Basic Pharmacokinetics and Beta-2 Adrenoceptor

Basic Pharmacokinetics

• Facilitated passive diffusion occurs against a concentration gradient.
• Increased first-pass metabolism results in less drug needing oral administration.
• A higher pH than pKa value indicates a larger proportion of the drug is in its unprotonated form.
• Volume of distribution (Vd) calculation determines loading dose.
• Constant Vd and prolonged drug half-life lead to decreased drug clearance.

Pharmacokinetics

• Drug elimination follows zero-order kinetics when metabolism is saturated.
• First-order kinetics: elimination rate is proportional to the plasma drug concentration.
• Infusion rate changes the time to steady-state drug concentration.
• Area under the curve (AUC) represents the total amount of absorbed drug.
• Time to reach steady-state depends on the drug dose.

Second Messenger System for Beta-2 Adrenoceptor on Bronchial Smooth Muscle

• Adrenaline increases cAMP activity.
• Inhibition of phosphodiesterase (PDE) decreases cAMP levels.
• Increased cAMP lowers intracellular calcium levels.
• Caffeine increases cAMP levels.
• Theophylline increases myosin light chain kinase (MLCK) phosphorylation.

Signal Transduction and Drug Action

• Dopamine increases cAMP concentration in myocardial muscle.
• Adrenaline increases phospholipase C activity in vascular smooth muscle.
• Inositol triphosphate increases smooth muscle relaxation.
• Alpha-1-adrenoceptor stimulation increases diacylglycerol concentration.
• Beta-2-adrenoceptor stimulation activates myosin light chain kinase (MLCK).

Antifungals

• Fluconazole is more effective against Aspergillus than voriconazole.
• Posaconazole is used as a prophylaxis against invasive fungal infections.
• Itraconazole inhibits cytochrome P450 enzymes.
• Voriconazole is preferred to amphotericin B in pregnant patients with invasive fungal infections.
• Caspofungin is a fungal cell membrane synthesis inhibitor.

Antiretrovirals

• Tenofovir is associated with a higher incidence of lactic acidosis than stavudine.
• Efavirenz is preferred to etravirine in patients with K103N viral isolates.
• Atazanavir is favored over lopinavir for patients with dyslipidemia.
• Combination of emtricitabine and lamivudine is synergistic.
• Darunavir is contraindicated for patients with a previous history of sulphur-containing drug anaphylaxis.

Antivirals

• Ganciclovir is preferred to valaciclovir for CMV retinitis
• Oseltamivir is preferred to annual flu vaccine prophylaxis for influenza.
• Higher doses of acyclovir are needed for herpes encephalitis than for genital herpes.
• Ribavirin is ineffective against RSV (Respiratory Syncytial Virus).
• Pegylated interferon treats chronic hepatitis B.

Beta-Lactam Antibiotics

• Flucloxacillin is beta-lactamase sensitive.
• Co-amoxiclav treats urinary tract infections.
• Penicillin G half-life decreases with probenecid.
• Meropenem treats bacterial meningitis.
• Cefepime is preferred to cefadroxil for Pseudomonas aeruginosa infections.

Cell Wall Synthesis Inhibitors

• Vancomycin oral administration is for treating respiratory tract infections.
• Cefotaxime crosses the blood-brain barrier.
• Metoclopramide increases urinary fosfomycin levels.
• Cefamandole metabolism decreases alcohol.
• High penicillin G doses increase seizure risk.

Fluoroquinolones

• Urine alkalization increases ciprofloxacin crystalluria risk.
• Moxifloxacin prolongs QTc interval.
• Fluoroquinolones are to treat toxoplasmosis.
• Fluoroquinolones can increase seizure risk in patients with epilepsy.
• Fluoroquinolones are safe in growing children under 18.

Metronidazole

• Used in acute necrotizing ulcerative gingivitis.
• Increases bleeding risk with warfarin co-administration.
• Eradicates Helicobacter pylori in peptic ulcer disease.
• Metabolism increases with cimetidine co-administration.
• Decreases lithium plasma concentrations.

Co-trimoxazole

• Long-term use increases folic acid deficiency risk.
• Increases digoxin plasma levels when combined.
• Converted vitamin K into active form in intestines.
• Contraindicated in G6PD deficiency.
• Safe during the last month of pregnancy.

Folic Acid Synthesis Inhibitors

• Silver sulfadiazine used orally for burn wound treatment.
• Trimethoprim excreted in urine.
• Sulfamethoxazole inhibits dihydrofolate reductase.
• Sulfamethoxazole combined with glibenclamide increases hypoglycemia risk.
• Sulfacetamide used topically for conjunctivitis.

Nitrofurantoin

• Absorption reduced by food.
• Treats bacterial meningitis.
• Inhibits folic acid synthesis.
• Contraindicated after the 38th gestational week.
• Long-term use increases risk of lung fibrosis.

Aminoglycosides

• Gentamicin treats Staphylococcus aureus infections.
• Streptomycin is ototoxic.
• Safe to use in patients with myasthenia gravis.
• Treats Pseudomonas aeruginosa infections.
• Elimination half-life decreases with renal impairment.

Antibiotics (Various)

• Telithromycin increases bleeding risk with warfarin.
• Tigecycline is safe in young children.
• Quinupristin-dalfopristin inhibits DNA gyrase.
• Linezolid treats MRSA.
• Fusidic acid treats osteomyelitis.

Drugs used for bacterial infections

• Azithromycin has shorter half-life than erythromycin.
• Tetracycline treats tick bite fever (Rickettsia).
• Clindamycin treats pseudomembranous colitis.
• Chloramphenicol is preferred to ceftriaxone in neonatal bacterial meningitis.
• Daptomycin depolarizes the bacterial cell membrane.

Matching Antibiotics to Mechanism of Action

• Metronidazole: Forms reactive intermediates, interact with bacterial DNA.
• Clindamycin: Inhibits protein translocation.
• Doxycycline: Inhibits protein synthesis on bacterial 30S ribosomes.
• Vancomycin: Inhibits bacterial cell wall synthesis.
• Fosfomycin: Inhibits codon anticodon interactions.

Antibiotics and Side Effects

• Telithromycin: Hepatotoxicity.
• Imipenem: Seizures.
• Erythromycin: Constipation.
• Vancomycin: Red Man Syndrome.
• Minocycline: Skin discoloration.

Malaria Prophylaxis

• Mefloquine is a blood schizonticide.
• Doxycycline is safe during third trimester of pregnancy.
• In other malaria prophylaxis cases: Mefloquine is preferred to atovaquone-proguanil in certain patients; proguanil inhibits folic acid synthesis, and mefloquine is teratogenic.

Treatment of malaria

• Quinine is contraindicated in cerebral malaria.
• Primaquine is contraindicated in pregnancy.
• Artemether inhibits the erythrocytic phase of the malaria life cycle in humans.
• lumefantrine has longer duration of action compared to Artemether
• Doxycycline antagonizes the effect of quinine.

Treatment of Helminth Infections

• Mebendazole treats Strongyloides stercoralis.
• Albendazole is safe during first trimester of pregnancy.
• Praziquantel effectively treats schistosomiasis.
• Praziquantel causes paralysis of helminth.
• Niclosamide prevents polymerization of cytoplasmic microtubules in susceptible helminths.

Treatment of Protozoal and Ectoparasitic Infections

• Metronidazole is contraindicated during pregnancy's first trimester.
• Tinidazole has shorter duration of action than Metronidazole.
• Chloroquine is preferred to metronidazole for luminal amoeba infections.
• Co-trimoxazole treats pneumocystosis.
• Lindane is readily absorbed through the skin.

Rifampicin

• Increases digoxin clearance.
• Induces verapamil metabolism.
• Effective prophylaxis against meningococcal carriage.
• Increases warfarin anticoagulant effect.
• Effective against multidrug-resistant strains of Mycobacterium tuberculosis.

Ethionamide

• Inhibits cytochrome P450 enzymes.
• Does not penetrate the blood-brain barrier.
• Causes pyridoxine-sensitive peripheral neuropathy.
• Precipitates seizures in susceptible individuals.

• 95% excreted unchanged in the urine.