Pharm final 5

kelseyfmeyer's version from 2015-05-08 19:24


Question Answer
excretion of a weak acid in a ....urine with low pH. urine with high pHweak acid=low pH. if very diff, ie, basic urine(high pH) will ionize and get excreted. If similar pH (acidic urine, low pH) will not ionize, get resorbed, and not get excreted
active secretion of drugs (weak acids and weak bases) is where?prox tubule
what are some acidic DRUGS (and related substances) which are ACTIVELY SECRETED in proximal tubule?furosemide, glucuronic acids conjugates, glycine conjugates, penicillin, uric acid, sulphate conjugates, thiazide diuretics
what are some basic drugs (/related substances) which are actively SECRETED in the proximal tubule?dopamine, histamine, morphine, quarternary ammonium compounds, serotonin, pethidine, amiloride(<--K+ sparing diuretic)
how do mesengial cells affect GFR? what are three substances/innervations which can affect the behavior of mesengial cells?Constriction of mesengial cells leads to DECREASED GFR! (1) Atrial Natriuretic Peptide: relaxation (2) Angiotensin II: constriction (3) Sympathetic innervation: contraction
Where along the nephron is there high, none, or variable water permeability?high water permeability in PCT and descending LOH. NO water permeability in ascending LOH. Variable water permeability in the DCT and collecting ducts (hormone dependent)
whats the direction of the flow like in the PCT?most from the lumen goes back into blood, incld like 60-70% of Na and H2O
which class of drugs work in the PCT?Carboanhydrase inhibitors
which specific drug works in the PCT?Acetazolamide
Acetazolamide increases the excretion of what substances? What affect does this have on the urine and the body pH?(PCT) inhibiting carbonic anhydrase(a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons, which is how bicarb is broken down, resorbed, and then reassembled) means there will be a INCREASED EXCRETION of bicarbonate (basic) with accompanying Na+, K+, and H2O (H+ is more retained since it moves opposite of Na and K). This will make the urine mildly alkaline, which means you are losing base, and retaining acid which means you have a metabolic acidosis
what is Acetazolamide used to treat?glaucoma
how do loop diuretics work? (2)they inhibit the Na+/K+/Cl- carrier, and act as venodilators (dilate VEINS-- through endothelin derived kinin (NO/PGI) )
What is the result of loop diuretics on the various ions, and then on the body's pH status?Increase [Na+] in distal tubules results in increase loss of H and K--> metabolic alkalosis.There is also a Increase secretion of Ca and Mg and decrease secretion of uric acid (bc uric acid is active tubular secretion, and so is furosemide, so they compete and overall less uric acid is able to be secreted)
what is the pharmacodynamics (protein binding) of a loop diuretic drug like?STRONGLY protein bound (looped around that protein)
NAME the three loop diuretics we care abouttorasemide, furosemide, bumetanide (that tora has a furious bum)
where is torasemide/furosemide/bumetanide metabolized?(1) tora=CYP450 (2) fursomide=CYP450 (3)bumetanide=glucoronidation (bum is a bum and doesnt bother with the intense route, decides to glucoronidate instead)
What are the side effects of loop diuretics?hypokalemia! and metabolic alkalosis (inc Na+ in the tubule from inhibiting the Na/K/Cl carrier means losing lots of H+ and K+ b/c they follow Na). Also, because so strong, will see hypovolemia and hypotension from the vasodilation effect
which group of antidiuretics works on the DCT?thiazides
what are the thiazide drugs?Chlorothiazide and Hydrochlorothiazide
MOA of thiazidesBlocks Na/Cl transporter(symport, so both in the same direction) by binding to the Cl site (salty between your thighs-NACL)
thiazides used to tx?hypertensions, mild heart failure, diabetes insipidus (central or nephrogenic) (inspid thighs)
what are the RENAL side effects of thiazides? (3)hypokalemia, metabolic alkalosis (losing H+, Na+, K+, etc), increased plasma uric acid (uric acid is actively secreted into nephron, but so are thiazides, so there is competition and less uric acid secreted which means there's more uric acid in the plasma) (pee between your thighs--> uric acid thing)
what are the NON-renal side effects of thiazides? (5)Hyperglycemia, Vasodilation, Increases plasma cholesterol, Male impotence, Hypersensitivity reactions (his DCT between this THIGHS wont get up because it's clogged with chlosterol and the vessels wont constrict to keep the blood in. It's esp not sweet, because it's still hypersensitive)
are thiazides lipophilic or hydrophilic?hydrophilic (they love peeeee) (think that youd want water between your thighs, not fat)
what dzs are thiazides benificial in? why? (relating to things outside of just the diuretic effect) (2)(1) diabetes insipidus, because they have a paradoxical effect where they reduce the urine output! (2) may reduce bone loss issues in postmonopausal women and elderly men, since Ca++ is retained w these drugs (insipitus thighs, and the bones in yoru thighs will be spared)
thiazides have competition for tubular secretion with what?uric acid
how do thiazides affect diabetes mellitus?make it WORSE. why? cause HYPERglycemia. (internet says: K+channels are responsible for releasing insulin from beta cells, no k, no release, hyperglycemia)
what controls Na/Cl absorption in the in the collecting ducts?aldosterone
what controls water reabsorption in the collecting ducts?ADH/vasopressin
explain how K+ balance and K-sparing diuretics workK loss will be ↓ when Na reabsorption is ↓ in the collecting ducts (this is what K-sparing diuretics do)
(group?) how does Spironolactone work? where is it absorbed/how well is it absorbed? Side effects?K-SPARING! works by competing with aldosterone. Well absorbed from GIT. SEs are GI upset, hyperkalemia, gynaecomastia, mestrual disorders, testicular atrophy, peptic ulcers
which K-sparing diuretic has an active metabolite? what is the name of the a.m.?Spironolactone does, the a.m. is called canrenone (SPIRO CAN do it!)
which K-sparing diuretic's onset takes several days?spirinolactone
(group?) how does Amiloride work? where/how is it absorbed? how is it excreted? side effects?(KSPARING) Directly decreases activity of the pump(Na/K). Poorly absorbed from GIT. It is excreted mostly unchanged. SE is hyperkalemia (Ami wont let much change her, and she doesnt care that you can't stomach her. she'll punch you right in the pump)
(GROUP?) how does Triamterene work? where/how well is it absorbed? How is it excreted? Side effects?(KSPARING) Directly decreases activity of the pump(Na/K). Well absorbed from GIT. excreted partly unchanged. SE is hyperkalemia (Tri-s to be like Ami, but that's why it partly changes itself in order to convince itself to punch you in the pump. However, when not around any, is easy to stomach)
what are K-sparing diuretics used to treat?decrease hypokalemia secondary to other diuretic use (CHF), treat edema and ascites (think hepatic disease and portal hypertension) (special K for your liver, eat it up and your belly will swell and your heart will explode)
what are the aldosterone-mediated effects on the tubule? (6)(COLLECTING DUCTS) [remember, aldosterone is interested in absorbing Na+Cl and excreting K]. (1) activate Na channels (2) redistribute Na channels to luminal membrane (3) De novo(new) synthesis of Na channels (4) Activation of K/Na ATPase(pump) (5) Redistribution of K/Na ATPase to the basolateral membrane (6) De novo(new) synthesis of K/Na ATPase
what are the three K-sparing diuretics?spirinolactone, amiloride, triamterine (AMI took special K and then TRIed to ride SPIRO the dragon)
*supportive therapy--> management of oliguria or anuria. How do we do this?Start with furosemide(loop diuretic) when lack of urinary output. Then use osmotic diuretics. Then use fenoldopam (a dopamine agonist which works better than dopamine because it doesnt get degraded so quickly- works on D1 receptors which cause vasodilation for inc GFR), then diltiazem (a Ca++ antagonist which causes vasodilation to inc GFRs)
supportive therapy--> treatment of uremic complications (what are the two complications, basic idea on how you tx it?)(1) vomiting--> anti-emetics and inhibitors of gastric acid secretion (2) hypertension--> adjust fluid administration rates- diuretics - antihypertensives
Chronic kidney disease--> how is severity of dz usually reflected?reflected in the magnitude of proteinuria (urine protein-to-creatinine ratio) (if proteinuria is persistant higher than 0.5, def a prob, he said, but this isnt in notes)
what is the RAAS? If you have kidney dz, what do you wanna do with the RAAS?Renin-angiotensin-aldosterone...inhibit
what are the 4 ways to inhibit the RAAS system?(1) Angiotensin-converting-enzyme inhibitors (2) Angiotensin receptor blockers (losartan -telmisartan) (3) Aldosterone receptor blockers (spironolactone) (4) Renin inhibitors (used in humans and not extensively yet in dogs: aliskirine)
aldosterone receptor blocker?spirinolactone
losartan/telmisartan do what?antigotension receptor blockers (SARTANS were a tense group of greeks)
Angiotensin receptor blockers--> what are the receptors these drugs act on? Describe the properties of the receptors(1) AT1. The Classic effects of angiotensionII work here. vasoconstriction--> aldosterone and vasopressin release - sodium and water retention (sympathetic facilitation). cell prolif--> left ventricular hypertrophy, nephrosclerosis, endothelial dysfunction. (2) AT2. usually does opposite of the classical AT1, in order to limit the detrimental effects of AT1 activation. Actions are: vasodilation - sodium excretion - anti proliferative effects
which receptors does telmisartan bind to? what are the strong effects it exerts?Binds strongly to AT1 (the classic effect receptor) to reverse effects by inhibiting. This causes strong antihypertensive effects
what are the properities of telmisartan? (hydro or lipophilic? is there prot binding? how is it absorbed, and how is it metabolized?)Lipophilic, binds reversibly to plasma proteins, oral bioavail is 33% in cat, and is GLUCORONIDATED (oddly enough, cats still do well with it) (my FAT CAT loves to EAT PROTEIN and GLUCOSE, and will TEL MI when he wants to)
what are the two treatments for benign prostatic hyperplasia?(1) finasteride (synthetic steroid type-II 5α- reductase inhibitor: block the pathway for conversion of testosterone into DHT) (2) sx (castration) (finas off those balls by cutting them off)
If you have an acute prostatitis, why do you care about/what is the pH of the prostate?the prostate's pH is < blood pH. So, acidic tissue. Since acute prostatitis is usually due to a bact infection, you want to pic an abx which will be attracted to the acidic pH of the prostate/be ionized once it gets into prostate so it wont leave---so you want BASIC abx, such as erythromycin, trimethoprim ) and LIPOPHILIC drugs such as fluoroquinolones, chloramfenicol, TMPS
do you want a static or a cidal abx for treating cystitis?CIDAL, because static just stops them and then the phagocytes are supposed to take over, but in the bladder its not super easy for phagocytes to get in, etc)
what would symptomatic (symptom is bladder contractions) treatment of cystitis ential? what kinda drugs would you use, and which type(structure) is preferred?inhibition of bladder contractions (oxybutynin - propanthelin). Want the drugs with quartenary structures, because these cant get into the brain and cause CNS side effects like the tertiary do (bc they are much bigger) d))
incontinance in the bitch is usually due to what?urethral sphincter mechanism incompetence (dec estrogen--> dec alpha receptors--> less contraction)
which drugs to tx bladder contractions?Oxybutynin, Propanthelin (TCA too) (oxy will relax your bladder for sure, and so will huffing propane) (wont mix up with drugs for hypertonic urethra because oxys are REALLY strong and the bladder is WAY bigger) (bladder contractions are not phen, so no phen in these drugs)
explain how innervation differs between the storage and voiding phases of the bladder(storage) SYMPATHETIC innervation innervation of the bladder(relaxation) and urethra (contraction). (voiding)controlled by voluntary control centres and mediated by spinal pathways and the pelvic nerve (parasympathetic innervation to the bladder and inhibition of sympathetic pathways)
bladder contraction and opening of the internal sphincter is controlled by what nerve?pelvic n
contraction of internal sphincter and relaxation of detrusor muscle is controlled by what nerve?hypogastric n
what are the two types of receptors which control the bladder? which nerve effects which receptor for what result?(1) M3 receptor--> pelvic nerve--> contract bladder ("M three for pee") (2) B2 receptor--> hypogastric nerve--> relaxation of bladder (remember that 2 is on the inside and pushes out= relaxation. so beta 2) (BM for bladder movement)
what is the receptor in the internal urethral sphincter? what nerve effects it, to do what?alpha-1 receptor--> hypogastric nn--> contraction of internal sphincter ( the internal sphincter is A #1 defense against pissing yourself and then vomiting (gastric) from the embarassment)
what is the receptor of the external urethral sphincter? what nerve effects it, to do what?nicotinic receptor--> pudendal nerve (SOMATIC nerve)--> contraction of external sphincter (nicotine will make you tense up and not pu)
why do estrogens help a hypotonic urethra (sphincter incontinance) drugs?estrogen causes sensitisation and upregulation of alpha-receptors. diethylstilbestrol, stilbestrol
Hypotonic urethra can be treated with what two types of things? (name drugs)(1) estrogens (2) alpha-adrenergic agonists (phenylpropanolamine) (also no phen when you're always peeing. remember that you can have more phen by PROPing the urethral door closed)
what are the two categories of drugs youd use to tx Hypertonic urethra?(1) alpha-adrenergic antagonists(phenoxybenzamine, prazosine) (2) striated muscle relaxants(diazepam, dantrolene) (b/c two sphincters that are diff types of mm, so need two diff categories)
what are striated muscle relaxants used for, and what are the drugs in this category?treat hypertonic urethra. diazepam, dantrolene (dan takes diazepam to relax his tense urethra in his dick)
what are alpha-adrenergic antagonists used for, and what are the drugs in this category?treat hypertonic urethra. phenoxybenzamine, prazosine ( an ox and praz hilton will force open your upper urethra)