Table of content
- Pharmacology I
- 🧑🏽🔬 New Drugs and Clinical Trials
- 🚁 Peptic Ulcer Treatment
- 🍤 Gut Pharmacology
- 🍑 Hepatitis Treatment
- 🧈 Dyslipidemia and Obesity Treatment
- 🩸 Anticoagulants, Anti-Platelet Drugs and Thrombolytics
- 🐼 Anemia Treatment
- 🌊 Diuretics and ADH
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Pharmacology I
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1 - t
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5 - l
6 - sch
7 - k
8 - f
9 - p
🧑🏽🔬 New Drugs and Clinical Trials
“McBogi”
- Modulation of the molecule → add or eliminate a structural component of a drug → changed pharmacodynamic, potency, interactions + higher selectivity
- Chemical combination → Combine differnt AA or Nucleotides → Big archieve on Computer → screen with robot if might be useful (positive response) → traditional clinical evaluation test → incr. efficacy, potency, safety
- Biotechnology → for production of hormones, vaccines, interferons etc. that cant be artificially synthesized by recombinant DNA technique (clone human genes in microbial cells + animals). → Transgenic animals (genetic manipulation to induce "pathologic" gene structure to test therapeutic targets → PCR gene amplification
- Oligonucleotides, mRNA → targets DNA sequence, genes or mRNA → inhibit synthesis of specific proteins involved in the pathogenesis without affecting healthy tissue + genom → i.e. in cancer + viral infection
- Genetic therapy → Administer nucleic acid via vector-virus or encapsulated in liposome → modify gene structure → i.e. in cystic fibrosis
- Immune-pharmacology → identify specific mediator of immune response → target it → i.e. infections, cancer, autoimmune d, organ transplants
PET
safety & toxicitiy: identification, designing test to define toxic mechanism + to monitor in clinical trials
Pre-clinical trial = Assessment of safety, toxicity, pharmacodynamic and pharmacokinetic information
assessing dose-effect-relationship → efficiency + potency
→toxicity effect (acute, subacute, chronic, teratogenic, mutagenic, carcinogenic)
- No effect dose
- Minimum lethal dose
- LD50
- Acute Toxicity: Determine the no-effect dose and the maximum tolerated dose in two species. Also, assess the acute dose that is lethal in approximately 50% of animals.
- Subacute or Subchronic Toxicity: Test three doses in two species for two weeks to three months. Evaluate biochemical and physiological effects.
- Chronic Toxicity: Conduct tests in rodents and at least one nonrodent species for 26 months. Assess the same endpoints as in subacute toxicity tests. This is required for drugs intended for prolonged human use.
- Effect on Reproductive Performance: Examine two species, typically one rodent and rabbits. Evaluate effects on animal mating behavior, reproduction, parturition, progeny, birth defects, and postnatal development.
- Carcinogenic Potential: Conduct a two-year study in two species to determine gross and histologic pathology. This testing is required for drugs intended for prolonged human use.
- Mutagenic Potential: Test for effects on genetic stability and mutations in bacteria (Ames test) or mammalian cells in culture. Also, conduct a dominant lethal test and evaluate clastogenicity in mice.
- Simple screening: One or two simple tests to identify substances with specific actions.
- Blind screening: Set of simple tests to define the general pharmacological profile of substances in a fast and economical manner.
- Programmed screening: Rigorous tests focused on the pharmacological profile of substances, including semi-quantitative methods.
- discover/confirm clinical, pharmacological + pharmacodynamic effects
- identify sideffect
- study pharmacokinetics
- retroperspective vs prospective
- Retrospective: Assess the relationship between a drug and a specific reaction or effect using patient medical records.
- Prospective: Evaluate the efficacy and safety of a drug through a pre-defined protocol.
- experimental (interventional) vs. observational (epidemiological)
- therapeutic trials
- specific population groups
- *bioequivalence studies
- *fixed-dose combinantions + drug-drug-interaction
- pharmacokinetic studies
PHARMA:
- pharmacodynamics: dose-effect- dose-efficiency, MOA
- Pharmacokinets: absorption, distribution, metabolism, elimination
- interactions
THERAPEUTIC
- regarding efficacy + adverse effects
3 ⇒ 📷
(phase 4 = long-term effects when drug is already used)
20-100 in 1-2 clinics
healthy volunteers
- pharmacodynamic + kinetics
- toxicology
→ safety + tolerability
only a clinical phamacologist
open study (everyone know the drug they are taking)
- 50-500 sick patients → exploratory therapeutic phase
- controlled study (experimental vs control)
define dose + therapeutic regimen
speciality physician + clinical phamacologist
extensive therapeutic evaluation / therapeutic confirmation
- authorization
- definition dose-effect relationship
- definition of adverse effects
- risk-benefit ratio
- further efficacy evaluation
300-3000
randomized controlled
speciality physician
- Open study: Both patients and doctors are aware of the drug's identity.
- Simple-blind study: Only doctor knows the identity of the drug.
- Double-blind study: Neither the patients nor the doctors know the identity of the drug, which is administered by a pharmacologist.
Post-marketing studies: Investigate the efficacy, dose definition, and safety of the treatment, referring to the approved indication.
- Aims of the study: Identify study objectives.
- Study design: Determine the methodology used in the study.
- Results assessment: Analyze the outcomes and evaluation methods.
- Studied interventions or therapies: Identify the treatments or interventions under investigation.
- Potential bias: Evaluate any possible sources of bias in the study.
- Selection criteria: Define the criteria used to select the study population.
- Clinical significance of results: Determine the practical importance of the findings.
- Aims (Why/What?)
- Methods (How?)
- Finances (What motherfucker pays for that?)
- Conflict of interests (What are the differnt opinions on the study?)
- Membership of investigation to one or more institution
- Expected results + potential risk
- Potential constraint
- responsibility of subject
- alternative procedures
The individual must possess the capacity to provide informed consent voluntarily.
→ If the individual lacks this capacity, a legal representative may sign the contract on their behalf.
clinical pharmacologist, speciality physician, statistician
identification and response to the problems related to a drugs safety
voluntarily (by docs/ nurses)
🚁 Peptic Ulcer Treatment
Chief aka peptic cells
Parietal cells
Parietal via HCl
- PGE2 [+PGI2] (synthesis by gastric mucosal cells aka Mucus-neck-cells) → mucus and bicarbonate
- protective coat against HCl
- G-cells
- Stimulates HCl secretion (directly on H+/K+ ATPase and indirectly by stimulating Histamine releasing cells)
ECL cells (Entero-Chromaffin-like cells) → on Parietal H2-R → HCl secretion
Intrinsic factor → VitB12 binding+absorption
vagus stimulation
→ ACh on M3-R of parietal cells + entochromafin cells(Histamin release)
→ Stimulate GRP of G-cells → Gastrin
Somatostatin (released by D cells) 📷
pH<3
PGE2 + PGI2(Prostacyclin)
Gastrinoma (Zollinger-Ellison syd.)
protective if normal
- HP associated
- Zollinger-Ellison sdr.* associated
- NSAID induced
- stress induced (esp. on ICU)
- non-Zollinger-Ellison, non HP
- 🚬 (smoking)
- family history
- NSAIDs
- Corticosteroids
- Stress
- Zollinger-Ellison
- Non-erosive esophagitis
- Erosive esophagitis
- Barret's esophagus (metaplasia)
→ Decr. HCl (Acid supression)→ antisecretory drugs + antacids
→ incr. mucosal defense mechanism → mucosa protective drugs
→ eradication HP
→ lifestyle modification
- symptoms relieve
- Healing
- Risk reduction of complications
- Prevent recurrance
Acid suppressing drugs
- Antisecretory agents
- PPIs
- H2 Antagonists
- M-cholinolytic agents
- Antacids
Mucosal protecting agents
- Sucralfate
- Bismuth
- Prostaglandin analogues
surgery of LES
- irreversible blocking H+/K+ ATPase
- prodrug → systemic absorption → parietal cells→ leaves parietal cells → prodrug is activated in low pH (in lumen of parietal cell canalliculi) → binding to proton pump
"Meine eso Oma reitet auf nem Panter mit ner Lanze in der Hand + einem Raben auf der Schulter"
-"prazol"
- ome-
- ezome-
- panto-
- lanzo-
- rabe-
rebound acid hypersecretion 🥴
- enteric-coated capsules+tablets+microgranules → absorbed in bowel
- i.v. ()
- 30-60 min before first meal of the day
"all except rrrrrrabe 🐦"
ome, esome, panto, lanso -prazole
- Liver CYP450
- Renal excretion (Lansoprazol also stool)
18 hrs
renal + hepatic failure
genetic polymorphism (CYP450 enzyme activity)
Highest variations - omeprazole, lansoprazole, pantoprazole Lowest variations - rabeprazole
- usually well tolerated
- Low 2+ Cations: → Decreased Mg2+, Ca2+, Fe2+
- Clostridium difficile diarrhea
- pneumonia (community acq. + nosocomial)
- nonspecific-GI-symtoms: nausea, constipation, diarrhea
- Hypergastrinemia might lead to GI-tumor development *
- mask gastric cancer symptoms *
- Kidney diseases → ARF, CRF, AIN*
- skin eruptions
- cardiac conduction disturbances
- reduced absorption ampicillin and ketoconazole
- reduced VitB12 absorption
- inference with warfarin, cyclosporin
- Gastric + duodenal peptic ulcer
- GERD
- HP triple therapy
- zollinger ellison snd (first line)*
- Maintainance therapy* → lowest dose! (reduce ulcer recurrance + in GERD with severe symptoms)*
- Prophylactic in chronic NSAID use *
- Heartburns (OTC) (ome, lanso, esome)
same efficiancy when equivalent doses (aka angepasste dosis)
"Nase Reh"
- 20mg/day (can be increased to 40mg/day after 4 weeks)
- 4 weeks
- 20mg/day (can be increased to 40mg/day after 4 weeks)
- 4-6 weeks
4-8 weeks, same dose as ulcer
Omeprazole, Esomeprazole
"Hepatic master"
Omeprazole (+Dexlansoprazole)
20mg/day → can be incr. to 40 in severe cases
- coated tablets (10,20,40mg)
- i.v. 40mg (powder)
- 20-40mg coated tablets
- i.v. 40mg (powder)
→ lower variability of hepatic metabolism
→ prolonged T1/2
→ reduced dosage in hepatic failure needed!
Zollinger Ellison syd → ↑dose(160-240mg/day)
40 mg/day- one dose
Ayyyy, much rather used in GERD + erosive esophagitis
“PPIs at standard doses for eight weeks relieve symptoms of GERD and heal esophagitis in up to 86 percent of patients with erosive esophagitis. There are no major differences in efficacy among PPIs and no consistent increase in symptom resolution or esophagitis healing rates between different doses or dosing regimens of PPI therapy”
"esophagitis master" → Lange Lanze für den langen esophagus
PPI is the boss (compare sketchy)
→ less Acid secretion (reduced stimulation by HIS)
→ reduced stimulation by Ach + Gastrin
→ reduced pepsin
- Ulcer (gastric + duodenal)
- prevention of stress ulcers (pre-OP)
- GERD
acutally same as with PPI
vierrrrrrr
duodenal ulcer 4 weeks
gastric ulcer 4-6 weeks
As a result of stronger acid suppression as compared with H2RA, PPI use results in faster control of peptic ulcer disease symptoms and higher ulcer healing rates [24-26]. PPIs are also more effective in preventing nonsteroidal anti-inflammatory drug (NSAID)-induced gastroduodenal toxicity and in healing gastroduodenal ulcers associated with NSAIDs when they cannot be discontinued
less efficient
tolerance develops
(stinkt ab)
75% uffff
→ single maintenance dose (→only 15% relapse)
Cimetidine
orally
i.v. (+i.m.) possible as well → in gastric bleeding or preoperative to prevent stress ulcer
only dose reduction in altered renal function (50% reduction in severe renal failure)
can be used in hepatic failure
passes through placenta + excreted in breast milk
gucccci
- general GI shizzl: nausea, vominting, diarrhea
- Gynecomastia, galactorrhea erectile dysfunction
- CNS shizzl: confusion, somnolence
- rare: hypergastrinemia
NO endocrine effects
poor CYP450 inhibition
Famotidine (40 mg/day in active ulcer)
Inhibits CYP450!
reduced metabolism of other drugs → toxic-effect:
- oral anticoagulants
- theophylline
- alprazolam
- tricyclic antidepressant
"Rami (Daka) aus Nizza ist ein famous Rockstar"
- Cimetidine (800mg)
- Ranitine (300mg)
- Nizatidine (300mg)
- Famotidine (40mg)
- Roxatidine (150mg)
before bedtime 😴 (PPIs 30-60 min before 1st meal)
in general half the dose
i.e 150mg Ranitidine
- tolerance (already relevant after 3 days of treatment)
- rebound acid hypersecretion → to prevent progressively reduce dose + consider antacids
weak bases → neutralize gastric acid → incr. pH + reduced pepsin activity
- duodenal ulcers! → healing + symptomatic (pain)
- poor efficacy in esophagitis + gastric ulcer
nonsystemic (neutralize acid → insoluble salts)
systemic (absorbed systemically → metablic alkalosis i.e. sodium carbonate)
ORAL
- chewable tablet (chew for max effect)
- powder
- suspension
after eating (1-3hours after) + before sleep
Antacids on empty stomach -short effect (30') Food in the stomach - may prolong the effect to 4-5 hours
- peptic ulcer
- intermittend symptoms GERD
- Heartburns
- frequent administration required
- no correlation symptoms - ulcer healing
- take drugs 2 hours after antacids, otherwise reduced absorption
- thyroid hormones, allopurinol, iron salts, -azoles → need acidic environment for absorption → reduced absorption
- reduced absorption tetracyclin (+some fluros)
aluminium compounds*
magnesium compounds*
calcium carbonate
*(most used)
- aluminium hydroxide
- aluminium carbonate
- aluminium phosphate
- GI shizzl: constipation, nausea, vomition
- phosphate deficiency after prolonged treatment (binding + incr. stool elimination)
Aluminum CHOPS
C-onstipation
H-ypophosphatemia
O-steodystrophy
P-roximal muscle weakness
S-eizures
high conc → osteodystrophy, prox myopathy, encephalopathy
(CHOPS)
alzheimer
5-30ml / dose
"Love-Möse mit Aluminium-Helm" (läuft aus, deswegen mL)
Mg hydroxide, carbonate oxide, trisilicate,
hydroxide → rapid + short action
oxide → reaction with water → hydroxide
trisilicate → slow + prolonged action
carbonate → weak + prolonged
laxative (esp. Mg-hydroxide)
might also produce toxic effects!
"remember, all = caution in kidney-impairment"
Mg-carbonate ⇒ Rennie
Mg-carbonate + Mg-Trisilicate ⇒ Dicarbocalm
rapid + prologed
anti-diarrheeeeeea effect 💩
- rebounds hypersecretion*
- hypercalcemia → renal stones
- constipation
Ca-carbonate trinkt auch Tee mit Norbi + Noah
1-2g/day
- =synthetic PGE1 analog
- reduced acid secretion (esp. food-stimulated, little basal)
- cytoprotective via incr. local circulation + incr. mucus + Bicarbonate production
- in combination with NSAID treatment to prevent peptic ulcer (prophylaxis)
- also in NSAID induced peptic ulcer treatment (but rather PPI)
- 0,2mg x4 /day as as long as NSAID treatment in prophylaxis
- 0,2mg x4 /d or 0,4x2 in Ulcer treatment
- contraindicated in pregnancy!
- exacerbates IBD!
- might cause diarrhea + abdominal pain
complex compound of aluminiumhydroxid (antacid) + saccharose-sulfate
activated by acidic pH
→ form a cross-linking →protective gel
→ also binds to proteins on ulcer-surface (albumin, fibrinogen) → formation of insoluble complexes
⇒ protection of gastric mucosa, reduced inflammation, favors healing
⇒ also incr. mucus secr. + stimulation of PG secr.
- esp. duodenal ulcer or gastric ulcer with biliary reflux
→ also reduced relapses + recurrances
- prophylaxis stress-induces ulcer in immune-compromised
- rectal ulcer, irradiation induced proctitis, oral mucositis
- esophagitis
- NSAID induced peptic ulcer
oral (tablet / suspension)
on EMPTY stomach (1h before meal) (passt perfekt zu PPI, niemals mit H2+Antacids)
- dont give with H2-antagonist + antacids
- theophillin
- quinolones
- digoxin
kidney insuff
- constipation (most common)
- vomiting
- dry mouth
- headache
- skin eruption
- similiar like sucralfate → precipitation in acid environment → coat ulcer + erosions with protective layer
- stimulation of PG secr.
- anti-HP! (antimicrobial)
orally (tablet/solution)
→ 1200mg/d [30min before breakfest or dinner] - passt auch super zu PPI
→ 600mg x2 or 300mg x4
⇒ take 1 month, then 1 month break!
- black stools
- nausea
- RF
- pregnancy
- not when already on antacids (also no milk)
"Die 2 schwarzen Schweine aus der Tonne (1200mg) nehmen nen dicker Biss (Bismuth) von der Miso-Suppe mit NSAIDs (ind.)und prosten (Misoprostol) nochmal vor dem Nachtisch (Sucralfate ,Saccarose-sulfate + aluminium-hydrox)". Schwangere mit IBD sollten nicht anstoßen. Der immune supressive Kidney boy isst den Nachtisch so gestresst, dass es ihm wieder hochkommt deshalb isst er n leckeren PPI + kriegt constipation, NSAIDs gibts leider nicht. Auch die Schweine haben keine Kidney + sind geschwängert"
- duodenal ulcer + gastric ulcer
- in pat. under chronic NSAID/aspirin treatment
- before starting NSAID treatment in patient with history of peptic ulcer
- after gastric bleeding → prevent re-bleeding
!notice: no influence on GERD
Triple T with Levofloxaxin (PPI, Amoxi, Levoflox) only 10 days
Triple T with Rifabutin (PPI, Amoxi, Rifabutin)
PPI
Amoxi day 1-5
Clarithro day 6-10
Metronidazole/Tinidazole Day 6-10
ALL 14 days!
exception: triple with levoflox, sequential therapy ⇒ 10d
- PPI standard dose x2 / d (see below)
- Amoxi 1000mg x2
- Clarithro + Metronidazole 500mg x2
- Levoflox 1000mg x2
- Rifabutin 25mg x2
- Bismuth subcitrate 120mg x4
- Tetracyclin 400mg x4
Esomeprazole 20mg 2x/day Or Lansoprazole 30mg 2x/day or Omeprazole 20-40mg 2x/day Or Pantoprazole 40mg 2x/day or Rabeprazole 20mg 2x/day
Check for HP after 4 weeks via UBT or stool-Antigens
only in complicated ulcers (gastric + duodenal)
→ non-complicated duodenal ulcer dont need maintance therapy
give H2-Antagonist
- NSAIDs
- steroids
- KCl
- Alcohol
prophylactic treatment with misoprostol
PPI
fixed dose combination naproxen + esomeprazole is available
- High risk = History of complicated ulcer or >2 risk factors
- Moderate risk = >65y, high dose NSAIDS, history uncomplicated U, anticoagulants/aspirin/steroid therapy
- Low = no risk factors
HP is an independent additonal risk factor!
🍤 Gut Pharmacology
- GI lesions (inflammation, obstruction*, toxins[chemo])
- Extradigestive infections *(hepatitis, pneumona, renal infection)
- *CNS lesions → central vomiting* (anything that produces pressure)
- Vestibular stimulation - motion sickness
- Pregnancy*
- MI*
- Endocrine disorders
- Toxic *substances(alcohol) + drugs [see next Q]
- Radiotherapy*
- Neurological, psychiatric diseases*
- Chemotherapy (not only GI irrittion)
- Opiates + NSAIDS*
- Antibiotics*
- Anestetics* (give with ondasetron)
- Anti-arrhythmics (i.e. Digoxin)
- Contraceptives
- Metformin
- Antiparkinsonian drugs (i.e. L-Dopa)
- Anticonvulsants
- Teophylline (COPD/asthma drug)
vomiting center in the medulla (nucleus of tractus solitarius)
- CNS
- stomach via vagus to NTS
- area postrema (aka ChemoR trigger zone)
- NTS
- Vestibular system
- Chemo + Radiotherapy
- Motion sickness
- Pregnancy*
- Post-OP nausea
- GI disorders (inflammation, obstructions)
- Extradigestive diseases that induce nausea + vomiting
5-HT3-R Antagonist
block 5ht3R 📷 → block activation of serotonin
→ no peripheral vagal stimulation
also Block R centrally (VC + CTZ)*
antipsychotic + anxiolytic
- Chemo induced nausea
- GI irritation nausea
- Post-OP*
- pregnancy*
Give it together with dexamethasone (8-20mg/day)
(+Olanzapine / NK1-Antagonist)
- Headache + dizziness
- constipation
- Torsades (QT-prolongation)
- Serotonin syndr.
- Macrolides
- Antiarrthytmics
→ Prolong QT!
- SSRI
→ Serotonin syd.!
"Die Granni fliegt mit ner Cola mit dem Dick drauf mit dem Balon (Palono) zum Dancer"
"Honda, Granini, Cola, (Marco) Palo" (Cola und Granini trinkend sitzt Palo im Honda"
- Ondasetron
- Granisetron, Transdermal Patch
- Dolasetron
- Palonosetron
- (Most commonly used) effecitve in acute and delayed nausea in chemo if combined w neurokinin antagonist (eg aprepitant)
- 2nd Gen
- iv 0.25 mg
= 2nd generation
- Long T1/2 (40h)!
- → good in acute+delayed naused (beste für Chemo!)
- (with Nk1 antagonist)
orally or iv
Name | iv | orally |
Onda | 0.15mg / kg | 32mg/d (in 2-3 dosages) |
Grani | 10 microg /kg | 2mg/d |
Dola | 1.8mg /kg | 100mg /d |
Palono | 0.25 mg single dose | only in Canada |
"Mona (32) danced auf dem Teller (15 = 0.15)" - oral/iv doses for ondasetron
motion sickness
PostOP nausea + vomiting *
pregnancy*
- sedation
- Urinary retention
- blurred vision
→ Contraindicated: glaucoma (↑ICP), BPH + bladder dysfunction, !drug interaction with alcohol+other sedative agents
Die Delphine + Hydras am Inn ziehen pro meter den China-Litzen"
- Diphenhydramine
- Promethazine
- Cinarizine
- Cyclizine
- Dimenhydrinat (Vomex)
- Doxylamine + Pyridoxine first line in Pregnancy
- All have anticholinergic properties
- Promethazine: +AntiD2
block D2 in area postrema
- sedative
- Extrapyramidal symptoms - dystonia, akanthisia, parkinosonian features + tardive dyskinesia
- Elevated Prolactin
- QT prolongation
Antipsychotics
(exeption: Motilium → cant pass BBB)
"HalloooooO Lanza. Lass ein Pain game spielen: Phenotypeziehen(aka ausziehen) während wir uns ticklen + Domperidone schlürfen."
Anticholinergic + Antihistaminic → motion sickness
viral enteritis
motion sickness (not 1st line)
- sedation + extrapyramidal effects
- contraindications: alcohol, renal+hepatic insuff
"Maus aufm Teller"
Prochlorperazine - 15-30mg/d p.o.
Chlorpromazine - 25-50mg i.m
"der verückte winker(Hallo) macht den ganzen tag diagnostics + OP"
Post-OP nausea
neuroleptanalgesic - endoscopic + surgical procedures
- Sedation
- Extrapyramidal
- QT prolongation
- Hypotension
- 5HT3 antagonist in high dose
- 5HT4 Agonist → Prokinetic effect
- Chemo induced nausea + vomiting - second line
- Post-OP nausea
- GI dysmotility syndromes with nausea+vomiting
- as prokinetic (Gastroparesis)
not more than 5 days
- 15-30mg/d p.o (like prochlorperazine)
- 10mg intrarectal
- severe: 10mg i.v. or i.m
- sedation, insomnia, anxiety, depression
- Extrapyramidal symptoms - dystonia, akanthisia, parkinosonian features + tardive dyskinesia
- NMS
- Elevated Prolactin
- QT prolongation
- diarrhea
contraindication: obstruction, parkinson*, <1y old
- GI disorder w/ nausea+ vomiting
- chemotherapy induced nausea
- as prokinetics
(no passage BBB)
"Maus scheisse"
Suppositories (Zäpfchen)
30-60mg /d
- no central effect
- but torsades possible (QT-prolangation)
"Nach den 5 tagen (delayed) ist lanza komplett verstört + atypical + kotzt sich erstmal die seele aus dem Leib. Um wieder Happy zu sein(5ht3-serotonin) nimmt sie Steroide."
Atypical antipsychotic
good for delayed nausea + vomiting together with corticosteroid + 5ht3
block muscarinic R
Motion sickness
transdermal patch
see H1 antagonists (Contraindicated: glaucoma, BPH + bladder dysfunction)
glaucoma + BPH
block substance P(NK1) in VC + area postrema
Aprepitant + Fosaprepritant
Chemo
esp in HEC (highly ematogenic chemo)→ together with 5Ht3 (Palonsetron) + corticosteroid
stimulate CB1-R in CTZ + VC
→ prophylactic in chemo when others are not effective
"Norbi ist alone" ☹️, "deswegen trinkt er nen Tee mit Noa"
Nabilone
1-2mg p.o. (3h before chemo + after)
- tachycardia
- vasodilation + hypotension
- anxiety, euphoria, sonolence, paranoia
- withdrawal syndr
- in high dose → antiemetic
- incr. efficacy of other drugs (metoclopramide + 5Ht3 inhibitors)
"Dexter hat ne gute Nase"
- Dexamethasone 20mg iv
- Methylprednisolone 125-375 mg iv
- Prednisone
give with metoclopramide or 5ht3 inhib
not antiemetic but reduce anticipatory nausea + vomiting prior to chemo (anti-axniety, sedative, amnesic)
Lorazepam
Where available, we suggest pyridoxine-doxylamine succinate combination therapy for initial pharmacologic treatment of nausea of pregnancy (Grade 2B). If this drug is not available, we suggest pyridoxine, adding doxylamine succinate if pyridoxine alone is not effective.
- enhance coordinated GI motility + transit
- mainly on upper GI tract (esophagus, stomach, duodenum)
- via Dopaminergic or cholinergic mechanism
- GERD*
- Gastric or duodenal stasis*
- Biliary dyskineasia*
- Diabetic gastroparesis
- Adjuvant for radiologic procedure
long term (but you cant)
Domperidon (Motilium) and Metoclopramide
antiemetic
- GERD (incr. LES pressure)
- To incr. gastric + duodenal emptying → GI dysmotility with nausea + vomiting
- biliary dyskinesia
30-60mg/d (s. antiemetic→ Mauss scheisse lel)
gastroparesis (first prokinetic option)
GERD (no routine recommentation)
- Itoprid - minimal BBB penetration, no risk for QT prolongation
- Levosulpid - Prokinetic + antipsychotic !incr. stroke risk
Neostigmine (+ Pyridostigmine)
inhibit AcHE → more AcH availible
- paralytic ileus, colon distension
- myasthenia gravis
- asthma *(bronchoconstr)
- obstruction* (intestinal or urinary)
- ↓cardiac activity →bradycardia * + AV block *
stimulation of sensory neurons in myenteric plexus (i.e. 5Ht4 stimulation)
adverse cardiac events
chronic constipation 2nd line when laxatives fail
(stimulate colonic mass movement)
Prucalopride
"Der Smiley-Meister hat ne brutale pride, weil er der Auswechselspieler der Laxativ-Mannschaft ist. Er ist nur Auswechselspieler weil er ein schwaches Herz hat."
Stimulate Motilin R on SM + Enteric neurons → incr. LES pressure + incr. gastric+small bowel contractions
NO effect on colon
Diabetic gastroparesis (2nd line - after Metoclopramide)
Erythromycin 250-500mg
Clarithromycin, azithromycin
"Der Rabe(erythromycin sketch) fliegt super gut (Motilin) zu Henne für n halbes G, die Verdauung ist leider nicht so gut, weil er kein Colon hat. Dafür ist er auch Auswechselspieler in der Diabetiker-Mannschaft (2nd line diabetic gastroparesis)"
inhibit SM contraction of:
- GI
- biliary
- urinary
- genital
- spastic abdominal disorders
- IBS
- diverticulosis
block M3 in SM of stomach, intestine + urinary
(not really in biliary tract)
Atropine
0,3-1mg (max 4mg/d)
orally (or sc)
- constipation / ileus
- urinary retention
- blurred vision
- IBS
- Spasm in the GI tract
- Enuresis*
- Reno-ureteral colic pain *
- Butylscopolamine → no BBB passage → no sedative effect ; used in diarrhea (acute+chronic)
- Otilonium bromide
- Butylscopolamine → no BBB passage → no sedative effect ;; used in diarrhea (acute+chronic)
- Otilonium bromde → block M1-5, block Ca-channel, block NK2-R → antispasmotic + antisecretory → Only used in IBS!
Block Phosphodiesterase + Ca-channel → antispasmotic + vasodilative effect
(Mebeverine also blocks K + Na channels)
"Wer's in (verin) der Mibimilf die Dota spielt? Papa-der Antispast! Papa ist ein Kumpel vom Raben. (500mg), und hasst Calcium+PDE. Die Dota-Mibi-milf hat kackt sich immer beim zocken ein (IBS) und ihr lieblings-spiel ist periode-simulator (dysmenorrhea). Papa hat nen riesen Cock (urinary spasm) und nen riesen Darm (digestive spasm) und Constipation Deswegen ergänzen sie sich so., und das Herz von Papa schlägt extrem schnell. PS i love you-daddy"
- Papaverine - 300-500mg po/d OR 40mg x3/d iv./im
- Mebeverine - 200mg p.o 3-4x/d
- Drotaverine - 40-80mg po/iv/im
Name | Papaverin | Mebeverine | Drotaverine |
IBS | x | x | |
Digestive + urinary spasms | x | ||
Biliary spasm | |||
dysmenorrhea | x |
- constipation
- ↑cardiac activity :hypertension,tachycardia, arrythmias
stimulate mu, kappa, delta R on enkepahlinergic neurons → motilin release
- IBS (vgl. anticholinergic antispasmotics)
- Biliary dyskinesia
- Constipation (see dual effect)
- Abdombinal pain + intestinal disorders in children
- functional disorders
300mg /d p.o.
(start with 600mg/d for 6days → then 300mg/d for 20days)
Overdose → CNS manifestation (dizziness, convulsion coma) → !abuse
Bradycardia + Hypotension
"Der Enkel trimmt(Trimebutin) die Maus-Butter in der Sau. (300), die auf dem Billiard-Tisch (billiary dyskinesia)steht. Von der ganzen Butter kriegt er IBS mit Constipation. Aber das kriegt er nicht mit denn er ist am Over-dosen und kippt um (Bradyc+Hypotension)"
Pinaverium bromide
Alosetron
high incidence of ischemic colitis → only used in diarrhea-predominant IBS
- infections
- drugs
- malabsorption of biliary salts*
- Cancer, Diabetes,
- IBS, IBD*
- Stress*
- Incr. content osmolarity* (i.e. lactose intolerance)
- Laxatives
- Antacids with Mg*
- ABs*
- ...
"knall das wasser, fick die keime, stop den dünnpfiff"
- maintain water + electrolyte balance
- AB
- Antidiarrheal therapy (nonspecific)
- “Inflammatory” diarrhea: bloody diarrhea, high fever, or systemic toxicity → Risk of worsening
- Discontinue: if diarrhea worsens despite therapy
- µ receptor agonist → ↑colonic phase segmental activity → ↑.colonic transit time
- decr. secretion of water + electrolytes by stimulating delta-R*
⇒ incr. absorption
"Der Hase (Loperamide) der rumhüpft hat n Koffer in der Hand von der letzten Reise (travellers) und sein eines Ohr ist ein Ileum."
- acute + chronic diarrhea
- travellers diarrhea
- ileostomy
"Der Hase hüpft auf nem Reh (4)"
4mg → then 2mg after each following loose stool (max16mg)
- Paralytic ileus + toxic megacolon in IBD *
- constipation→ nausea + vomiting
- CNS effect
- only in high doses in children
- Abuse in adults
- Infectious diarrhea, acute UC
- Paralytic ileus
- Alles mit Kindern <2y
- Pregnancy, Lactation
- shorter effect (↓T1/2)
- passes BBB → given together with Atropin to prevent abuse
"Der Delfin (Diphenoxylate) schwimmt mit ner Kuh(7) in ner riesen tasse(10)"
7-10mg /d
inhibit Enkephalinase → incr. stimulation of delta-R → ↓secretion of water+electrolytes
in children >3 month + adults in acute diarrhea
headache + angioedema 📷
Race cat mit Trillerpfeife spielt mit dem 3 monaten alte Enkel mit der riesen Nase + dem geschwollen Gesicht in der Delta-R-line.
bind irritants from intestine
"Moin Karolin, smack that charcoal on Mr. Bismuth's Water-Telescope."
- Diosmectite (Smecta)
- Charcoal
- Kaolin
- Bismuth
- ..
alpha2 agonist → inhibit Ach release
→ ↑absorption + ↓ secretion of water+electrolytes
→ ↑ intestinal transit time
- Chronic diarhea → esp. witi diarrhea by opiate withdrawal
- IBS with diarrhea
Depression + Hypotension+ fatigue
"Der 2. geborene alpha Sohn-Clon (alpha2) ist chronic(chronic diarrhea) Depressiv, schlapp + hypotensive weil er auf Opiat-withdrawel is. Außerdem hat er IBS armer boy."
"Die fette VIP-Oma mit Diabetes kommt nach Hause von der Chemo und dreht am Thermostat, und dumped ihren Mann weil er ihr AIDS gegeben hat"
Somatostatin analog
- VIPoma or other hormon secretion tumors that cause diarrhea
- dumping syndrome
- chemo-induced diarrhea
- diabetes assoc. diarrhea
- AIDS assoc. diarrhea
Cholestyramine esp in resection of distal ileum
"Der Wanker hat ne neue Rifle und macht faxen"
- systemic
- intestinal effect
- Neomycin
- Vancomycin
- Rifaximin
more important = ETIOLOGICAL TX!
Der Hase hat 2 Ohren beide haben ein Scope in der Hand, aber auf dem einen ist echt viel Butter"
Diet (high fiber, drink enough blablablubbb)
at least 2 weeks
- Idiopathic
- Cancer
- Obstruction
- Drugs → Opiods, Anticholinergics, Antacids with Al+Ca, Ca-Channel blocker
- Neurological, Endocrine, Psychologial disease
- Laxative: Evacuation of formed feces from the rectum
- Catharsis: Evacuation of unformed, usually watery feces from the entire colon
- chronic idiopathic constipation
- prior surgery or endoscopy/Rx
- in stroke, hemorrhoids, hernia (→ smoother shit without much pressing)
- chronic constipation + acute abdominal pain of unknown etiology*
- mechanical obstruction
- perforation, abcess*
- UC*
- Luminally active agents
- Nonspecific stimulants
- Prokinetics (→ Primarly on motility): 5HT4 Agonist + Opioid antagonist) [not mentioned below]
Der fiber-fießling Hulk (fiber / cellulose + Bulk forming) ist komplett gebloated (SE) weil er zuviel psychodelische (psyllium) substanzen konsumiert hat. Deshalb geht er zum eingenässten (stoolwetting) Doc aber versteht ihn nicht und sag deswegen: Doc, you said? (Docusate). Der Doc fickt ihn darauf hin in arsch (penetration →mixing water + fat). Sie stehen neben einem EDEKA (long term-fat sol Vit def). Deneben steht der magnet + milch verkäufer Henne (Mg+Lactulose, DOsis in gram) und sieht zu wie der Doc und Hulk Love (5g) machen. Hinter Ihm führt ein Bach (cathartic) ins Tal, im Bach schwimmt eine Tasse (10-15g). Von der ganzen Milch muss er ganz viel furzen. Aufgepasst: Da kommt der Bösewicht, der furzende braun gebrannte eingecremte (Senna-Sunscrean) Delphin (Diphenylmethane + SE: melanosis coli).
indigestible hydrophilic fibers → absorb water → bulky emollient gel → colon distension → peristalsis
bloating
- Psyllium
- Methycellulose
- Bran
"What you said, Doc you said"
Docusate
Decr. surface-tension of stool → penetration + mixing of aqueous + fatty substances → softening
impaired absorption of fat soluble vitamins
soluble, non-absorbable compounds → attrackt fluid → stool gets more liquid
- Magnesium compounds: MgHydroxide, MgCitrate, MgSulfate
- PEG
- Lactulose
- Saline Laxatives
prolonged use → hypermagnesemia
5g → laxative
10-15g → cathartic
distension + flatulence due to metabolism by colonic bacteria
induce low grade inflammation in small+large bowel → ↑motility + accumulation of water+electrolytes ⇒ complete catartic effect
"Der furzende braun gebrannte delphin schmiert sich n bisschen Senna Sonnencreme auf die Wampe"
- Antraquinone Laxatives (Senna)
- Diphenylmethane derivates (Bisacodyl + Phenolphthalein)
- Castor Oil - no really used
- Melanosis coli (brown pigmentation of colonic mucosa) 📷
- Cathartic colon (in long standing treatment)
Pancreatin
Presence of Pancreatin (Lipase) → negative feedback:
→ ↓. pancreatic secretion → ↓. intra-ductal pressure → ↓. pain
- Cystic fibrosis
- Pancreas stuff: Pancreatic cancer, Post pancreatectomy
- Gastrectomy
before lipid-enriched meal
- Hyperuricosuria in cystic fibrosis (incr. purine intake due to pankreatin)
- Folate + Iron malabsorption
- diarrhea + nausea
"Cheno der Bär (Cheno+Urso) ist ein negative Billiard-Spieler, Cheno hat früher Seifenblasen geliebt (Post-cholecystectomy), heute liebt er es kleine Steine zu schmeißen (small gallstone), weil seine schwangere Frau keine Seifenblasen mag. In der einen Hand hält er einen AST in der anderen eine Fahne (LFT) die er von einem LDL-Boot geklaut hat. Mit seiner Bärentaze legt er die Kohle ab (Cholestasis) um sich um seinen 1. liebstes Hobby zu kümmern: Billiard (Primary biliary cholangitis)"
- gallstone dissolution (small gallstones)
- post-cholecystectomy (for residual stones)
itself is a primary acid (1/3 of total biliary bile acid) excreted into the bile; drug action on gallstone dissolution relies on negative feedback effect on the rate-limiting enzyme for ↓synthesis of cholesterol and bile + ↑excretion of cholesterol + absorption of lipid&fat-soluble vitamins
Side effects:
- ↑. AST + LDL
Contraindications:
- Cholestasis
- pregnancy
- Renal failure
- GI diseases
- primary billiary cholangitis
- cholestic liver diseases
Give it together with Chenodeoxycholic acid 😎
- Ulcerative colitis: begins in the rectum and may extend continuously to involve the entire colon. Affects mucosa and submucosa.
- Crohn's disease: most commonly involves the end of the small intestine and beginning of the colon and may affect any part of the gastrointestinal tract in a patchy pattern. Affects all bowel wall layer (transmural).
induction therapy
- Mesalamine (=5-ASA)
- Sulfasalazine (5-ASA bound to Sulfapyridine)
- Olsalazine (Two bound 5-ASA)
- Balsalazide (5ASA + ABA)
⇒ cleaved by colonic bacteria to active 5-ASA
"Wir schneiden die Metsalami während das Öl, Sulfa + der Balsam im Salat ziehen."
ligand of PPARgamma 📷
"Während der Salat zieht, lesen wir ein bisschen in der News-PPApeR(PPAR)"
→ downregulates it.
- NF-κB is crucial for regulating the immune response, cell proliferation, and cell death.
- Activation of NF-κB is critical for the development of inflammation.
- NF-κB plays important roles in the development of the immune system and lymphoid organs.
- mild to moderate active UC+CD
- maintenance mild-moderate UC (but acutally also Crohns-compare table)
- long term treatment: prevent colon cancer in IBD
more effective in UC
"Bei der Verdauung der Metsalami hatte der Körper große Schwierigkeiten und konnte sie selbst nach großer Anstrengung der Pancreas nicht verdauen und sorgte für Diarrhea. Ein Teil wurde verdaut, ist aber im interstitium der Niere stecken geblieben
- interstitial nephritis (→monitor renal fct)
- pancreatitis
- diarrhea
"Remember Sulfur compound goes wild systemically→ Hypersensitivity: Du schälst dich wie ne Zwiebel (exfoliation dermatitis) und bist rot wie ne Tomate (hemolytic anemia). Verschiedene Organ-Inflammation plagen dich auch. Wickel dich lieber in Folie ein. "
Sulfapyridine is completly absorbed systemically!!
→ Hypersensitivity: Exfoliative dermatitis 📷, hemolytic anemia, inflammation of different organs (pneumonitis, pericarditis, hepatitis)
- impaired folate absorption → give folic acid supplements
- athralgias, myalgias, bone marrow suppression in high dose
mild, moderate + severe CD + UC
only in acute episodes + not for maintenance
"No fucks (NF), NO Cox, no Cytokines"
"I see, (so) I AM" → ICAM
mild, moderate → oral
severe → i.v.
rectuom or sigmoid → topical
high topical activity low systemic bioavailability → low systemic adverse effects
hydrocortisone
Prednisone + Budesonide
(mild) - (moderate) - (severe)
Active
Crohns: Bude - bude - hydro
UC: x - predni - hydro
"Du musst wissen, der Atze hasst nur 2 Dinge: Purine + Lymphocytes"
purine antimetabolite
→ inhibited nucleotide + protein synt → ↓inflammation related factors (TRAIL, TNFRS7 + alpha4-integrin)
→ lymphocyte ↑apoptosis + ↓proliferation
"Der Atze ist der Maintenance boy"
UC: Maintenance in steroid dependent or 5-ASA is not enough
Crohns: Maintenance (together with infliximab)
"Die Lymphocytes lassen sich das nicht gefallen, sie schlagen zurück als Lymphoma. Der Atze wird jetzt richtig wütend (hypersensitive) und saugt ihnen die Knochen aus + klaut die Leber"
- Lymphoma
- bonemarrow suppression, hepatic tox in high dose
- hypersensitivity
"MAX (MTX) ist der substitution man vom Maintenance Atzen"
refractory or intolerant to AZA
→ esp. in Crohn induction + maintenance, less effective in UC
"Um ihn frisch zu halten, ist er eingewickelt in Folie"
folate supplementation → decr. risk for megaloblastic anemia, bonemarrow suppression
"Besonders an ihm ist seine Steinweste (pulmonary fibrosis) nur drückt die leider auf seine Leber + Niere"
- hepatitis
- pulmonary fibrosis
- renal insuff
Block Calcineurin in T-cells 📷 → ↓transcription of Cytokine genes
"Der kleine zyklopen bruder vom Atze der sich im kreis dreht hasst T-cells und klaut ihnen ihren calcium haltigen Urin" (ekliger typ)
induction in severe UC
"Die T-Lymphcytes schlagen zurück: Die Niere + Leber wird geklaut"
- Nephrotox (esp. when low Cholesterol! → contraind: in Cholesterol <120mg%)
- Hepatotox
induction + maintenance in
moderate - severe CD + UC(esp. in patient which are steroid-dependent/refractory)
Neutralization of TNF
maybe:
- Induction of Apoptosis in TNF-expressing cells
- Cytotoxicity → TNF-expressing cells
"block TNF + the TNF-cells"
- Infliximab
- Adalimumab
- Certolizumab
- Golmumab
all sc., except influxi→ iv
- infections
- infusion reactions *
- Lymphoma * (like AZA)
- Autoimmunity
→ esp. reactivation of latent tuberculosis + HepB*
- Ab against influximab* (murine part) → use Adalimumab instead
"Natalie legt n dickes Veto gegen IBDs ein" (passt ihr gar nicht)
- Natalizumab
- Vedolizumab
CD induction when everything else fails (anti-tnf + convential therapy)
Inhibit IL-12 +23
"Wenn alles versagt, nimmt Luke (IL) das Hustekind und pack es zu Nemo (23) in die Tonne(12)"
induction CD+UC
esp. pouchitis after colectomy in UC
reduction discharge anal fistula CD
in ACTIVE UC/Crohn’s:
- 5-ASA
- +- steroids (predni in UC, bude in Crohns)
- +- biological (#1 Infliximab in both; natalizumab & ustekinumab: alternative in crohns)
- +- Immunosuppressants (Cyclosporin in UC, MTX in Crohns)
- +- AB (in crohns, Øin UC)
in MAINTENANCE UC/Crohn’s:
- 5-ASA
- +- infliximab
- +- Immunosuppressant (#1 AZA in both; MTX: alternative in crohn’s)
🍑 Hepatitis Treatment
virus infection → IL → Interferons:
- anti-viral (direct) → anti-viral protein synth.
- immunomodulatory → Ag presentation, incr. Phagocyte activity, inc MHC1 expression
- anti-proliferative → decr. cellular protein production
im or sc
- incr. T1/2
- steadier conc. of the drug
→ less frequent dosing
- HBV, also in children>1 (+ HCV→largely replaced by oral antivirals; see later)
- Leukemia (hairy cell, CML + CLL)
- Malginant melanoma +MM
- Kaposi sarcoma (HIV)
- Condyloma acuminata
- MS
- renal cancer
- Non-Hodkin Lymphoma
HBeAg + HBsAg
- flu-like syndrome (headache, fatigue, arthralgias)
- Myelosuppression* (Anemia, Thrombocytopenia, Granulcytopenia)
- Drug induced lupus
- Neuropsychiatric side effects*
- Incr. Aminotransferases*
- Auto-ABs*
- Hypotension *
- psychosis, depression*
- Neutropenia + thrombocytopenia
- heart disease*
- decompensated cirrhosis
- pregnancy*
180 microg/week for 48weeks
-"vir" + -"vudin"
Adolf geht vor und singt Tenor, (Adefovir + Tenofovir)
die Ente spielt Klavir (Entecavir) und das Lamm telefoniert(2x) mit Hudini (Lamivudin + Telbivudin)
- inhibit HBV-DNA polymerase
- Teno, Ade, Lami → also inhibit reverse transcriptase
TDF + TAF → Tenofovir Alafenamide (TAF) inhibit rev. transc.
Entecavir
yes, in combination with Tenofovir
Lamivudine
Incr. Resistance development!
- Lamivudine - 70% 5y-resistance
- Adefovir - 30% 5y-resistance
- Telbivudine - 20% 2y-resistance (can be used in naive (#1) treatment of chronic HBV)
- Teno
- Lami
- Ade → esp. in Lami-resistance strains
Entecavir + Adefovir
All -vir's
- Entecavir
- Tenofovir
- Adefovir
The fovirs
Teno + Ade
Lami → incr. Transferases when stopped
Telbi → Myopathy + incr. CK
0.5mg/d 1-5years
every 6month
- ALT
- HBV DNA
- Check Ab (Anti-HBe + Anti-HBs)
IFNalpha + Ribavirin
no alcohol→ can accelerate liver damage
no cigarettes+ marijuana
coffee consumption can be benificial
- Direct antiviral effect - directly target step in HCV lifecyle
- oral
- without interferons side-effects
- shorter treatment (8-24w)
- SVR > 90% (↑high efficacy)
-buvir
(b für 5B; Bu = boobs)
"Da sah ich das Sofa"
Sofosbuvir + Dasabuvir
- sofa → all
- Dasa → 1a (combination with Ribavirin)+1b
"Uhr überm Sofa"
yes, uridine analogue
- Ribavirin (in decomp. cirrhosis)
- Simeprevir
- NS5A inhibitors: daclata,ledip,velpat,-asvir
"Erschöpft(Asthenia) auf dem Sofa, aber das Sofa hat Bettwanzen(itching) arrrrg das juckt. Plötzlich kommt ein Amigo (Amiodaron) und haut ihm aufs Herz"
- asthenia
- itching (pruritus??)
- cardiac arrest with amiodarone
"Die Sofa-Bettwanzen knabbern an der Niere, wie ne Maus(GFR<30)"
GFR <30
"Neben dem Sofa erblickst du eine Rose im Sau-Mund (400)"
400mg/d
-asvir
(A für 5A, as = ass)
"Ein lediger Dackel-Welpe sitzt an der Elbe"
- Daclatasvir
- Velpatasvir
- Ledipasvir
- Elbasvir
Daclatasvir + Velpata
"Der Dackel Welpe der ist ja auch süß af" 📷
"Keiner macht 2+3, Ledi macht alle anderen, Elbas nur 1+4"
Ledipasvir - 1,4,5,6
Elbasvir - 1,4
all with sofosbuvir
except: Elbasvir - Grazoprevir
ledipasvir (ist ledig liegt deshalb auf dem sofa→ sofosbuvir)
"Der Dackel liegt bei dem Boy aufm dem Sofa und wird in Arsch gefickt"
- HepC
- HepC w/ HIV co-infection
"Merke: in cirrhosis immer mit Riba, außer die NS3"
A für ja
yes, with ribavirin
"Vom ganzen Arschfick ist der kleine Dackel müde und hat Kopfschmerzen" "Schau mal was im Hintergrund parkt"
- fatigue
- headache
- CYP450 inhib
"Was macht ein Dackel? Er macht Scheiße aufs Sofa (evtl. auch prokinetic effect vom arschfick?? hmmmM)"
60mg/d
-previr
(act before the others → hence "pre")
2, but 1. generation replaced in HCV treatment
side effects!
- anemia
- rush + hyperbili
- Dysgeusia
Simeprevir ("simmering") → Sofosbuvir
Grazoprevir ("kratzt sich am Bein") → Elbasvir
1+4
"wie die Elbe so die previrs, nähmlich vier." 🎙️
- CYP450 inhibition
- Photosensitivity + Rash (Sime)
- incr. Transaminases +bili (Grazo)
"An der Feuerstelle ist das CYP450-Auto, eine Kamera + eine LFT Fahne"
"Transaminases already incr. due to side effect"
nope
- with renal impairment
- Genotype 1+4
- HIV coinfection
"Special combo: Endlich haben die Nierenpatienten auch ne Chance und auch er hat bock auf Arschfick"
"Neben der Feuerstelle ist ein Tal, ganz unten sieht man eine Sau"
150mg/d
Neben dem Sofa ist die Rose mit der Sau (400mg), der Dackel macht Scheisse (60mg) auf die Couch, im Tal ist die Sau (150mg)
Guanosin analog
→ interference with GTP synthesis
→ inhibit capping of viral mRNA
→ inhibit RNA polymerase
- Respiratory synctial virus (RSV)
- influenza
- HIV
"Im Hintergrund ist ein RSV-Grabstein, der Mexikaner (ariba =ribavirine) ist so ein fame influenzer, durch sein legendäres Arschfick video (HIV)"
"Das i in influenzer steht für i.v., RSV ist in der Lunge (Aerosols), und der Mexikaner mag es zu rauchen deswegen holt er 1g bei Henne"
capsules - 1000-1200mg/d
aerosols - in RSV
i.v. - influenza
- decompensated cirrhosis:
- Sofosbuvir
- NS5A protease inhib.
"Der Mexikaner lag wohl auch auf dem Sofa shit + er liebt tomatenlastiges (hemolytic anemia)Chili con carne
- hemolytic anemia
- pruritus +rash
- depression
"Auch ihm wurde an der Niere geknabbert, außerdem chillt oben in der Ecke ne Tarantula und er hat ein großes Herz. Tomaten hat er wohl zuviel gegessen"
- Anemia
- RF
- heart disease
- pregnancy (Teratogenic)
🧈 Dyslipidemia and Obesity Treatment
"Arthur + Simba machen Love, keine Praven boys"
- Atorvastatin (most efficient in LDL reduction)
- Lovastatin
- Simvastatin
- Pravastatin
(1) Converted to cholesterol esters (2) Packaged in chylomicrons
A,B,C,E
LPL (lipoprotein lipase)
Receptor: LDL receptor Ligand: ApoE
Mevalonate
ApoB100
Receptor: LDL receptor Ligand: ApoB100
LCAT
(Lecithin cholesterol acyltransferase)
(1) Deliver to LDLs (2) Receptor mediated endocytosis via Scavenger Receptor-1
Inhibits HMG-CoA reductase
(↓ Intracellular Cholesterol ⇒ Upregulation of LDL receptors ⇒ ↑ Rate of peripheral cholesterol removal)
- incr. NO → vasodilation → improved endothelial function
- Arterioscl plaque → stabilization + reduced progression
- Immunosuppressive, Decr. CRP → sepsis protection
- Antioxidation
- incr. revascularization after MI*
- Decr. thrombotic risk → Decr. Aggregation + incr. Fibrinolysis
(1) ↓↓↓ LDL (2) ↓ TGs (3) ↑ HDL
- first line Hypercholersterolemia (exept. homozygous familiar HC)
- Prevention MI + Stroke
- Diabetes prevention
Pravastatin (no CYP450)
Statins
(1) Myopathy + Rhabdomyolysis (↑ CK)
(2) ↑ LFTs + hepatox
(3) Teratogen → contraindicated in pregnancy!
Pravastatin
- initial 20mg
- standard dose = 40mg
- (exception Atorvastatin = 10mg)
"Die Piraten haben alle ne Rose (40) im Mund, außer Arthur, der schlürft aus der Tasse im Fass (10-80)"
- w/ Fibrates - efficient in high LDL+TG; !!myopathy+rhabdomyolysis* (gemfibrozil → fenofibrate instead)
- w/ Ezetimib → first option when statin not enough (esp with simvastatin, or fixed dose with atorvastatin)
- w/ Bile acid sequestrant → second agent if statins do Ø work sufficiently
- w/ Niacin → side effects, Ø CV benefit
- Gemfibrozil (use fenofibrate)
- Warfarin, Macrolides (CYP450)
- elderly
- DM
- renal/hepatic failure
Simvastatin
"Note: PC has 1 "C"
Inhibits intestinal absorption of cholesterol → by blocking NPC1C receptor
(1) ↑ LFTs (2) Diarrhea
- add-on to statins in dyslipidemia
- when statins are contraindicated
"Der Boy hasst den Lobster + die Qualle mit dem Gem"
- Fibrates
- Bile acid sequestrants
"Der Al hält ne Tasse aufm Kopf"
10mg/d
Inhibits bile acid reabsorption ⇒ decr. bile back to the liver + depletion cholesterol stores → Stimulate HMG-CoA reductase & Upregulate LDL receptors
- Cholesthyramine
- Cholestipol
(1) ↓↓↓ LDL (2) ↑ TGs
(3) ↑ HDL
- second agent if statins doesnt work sufficiently
- Pruritus in biliary obstruction
↑ Risk of gallstones
Fat soluble vitamin + folic acid deficiency
(A, D, E, K)
Administer >4 hrs apart
500g powder
"Der lobster fängt mit einem Lasso die Sau um von ihrem Rücken zu koksen"
Inhibits PCSK9
(∴ Inhibits degradation of LDL receptors)
"Der Rumänisch Ali (Aliro-) reitet auf der Ebola-Kuh (Evolo-cumab)
Alirocumab
- with Statins in FH (hetero+homozygout)
- with Statins if LDL still >70
iv
neurocognitive effects
incr. HDL the most of all drugs
- stimulation orphan G coupled R on adipocyte → ↓Lipolysis of TG
- ↓ hepatic TG + VLDL production
- ↓LDL + Lp(a)
- ↑HDL
- ↓TG + ↓LDL
- Hypercholesterolemia - Combination with Statins
- to ↑HDL
2-6 g/day
"Noah hat riesen Schuhe mit ner Henne 🐓(gram) auf der Schulter aufm Rücken von Nessi "
- Cutaneous flushing
- Dyspepsia
- Hepatotox
- Hyperglycemia
- Incr. Uric acid
Contraindication:
- Peptic ulcer
- Liver diseases
- Diabetes
- Gout
NSAIDs
- Gemfibrozil
- Fenofibrat
- Pemafibrat (new motherfucker - high potency + effect)
Der brazilianische Gem, sieht aus(Phenotype)wie der Hema-Prof"
(1) Used by muscle (2) Coverted back to TG in adipose tissue
Activate PPAR-α
→ ↓TG + ↓VLDL → +↑hepatic uptake of LDL ⇒ decr. LDL
→ ↑Lipolysis (due to ↑LPL + ↑ApoA5& ↓ApoC3)
→ ↑betaoxidation → decr. FA
→ ↑HDL (incr. ApoA1)*
- Gallstones*
- Myopathy (esp in renal failure)
- Cancer
- Pregnancy
- Renal failure
- Biliary dyskinesia
- Alcoholics
- children
- type 3 hyperlipoproteinemia* - drug of choice (abnormal ApoE→Burn those TGs)
- ↑TG
- Dyslipidemia
- + hyperuricemia*
- + diabetes*
- severe dyslipidemia with statins (!!rhabdomyolysis)
- Warfarin → potentiated action
- Alcohol → should be stopped
"An der Tanne klettern 2 Schweine hoch mit Gems in der Nase"
1200mg /d
Synthetic Lipstatin → Selective inhibition GI-lipase → ↓FA
"Ein Jahr Training für die Fetten"
360mg/d
yes if >12y
Hälfte bruder
180mg/d
Eat fatty food concomitantly
fat-soluble vitamins
- diarrhea (steatorrhea)
- abdominal pain
- Malabsorption liposoluble vitamins
- Decr. Cyclosporin
- pregnancy
- gallstones
- not-overweight patient
(Am)Phetermine + kleinere Dietpropertionen (Dietylproprion) für den fetten Tobi der gerne Mate (Topiramate)trinkt. Er hat immer einen roten Kopf (CV+HT) vom SUff (Alkohol addicition) und seine schwangere Maus dabei.
- similar structure with amphetamine
- ↑Noradrenergic + dopaminergic transmission → suppressed appetite (hypothalamus)
- less CNS stimulation + addiction
stimulation presynaptic vessel to release noradrenalin → suppressed appetite (hypothalamus)
Topiramate → potentiate the effect
- CV diseases
- HT
- MAO inhib
- pregnancy
- alcohol addiction
Phentermine
(double trouble: NE+Dopa)
- CV-D
- HT
- better control of weight loss - different MOA
- better safety - lower doses
✊🏽
- Bupropion - inhibitor of NA+DA reuptake + stimulation of pro-opiomelanocyte
- Naltrexone - ↑effect of bupropion
“Simba liebt 📔 Buchproben in der No-tricks-zone”
BMI >30
BM 27-30 + dyslipidemia or HT
- HT
- Withdrawal symptoms (benzos + alkohol)
- Opiate + MAO inhib treatment
- other anti-obesity therapy
- Epilepsy, brain tumor
- psychiatric disorders
- Renal + hepatic insuff
prolonged therapy >1y
Pramlintide → Anorexic
Leptin → Anorexic
🩸 Anticoagulants, Anti-Platelet Drugs and Thrombolytics
Xa
antithrombin III
IIa + Xa (13,12,11)
aPTT intrinsic
- DVT (acute + prophylaxis)
- PE (acute + prophylaxis)
- MI (acute)
- DIC*
- surgery (prophylactic in orthopedic + gynecologic)*
iv. → inital 5.000 U → continous: 800-1.6k U
sc. 5-10k U 2-3x/d
Platelet Factor 4
🧠 Fun fact: Platelet factor 4 is also the antigenic target in thrombosis associated with AstraZeneca against Covid.
- Bleeding
- Hypoaldosterosim*
- →Type IV RTA with HyperK+*
- Osteoporosis
- Alopecia *
- HIT
Protamine (sulfate)
- any type of bleeding or bleeding disorder
- esp. avoided in patients with surgery in head region or spinal cord
- severe HT
- advanced hepatic disease
- any signs of recurrent or new thrombosis (clinic)
- Hb, Ht + BP → bleeding?
- aPTT - daily
- Platelet count - daily
yessssir (compare warfain which is not indicated)
- LMWH is more specific for Factor Xa and not for Factor II
- LMWH longer T1/2
- LMWH less HIT (LMWH doesnt requite routine monitoring)
- Protamine has less of a effect on LMWH
- LMWH eliminated by kidney/Heparin by liver*
kidney insuff (or when used closly monitor kidney function!)
sc 1-2x/d
"ALTE ADRO"
dALTEparin
nADROparin
+others
more specific binding of antithrombin - only against Factor Xa
Fondaparinux 🦊
"Der Hund hält die LFT fahne + und hat n grünes Skalpel im Mund"
- Postsurgery infections
- incr. liver enzymes
- thrombemolic events
- esp. as alternative in HIT
i.v.
LepiRUDIN
bivaliRUDIN
oral
dabiGATRAN
arGATROban
- prophylaxis thromboembolism
- after 5days of Heparin in thromboembolism - alternative to Warfarin
- stroke prevention in nonvalvular afib
- Bleeding esp in renal imparment or with concomitant NSAID
oral 👄
- afib (long term prophylaxis - alternative to warfarin + dabigatran)
- HIT
no, fixed dosages
RivaroXaBAN
ApiXaBAN
gamma carboxylation
VKOR (vitamin K epoxide reductase)
→ converts vitamin K epoxide (inactive) into vitamin K (active)
(1) Factor II (2) Factor VII (3) Factor IX (4) Factor X
(5) Factor C (endog. anticoagulant) (6) Factor S (endog. anticoag.)
Inhibit VKOR
7
oral
PT + INR
→ target INR 2-3
INR=PT(patient)/PT(normal)- Afib (prophylaxis stroke)
- mechanism heart vales
- DVT prophylaxis
- after Heparin in acute (PE, DVT)
NOPE
🕷️teratogenic (abnormal bone formation) + might induce hemorrhage in fetus
Early inhibition of Protein C (similar short T1/2 compared to Factor VII) (normally binds F5 and F8
Warfarin-induced skin necrosis 📷
→ Bridging therapy with Heparin
(1) Delayed:Administer Vitamin K (2) Immediate: Plasma transfusion
CYP450
Genetic Polymorphism of CYP450 + VCORC1
- CYP2C9 genetic variants impact warfarin pharmacokinetics.
- VKORC1 genetic variants affect warfarin pharmacodynamics.
- Patients with these polymorphisms may require dosage reduction.
- Other drugs decr. coagulation or platelet function: Heparin, Aspirin, Clopidogrel, etc
- ABs (Cephalos, Metronidazole)
- Hyperthyroidism, Hepatic disease
- Vit K
- Hypothyroidism
- Barbiturates
- Rifampin
- Bleedings (peptic ulcer, hemorrhagic stroke)
- optha + neurosurgery (merke keine anticoagulants in head + neck + spinal cord surgery)
- HT (auch nicht in HT)
- non-compliant patient
initially 5-10mg
→ maintenance dose: 5-7mg/d
⇒adjust according to serial INR measurements
- Phenprocoumon (marcumar)
- Acenocoumarol
- Dicumarol
- tPA
- rtPA = Alteplase
- Rete + Tenecteplase (modified Alteplase with longer T1/2)
- Streptokinase
- Urokinase *
inc PT + PTT
D-dimer
(1) Acute ischemic stroke (2) Deep venous thrombosis (3) Pulmonary embolism (4) Acute myocardial infarction (STEMI)
(5) Arterial Thrombosis *
Within 3-4.5 hours
PCI (percutaneus coronary intervention) [coronary angioplasty]
within 2h
- preclinical setting
- PCI not availible
- >2h
hemorrhagic stroke (or other types of bleeding)
- Recent head trauma
- Recent surgery (esp. intracranial)
- Severe HT
- Cerebral hemorrhage (even if only had in the past)
- GI bleeding recently or Hemorrhagic disorders
- Cerebral Tumors, Aortic dissection, Acute pericarditis
streptokinase
- Aminocaproic acid (fast i.v injection)
- Tranexamic acid (oral+iv)
- Fresh frozen plasma + blood transfusion
→ inhibit plasminogen activation 📷
- gynecological/GI bleeding
- Leukemia (pancytopenia)
- cirrhosis (coagulopathy)
- post surgery → esp. prostatectomy, dental extraction, amigdalectomy
cardiac patient + liver+kidney failure uffff
vWF + Collagen
GP1b → degranulation + release of ADP, 5-HT + TxA2
P2-Y12 → causing aggregation
(1) ↑ Platelet aggregation (2) Vasoconstriction
Cox1
irreversible inhibition COX-1+2
CV-event reduction in:
- PAD
- MI + other ACS
- CAD/Angina
- Stroke (ischemic)
Chewable aspirin
acute MI + prevention coronary stent thrombosis
Ø recommended for primary prevention of CVD
- IHD: 75-160mg (low-dose)
- CVD (Cerebro-vascular): 300 mg for 2 weeks after acute ischemic stroke → long term clopidogrel 75mg
"Känguru (Cangrelor) isst Tica Masala (ticagrelor) + macht ne Rasur (prasur-grel)"
- Clopidogrel
- Prasugrel
- Ticagrelor
- Cangrelor
Ticlopidine
Aspirin -1h
Ticlopidin 3-4d
- Secondary prevention: stroke, angina (CV in CAD)
- Dual therapy: acute MI + coronary stent
- intolerance to aspirin (pseudo-allergy)
- bleeding (ulcer, other)
- hepatic failure
- neutropenia
- Thrombocytopenia
- bleeding
- clopidogrel - see above
- Prasugrel - esp in PCI - CV intervention - also higher bleeding risk
- Ticagrelor - esp. in MI + stroke - also higher bleeding risk
- Cangrelor - prevention periprocedural MI during PCI
- Clopidogrel + Prasugrel - bind irreversibly to P2Y12 → longer duration of action (10d)
- Cangrelor - iv. - quick onset + offset
Drug | Administration Route | P2Y12 Receptor Binding | Onset of Antiplatelet Effect | Offset of Antiplatelet Effect |
Clopidogrel | Oral | Irreversible | 2–6 hours | 3–10 days |
Prasugrel | Oral | Irreversible | 30 min | 5–10 days |
Ticagrelor | Oral | Reversible | 30 min | 3–4 days |
Cangrelor | Intravenous | Reversible | 2 min | 1–2 hours |
To recreate this table in a word processor, you can use the Insert Table function and fill in the information as listed above, ensuring that any highlighted terms are appropriately formatted. If there's any specific aspect you want to alter or any additional detail needed, please let me know!
fibrinogen → aggregation
- Abciximab
- Eptifibatide
- Tirofiban
"Abdi + Tirol-IBAN (TI34 1345 5832)"
thrombocytopenia + bleeding
Vit K1 (natural from plant) + K3 (synthetic)
cofactor in synthesis of Factor II, X, VII, IX
- oral anticoagulant overdose (Warfarin)
- Prophylaxis of hemorrhage in prematures (reduced uptake)
- biliary obstruction+malabsorption (Inadequate absorption by bile salts)
- Not useful in VitK defic. caused by intrahepatic diseases
"der neugeborene ist ne Maus" (30mg)
20-40mg (im or iv)
like omeprazol
large doses of vitamin K can produce hemolytic anemia and jaundice in the infant, due to toxic effects on the membrane of red blood cells
"Was haben eig alle newborns? Kernicterus + hemoyltic anemia"
- hemolytic anemia
- hyperbili → nuclear jaundice
🐼 Anemia Treatment
- heme iron in meat proten (hemoglobin + myoglobin)
- bound to complex agents in vegetables + grains → less absorption availability
duodenum + prox. jejunum
ca 1mg
reduction to ferrous iron (Fe2+)
inc: HCl + VitC
decr: complexing agents, antacids
- Fe3+ → Fe2+
- active transport into mucosal cell
- can be stored here → as Ferritin (Fe3+)
- or as Fe2+ through Ferroportion out of the cell → conversion to Fe3+ + binding to Transferrin
mucosal iron stores (Ferrtin)
transferrin-ferric-iron complex 📷 → transferrin R on maturing erythroid cell
- Incr. in Transferrin R* on Erythroid cells
- Incr. Transferrin conc.
- Inhibition of Apoferrtin* (Ferritin=Apoferritin+iron) synthesis → iron balance shift towards transferrin
- Lowers the iron levels in the blood
- Binds Ferroportin (📷) in enterocytes → no more transport of iron outside of the cell + less absorption
- Ferroportin also on Macrophages → inhibit release of iron
stim: ↑iron overload, inflammation*
inhibition: hypoxia, bleeding → EPO
- mainly kept inside 🤡
- small amount → exfoliation of intestinal mucosal cells → stool
- trace amounts → bile, urine, sweat
Treatment + Prevention of iron def. anemia
- incr. requirements → premature, growth periods, pregnant+lactating woman)
- inadeq. absorption → gastrectomy, small bowel disease*
- blood loss
- functional iron def. * nicht mit oral iron sondern mit EPO
nope, oral as rapidly + completely as parenteral if absorption is normal
Ferrous iron → only ferrous salts!
Best percent elemtal iron → Ferrous fumurate + chloride
200-400mg / day divided in 2-3dose
coating is essentail
3-6 month
in persistent bleeding → continous high doses
- Reticulocytes
- MCV MCHC
- Serum iron
- Iron binding capacity
- Serum ferritin
- non-specific GI → nausea, epigastric pain, cramps, constipation/diarrhea
- dark coloration of teeth
- black stool
- lower dose
- take tablets with or immediately after meal
- change iron preperation (subtype)
- unable to absorb/tolerate oral iron
- post gastrectomy
- small bowel resection
- IBD
- malabsorption syndromes
- extensive chronic blood loss*
- EPO therapy*
- immediate iron store replacement necessary *
im* or iv
iron dextran
iron sucrose (gib dem 🙊 zucker)
Die Anaphylaktischen-Affen Eltern (parenteral) sind braun, Husten + Scheißen sich die Seele ausm Leib
- brown discoloration at injection side
- flu like symptoms (headache, fever, athralgias)
- GI non-specific (nausea + vomiting)
- Allergic symptoms (urticaria, bronchspasm, anaphylaxis)
Typical patient: young child
→ Potential lethality: >10 tablets of oral iron preparations ingested
- 🍤 GI:
- necrotizing gastroenteritis → bloody diarrhea
- vomiting + pain
- 🍫 shock + 🧪metabolic acidosis
- 🍑 liver failure
- 🚧. bowel obstruction due to scarring
- whole bowel irrigation → flush out the unabsorbed pills
- chelation therapy: Deferoxamine → bind systemic iron
- supportive
- inherited hemochromatosis
- long term blood infusions
deposition in various organs (heart, liver, pancreas, etc)
→ organ failure + death
phlebotomy (1U blood every week)
→ if doesnt help enough: Chelation therapy: Deferoxamine(parenteral), Deferiprone (oral)
it only correct the anemia + doesnt prevent the neurologic manifestations! (neuro masking)
only prevent further progression, not fully reverse the already developed
- macrocytics, hyperchromic
- leuko + thrombocytopenia*
- megaloblastic hypercellular bonemarrow
- neurological abnormalities
- lack of intrinsic factor, pernicious anemia
- ↓absorption:
- gastrectomy
- diseases of distal ileum(malabsorption syd, IBD, resection)
- nutritional deficiency (vegy, no meat, eggs, dairy)
- Correct high homocystein to prevent CAD *
- Cyanide intox → hydroxycobalamin*
lifelong injections
evaluation 6-12m
- hydroxycobalamin (preffered)
- cyanocobalamin
im or sc
never iv!
- initial: 100-1k microg daily 1-2weeks
- maintenance: same dosage once a month for life
→if neurologic symptoms → every 1-2 weeks for 6month → than once a month
100microg VitB12 i.m.
5mg folic acid
for 2 weeks
- disappearance of megaloblastic bonemarrow
- decr iron
- reticulocytes incr.
nope
- inadeq. dietary intake
- alcoholics + liver disease
- pregnancy
- hemolytic anemia
- >65y
- incr. homocysteins
- malabsorption synd
- cancer + leukemia
- chronic skin disorders
- renal dialysis
- drugs
- interference with absorption: anticonvulsants, contraceptives
- inhibition of dihydrofolate reductase (DHFR): MTX 📷
- oral (also in malabsorption synd)
- 1mg (-5mg)
- until unterlying cause corrected
- for ever - in malabsorption synd + dietary inadequacy
- pregnancy
- alcoholics
- hemolytic anemia, liver diseases, dialysis, skin diseases
- incr. homocysteine - Remember VitB12+Folic acid both ↓Homocysteine
- Erythroid prolif + differentiation
- Release of reticulocytes
- Recombinant human EPO
- Darbopoetin
- CRF
- After phlebotomy to accelerate erythropoesis
- Anemia due to:
- Cancer + chronic inflammation assoc. anemia*
- Primary bone marrow disorder*
- aplastic, myeloprolif+dysplastic, MM
- drug induced anemia (HIV treatment)*
- Anemia of prematurity *
ca. 100x3 + 200x3 in U/kg
CRF - 50-150 IU/kg iv/sc 3x week
others -150-300 IU/kg iv/sc 3x week
- ↑ Reticulocytes - 10days
- ↑ Ht + Hb - 2-6 weeks
- iron also low??
- folate supplementation needed??
- due to rapid incr. Ht+ Hb
- HT
- Thrombotic events
- allergies
→ incr. these values slowly
- G-CSF (Granulocyte colony-stimulating factor)
- Recombinants: Filigrastim, Pegfilgrastim
- GM-CSF (Granulocyte-macrophage colony-stimulating factor)
- Recombinant: Sargramostim
"Der filigrane G Gras-Tim + der Gamemaster (GM) Mo im Sarg"
G-GSF | GM-CSF |
prolif+diff of Np-lineage progenitors | prolif + diff of granulocytes, erythroid* + megakaryocyte progenitors |
stimulation of mature Np + prolonged survival | stimulation of mature Np |
mobilize hematopoietic stem cells | mobilize hematopoietic stem cells (less effective) |
stimulate T-cell prolif* |
Neutropenia → accelerated recovery, reduced duration
- Chemo
- postchemo in AML
- prior febrile neutropenia after chemo or high risk for febrile neutropenia
- high dose chemo
- congenital + primary bonemarrow
- stem cells transplantation (autologous + allogenic)
- G-CSF → better tolerated only bone pain; rare: splenic rupture
- GM-CSF
- allergic reactions
→ capillary leak syndrome (edema + pleural/pericardial effusion)
→ flu-like symptoms: fever, malaise, arthralgias, myalgias
“Tim ist zu viel Schlitten gefahren(splenic rupture) und Mo hat von der Kälte flu + leaked deswegen sehr viel rotze aus seiner nase (Capillary leak synd)”
🌊 Diuretics and ADH
Na+/K+/2Cl- Cotransporter in TA loop of henle
Mg2+ + Ca2+
induce expression of COX2 → ↑Pg → dilate afferent arteriole + enhance salt excreation
↓LV Preload (via different mechanism than volume reduction): ↑ venous capacity and ↓ filling pressure
→ Benefits in acute pulmonary edema, before diuretic effect
NSAID - reduce diuretic effect by blocking effect of PG
- Pulmonary edema
- Cardiac failure (1st line)
- Hypertension
- Hypercalcemia
- Other types of edema (i.e. ascitis)
- ARF with oliguria (compare with other diuretics)
Comparison Factor | Thiazide | Furosemide |
Diuretic potency | + | +++ |
Antihypertensive effect | ++ | + |
Renal blood flow and GFR | May ↓ | May ↑ |
Effective in renal failure | No | Yes |
Effective for hypercalciuria | Yes | No |
Effective for hypercalcemia | No | Yes |
Thiazides
- Ototoxicity (dont combine with other ototoxic drugs!)
- Sulfa allergy
- interstitial nephritis
- Hyperuricemia
- Dehydration + Contraction alkalosis
- Low Na, K, Mg, Ca
- ↓ K + Na
- Hypovolemia
- Severe Cirrhosis*
- Hypersensitivie Sulfa drugs*
!Caution in urinary stones* + pregnancy
- Ethacrynic acid is NOT a sulfa drug (no allergy)
- orally
- i.v. in emergency
Hydrochlorothiazide
"Das Klorwasser (Hydrocholoro-) der Thaliban (Chlor-thalidone)" Die Talban ist "done".
Thiazide-type: Hydrochlorothiazide
Thiazide-like: Chlorthalidone
NaCl cotransporter in DCT
in contrast to loops: enhances Ca reabsorption
NaCl cotransporter in DCT
in contrast to loops: enhances Ca reabsorption
(1) Hypertension 1st line (+ACE-Inhib.) (2) Heart failure + Edema (also due to liver + renal failure) (3) Nephrogenic diabetes insipidus (4) Ca2+ stones (5) Osteoporosis
Comparison Factor | Thiazide | Furosemide |
Diuretic potency | + | +++ |
Antihypertensive effect | ++ | + |
Renal blood flow and GFR | May ↓ | May ↑ |
Effective in renal failure | No | Yes |
Effective for hypercalciuria | Yes | No |
Effective for hypercalcemia | No | Yes |
(1) Hypercalcemia (2) Hyperglycemia (3) Hyperlipidemia (4) Hyperuricemia
(5) ↑ Serum Li+* (in pt receiving lithium)
(6) Hyponatremia (7) Hypokalemia ⇒ Ventricular arrythmias❗
(8) Hypersensitivity to Sulfa drug*****
(9) contraction alkalosis***
- Severe RF* (compare loops: Furo→liver; thiazide,k-sparing→kidney)
- Thiazide allergy
- Pregnancy / Lactation
Caution in Hyperuricemia/Gout, DM
- NSAID (reduce diuretic effect [also in Loop+K+sparing])
- Sulfonylureas
- Incr. Lithium (cardio+nephrotox)
- Hypertensive drugs → Risk of hypotension
-Like!
- Vasdilator effect → preferred in BP reduction
- prolonged effect (24h vs. 12h)
- Less adverse effects
- “Randomized controlled trials should compare thiazide-type diuretics with thiazide-like diuretics.
- Thiazide-like diuretics have higher efficacy in reducing blood pressure.
- Thiazide-like diuretics do not pose a risk of electrolyte disturbance or metabolic disorders.
- The conclusion from the analysis suggests replacing thiazide-type diuretics with thiazide-like diuretics.”
- The available evidence supports thaiazide-like diuretics as the preferred treatment for hypertension when considering thiazide treatment.
Collecting Duct
- ENaC (epithelial Na Channels)
- K- channel
- H+ ATPase
- Na/K pump (basolat.)
(-) Lumenal voltage
(Na+ reabsorption ⇒ (-) Lumenal voltage ⇒ Pulls K+ through channels)
"A ride with Milo (Amiloride) and Terry in the tram"
Amiloride
Triamterene
Amiloride + Hydrochlorothiazide
Triamterene + Hydrochlorothiazide
Mineral corticoid antagonists
→ Eplerenone + Spironolactone
- HyperK
- HypoNa
- Gynecomastia (Spirono)
- Impotence (Spirono)
- metabolic acidosis* (type 4 renal tubular)
- BPH
- inc. BP due to Hyperaldosteronism (edema)
- primary
- secondary :
- Cardiac failure → cardioprotective: inhibit fibrosis + remodeling induced by hyperaldosteronism
- MI with LVD → reduced mortality
- To ↑K+ → myastenia gravis*, hypoK, ileus*
- Treatment of PCOS (spironolactone)
- HyperK
- HypoNa
- Gynecomastia (Spirono)
- Impotence (Spirono)
- metabolic acidosis* (type 4 renal tubular)
- BPH
- Hyperkalemia
- Severe acute RF* (like-thiazides!!)
!other drugs incr. K!
- Eplerenon more specific inhibition of MR
+Lower affinity Androgen+progesteron R
Amiloride:
- Secondary Hyperaldosteronism (with Thiazides+furosemide)
- Liddle syndrome
- Nephrogenic DI produced by Li
- Cystic fibrosis***
Triamterene:
- Ascitis (second. edema) ??
- Nephrotic synd (secon. edema)??
- orthostatic hypotension + weakness
- Acidosis
- HyperK
- HypoNa
- Muscle cramps
- GI (diarrhea/constipation)
in proximal tubule + Loop of henle
Osmotic mechanism → Mannitol not reabsorbed → pulls + excretion water + nearly all electrolytes
- First phase ARF (too prevent ischemia)
- incr. water excretion + electrolytes
- acute drug intox *(nephrotoxic agents)
→ maintain urine volume + prevention anuria
- Reduce ICP + IOP*
- works not only in the kidney → expansion extracellular V → exacerbates HF + may produce pulmonary edema
- HypoNa + others
- incr. plasma osmolarity
- Hypovolemia or Hypotension
⇒ osmo + baro R 📷
- kidney: Water reabsorption
- blood vessels: Vasoconstriction
- Incr. Intestinal peristalsis (ileus)
- Promotes platelet aggregation
Chronic DI
- water intox
- HTN + ischemia → contraind. : ischemic heart diseases, MI
- Abdominal pain (→ ↑peristalsis)
Desmo = high affinity for V2 + long lasting + more intense
Vaso - i.v.
Desmo - nasal, oral
