Pharm Flashcards
Describe a michaelis menten kinetics curve including Km, Vmax, and the significance of them (what they determine/depend on).
It is a hyperbolic curve with velocity on the y axis and substrat conc. on the x axis.
V max is the maximum velocity that can be reached (when all the enzymes are saturated with enzyme).
It is proportional to the enzyme conc.
Km is the subs. conc. at 1/2Vmax.
It is inversely related to the affinity of the enzyme for its substrate.
Describe a lineweaver burk plot including what the y intercept and x intercept and slope are and what they signify.
A straight line with 1/V on the y axis and 1/S on the x axis.
Y intercept is 1/Vmax so the higher that the y intercept is, the lower the v max is.
X intercept is 1/-Km so the further to the right it is (less negative) the greater Km is and thus the lower the affinity.
Compare and contrast comp. inh (revers), comp. inh. (irrev), and non comp inh. according to whether they resemble substrate, are overcome by incr. in substrate, bind active sit, how they effect Vmax, how they effect Km, and how they effect potency/efficacy.
COMP INH, REVER
resemble substrate: Yes overcome by incr. in substrate: Yes bind active site: Yes how they effect Vmax: None how they effect Km: Decr how they effect potency/efficacy: decr. potency
COMP INH, IRREVER
resemble substrate: yes overcome by incr. in substrate: no bind active site: yes how they effect Vmax: decr how they effect Km: none how they effect potency/efficacy: decr. efficacy
NON COMP INH
resemble substrate: no overcome by incr. in substrate: no bind active site: no how they effect Vmax: decr how they effect Km: none how they effect potency/efficacy: decr. efficacy
What is the bioavailability? What is it IV? Oral? Why?
Fraction of administered drug reaching systemic circ. unchanged.
For IV=100%
Oral < 100%, incomplete absorption, first pass metabolism
What is Vd? How can the Vd of plasma protein bound drugs be altered? How is it calculated? What compartment does a low Vd drug enter? What types of drugs are they? Medium? High?
Theoretical volume occupied by the total amount of drug in the body relative to its plasma conc.
They can be altered by liver and kidney disease (decr. protein binding leads to incr. Vd)
Vd=(amount of drug in the body)/(plasma drug concentration)
Low: Blood; large/charged molecules, plasma protein bound
Medium: ECF, small hydrophilic molecules
High: all tissues including fat; small lipophilic molecules, especially if bound to tissue protein
What is clearance? What might iimpair it? What are two equations for it?
Volume of plasma cleared of drug per unit time.
May be impaired with defects in cardiac, hepatic, and renal function
CL=rate of elimination/plasma drug concentration
CL=Vd x Ke (elimination constant)
What is the half life? How many half lives til steady state? Til 90% of steady state? How is halflife calculated?
Time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion).
4-5 half lives til steady state
3.3 half lives to reach 90%
t1/2= (.693 x Vd)/CL
How is loading dose calculated? How is maintenance dose calculated? How do they change in renal or liver disease? How do they determine tie to steady state?
Loading dose=(target plasma conc. at steady state x Vd)/F
Maintenance dose=(target plasma conc. x CL x dosage interval)/F
In renal or liver disease, maintenance dose will change but loading dose will not
Time to steady state depends on half life, not the loading or maintenance dose
What is zero order elimination? What are some examples?
Rate of elimination is constant regardless of the amount of substrate (constant amount of drug eliminated per unit time)
Decreases linearly
Phenytoin, ethanol, aspirin (PEA=a pea is round like a 0)
What is first order elimination?
Rate is proportional to drug concentration (constant fraction of drug eliminated per unit time)
Decreases exponentially
Explain how ion trapping works? What are some weak acids? How can they be trapped in basic environments? What are some weak bases? How can they be trapped in acidic environments?
Ionized species are trapped in urine and cleared quickly. Neutral forms are reabsorbed. By making something ionic, you can eliminate it quickly.
WA: Phenobarbital, methotrexate, aspirin, TCAs
Treat overdose with bicarb
WB: Amphetamines
Treat overdose with ammonium chloride
What reactions occur in phase I drug metabolism? Where? What are the results? What reactions occur in phase two drug metabolism? Results? What do geriatric patients lose? What is a genetic condition that can decr. rate of metabolism? Clinical effects?
Reduction, oxidation, and hydrolysis with cytochrome p-450
Slightly polar, water soluble molecules (often active)
Conjugation (glucoronidaiton, acetylation, sulfation)
Very polar, inactive metabolites (excreted in urine)
Geriatric patients have GAS (phase I lost first)
Slow acetylators have decr. rate of metabolism which may lead to incr. side effects.
Compare and contrast efficacy and potency.
Efficacy is the maximal effect a drug can produce. It is represented by Vmax. It is unrelated to potency. Partial agonists have less efficacy than full agonists
Potency is the amount of drug needed for a given effect. It depends on Km. Left shifting mean increased potency. Unrelated to efficacy
What are dose response curves? How do comp. antag. affect dose response curves? How does the dose response curve of a partial agonist compare to that of a full?
Dose on x axis, perecent of maximal effect of y axis
Comp. antagonist: shifts curve right (decr. potency). No change in efficacy.
Non comp. antag: Shifts curve down (decr. efficacy).
Partial agonist: Lower maximal effect (decr. efficancy).
What is the therapeutic index? How is it calculated? What are some drugs with low TI values? What does this mean? What is the therapeutic window?
Measurement of drug safety
TD50/ED50=median toxic dose/Median effective dose
Digoxin, lithium, theophylline, and warfarin
Window: measure of clinical drug effectiveness for a patient.
Describe the presympathetic and postsympathetic nerve terminals in the autonomic pathways from the CNS to the parasympathetic pathway to cardiac and smooth muscle, gland cells, and nerve terminals? The symp. pathway to sweat glands? The symp pathway to cardiac and smooth muscle, gland cells, and nerve terminals? The symp. pathway to renal vasculature and smooth muscle? The somatic pathway to skeletal muscle? The symp. pathway to adrenal medulla?
Parasymp=long presynaptic, short postsynaptic
Symp: short presynaptic, long postsynaptic
Para: Nicotinic cholinergic then muscarinic
Symp sweat glands: Nicotinic then muscarinic
symp cardiac, etc: nicotinic then alpha/beta receptors
symp renal: nicotinic then D1
symp adrenal: nicotinic then epi/NE
somatic: nicotinic only (no ganglion)
What is the difference between nicotinic and muscarinic receptors?
Nico: ligand gated Na/K channels
Musc: G protein coupled receptors that use second messengers
What are the major functions of alpha 1, alpha 2, beta 1, and beta 2 receptors? What g protein class do they use?
alpha 1 (Gq): incr. vasc smooth muscle contraction, incr. pupillary dilator muscle contraction (mydriasis), incr. intestinal and bladder sphincter muscle contraction
alpha 2 (Gi): Decr. symp outflow, decr. insulin release, decr. lipolysis, incr. platelet aggregation, decr. aqueous humor production
beta 1 (Gs): Incr. heart rate/contractility, incr. renin release, incr. lipolysis
beta 2 (Gs): Vasodilation, bronchodilation, incr. lipolysis, incr. insulin release, decr. uterine tone (tocolysis), ciliary muscle relaxation (look far away), incr. aqueous humor production
Qiss
What are the major functions of M1, M2, and M3 receptors? What G protein class do they use?
M1 (Gq): CNS, enteric nervous system
M2 (Gi): Decr. heart rate and contractility of atria (incr. av node refractory period)
M3 (Gq): incr. exocrine gland secrections (lacrimal, salivary, gastric acid), incr. gut peristalsis, incr. bladder contraction, bronchoconstriction, incr. pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accomodation)
qiq
What are the major functions of D1, D2, H1, H2, V1, V2 receptors? What G protein class do they use?
D1 (Gs): Relaxes renal vascular smooth muscle
D2 (Gi): Modulates transmitter release, especially in brain
H1 (Gq): Incr. nasal and bronchila mucus production, incr. vasc. permeability, contraction of bronchioles, pruritus, pain
H2 (Gs): Incr. gastric acid secretion
V1 (Gq): Incr. vasc. smooth muscle contraction
V2 (Gs): Incr. H20 perm. and reabsorption in collecting tubules of kidney (V2 is found in the 2 kidneys)
What is the pathway of Gq receptors? Which receptors are Gq receptors?
Phospholipase C converts PIP2 to DAG and IP3
DAG forms protein kinase C
IP3 releases Ca from the SR
These actions lead to smooth muscle contraction
HAVe 1 M&M
H1, A1, V1, M1, M3
What is the pathway of Gs receptors? Which ones are Gsreceptors? Same questions for Gi receptors?
Gs activates adenylate cyclase leading to more cAMP
This activates protein kinase A
This leads to more calcium inflow in the heart and inhibition of myosin light chain kinase in smooth muscle
B1, B2, D1, H2, V2
Gi inhibits adenylate cyclase thus leading to less calcium inflow in heart and less inhib. of MLCK in SM
MAD 2s
M2, A2, D2
What type of drug is bethanacol? Clinical applications? Action?
Direct cholinnomimetic agonist
Postoperative ileus, neurogenic ileus, urinary retention
Activates bladder and bowel smooth muscle
“Bethany, call me to activate your bowels and bladder”
Resistant to AChE
What type of drug is carbachol? Clinical applications?
Direct cholinomimetic agonist
Constricts pupil and relieves intraocular pressure in glaucoma
