pharmpath Flashcards
Lineweaver-Burk plot. What does the X intercept mean and what does the Y intercept mean?
X intercept is 1/-Km. So the more to the right that is, the bigger Km is, and the lower the affinity. Y intercept is 1/Vmax. The higher that is, the lower Vmax is. Can remember this because V looks kind of like a Y.
Bioavailabilty equation
Fraction of drug that reaches circulation unchanged. F = 100% IV. Area under oral curve/ area under IV cure (227)
Volume of distribution equation
Amount of drug in body/ plasma concentration of drug.
What is the range for a low volume of distribution and what are some drug types?
Low means mostly in the blood. 4-8 L. Large, charged molecules, plasma protein bound
Where do medium volume of distribution drugs go and what are some drug types?
Medium go to the ECF. Small, hydrophilic molecules. Small so can get through, but not lipophilic so can’t really spread too far
Where do high volume of distribution drugs go and what are some drug types?
Go to all tissues. Small, lipophilic, bound to tissue proteins
Half life equation. What can you calculate from half life?
t1/2 = (.7 x Vd) / CL
How long does a drug infused at a constant rate take to reach steady state?
4-5 half lives
Clearance equation
Clearance = rate of elimination of drug/ concentration of drug in plasma. = Vd x Ke (elimination constant) –> amount of drug in body x elimination constant/plasma concentration of drug
Loading dose equation
Cp x Vd / F. Cp = target plasma concentration. So for loading, need to take into account the spread and how much is going to get hit by first pass. F is how much will make it, so the bigger F is, the lower dose you need. The bigger Vd, the higher dose you
Maintenance dose equation
Cp x CL/F. Now we are maintaining, so have to increase dose with clearance and decrease dose if more makes it through first pass.
Zero order vs first order elimination
Zero: constant amount eliminated no matter what the concentration. Called capacity dependent elimination (maxed out already so doesn’t matter what concentration is). First order: constant fraction eliminated. Called flow dependent elimination
How can you treat phenobarbital, MTX, and aspirin overdose all at once?
Bicarb. These are all weak acids and can get trapped in basic environments by ionizing them.
How can you treat an amphetamine OD?
Ammonium chloride. Weak base, can trap with acid.
What do phenytoin, ethanol, and aspirin have in common?
Zero order kinetics at high or toxic concentrations
Phase I vs Phase II metabolism
Phase I is P450, does reduction, oxidation, hydrolysis that yields slightly polar, water-soluble metabolites (often still active). Phase II does conjugation and yields very polar, inactive metabolites that are excreted. This is where slow acetylators come
Therapeutic index
Median lethal dose/ median effective dose. Safer drugs have higher TI’s, takes a way bigger lethal dose than effective dose
Therapeutic window
Range of minimum effective dose to minimum toxic dose.
What type of G protein does mydriasis via pupillary dilator muscle contraction?
Alpha 1 –> Gq
What type of G protein decreases HR and contractility of atria?
M2 is heart –> Gi
What kind of G protein increases sweat?
M3 –> Gq. Remember, this one is a muscarinic carrying out sympathetic activity!
What type of G protein does intestinal and bladder sphincter muscle contraction?
Apha 1 –> Gq
What kind of G protein relaxes renal vascular smooth muscle?
D1 –> Gs
What kind of G protein responds to ADH with increased vascular smooth muscle contraction?
V1 –> Gq
What kind of G protein increases aqueous humor production?
Beta 2 –> Gs
What kind of G protein decreases insulin release via autonomic signaling?
Alpha 2 –> Gi
What kind of G protein increases bladder contraction?
M3 –> Gq
What kind of G protein does accommodation?
M3 –> Gq
What kind of G protein is associated with the D2 receptor. What does the D2 receptor do?
Gi. Modulates transmitter release, especially in the brain
What kind of G protein does increased nasal and bronchial mucus production, contraction of bronchioles, pruritis, and pain
H1 –> Gq
What kind of G protein responds to H2. What does it do?
H2 –> Gs. Increased gastric acid secretion
What kind of G protein responds to ADH by increasing water reabsorption?
V2 –> Gs
What kind of G protein decreases uterine tone in response to an autonomic?
Beta 2 –> Gs (tocolytic)
What kind of G protein does ciliary muscle relaxation?
M3 –> Gq
What kind of G protein does bronchoconstriction?
M3 –> Gq
What kind of G protein does pupillary sphincter muscle contraction (mioisis)?
M3 –> Gq
What kind of G protein increases platelet aggregation via autonomic signaling?
Alpha 2 –> Gi
Now, M1, M2, M3, what do they do and what are their associated G proteins?
M1 = CNS –> Gq. M2 = heart –> Gi. M3 = everything else –> Gq
D1 and D2: what are their Gs?
Gs, Gi. Si! Kidney and brain
H1 and H2: what are their Gs?
Gq, Gs. Gs –> acid Secretion, Gq –> rest
V1 and V2: What are their Gs?
Gq, Gs. Gq –> constriction (like alpha 1 that also uses Gq). Gs –> normal ADH stuff
Gs has what effect on the heart? Smooth muscle?
Gs –> increased PKA –> increases calcium in the heart. PKA also phosphorylates myosin light chain kinase to inhibit it! Inhibits smooth muscle contraction (D1, Beta 2)
PTEN: What is it and what is the pathway?
Growth factor –> TK –> PI3K –> phosphorylates PIP2 –> PIP3 –> activates Akt –> mTOR –> cell survival and anti-apoptosis. Now, PTEN is a tumor suppressor and dephosphorylates PIP3. See p 231
Pyridostigmine, neostigmine, edrophonium, and physostigmine. Who can enter the CNS? Uses?
Physostigmine, others can’t. Physo for atropine OD. Use neo and pyrido to treat MG and edrophonium to diagnose MG (short-acting). Neo is also for post-op ileus and urinary retention and reversal of NMJ blockade
What G protein does increased gastric acid secretion from autonomics?
Gq –> M3.
Pralidoxime
Regenerates active AChE in cholinesterase inhibitor poisoning
Tropicamide
Atropine for the eye
Glycopyrrolate
Muscarinic antagonist for GI and respiratory (reduce airway secretions and treat peptic ulcer)
What is the muscarinic receptor on endothelial surfaces?
NO (endothelial derived relaxing factor or EDRF). No innervation, only agonists hit it
What receptors is isoproterenol selective for? What do you use it to treat?
Beta 1 and beta 2 agonist. Treats torsades de pointes (tachy decreases QT interval) and bradyarrythmias (though may worsen ischemia)
What receptors does DA act on in increasing doses?
Low dose –> D1, medium –> betas, high –> alphas
Where does dobutamine act?
beta 1 primarily. Use for heart failure, cardiac stress testing (increases conduction speed)
Ritodrine. Uses?
Beta 2 selective agonist for reducing premature uterine contractions
Amphetamine MOA vs ephedrine vs cocaine
Amphetamine releases stored catecholamines and decreases reputake, cocaine decreases reuptake, ephedrine releases stored catecholamines
What would happen if you gave beta blockers to someone on cocaine?
Unopposed alpha 1 activation and extreme HTN
Methyldopa MOA
alpha 2 agonist, decreases central sympathetic outflow. Can treat HTN, especially with renal disease (doesn’t decrease renal blood flow to kidney). Same with clonidine
Name the partial beta agonists
Pindolol, acebutolol
Name the nonselective alpha and beta antagonists
carvedilol, labetolol
What do you give someone who overdoses on salicylates
Alkalinize the urine (NaHCO3)
What do you give someone who overdoses on beta blockers
Glucagon.
What do you give someone who overdoses on digitalis
Normalize K and magnesium, Lidocaine, Anti-Fab,
What do you give someone who overdoses on iron
Deferoxamine, deferasirox
What do you give someone who overdoses on lead
CaEDTA, dimercaprol, succimer, penicillamine
What do you give someone who overdoses on mercury
Dimercaprol, succimer
What do you give someone who overdoses on copper
Penicillamine
What do you give someone who overdoses on arsenic
Dimercarpol, succimer, penicillamine
What do you give someone who overdoses on gold
Dimercaprol, succimer, penicillamine
What do you give someone who overdoses on cyanide
Nitrate + thiosulfate, hydroxocobalamin
What do you give someone for methemeglobin
Methylene blue, vitamin C
What do you give someone for warfarin OD
Vitamin K, fresh frozen plasma (faster)
What do you give someone for tPA, streptokinase, or urokinase OD
Aminocaproic acid. Inhibits plasmin
What do you give someone for theophylline OD
Beta blocker
3 drugs that cause coronary vasospasm
Cocaine, sumatriptan, ergot alkaloids
4 drugs that cause cutaneous flushing
Vanco, adenosine, niacin, Ca blockers
2 drug types that cause torsades
Class III and IA antiarrythmics
6 drugs that cause agranulocytosis?
Clozapine, carbamazepine, colchicine, PTU, methimazole, dapsone (an antibiotic)
5 drugs that cause aplastic anemia?
Chloramphenicol (gray baby), benzene, NSAIDs, PTU, methimazole
What 2 drugs cause direct Coombs positive hemolytic anemia?
Methyldopa, PCN
6 drugs that cause hemolysis in G6PD deficient patients
INH, sulfonamides, primaquine, aspirin, ibuprofen, nitrofurantoin
3 drugs that cause megaloblastic anemia?
Phenytoin, MTX, sulfa drugs
Drug that you think of with acute cholestatic hepatitis and jaundice?
Erythromycin
3 drugs that cause hepatic granulomatosis?
Methyldopa, hydralazine, quinidine
3 drugs that cause cholethiasis?
Fibrates, octreotide, ceftriaxone
5 drugs that cause gynecomastia?
Spironolactone, digitalis, cimetidine, chronic alcohol use, ketoconazole
5 drugs that cause hyperglycemia?
Niacin, tacrolimus and cyclosporine, protease inhibitors, HCTZ, corticosteroids
3 drugs that cause hypothyroid?
Lithium, amiodarone, sulfonamides
4 drugs that cause gout?
Furosemide, thiazides, niacin, cyclosporine
Which 3 drugs do photosensitivity?
Sulfonamides, amiodarone, tetracycline
2 drugs that cause siADH
Carbamazepine, cyclophosphamide. Cyclophosphamide also causes hemorrhagic cystitis
What CNS effects does metoclopramide have?
Seizures and PD like symptoms
