Pharmacology: Drugs and Their Targets

Benzodiazepines

• Enhance GABA-activated Cl- channel opening for anxiety

Analgesic

• the enzyme responsible for the production of prostaglandins, which are hormones that can cause pain and inflammation. This inhibition explains paracetamol's use as an analgesic and anti-inflammatory medication.

Anti-Cancer Drug

• Fluorouracil blocks DNA synthesis by replacing uracil in purine biosynthesis

Prodrugs

• Ciclesonide is converted to active metabolite in the lung
• Codeine is converted to morphine via CYP2D6
• Tenofovir disoproxil is hydrolysed to tenofovir by esterase

Neurotransmitters

• GABA, also known as γ-aminobutyric acid, is a major inhibitory neurotransmitter in the central nervous system, responsible for reducing the activity of neurons.
• Glycine is an inhibitory neurotransmitter, activates ion channel receptors, and is mainly found in the spinal cord
• Glutamate is a fast-acting excitatory neurotransmitter, activates ion channel receptors, and is found in the CNS
• 5-hydroxytryptamine (5HT) activates ion channel receptors, increases motility, vasodilation, and platelet aggregation

Adverse Drug Reactions (ADRs)

• Type A ADRs are related to pharmacological effects and show a dose-response relationship (e.g., morphine)
• Type B ADRs are idiosyncratic and unpredictable (e.g., penicillin)
• Type D ADRs are time-related and occur after use (e.g., teratogens)
• Type F ADRs are unexpected failures of a drug to produce therapeutic effects (e.g., antibiotic resistance)

Organophosphates

• TOCP causes delayed neuropathy, muscle weakness, and ataxia

Teratogens

• Diethylstilbestrol is a synthetic estrogen linked to severe birth defects
• Thalidomide causes severe birth defects
• Fetal alcohol syndrome is caused by prenatal alcohol exposure

Antifungal Drugs

• Allylamines alter cell membrane integrity or permeability (e.g., terbinafine)
• Azoles alter cell membrane integrity or permeability and inhibit ergosterol biosynthesis (e.g., itraconazole)

Anti-HIV Drugs

• Integrase inhibitors (e.g., elvitegravir) and protease inhibitors (e.g., ritonavir) are used to treat HIV
• Tenofovir disoproxil fumarate is a prodrug for HIV reverse transcriptase inhibition

Metabolism

• Enterohepatic recirculation involves lipophilic drug absorption, hepatic metabolism, conjugate excretion into bile, and hydrolysis by B-glucuronidase
• Ethanol is metabolized to acetaldehyde via alcohol dehydrogenase
• Probenecid inhibits OAT1 and OAT3, increasing the action of Cephalexin is a first-generation cephalosporin antibiotic that inhibits bacterial cell wall synthesis. It is effective against a wide range of gram-positive and gram-negative bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, and E. coli. Cephalexin is often used to treat respiratory tract infections, skin and soft tissue infections, and urinary tract infections.

Drug Interactions

• Ritonavir, also known as Norvir, is a potent inhibitor of cytochrome P450 3A4 (CYP3A4), one of the primary enzymes responsible for the metabolism of various medications. Its primary use is as a pharmacokinetic enhancer for protease inhibitors, increasing their bioavailability and potency.
• Cobicistat is a pharmacokinetic enhancer that is used in combination with elvitegravir, an HIV-1 integrase inhibitor, to treat HIV infection. Cobicistat increases the bioavailability and efficacy of elvitegravir by inhibiting its metabolism.
• Phenobarbital induces CYP expression, reducing drug effects due to enhanced hepatic metabolism

Benzodiazepines and Anxiety

• Benzodiazepines enhance GABA-activated Cl- channel opening for anxiety.

Analgesic and Anti-Cancer Drugs

• Paracetamol is an analgesic that inhibits cyclooxygenase.
• Fluorouracil is an anti-cancer drug that blocks DNA synthesis by replacing uracil in purine biosynthesis.

Respiratory and Antidepressant Drugs

• Ciclesonide is a prodrug converted to active metabolite in the lung.
• Fluoxetine inhibits serotonin re-uptake for antidepressant effect.

CNS Stimulants and Toxicity

• Amphetamine is a CNS stimulant that uses noradrenaline transporter to enter nerve terminals and replace/release neurotransmitters noradrenaline and serotonin.
• Ethanol increases drug metabolism leading to lower plasma concentrations.
• Chronic ethanol consumption leads to evidence of toxicity including acute toxicity - CNS depression and chronic toxicity - alcohol-related liver disease.

Barbiturates and Neurotransmitters

• Barbiturates increase metabolism resulting in lower drug response.
• GABA (³-aminobutyric acid) activates ion channel receptors and is an inhibitory transmitter formed from glutamate.
• Glycine activates ion channel receptors, stimulates glycine receptors, and is an inhibitory neurotransmitter mainly in the spinal cord.
• Glutamate activates ion channel receptors, stimulates glutamate receptors, and is a fast-acting excitatory neurotransmitter in the CNS.
• 5-hydroxytryptamine (5HT) activates ion channel receptors, increases motility, vasodilation, and platelet aggregation.

Muscle Relaxants and Pharmacological Effects

• Suxamethonium is a long-acting agonist causing neuromuscular block and is a short-acting muscle relaxant/paralysis.
• Morphine and codeine are linked to pharmacological effects and show a dose-response relationship.
• Morphine and codeine are associated with type A ADR, which includes respiratory depression.

Adverse Drug Reactions (ADRs)

• Type B ADR is idiosyncratic, unpredictable adverse drug reactions, such as anaphylaxis seen with penicillin.
• Type D ADR is time-related, occurs after use, and includes agents causing birth defects by altering fetal growth.
• Type F ADR is antibiotic resistance, which is an unexpected failure of a drug to produce therapeutic effects.

Teratogens and Toxic Substances

• Diethylstilbestrol is a synthetic estrogen linked to severe birth defects, including clear-cell adenocarcinoma in the vagina of female offspring of DES-treated mothers.
• Thalidomide is a sedative causing severe birth defects.
• Fetal alcohol syndrome results from prenatal alcohol exposure, including facial defects.

Liver Injury and Toxicity

• Paracetamol type DILI is intrinsic, predictable, common, dose-related, and reproducible in animal models.
• NSAIDs type DILI cause idiosyncratic liver injury, which is rare, unpredictable, not dose-related, and not reproducible in animal models.
• Diclofenac causes idiosyncratic liver injury due to reactive metabolites causing mitochondrial injury and oxidative stress.

Antibacterial Drugs

• Penicillin inhibits bacterial cell wall synthesis.
• Amoxicillin is a broad-spectrum penicillin not β-lactamase resistant.
• Clavulanic acid is a β-lactamase inhibitor, semisynthetic.
• Augmentin is a combination drug for penicillin resistance, consisting of amoxicillin and clavulanic acid.
• Cephalosporin inhibits bacterial cell wall synthesis.

Anti-HIV Drugs

• Integrase inhibitors are a mechanism of action for anti-HIV drugs, including INSTIs such as elvitegravir.
• Protease inhibitors are anti-HIV drugs that inhibit viral protease, including PIs such as navir.

miscellaneous

• Codeine is a prodrug example, converted to morphine by CYP2D6 (dealkylation).
• Esterase hydrolyzes tenofovir disoproxil to tenofovir.
• Morphine is metabolized to morphine-3-glucuronide and morphine-6-glucuronide by UGT2B7.
• Enterohepatic recirculation occurs with morphine, undergoing absorption, hepatic metabolism, conjugates excreted into bile, glucuronides in the GI tract hydrolysed by β-glucuronidase, and generating unconjugated drug.

Drug Metabolism and Elimination

• Paracetamol is metabolized to NAPQI by GST.
• Activated charcoal prevents aspirin overdose by adsorbing the drug, which is then excreted from the body.
• Sodium bicarbonate prevents salicylate overdose by alkalizing urine, increasing urine pH, increasing salicylic acid ionization, and decreasing reabsorption.
• MDR1, MRP2, and BCRP are important ATP-binding cassette (ABC) drug transporters.
• OAT1 and OAT3 are solute carrier transporters (SLC).
• Ethanol is stored in total body water.
• Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (oxidation).
• Ethanol follows zero-order kinetics.
• Tetracyclines should be avoided in pregnant people or young children due to their high affinity for calcium, which slowly accumulates in bones and teeth.

This quiz covers various drugs, their mechanisms of action, and targets, including benzodiazepines, paracetamol, and fluorouracil.