Pharm 2 - Final 5

drraythe's version from 2015-11-10 19:53


Question Answer
Excretion of a weak acid in a ....urine w/ low pH. Urine w/ high pHWeak acid = low pH. If very diff, ie, basic urine(high pH) will ionize & get excreted. If similar pH (acidic urine, low pH) will not ionize, get resorbed, & not get excreted
Active secretion of drugs (weak acids & weak bases) is where?Prox tubule
What are some acidic DRUGS (& related substances) which are ACTIVELY SECRETED in proximal tubule?Furosemide, Glucuronic Acid 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, Quaternary Ammonium Compounds, Serotonin, Pethidine, Amiloride (← K+ sparing diuretic)
How do mesangial cells affect GFR? What are 3 substances/innervations which can affect the behavior of mesangial cells?Constriction of mesangial 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 water permeability?High water permeability in PCT & descending LOH. NO water permeability in ascending LOH. Variable water permeability in the DCT & 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 & H2O
Which class of drugs work in the PCT?Carboanhydrase Inhibitors
Which specific drug works in the PCT?Acetazolamide
Acetazolamide ↑ the excretion of what substances? What affect does this have on the urine & the body pH?(PCT) inhibiting Carbonic Anhydrase(a family of enzymes that catalyze the rapid interconversion of carbon dioxide & water 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 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)
What is the pharmacodynamics (protein binding) of a Loop Diuretic drug like?STRONGLY protein bound (looped around that protein)
NAME the 3 Loop Diuretics we care aboutTorasemide, Furosemide, Bumetanide (that tora has a furious bum)
Where is Torasemide/Furosemide/Bumetanide metabolized?(1) Tora = CYP450
(2) Furosemide = CYP450
(3) Bumetanide = Glucoronidation (bum is a bum & doesnt bother w/ the intense route, decides to glucoronidate instead)
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
Which group of antidiuretics works on the DCT?Thiazides
What are the Thiazide drugs?Chlorothiazide & Hydrochlorothiazide
MOA of ThiazidesBlocks Na/Cl transporter (symport, so both in the same direction) by binding to the Cl site (salty btwn your thighs-NACL)
Thiazides used to Tx?Hypertensions, mild heart failure, Diabetes Insipidus (central or nephrogenic) (inspid thighs)
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) (pee btwn your thighs → Uric Acid thing)
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 water btwn your thighs, not fat)
What dzs are Thiazides benificial 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 postmenopausal women & elderly men, since Ca++ is retained w these drugs (insipidus thighs, & the bones in your thighs will be spared)
Thiazides have competition for tubular secretion w/ what?Uric Acid
How do Thiazides affect Diabetes Mellitus?Make it WORSE. Why? Cz HYPERglycemia. (Internet says: Channels are responsible for releasing insulin from β-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 & 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? SFx?K-SPARING! Works by competing w/ Aldosterone. Well absorbed from GIT.
Sfx are:
GI upset
Menstrual 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?Spironolactone
(Group?) How does Amiloride work? Where/how is it absorbed? How is it excreted? SFx?(KSPARING) Directly ↓ activity of the pump (Na/K). Poorly absorbed from GIT. It is excreted mostly unchanged. SFx is hyperkalemia (Ami wont let much change her, & 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? SFx?(KSPARING) Directly ↓ activity of the pump (Na/K). Well absorbed from GIT. Excreted partly unchanged. Sfx 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 Tx?hypokalemia 2⁰ to other diuretic use (CHF), Tx edema & ascites (think hepatic Dz & portal hypertension) (special K for your liver, eat it up & your belly will swell & your heart will explode)
What are the Aldosterone-Mediated Effects on the tubule? (6)(COLLECTING DUCTS) [remember, Aldosterone is interested in absorbing Na+Cl & 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 3 K-sparing diuretics?Spirinolactone, Amiloride, Triamterene (AMI took special K & then TRIed to ride SPIRO the dragon)
*Supportive therapy → management of oliguria or anuria. How do we do this?Start w/ Furosemide (Loop Diuretic) when lack of urinary output. Then use osmotic diuretics. Then use Fenoldopam (a Dopamine agonist which works better than Dopamine bc it doesnt get degraded so quickly- works on D1 receptors which cz vasodilation for ↑ GFR), then Diltiazem (a Ca++ antagonist which cz vasodilation to ↑ GFRs)
Supportive therapy → Tx of uremic complications (what are the 2 complications, basic idea on how you Tx it?)(1) Vomiting → anti-emetics & inhibitors of gastric acid secretion
(2) Hypertension → adjust fluid administration rates- diuretics – antihypertensive
Chronic kidney Dz → how is severity of dz usually reflected?Reflected in the magnitude of proteinuria (urine protein-to-creatinine ratio) (if proteinuria is persistent 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 w/ the RAAS?Renin-Angiotensin-Aldosterone...inhibit
What are the 4 ways to inhibit the RAAS system?(1) Angiotensin-Converting-Enzyme (ACE) Inhibitors
(2) Angiotensin Receptor Blockers (Losartan-Telmisartan)
(3) Aldosterone receptor blockers (Spironolactone)
(4) Renin inhibitors (used in humans & not extensively yet in dogs: Aliskirine)
Aldosterone receptor blocker?Spirinolactone
Losartan/Telmisartan do what?Angiotensin 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 Angiotensin II work here. vasoconstriction → Aldosterone & Vasopressin release - sodium & water retention (sympathetic facilitation). cell prolif → left ventricular hypertrophy, nephrosclerosis, endothelial dysfxn.
(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 cz strong antihypertensive effects
What are the properties of Telmisartan?
(hydro or lipophilic? Is there prot binding? How is it absorbed & how is it metabolized?)
Lipophilic, binds reversibly to plasma proteins, oral bioavail is 33% in cat, & is GLUCORONIDATED (oddly enough, cats still do well w/ it) (my FAT CAT loves to EAT PROTEIN & GLUCOSE, & will TEL MI when he wants to)
What are the 2 Txs 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 infxn, 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 ) & LIPOPHILIC drugs such as Fluoroquinolones, chloramphenicol, TMPS
Do you want a static or a cidal ABx for Txing cystitis?CIDAL, bc static just stops them & 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) Tx of cystitis entail? What kinda drugs would you use, & which type (structure) is preferred?Inhibition of bladder contractions (Oxybutynin - Propanthelin). Want the drugs w/ quaternary structures, bc these cant get into the brain & cz CNS SFx like the tertiary do (bc they are much bigger) d))
Incontinence in the bitch is usually due to what?Urethral sphincter mechanism incompetence (↓ estrogen → ↓ α-receptors → less contraction)
Which drugs to Tx bladder contractions?Oxybutynin, Propanthelin (TCA too) (oxy will relax your bladder for sure, & so will huffing propane) (wont mix up w/ drugs for hypertonic urethra bc oxys are REALLY strong & the bladder is WAY bigger) (bladder contractions are not phen, so no phen in these drugs)
Explain how innervation differs btwn the storage & voiding phases of the bladder(storage) SYMPATHETIC innervation of the bladder (relaxation) & urethra (contraction). (Voiding) controlled by voluntary control centers & mediated by spinal pathways & the pelvic nerve (parasympathetic innervation to the bladder & inhibition of sympathetic pathways)
Bladder contraction & opening of the internal sphincter is controlled by what nerve?Pelvic n
Contraction of internal sphincter & relaxation of detrusor muscle is controlled by what nerve?Hypogastric n
What are the 2 types of receptors which control the bladder? Which nerve effects which receptor for what result?(1) M3 receptor → Pelvic nerve → Contract bladder ("M 3 for pee")
(2) B2 receptor → Hypogastric nerve → Relaxation of bladder (remember that 2 is on the inside & pushes out = relaxation. so β-2) (BM for bladder movement)
What is the receptor in the internal urethral sphincter? What nerve effects it, to do what?α-1 receptor → hypogastric nn → contraction of internal sphincter (the internal sphincter is A #1 defense against pissing yourself & then vomiting (gastric) from the embarrassment)
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 & not pu)
Why do estrogens help a hypotonic urethra (sphincter incontinence) drugs?Estrogen cz sensitization & upregulation of α-receptors. Diethylstilbestrol, Stilbestrol
Hypotonic urethra can be Txd w/ what 2 types of things? (Name drugs)(1) Estrogens
(2) α-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 2 categories of drugs youd use to Tx Hypertonic urethra?(1) α-Adrenergic antagonists (Phenoxybenzamine, Prazosin)
(2) Striated muscle relaxants (Diazepam, Dantrolene) (bc 2 sphincters that are diff types of mm, so need 2 diff categories)
What are striated muscle relaxants used for, & what are the drugs in this category?Tx hypertonic urethra. Diazepam, Dantrolene (Dan takes Diazepam to relax his tense urethra in his dick)
What are α-Adrenergic antagonists used for, & what are the drugs in this category?Tx hypertonic urethra. Phenoxybenzamine, Prazosin (an ox & praz hilton will force open your upper urethra)