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