Renal Pharmacology PDF

**Renal** Renal clearance = volume of plasma containing the drug removed. By the kidney per unit time 3 fundamental processes to renal clearance: 1. Ultrafiltration: in the glomerulus all drugs under a certain size will pass through the glomerulus into filtrate (most are small enough for...

**Renal** Renal clearance = volume of plasma containing the drug removed. By the kidney per unit time 3 fundamental processes to renal clearance: 1. Ultrafiltration: in the glomerulus all drugs under a certain size will pass through the glomerulus into filtrate (most are small enough for this) 2. Secretion: in the proximal and distal tubule everything that doesn't go through glomerulus will be transferred in here by one of either: a. Organic anion transporters (for acidic drugs against the electrochemical gradient) b. Organic cation transporters (for basic drugs, facilitated down the gradient) i. These mechanisms can remove bound drugs making it really effective 3. Resorption: in the proximal/distal tubule passive resorption of lipophilic drugs. Drugs that cross membranes freely will be reabsorbed down the concentration gradient therefore lipid soluble drugs are poorly excreted by the kidney **Nephrotoxicity:** **Aminoglycosides** renal tubular cells particularly in the PCT are vulnerable as they concentrate and reavsorb glomerular filtrate. They cause tubular cell toxicity by: - Accumulating in lysosomes of the PCT epithelial cells - Impair mitochondrial function thereby increasing oxidative stress and free radicals - Thus interfering with tubular transport **NSAIDS** the kidney autoregulates intra-glomerular pressure by modulating the afferent and efferent arterial tone to preserve GFR and urine output - Prostaglandins normally dilate the afferent arteriole - NSAIDS are COX2 inhibitors and thus BLOCK prostaglandin production - Therefore they can decrease blood flow to the kidneys and lack of oxygen would cause acute kidney injury - They also cause acute interstitial nephritis by inducing an immunological reaction after period of NSAID exposure leading to the presence of inflammatory cell infiltrate in the kidney interstitium. **Diuretics:** Diuretics **increase** the rate of urine flow and excretion of Na and water from the filtrate. They **decrease** the reabsorption of Na and usually Cl from the filtrate Helpful for oedema, AKI, forced diuresis and correcting ion imbalances **DIURETICS:** +-------------+-------------+-------------+-------------+-------------+ | **Drug | **Mechanism | **Indicatio | **Unwanted | **Example** | | class** | of action** | ns** | effects** | | +=============+=============+=============+=============+=============+ | **Osmotic | Filtered in | Forced | Transient | Mannitol | | Diuretics** | the | diuresis | expansion | | | | glomerulus | (intoxicati | of | | | **Requires | but not | on, | extracellul | | | IV | reabsorbed | impending | ar | | | admin!!** | | kidney | fluid | | | | Increase | failure) | volume | | | | osmolarity | | | | | | of the | Emerg Tx of | Hyponatremi | | | | filtrate in | acutely | a | | | | PCT, | raised | (acute) | | | | descending | intracrania | | | | | limb and | l | | | | | collecting | or | | | | | ducts | intraocular | | | | | | pressure | | | | | Water | | | | | | retained in | | | | | | urine | | | | | | | | | | | | leading to | | | | | | decreased | | | | | | concentrati | | | | | | on | | | | | | of Na in | | | | | | lumen and | | | | | | decreased | | | | | | reabsorptio | | | | | | n | | | | | | of Na | | | | +-------------+-------------+-------------+-------------+-------------+ | **Carbonic | block | glaucoma | | | | anhydrase | reaction of | | | | | inhibitors* | CO2 with | idiopathic | | | | * | H2O | benign | | | | | | intracrania | | | | | Thus | l | | | | | prevent | hypertensio | | | | | Na/H | n | | | | | exchange | | | | | | and HCO3 | altitude | | | | | ion | sickness | | | | | reabsorptio | | | | | | n | | | | | | in PCT and | | | | | | Na | | | | | | reabsorptio | | | | | | n | | | | | | also | | | | | | reduced | | | | | | | | | | | | Increased | | | | | | HCO3 in | | | | | | filtrate | | | | | | opposes | | | | | | water | | | | | | reabsorptio | | | | | | n | | | | | | | | | | | | HCO3 | | | | | | eliminated | | | | | | in urine = | | | | | | systemic | | | | | | acidosis | | | | | | | | | | | | Consequentl | | | | | | y | | | | | | plasma HCO3 | | | | | | also | | | | | | depletes | | | | | | which makes | | | | | | its | | | | | | diuretic | | | | | | effects | | | | | | self | | | | | | limiting | | | | +-------------+-------------+-------------+-------------+-------------+ | **Loop | Na, K and | oedema | excessive | Furosemide | | diuretics** | Cl enter | (hepatic, | water loss | | | | blood by a | cardiac, | | | | | co | renal) | sodium and | | | | transport | | potassium | | | | system | heart | loss | | | | | failure | following | | | | act on Na, | | long term | | | | K and 2Cl | forced | use | | | | symporter | diuresis | | | | | in the | | hypoCa | | | | thick | | | | | | ascending | | adaptive | | | | limb of the | | changes in | | | | loop of | | circulation | | | | henle | | (activation | | | | | | of RAAS) | | | | inhibit Na, | | | | | | K and Cl | | | | | | reabsorptio | | | | | | n | | | | | | causing | | | | | | diuresis | | | | | | WITH loss | | | | | | of | | | | | | electrolyte | | | | | | s | | | | | | | | | | | | principal | | | | | | cells in | | | | | | the | | | | | | collecting | | | | | | ducts will | | | | | | respond to | | | | | | increased | | | | | | Na in urine | | | | | | by | | | | | | increasing | | | | | | K secretion | | | | | | in return | | | | | | for Na | | | | | | reabsorptio | | | | | | n | | | | | | | | | | | | don't pass | | | | | | directly | | | | | | into | | | | | | glomerular | | | | | | filtrate | | | | | | but are | | | | | | secreted by | | | | | | organic | | | | | | anion | | | | | | transporter | | | | | | s | | | | | | | | | | | | interfere | | | | | | with | | | | | | tubular | | | | | | feedback | | | | | | control of | | | | | | GFR thus no | | | | | | decrease in | | | | | | GFR | | | | +-------------+-------------+-------------+-------------+-------------+ | **Thiazides | bind to the | oedema | adaptive | | | ** | Cl site of | | changes in | | | | the distal | heart | circulation | | | | tubules | failure | | | | | Na/Cl co | | potassium | | | | transport | | loss | | | | system | | following | | | | | | long term | | | | act to | | use (rare | | | | inhibit Na | | in vet med) | | | | reabsorptio | | | | | | n | | Ca | | | | | | excretion | | | | thus more | | reduced by | | | | Na | | Mg enhanced | | | | delivered | | | | | | to | | | | | | collecting | | | | | | duct and | | | | | | some Na | | | | | | will be | | | | | | reabsorbed | | | | | | in exchange | | | | | | for K | | | | | | excretion | | | | | | | | | | | | less | | | | | | powerful | | | | | | than loop | | | | | | diuretics | | | | | | but better | | | | | | tolerated | | | | | | | | | | | | Can be | | | | | | combined | | | | | | with other | | | | | | diuretics | | | | | | as act on | | | | | | different | | | | | | site (DT) | | | | +-------------+-------------+-------------+-------------+-------------+ | **Potassium | directly | during long | hyperkalaem | Triamterene | | sparing | blocks the | term tx in | ia | and | | diuretics** | epithelial | combo w/ | | amiloride | | | Na channel | thiazides | | | | | | and loop | | | | | inhibits Na | diuretics | | | | | reabsorptio | (can | | | | | n | prevent | | | | | in the | hypokalaemi | | | | | collecting | a | | | | | ducts | associated | | | | | | with loop | | | | | promotes | diuretcis) | | | | | loss of Na | | | | | | and water | oedema due | | | | | from the | to | | | | | body but | hyperaldost | | | | | without | eronism | | | | | depleting K | | | | +-------------+-------------+-------------+-------------+-------------+ | **Aldostero | tubule | | | spirolacton | | ne | cells are | | | e | | antagonists | impermeable | | | | | ** | to Na in | | | | | | the absence | | | | | **Well | of | | | | | absorbed PO | aldosterone | | | | | and | | | | | | extensively | aldosterone | | | | | metabolised | acts via | | | | | by liver to | mineralocor | | | | | active | ticoid | | | | | metabolite* | receptor | | | | | * | within the | | | | | | collecting | | | | | **Onset of | duct | | | | | action is | therefore | | | | | slow** | increasing | | | | | | ENaC | | | | | | channel and | | | | | | Na/K ATPase | | | | | | expression, | | | | | | increasing | | | | | | Na and Cl | | | | | | reabsorptio | | | | | | n | | | | | | and K and | | | | | | Ca | | | | | | excretion | | | | | | from renal | | | | | | tubules | | | | | | | | | | | | competes | | | | | | with | | | | | | aldosterone | | | | | | at its | | | | | | receptor | | | | | | site and | | | | | | causes mild | | | | | | diuresis | | | | | | and | | | | | | potassium | | | | | | retention | | | | +-------------+-------------+-------------+-------------+-------------+ **GIL pharm** +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Affects** | **Mechanism | **Side | **Used | | | | ** | effects** | for/notes** | +=============+=============+=============+=============+=============+ | Magnesium | Gastric | Neutralises | May cause | Ruminal | | hydroxide | secretion | gastric | diarrhea | acidosis | | | | secretions | | | | Aluminium | | | | Gastritis | | hydroxide | | | | | | gel | | | | oesophagiti | | | | | | s | | Alginates | | | | | | and | | | | | | simeticone | | | | | +-------------+-------------+-------------+-------------+-------------+ | sucralfate | Gastric | Mucosal | May prevent | | | | secretion | protection | uptake of | | | | | | other drugs | | | | | | that are | | | | | | absorbed | | | | | | through | | | | | | stomach | | | | | | lining | | +-------------+-------------+-------------+-------------+-------------+ | Activated | Gastric | Absorbs | | | | charcoal | secretion | toxins -- | | | | | | coats | | | | Bismuth | | stomach to | | | | | | mop up acid | | | | Kaolin/pect | | and binds | | | | in | | to | | | | | | bacteria/to | | | | | | xins | | | +-------------+-------------+-------------+-------------+-------------+ | Ranitidine | Gastric | Histamine | Rebound | | | | secretion | antagonist | increase on | | | cimetidine | | -- inhibits | withdrawal | | | | | gastrin, | | | | | | histamine | Cimetidine | | | | | and | inhibits | | | | | acetylcholi | cytochrome | | | | | ne | P450 and | | | | | stimulated | slows | | | | | secretion | metabolism | | | | | | | | | | | Pepsin | | | | | | secretion | | | | | | falls | | | +-------------+-------------+-------------+-------------+-------------+ | Omeprazole | Gastric | Proton pump | | | | | secretion | inhibitors | | | | lansoprazol | | | | | | e | | Irreversibl | | | | | | y | | | | | | bind to | | | | | | ATPase | | | | | | | | | | | | Basal AND | | | | | | stimulated | | | | | | release | | | | | | inhibited | | | +-------------+-------------+-------------+-------------+-------------+ | misoprostol | Gastric | Stable | Do not give | | | | secretion | analogue of | in late | | | | | PGE1 | gestation | | | | | | as will | | | | | Inhibits | cause early | | | | | acid | labour/abor | | | | | secretion | tion | | | | | | | | | | | Increases | | | | | | mucosal | | | | | | blood flow | | | | | | | | | | | | Increases | | | | | | uterine | | | | | | contraction | | | +-------------+-------------+-------------+-------------+-------------+ | apomorphine | emetic | Dopamine | Makes cats | Given IV or | | | | agonist | psyhcho | mucosa, | | | | | | rapid | | | | | | effect | +-------------+-------------+-------------+-------------+-------------+ | xylazine | emetic | Alpha 2 | | | | | | agonist | | | +-------------+-------------+-------------+-------------+-------------+ | Syrup of | emetic | Direct | Cause | | | ipecac | | irritant | cardiotoxic | | | | | | ity | | | | | | in high | | | | | | doses | | +-------------+-------------+-------------+-------------+-------------+ | chlorpromaz | Anti emetic | Dopamine | | | | ine | | antagonist | | | | | | (centrally | | | | | | acting | | | +-------------+-------------+-------------+-------------+-------------+ | Metoclopram | Anti emetic | Dopamine | Contraindic | Must be | | ide | | antagonist | ated | given IV, | | | | | if vomit | short | | domperidone | | | due to | acting | | | | | obstruction | | +-------------+-------------+-------------+-------------+-------------+ | Maropitant | Anti emetic | Neurokinin- | Specificall | | | (cerenia) | | 1 | y | | | | | antagonist | designed | | | | | | for dogs | | | | | Competes | but also | | | | | with | used in | | | | | substance P | cats | | +-------------+-------------+-------------+-------------+-------------+ | Opiates: | Antimotilit | Increase | | Diarrhea/co | | | y | contraction | | lic | | Morphine | (spasmolyti | s | | and stasis | | | cs) | but | | | | Codeine | | decrease | | | | | | propulsion | | | | Loperamide | | increased | | | | (Imodium) | | LI tone | | | | | | leading to | | | | | | constipatio | | | | | | n | | | +-------------+-------------+-------------+-------------+-------------+ | Atropine | Antimotilit | Inhibits | Atropine | Diarrhea/co | | | y | acetylcholi | not really | lic | | Hyoscine | (spasmolyti | ne | specific | and stasis | | (buscopan) | cs) | stimulatory | enough | | | | | effects | | | | | | from vagus | | | | | | nerve | | | +-------------+-------------+-------------+-------------+-------------+ | Methylcellu | laxative | Adds bulk | | | | lose | | to | | | | | | stimulate | | | | Agar bran | | GIT | | | | | | motility | | | +-------------+-------------+-------------+-------------+-------------+ | lactulose | laxative | Broken down | | | | | | in lower | | | | | | gut to | | | | | | lactic acid | | | | | | therefore | | | | | | altering pH | | | | | | to more | | | | | | acidic and | | | | | | trapping | | | | | | ammonia and | | | | | | therefore | | | | | | water | | | +-------------+-------------+-------------+-------------+-------------+ | cisapride | motility | Serotenergi | | | | | | c | | | | | | 5-HT4 | | | | | | receptor | | | | | | agonsit | | | +-------------+-------------+-------------+-------------+-------------+ | Porcine | Digestive | For | | | | pancreatic | enzymes | exocrine | | | | enzymes | | pancreatic | | | | | | insufficien | | | | | | cy | | | +-------------+-------------+-------------+-------------+-------------+ | prednisolon | Anti-inflam | | | Inflammator | | e | matory | | | y | | | | | | bowel | | | | | | disease | +-------------+-------------+-------------+-------------+-------------+ | Bloat guard | Antifoaming | Detergent | | Bloat in | | (surfactant | agent | causes | | ruminants | | ) | | bubbles to | | (frothy) | | | | brea down | | | +-------------+-------------+-------------+-------------+-------------+