Clearance | Selective Alpha Blockers | Liver And Gall Bladder Drugs

Question 1

Clearance concept and formula

Answer 1

Clearance has two parts, Renal and Total Clearance

Renal Clearance:
- Volume of plasma cleared of drug per unit time by the kidneys
- Measured in ml/min
- Formula CLr = [Cu * Vu]/Cp
- Cu is concentration of drug in Urine | Vu is rate of flow of Urine | Cp is concentration of drug in plasma

Total Clearance:
- Volume of plasma cleared of drug per unit time by ALL routes of excretion
- Must know the steady state concentration of drug
- CLtot = X/Css
- X is constant-rate IV infusion [mg/hr] | Css is steady state plasma concentration

Other Clearance Formulas:
- Cl = Dose/[tou * Cp] | Calculated from per hour dosage, total dose administered and concentration in plasma at that time
- Cl = Kel * Vd | Calculated from Vd of drug and Kel aka elimination constant of a drug

Question 2

Selective Alpha Blockers, Drug names and main Clinical use

Answer 2

Selective alpha blockers refer to drugs that selectively block either Alpha-1 or Alpha-2 receptors in the body

Alpha-1 receptors are mainly found in** Arterioles** and Smooth muscles [Skin, viscera, veins, Eye radial muscle, male genitalia, bladder trigone, prostatic urethra, bladder spincter], doing the work of vasoconstriction on activation from Sympathetic nervous system

Alpha-1 Blockers:
- Prazosin [Anti HTN, vasodilation effect, decreased TPR and BP affecting mainly veins]
- Doxazosin [Same as Prazosin]
- Terazosin [BPH as most of BPH tissue is smooth muscle proliferation, thus allowing urination ease]
- Tamsulosin [BPH only]

Alpha-2 Blockers:
- Not many drugs as Alpha-2 receptors not functionally involved as alpha-1
- Mirtazapine [Alpha-2 blocker + 5HT2/HT3 receptor antagonist; Blocks presynaptic inhib neurons allowing NE release; Used as Antidepressant]

Question 3

Hepatotoxicity effects of drugs

Pharmacology of Liver and Gallbladder

Answer 3

Hepatotoxicity shows up as:
- Zonal necrosis
- Acute and Chronic Hepatitis
- Acute and Chronic Cholestasis
- Steatosis
- Granulomas
- Hepatic Encephalopathy

LiverTox is a searchable online database maintained by the NIDDK where there are > 1000 drugs and herbal remedies that cause potential hepatotoxicity

Hepatotoxicity can occur due to mainly two reasons:
- Intrinsic and Dose-dependent: due to drugs internal structure and/or therapeutic index dosages, it causes toxicity. There is PREDICTABLE and REPRODUCIBLE evidence
- Idiosyncratic: Toxicity is NOT PREDICTABLE or REPRODUCIBLE in everyone, it is highly individualistic. Risk factors can include Age, Sex, BMI, Hypersensitivity, Comorbidities, Polymorphism and genetic, Immune status, etc [Host factors | Drug factors | Environmental factors]

Idiosyncratic related drugs are: [in order of % makeup of this group of drugs]
- Antibiotics [AmoxiClav | INH | Ciprofloxacin]
- NSAIDS
- Herbal and Dietary supplements
- CVS drugs [Amiodarone | Statins]
- CNS drugs [Pheytoin]
- Antineoplastic/Biologics [Tyrosin Kinase inhib | TNF inhib | Methotrexate]

Testing for drug induced toxicity should include:
- List of meds patient takes
- ALT
- AST
- ALP
- GGT
- Total bilirubin
- Albumin ,PT, INR