Pharm 2 - Urogenital 1

drraythe's version from 2015-09-30 19:49


Question Answer
The 6 main renal functions he told us were...(1) Excretion/clearance of waste products
(2) Regulation of the NaCl & electrolyte content & acid-base balance
(3) Regulation of the volume of the extracellular fluid
(4) Bio-transformation
(5) High renal blood flow
(6) Large re-absorptive capacity
What substances undergo active proximal tubular secretion & what does this mean about their interaction? (& where does this occur?)Weak acids & weak bases bc it is an active process, they undergo competition! (Weak acids/bases are actively secreted from the PCT) (acids & acids compete. bases & bases compete, bc they have to share the same acid or base active pump)
Explain the EXCRETION of a weak acid in....(1) Urine w/ a low pH (2) Urine w/ a high pH(1) In a low pH, the urine is acidic. The weak acid is also acidic, so it is not ionized, which means it can pass the tubular membrane to be resorbed, so only a low or small amount of weak acid will be EXCRETED in acidic urine
(2) In a high pH urine, the urine is basic & a weak acid is acidic. The difference means the weak acid will be ionized, so it cannot pass the tubular membrane, which means that LOTS of the weak acid will be EXCRETED
Explain the EXCRETION of a weak base in...(1) Urine w/ a low pH (2) urine w/ a high pH(1) In a low pH, the urine is acidic, which is opposite from the basicity of the weak base. This means that the weak base will be IONIZED, so it will not be able to pass through the tubular membrane to be resorbed, so it will stay in the urine & be excreted (big difference = big excretion)
(2) In a high pH urine, the urine is basic. This means the weak base will NOT be ionized, so it CAN pass the tubular membrane to be resorbed, so not much will be excreted (small difference = small excretion)
(FYU) What is pKa?The acid dissociation constant. The larger the Ka value, the more dissociation of the molecules in solution & thus the stronger the acid. Thus, a strong acid "wants" to get rid of its hydrogen ion, much more so than a weak acid. (So, a high pKa is a strong acid & a low pKa is a weak acid)
(FYU) Explain relationship btwn pH & pKaWhen the difference btwn pH & pKa is big: The drug is ionized & cannot pass membranes
When the difference btwn pH & pKa is small: The drug is non-ionized & can easily pass membranes
What is the pH of a carnivore's urine like? Bc of this, when is there a delayed elimination of drugs w/ what pKa?Carnivores have acidic urine (low pH). This means there is a delayed elimination of drugs w/ low pKa, bc when the difference btwn pH & pKa is small, the drug is non-ionized & can easily pass membranes, so it goes into the body again & isn't excreted as quickly (remember: small difference = small excretion | large difference = large excretion)
What is the pH of a herbivore's urine like? Bc of this, when is there a delayed elimination of drugs w/ what pKa?Herbivores have alkaline (basic) urine (high pH). There is a delay in the elimination of drugs w/ a high pKa bc of this, since if there is only a small difference btwn pH & pKa, then the drug stays non-ionized & easily passes through membranes to get reabsorbed rather than excreted
Where does active secretion of a drug into a tubule take place?PCT
(Not sure how important) What are some acidic DRUGS ( & related substances) Which are ACTIVELY SECRETED in PCT?Furosemide, Glucuronic acids conjugates, Glycine conjugates, Penicillin, Uric acid, Sulfate conjugates, Thiazide diuretics
(Not sure how important) What is Probenicide? Why do we care?COMPETES w/ Penicillin for active secretion into tubule. Which means it is taking up transporter spots, which means less Penicillin gets secreted to get excreted, so Penicillin will stay longer in blood & last longer (DELAYS ELIM OF PENICILLIN)
(Not sure how important) What is Sulphinpyrazone? Why do we care?Actively competes w/ Uric acid active secretion, so DELAYS EXCRETION of URIC ACID
(Not sure how important) What are some basic drugs (/related substances) which are actively SECRETED in the PCT?Dopamine, Histamine, Morphine, Quaternary Ammonium Compounds, Serotonin, Pethidine, Amiloride (← K+ sparing diuretic)
Basic function of PCT?Reabsorption & secretion happens here (says VITAL here, implying it must happen I assume)
Basic function of LOH?Solute concentration happens here
Basic function of DCT/collecting duct?Reabsorption & secretion happens here (Says OPTIONAL here, in PCT it is reab & sec are regulated by hormones)
How do mesengial cells affect GFR? What are 3 substances/innervations which can affect the behavior of mesengial cells?Constriction of mesengial cells leads to ↓ GFR!
(1) Atrial Natriuretic Peptide: Relaxation
(2) Angiotensin II: Constriction
(3) Sympathetic innervation: Contraction
Where along the nephron is there high, none, or variable H20 permeability?High H20 permeability in PCT & descending LOH. NO H20 permeability in ascending LOH. Variable H20 permeability in the DCT & collecting ducts (hormone dependent)
Example of a substance which has 100% resorption, 1 that is half resorbed & 1 that undergoes secretion to excrete more than was filtered?Glucose, Urea & Penicillin
Renal ABSORPTION of weak acids in... a low urinary pH↑ absorption (bc not ionized)
Renal ABSORPTION of weak acids in... a high urinary pH↓ absorption (ionized)
Renal ABSORPTION of weak bases in.... a low urinary pH↓ (ionized)
Renal ABSORPTION of weak bases in...a high urinary pH↑ (bc not ionized)
CONSTRICTION of mesengial cells leads to what kinda change in the GFR?Constriction = ↓ GFR (when they constrict, they tighten up around the vessel & less gets through)
What causes mesengial cells to constrict? What causes them to relax?Atrial Natriuretic Peptide causes relaxation, Angiotensin causes constriction & sympathetic innervation causes constriction

Proximal Convoluted Tubule (PCT)

Question Answer
Describe the epithelium of the PCTIt is "leaky" which is why there is passive flow of H20/solutes in either direction (secretion or resorption)
In the PCT, what is the direction of most of the flow?High flow from lumen to the blood
How much H20 & Na+ are usually resorbed in the PCT?60-70%!
Explain the path the Na+ takes to get from PCT lumen to interstitium outside of lumenNa enters the cell from the lumen via the Na/H exchanger → Na leaves cell & enters interstitium via Na/K -ATPase (aka pump).
Explain how H20 goes from inside the PCT lumen to the interstitium outside of the tubule?H20 follows the osmotic gradient (passive resorption) which was created by Na+ being exchanged + pumped into the interstitium (see other card for details about Na+'s travels)
Which Class of drugs work in the PCT?Carboanhydrase Inhibitors (on a diet? carbs are the 1st thing to go)
Which specific drug works in the PCT?Acetazolamide (the Ace will always get in 1st, if yaknowwhatimean & TAZ was an ACE at pissing)
Acetazolamide ↑ the excretion of what substances? What affect does this have on the urine & the body pH?By inhibiting Carbonic Anhydrase (a family of enzymes that catalyze the rapid inter-conversion of carbon dioxide & H20 to bicarbonate & protons, which is how bicarb is broken down, resorbed & then reassembled) means there will be a ↑ EXCRETION of bicarbonate (basic) W/ accompanying Na+, K+ & H2O (H+ is more retained since it moves opposite of Na & K). This will make the urine mildly alkaline, which means you are losing base & retaining acid which means you have a metabolic acidosis
What is Acetazolamide used to Tx?Glaucoma
How strong is the diuretic effect of Acetazolamide?Mild
Is Acetazolamide K-sparing or K-losing?Losing
Which ions follow bicarbonate?Na+, K+, H2O

Loop of Henle (LOH)

Question Answer
Explain the "Countercurrent system" of the LOHH20 is permeable in the descending limb (passive bc of hyper-tonic interstitium) & Na is permeable in the ascending limb (active xport)
What are the 2 parts of the ascending limb of the LOH & how is NaCl xport different?Passive transport of NaCl in the thin ascending limb & active transport in the thick ascending limb (think of thin like a thin membrane so passive easier there)
How much Na is reabsorbed in the LOH?20-30%
How powerful are Loop Diuretics?MOST powerful!
How do Loop Diuretics work? (2)They inhibit the Na+/K+/Cl- carrier & act as venodilators (dilate VEINS-- through Endothelin Derived Kinin (NO/PGI) )
What is the result of Loop Diuretics on the various ions & then on the body's pH status?↑ [Na+] in distal tubules results in ↑ loss of H & Kmetabolic alkalosis. There is also a secretion of Ca & Mg & secretion of Uric acid (bc Uric acid is active tubular secretion & so is Furosemide, so they compete & overall less Uric acid is able to be secreted)
Where are Loop Diuretics absorbed & how well are they absorbed?Readily absorbed in GIT (effective w/in 1hr!)
What is the pharmacodynamics (protein binding) of a Loop Diuretic drug like?STRONGLY protein bound (looped around that protein)
Where/How are Loop Diuretics excreted?Excreted in the kidney by active transport
NAME the 3 Loop Diuretics we care aboutTorasemide, Furosemide, Bumetanide (that tora has a furious bum)
Where is Torasemide & Bumetanide metabolized & how?Liver → CYP450 pathways (Bum & Bull will always take the intense enzyme path)
Where is Bumetanide metabolized & how?Liver → CYP450
Where is Furosemide metabolized & how?Liver → Glucuronidation (less safe for cats)
What are the SFx of Loop Diuretics?Hypokalemia! & metabolic alkalosis (↑ Na+ in the tubule from inhibiting the Na/K/Cl carrier means losing lots of H+ & K+ bc they follow Na) . Also, bc so strong, will see hypovolemia & hypotension from the vasodilation effect
K-sparing or K-losing?Losing

Distal Convoluted Tubule (DCT)

Question Answer
Describe what is happening in the DCT (be sure to mention the pumps/transporters/ions/etc) (3 main points)(1) Further dilution of the solute takes place bc of the active Na/Cl transporter
(2) Excretion of H & K is driven by the Na/K transport
(3) Ca excretion is regulated by PTH & calcitriol (Vitamin D) – both ↑ Ca reabsorption
Which group of Anti-Diuretics works on the DCT?Thiazide Diuretics
Name the 2 drugs (& the group they belong to) that work on the DCT(Thiazide Diuretics) Chlorothiazide & Hydrochlorothiazide
How do Thiazides work?Blocks Na/Cl transporter (symport, so both in the same direction) by binding to the Cl site
What are Thiazides used to tx?Hypertensions, mild heart failure, Diabetes Insipidus (central or nephrogenic),
What are the RENAL SFx of Thiazides? (3)Hypokalemia, metabolic alkalosis (losing H+, Na+, K+, etc), ↑ plasma Uric acid (Uric acid is actively secreted into nephron, but so are Thiazides, so there is competition & less Uric acid secreted which means there's more Uric acid in the plasma)
Are Thiazides K-sparing or K-losing?Losing
What are the NON-renal SFx of Thiazides? (5)Hyperglycemia, vasodilation, ↑ plasma cholesterol, male impotence, hypersensitivity rxns (his DCT btwn this THIGHS wont get up bc it's clogged w/ cholesterol & the vessels wont constrict to keep the blood in. It's esp not sweet, bc it's still hypersensitive)
Are Thiazides lipophilic or hydrophilic?Hydrophilic (they love peeeee) (think that youd want H20 btwn your thighs, not fat)
When using Thiazides, what is excreted more, what is excreted less?(More): Sig. K+ loss, also lose Mg++ & Na+ & Cl- (& H+). (less): Uric acid & Ca
What dzs are Thiazides beneficial in? Why? (Relating to things outside of just the diuretic effect) (2)(1) Diabetes Insipidus, bc they have a paradoxical effect where they reduce the urine output!
(2) May reduce bone loss issues in post-menopausal women & elderly men, since Ca++ is retained w these drugs
How do Thiazides affect the blood vessels?Cause vasodilation
Explain the different ways that Thiazides Tx hypertensionWhen used in hypertension the initial fall in BP comes from ↑ volume of urine (= ↓d blood volume); the later phase seems to be the result of a direct action on the blood vessels
From where/how well are Thiazides absorbed?Well absorbed from the GI
Where are Thiazides excreted? How/notes?Excreted in urine by tubular secretion (competition w/ Uric acid for secretion mechanisms)
Thiazides have competition for tubular secretion w/ what?Uric acid
Explain why Thiazides are beneficial for treating central or nephrogenic Diabetes Insipidus(diuresis → ↓ in plasma volume → ↓ in GFR → ↑ reabsorption of Na PCT & loop of Henle)
Explain what is going on w/ Na, Cl, K & H & why, due to ThiazidesIn the early part of the DCT, the Na/Cl symporter is inhibited by the Thiazides. This causes an ↑ in the conc of Na in urine. the urine travels to the late part of the DCT & the membrane is permeable & the Na conc is very high, so Na starts to diffuse into the cells & the Na/K pump takes the Na from the cell into the interstitium, which forces K into the cell, which then gains a high conc there & causes it to go into the lumen (losing lots of K then). Also, H+ is being lost bc the Na/H pump is also pumping excess Na from the urine into the cell, which it exchanges for the H+ to go into the urine (or the H+ is following the K+, I’m not sure) Thus, hypokalemia & metabolic alkalosis
How do Thiazides affect Diabetes Mellitus?Make it WORSE. Why? Cause HYPERglycemia. (Internet says: K+ channels are responsible for releasing insulin from β cells, no k, no release, hyperglycemia)