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Some final year med students are under my tutoring before their exams, here's a talk about some important pharmacology pointers I think useful at least when entering 1st year post-graduation. Please comment and share as you see fit. Any problems with links, please let me know. more to follow...
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Pharmacology for Medical Students (Part 1)
Anti-Hypertensives / Diuretics
Antimicrobials – Antibiotics / Antifungals / Antivirals
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!
Format (mostly)
Drug
Usual Dose
Mode of Action
Indications
Side Effects
Interactions/Important Pointers
Anti-Hypertensives
Step 4
Summary of antihypertensive drug treatment
Aged over 55 years or black person of African or Caribbean family origin of any age
Aged under55 years
C2A
A + C2
A + C + D
Resistant hypertension
A + C + D + consider further diuretic3, 4 or alpha- or
beta-blocker5
Consider seeking expert advice
Step 1
Step 2
Step 3
KeyA – ACE inhibitor or low-cost angiotensin II receptor blocker (ARB)1 C – Calcium-channel blocker (CCB) D – Thiazide-like diuretic
Taken from NICE guidance CG127. Link here
ACE InhibitorsDrugs: 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 ACEIndications: Hypertension, Heart Failure, Post-Acute
Cardiac Syndrome, ProteinuriaSide 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
Angiotensin Receptor BlockersDrugs: 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)
*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
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 inhibit
metabolism and exacerbate exposure
*Nimodipine
Specific Indication: Prevents vasospasm after sub-arachnoid haemorrhage
Dose: 60mg every 4 hours (can be given via NG tube)
Calcium Channel Blockers (2)Non-DHP calcium channel blockersVerapamil (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 HyperplasiaInteractions / Important Pointers
– Loads of interactions: see here– Avoid Verapamil + Digoxin (Heart Block+++)
DiureticsImportant Classes to Know
– Loop– Thiazide– Potassium Sparing
Great summary of where diuretics work in the nephron via sketchymedicine.com
Loop DiureticsFurosemide (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
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)
ThiazidesBendroflumethiazide (2.5-5mg) HydrochlorthiazideMode of Action: Inhibits sodium absorption in distal
convoluted tubule through blockage of Na+/Cl- reabsorption
Indication: HypertensionSide Effects: Postural hypotension / Na/K, elevated
serum calcium / Gout / Impaired glucose toleranceInteractions/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
Potassium Sparing Diuretics
Epithelial Sodium Channel Blockers: Amiloride / Triamterene
Aldosterone Antagonists: Spironolactone, EpleneroneMode of action: Inhibits sodium re-absorption through
prevention of potassium/hydrogen secretionIndications: Adjunct for heart failure / hypertension
(Spironolactone used in elevated aldosterone states e.g. Conn’s syndrome, cirrhosis)
Side Effects: Hyperkalaemia / GynaecomastiaImportant 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
Beta Blockers
Selective: Bisoprolol, Nebivolol, MetoprololNon-Selective: PropanololMode of Action: Inhibits G protein-coupled signaling
through beta-receptors.Indications: Angina prophylaxis, Rate control of
arrhythmias, Hypertension, Essential Tremor, MigraineSide Effects: Numerous!
Hypotension, Heart Failure, Sleep Disturbance, Raynaud’s phenomena, Bronchospasm (uncommon)
Important Pointers/ Interactions:Treatment of Beta blocker OD - Glucagon
Antimicrobials
Antibiotics – there’s a lot!
• Beta-Lactams (Penicillins/ Cephalosporin / Carbapenems)
• Macrolides• Tetracyclines• Anti-TB drugs / Rifampicin• Glycopeptides• Aminoglycosides• Linezolid• Metronidazole
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
MacrolidesImportant 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
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
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 hereNICE guidance CG117 - Link
Rifampicin
Important Pointers:Mostly known for use in TB, but has activity
against Staph Aureus in combination with other antibiotics
Side effects: Ri- respiratory syndromeF- flu syndromeA- abdominal syndrome (deranged LFTs, nausea)P- purpura
Potent Cytochrome Enzyme Inducer and dose related hepatotoxicity
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
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
Aminoglycosides
Extended interval vs. Conventional Dosing
Extended interval (check local trust policies)– Single dose, check levels and dose again once below
trough levelCannot 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
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
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