Hey there, fellow medical enthusiasts! Ever wondered why the same drug can work wonders for one person but cause problems for another? Or why some people need a higher dose than others? Welcome to the fascinating world of factors affecting drug action!
Today, let’s break it down in a fun and interactive way—because pharmacology doesn’t have to be boring!
1. General Factors: Not All Bodies Are the Same!
Size Matters—Body Surface Area (BSA) vs. Weight
Imagine giving the same dose of a drug to a 50 kg person and a 100 kg person. Not fair, right? That’s why drug doses are often calculated based on body surface area (BSA) rather than weight. A bigger body means more distribution, which affects the drug's action!
Age—The Young and the Elderly Need Special Care
- Children: Their liver and kidneys are still developing, so they metabolize drugs slower. Some drugs (like tetracyclines) can even harm their growing bones!
- Elderly: Their metabolism slows down, so drugs stay in their system longer. This means they might need lower doses to avoid toxicity.
Sex—Hormones Play a Role!
Did you know that some drugs are avoided in females?
- Minoxidil, a drug for hair growth, is avoided in women because it can cause hirsutism (excessive hair growth).
- Women also have different fat distribution, enzyme levels, and hormone fluctuations that affect drug metabolism.
Race—Genetics and Drug Sensitivity
- The Japanese population experienced a severe neurological disorder called Subacute Myelo-Optic Neuropathy (SMON) after taking Quiniodochlor (an antimalarial drug).
- Some racial groups metabolize drugs faster or slower due to genetic variations in liver enzymes.
Route of Administration—How You Take a Drug Changes Everything!
- Intravenous (IV): Super fast! Used in emergencies like anaphylaxis or heart attacks.
- Oral: Takes longer because it has to pass through the digestive system.
- Sublingual (under the tongue): Bypasses the liver and works quickly (like nitroglycerin for angina).
Disease States—The Liver and Kidneys Are the Gatekeepers!
- The liver metabolizes most drugs. If it’s damaged (like in cirrhosis), drugs stay in the body longer, increasing toxicity.
- The kidneys excrete drugs. If kidney function is impaired (like in chronic kidney disease), doses need to be reduced.
2. Pharmacogenetics: How Your Genes Affect Drug Response
Genetics can make some people react differently to drugs. Let’s explore some cool examples!
A. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency—A Hidden Danger!
- G6PD protects red blood cells (RBCs) from free radical damage.
- Some drugs create free radicals, and in people with G6PD deficiency, these RBCs break down, leading to hemolytic anemia (bad news!).
- Drugs to avoid in G6PD deficiency:
- Primaquine (anti-malarial)
- Sulfonamides (like sulfamethoxazole)
- Nitrofurantoin (for UTIs)
B. Acetylation—Some Are Fast, Some Are Slow!
- Some drugs are metabolized by acetylation in the liver.
- People can be fast or slow acetylators, affecting how the drug works:
- Slow acetylators: Higher risk of drug accumulation and side effects.
- Fast acetylators: May need higher doses for the drug to work effectively.
- Drugs affected:
- Sulfonamides
- Hydralazine
- INH (Isoniazid)
- Procainamide
C. Succinylcholine-Induced Apnea—The Muscle Relaxant That Won’t Wear Off!
- Succinylcholine (SCh) is a short-acting muscle relaxant used in surgeries.
- Normally, it’s broken down by pseudocholinesterase (an enzyme).
- But if someone has atypical pseudocholinesterase, the drug stays in the system too long, causing prolonged apnea (breathing stops!).
D. Warfarin—Why Some People Bleed More Than Others!
- Warfarin, a commonly used anticoagulant, is metabolized by the VKORC1 and CYP2C9 enzymes.
- Genetic variations in these enzymes affect how fast or slow Warfarin is broken down.
- Risk? A slow metabolizer has an increased risk of bleeding, while a fast metabolizer might not get enough anticoagulation.
- Solution? Genetic testing helps adjust the dose before problems arise!
E. Azathioprine & 6-Mercaptopurine—A Bone Marrow Time Bomb?
- These immunosuppressive and anticancer drugs are metabolized by the TPMT (Thiopurine Methyltransferase) enzyme.
- Some people have a mutant TPMT gene, meaning they don’t break down thiopurines properly.
- What happens? Toxic accumulation leads to severe bone marrow suppression—a life-threatening condition!
Genetic test = lifesaver!
F. 5-Fluorouracil (5-FU)—A Cancer Drug That Can Turn Toxic!
- 5-FU, used in chemotherapy, is degraded by the DHPD (dihydropyrimidine dehydrogenase) enzyme.
- If this enzyme is deficient, 5-FU builds up and causes serious toxicity (think: nausea, vomiting, and bone marrow suppression).
- Genetic screening is a must to prevent severe reactions!
G. Succinylcholine—What If You Couldn’t Breathe After Surgery?
- Succinylcholine is a muscle relaxant used in anesthesia.
- Normally, it’s broken down by pseudocholinesterase.
- Some people have atypical pseudocholinesterase, meaning they can’t metabolize it properly.
- What happens? Instead of waking up quickly, they stay paralyzed for longer than expected!
- The Dibucaine Number (normally 80) helps detect this enzyme deficiency.
H. Irinotecan & Atazanavir—When Your Liver Fails to Detox!
- These drugs are cleared from the body by the UDP-GTA1 enzyme (Uridine Diphosphate Glucuronyltransferase).
- Some people have genetic conditions (Crigler-Najjar syndrome or Gilbert syndrome) where this enzyme is deficient.
- What happens? Drug levels rise, leading to toxicity and liver problems.
If you have these conditions, these drugs are contraindicated!
I. Abacavir—An HIV Drug That Can Turn Deadly!
- Abacavir is an antiviral drug for HIV but can cause life-threatening allergic reactions in some people.
- The culprit? HLA-B*5701 genetic variation.
- Solution? A simple genetic test before prescribing can prevent fatal hypersensitivity reactions!
Final Takeaway—Why Genetic Testing Matters!
Not all drugs work the same for everyone!
A genetic test can save lives by preventing drug toxicity and improving treatment effectiveness.
Pharmacogenomics is the future of medicine—because one size does NOT fit all!
3. Pregnancy and Lactation—Think Before You Prescribe!
Some drugs are safe in pregnancy, while others are teratogenic (cause birth defects). Here’s a quick cheat sheet:
Drugs Safe in Pregnancy
- Anti-hypertensives → Labetalol, Methyldopa
- Anti-diabetics → Insulin
- Anti-coagulants → Heparin
- Anti-microbials → Penicillins, Cephalosporins, Macrolides
- Anti-emetics → Doxylamine
Drugs to Avoid in Pregnancy
- ACE Inhibitors and ARBs → Cause kidney damage in the baby
- Warfarin → Causes nasal hypoplasia & skeletal defects
- Valproate → Neural tube defects
- Thalidomide → Phocomelia (limb deformities)
- Tetracyclines → Affects teeth and bone growth
- Fluoroquinolones → Cartilage and tendon damage
Drugs Safe in Lactation
- Most drugs are safe as the amount secreted in breast milk is negligible.
- Best practice? Breastfeed just before taking the drug to keep baby exposure minimal.
US-FDA category ofteratogenic drugs,5 categories
- A: Safestin pregnancy
- A,B, C,D:3 given in pregnancy ◦
- X: most dangerous (Absolutely contraindicated in pregnancy).
4. Enteric Coating—The Drug’s Protective Shield!
Ever wondered why some pills shouldn’t be crushed? It’s because of enteric coating!
- What is enteric coating?
- A special layer that dissolves only in an alkaline environment (i.e., intestines).
- Why use it?
- Protect acid-labile drugs from stomach acid (e.g., proton pump inhibitors like omeprazole).
- Protect the stomach from irritating drugs (e.g., aspirin).
- Ensure better absorption of drugs that need the intestine for uptake.
5.Adverse Drug Reactions (ADR)—When Medicines Turn Against You!
Not all drugs are friendly! Sometimes, they cause Adverse Drug Reactions (ADR)—unwanted, unintended, and harmful effects that occur despite proper use. But wait, isn’t that the same as an Adverse Event (AE)? Not exactly! AE is any harmful occurrence that may or may not be drug-related, while ADR is always due to the drug itself.
To determine whether a reaction is actually an ADR, doctors perform causality assessments, questioning the patient about symptom onset and using tests like the dechallenge test (stopping the drug to see if symptoms improve) or the rechallenge test (reintroducing the drug to check if the reaction reappears). This is where pharmacovigilance comes in—the science of monitoring, assessing, and reporting ADRs to ensure drug safety.
Healthcare professionals document ADRs using an ADR form, which is uploaded into Vigiflow software and sent to pharmacovigilance centers like the Indian Pharmacopoeia Commission (IPC) in Ghaziabad or the WHO-Uppsala Monitoring Center (WHO-UMC) in Sweden. The severity of ADRs determines the action taken—very harmful drugs may be banned, while mild reactions are reported as side effects.
But did you know that ADRs come in different types? Here’s how they are classified:
Type A (Augmented Dose-Dependent Reactions): These occur due to high drug doses and can be prevented by dose reduction. For example, excessive insulin can lead to hypoglycemia.
Type B (Bizarre Reactions): These are unpredictable, allergic, or hypersensitivity reactions, often linked to genetics. A classic example? Penicillin allergy, seen in 2 out of 100 people.
Type C (Chronic Use Reactions): ADRs that appear after long-term drug use—such as aspirin-induced peptic ulcers or proton pump inhibitors (PPIs) causing osteoporosis due to calcium deficiency.
Type D (Delayed Reactions): These show up years after drug administration. Cisplatin, an anti-cancer drug, can cause secondary cancer 3-5 years after stopping treatment.
Type E (End-of-Treatment Reactions): Sudden withdrawal of certain drugs can cause harmful withdrawal effects—for instance, stopping opioids abruptly leads to severe withdrawal symptoms.
Type F (Failure of Therapy): Sometimes, drugs fail to work as intended. This can happen due to antimicrobial resistance, such as TB drugs that don’t kill Mycobacterium tuberculosis effectively.
To classify ADRs, tools like the Naranjo Scale and the WHO-UMC Scale are used to establish a clear link between the drug and the reaction. So, the next time you take a medication, remember—your genes, your body, and even global monitoring systems are working together to keep you safe!
Final Thoughts—Why This Matters!
Understanding why drugs act differently in different people isn’t just a fun fact—it’s crucial for safe prescribing!
- A one-size-fits-all approach in medicine doesn’t work.
- Genetics, age, race, sex, disease, pregnancy, and drug formulation all play a role.
- This is why personalized medicine is the future!
So next time you pop a pill, remember—it’s not just about the drug, but how your body interacts with it!
Want more fun pharmacology insights? Drop your questions below! Let’s keep learning together!
Thank you.
%20(8).jpeg)
.jpeg)
0 Comments