t break it down.
myasthenic crisis
not enough ACh
cholinergic crisis
too much ACh
-can resemble myasthenic crisis
Which receptors do AChE inhibitors act at?
muscarinic & nicotinic