Pharmacology Talk for Med Students (1)
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This document provides an overview of several classes of antihypertensive drugs and antimicrobial medications. It summarizes the usual dose, mode of action, indications, side effects, and important interactions for drugs like ACE inhibitors, calcium channel blockers, beta blockers, diuretics, antibiotics, and antifungals. The document is intended as a guide for pharmacology knowledge and notes some drugs require monitoring or have specific usage guidelines.
Pharmacology Talk for Med Students (1)
- 1. Pharmacology for Medical Students (Part 1) Anti-Hypertensives / Diuretics Antimicrobials – Antibiotics / Antifungals / Antivirals
- 2. Disclaimer! • This is not medical advice! • This is the drug knowledge of a general/ renal physician • This is not exhaustive – Some self directed learning required!
- 3. Format (mostly) Drug Usual Dose Mode of Action Indications Side Effects Interactions/Important Pointers
- 5. Aged over 55 years or black person of Aged under African or Caribbean family Summary of 55 years origin of any age antihypertensive drug treatment A C2 Step 1 Key A+C 2 Step 2 A – ACE inhibitor or low- cost angiotensin II receptor blocker (ARB)1 A+C+D Step 3 C – Calcium-channel blocker (CCB) D – Thiazide-like diuretic Resistant hypertension Step 4 A + C + D + consider further diuretic3, 4 or alpha- or beta-blocker5 Taken from NICE guidance CG127. Link here Consider seeking expert advice
- 6. ACE Inhibitors Drugs: Ramipril (1.25-20mg), Lisinopril (2.5-20mg), Perindopril (2-16mg), Trandolapril (0.5-4mg) Mode of Action: Prevents production of Angiotensin II via inhibition of ACE Indications: Hypertension, Heart Failure, Post- Acute Cardiac Syndrome, Proteinuria Side Effects: Dry Cough (Bradykinin), Hypotension, Renal Impairment* Interactions/Important Pointers: – NSAIDS impair ACEi effect (and aggravate renal function) – BP effects of combined agents additive – Cannot be used in pregnancy (Teratogenic) – Can cause Angio-oedema and Anaemia
- 7. Angiotensin Receptor Blockers Drugs: Losartan (50-100mg), Valsartan (80- 240mg), Candesartan (2-32mg) Mode of Action: Inhibits Angiotensin II signalling through the AT1 receptor Indications: Hypertension, Heart Failure, Post- Acute Cardiac Syndrome, Proteinuria Side Effects: Similar to ACE inhibitors (without the cough!) Interactions/Important Pointers: – Similar to ACE inhibitors – Losartan is uricosuric (useful option in patients with gout)
- 8. *Tolerate rise in creatinine 20% from baseline and tolerate a serum potassium of 6 mmol/L Most evidence supports an ACE dose maximally tolerated reduces cardiovascular mortality post-MI For elderly patients, start low and increase dose slowly
- 9. Calcium Channel Blockers (1) Dihydropyridine Ca Channel Blockers: Amlodipine (5-10mg), Felodipine (2.5-10mg), Nifedipine MR (30-90mg), Lercancidipine (10- 20mg), Nimodipine* Mode of Action: Block voltage-gated calcium channels (VGCCs) in blood vessels → arterial relaxation and reduction in peripheral resistance Indications: Hypertension, Raynaud’s Phenomena Side Effects: Flushing, Headache, Dizziness, Tachycardia Interactions/Important Pointers: – Azole Antifungals / Macrolides / Grapefruit Juice
- 10. *Nimodipine Specific Indication: Prevents vasospasm after sub-arachnoid haemorrhage Dose: 60mg every 4 hours (can be given via NG tube)
- 11. Calcium Channel Blockers (2) Non-DHP calcium channel blockers Verapamil (60-240mg), Diltiazem (120-360mg) Mode of action: Inhibits voltage gated calcium channels in cardiac muscle (negative chronotrope) Indications: Angina, Arrthythmias (specialist guided) Side Effects: Bradycardic Arrthythmias, Exacerbates heart falure, Rashes, Gingival Hyperplasia Interactions / Important Pointers – Loads of interactions: see here – Avoid Verapamil + Digoxin (Heart Block+++)
- 12. Diuretics Important Classes to Know – Loop – Thiazide – Potassium Sparing Great summary of where diuretics work in the nephron via sketchymedicine.com
- 13. Loop Diuretics Furosemide (20-240mg), Bumetanide (1-6mg) Mode of action: Na+-K+-2Cl- symporter in thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. Indications: Oedema (Heart failure, Liver Cirrhosis, Nephrotic Syndrome) Side Effects: Hypotension / ↓Na+/K/Mg / Exacerbate Gout
- 14. Loop Diuretics Interactions / Important Pointers – Loop diuretics albumin bound and required to deliver to loop of henle – Gut wall oedema leads to diuretic malabsorption (consider IV switch) – Promotes urinary calcium loss, can be used in management of hypercalcaemia – Loop diuretic resistance • Sodium retention diminishes diuretic effect • Decline in GFR (Renal Failure) means less diuretic delivered to loop of henle (Need higher doses)
- 15. Thiazides Bendroflumethiazide (2.5-5mg) Hydrochlorthiazide Mode of Action: Inhibits sodium absorption in distal convoluted tubule through blockage of Na+/Cl- reabsorption Indication: Hypertension Side Effects: Postural hypotension / Na/K, elevated serum calcium / Gout / Impaired glucose tolerance Interactions/Important Points – Usually used in combination with other anti-BP drugs – Thiazides more likely to cause hyponatraemia than loop diuretics – Thiazide + Loop Diuretic = Bigger Diuresis
- 16. Potassium Sparing Diuretics Epithelial Sodium Channel Blockers: Amiloride / Triamterene Aldosterone Antagonists: Spironolactone, Eplenerone Mode of action: Inhibits sodium re-absorption through prevention of potassium/hydrogen secretion Indications: Adjunct for heart failure / hypertension (Spironolactone used in elevated aldosterone states e.g. Conn’s syndrome, cirrhosis) Side Effects: Hyperkalaemia / Gynaecomastia Important Interactions / Pointers – ACE inhibitors + Spironolactone: helpful for bad heart failure (RALES study), but increased risk hyperkalaemia – Effects of Spironolactone last well after stopping (>10 days) – Interactions: Numerous, check them out here
- 17. Beta Blockers Selective: Bisoprolol, Nebivolol, Metoprolol Non-Selective: Propanolol Mode of Action: Inhibits G protein-coupled signaling through beta-receptors. Indications: Angina prophylaxis, Rate control of arrhythmias, Hypertension, Essential Tremor, Migraine Side Effects: Numerous! Hypotension, Heart Failure, Sleep Disturbance, Raynaud’s phenomena, Bronchospasm (uncommon) Important Pointers/ Interactions: Treatment of Beta blocker OD - Glucagon
- 18. Antimicrobials
- 19. Antibiotics – there’s a lot! • Beta-Lactams (Penicillins/ Cephalosporin / Carbapenems) • Macrolides • Tetracyclines • Anti-TB drugs / Rifampicin • Glycopeptides • Aminoglycosides • Linezolid • Metronidazole
- 20. Beta-Lactams Important Points: Bacteriocidal – Stops cell wall synthesis Broad Spectrum Beta-lactams cover Gram positive and negative organisms Piperacillin – covers Pseudomonas Hypersensitivity – 10% crossover with cephalosporins Clostridium Difficile
- 21. Macrolides Important Points: Good option for Mycoplasma, Moraxella, Legionella infection. Side Effects: Can cause deranged liver function tests, prolongation of QT interval Tend to interact with lots of drugs as cytochrome P450 inhibitors: – Statins - provokes myositis – Amiodarone – provokes QT prolongation – Calcineurin Inhibitors – provokes CNI toxicity – Warfarin – provokes elevated INR
- 22. Tetracyclines Important Points: Bacteriostatic – inhibit protein synthesis Doxycycline most commonly used Has anti-malarial effect Teratogenic – deposits in bone/teeth Methotrexate and Doxycycline combination to be avoided – increased MTX toxicity
- 23. Anti-TB drugs Important Pointers: Ethambutol – Need eye check before starting (can cause optic neuritis) Isoniazid – Hepatitis and peripheral neuropathy (Vitamin B6) Pyrazinamide – Dose related hepatotoxicity Treatment Duration nicely summarised here NICE guidance CG117 - Link
- 24. Rifampicin Important Pointers: Mostly known for use in TB, but has activity against Staph Aureus in combination with other antibiotics Side effects: Ri- respiratory syndrome F- flu syndrome A- abdominal syndrome (deranged LFTs, nausea) P- purpura Potent Cytochrome Enzyme Inducer and dose related hepatotoxicity
- 25. Glycopeptides Important Pointers: Only useful for Gram Positive Bugs Both Vancomycin and Teicoplanin need levels checked Don’t forget Red Man Syndrome with Vancomycin! Oral Vancomycin – used to treat C. Diff
- 26. Aminoglycosides Important Pointers: Bactericidal – inhibit protein synthesis Synergistic with Beta-lactams Ototoxicity and Nephrotoxicity – Toxicity determined by trough rather than peak – Similar channels affected in renal tubules and inner ear – Furosemide + Gentamicin = Nephrotoxic combo
- 27. Aminoglycosides Extended interval vs. Conventional Dosing Extended interval (check local trust policies) – Single dose, check levels and dose again once below trough level Cannot be used in certain circumstances: – Pregnancy – Burns (>20% of body surface area) – Ascites – Renal Insufficiency (CrCl <40 mL/min) – Neutropenia (ANC <500) – Synergy for gram-positive endocarditis – Dialysis
- 28. Linezolid Important Points: Expensive but appears cost effective - Link Used for MRSA / Complex Soft Tissue Infection or Pneumonias Treatment guided by Microbiologists Side Effects – Bone Marrow Suppression Is a weak MAOI – can interact with other antidepressants and provoke serotonin syndrome
- 29. Metronidazole Important Points: Works only against anaerobic organisms – deactivates >150 enzymes Works against C.Difficile Can be used for Giardia or Trichomonas infection Interaction with alcohol – disulfram like reaction
Editor's Notes
- #6: NOTES FOR PRESENTERS. Key priority recommendations are identified with [KPI] in these notes. Step 3 treatment Before considering step 3 treatment, review medication to ensure step 2 treatment is at optimal or best tolerated doses. [new 2011] [1.6.16] If treatment with three drugs is required, the combination of ACE inhibitor (or angiotensin-II receptor blocker), calcium-channel blocker and thiazide-like diuretic should be used. [2006] [1.6.17] Step 4 treatment Regard clinic blood pressure that remains higher than 140/90 mmHg after treatment with the optimal or best tolerated doses of an ACE inhibitor or an ARB plus a CCB plus a diuretic as resistant hypertension, and consider adding a fourth antihypertensive drug and/or seeking expert advice. [new 2011] [1.6.18] For treatment of resistant hypertension at step 4 : Consider further diuretic therapy with low-dose spironolactone 4 (25 mg once daily) if the blood potassium level is 4.5 mmol/l or lower. Use particular caution in people with a reduced estimated glomerular filtration rate because they have an increased risk of hyperkalaemia. Consider higher-dose thiazide-like diuretic treatment if the blood potassium level is higher than 4.5 mmol/l. [new 2011] [1.6.19] [KPI] When using further diuretic therapy for resistant hypertension at step 4, monitor blood sodium and potassium and renal function within 1 month and repeat as required thereafter. [new 2011] [1.6.20] If further diuretic therapy for resistant hypertension at step 4 is not tolerated, or is contraindicated or ineffective, consider an alpha- or beta-blocker. [new 2011] [1.6.21] If blood pressure remains uncontrolled with the optimal or maximum tolerated doses of four drugs, seek expert advice if it has not yet been obtained. [new 2011] [1.6.22] Footnotes (1) Choose a low-cost ARB. (2) A CCB is preferred but consider a thiazide-like diuretic if a CCB is not tolerated or the person has oedema, evidence of heart failure or a high risk of heart failure. (3) Consider a low dose of spironolactone 4 or higher doses of a thiazide-like diuretic. (4) At the time of publication (August 2011), spironolactone did not have a UK marketing authorisation for this indication. Informed consent should be obtained and documented. (5) Consider an alpha- or beta-blocker if further diuretic therapy is not tolerated, or is contraindicated or ineffective.