Common drugs Flashcards
ACE-inhibitors: indications (5)
- HTN
- IHD
- Chronic HF
- Diabetic nephropathy
- CKD + proteinuria
ACE-inhibitors: mechanism of action
Prevent conversion of angiotensin I to angiotensin II
What does angiotensin II do?
- Vasoconstrictor
- Stimulates aldosterone secretion
What are the effects of blocking angiotensin II (i.e. using an ACE-inhibitor)?
- ↓ PVR (afterload) ∴ ↓BP
- Dilates efferent glomerular arteriole ⇒ ↓ intraglomerular pressure ⇒ slows progression of CKD
- ↓ aldosterone ⇒ promotes Na+ and H20 excretion ⇒ ↓ preload (good for HF)
ACE-inhibitors: adverse effects
- Hypotension (esp. after first dose)
- Persistent dry cough (ACE usually clears bradykinin, ∴ inhibition ⇒ ↑ bradykinin ⇒ cough)
- Hyperkalaemia (↓ aldosterone ⇒ ↑ K+ retention)
- Worsen renal failure
- Angioedema (R)
- Anaphylaxis (R)
ACE-inhibitors: contraindications
Absolute:
- Renal artery stenosis
- AKI
Relative:
- WOCP (caution - teratogenic)
- Breastfeeding (caution)
- CKD (use lower doses + monitor kidney function)
ACE-inhibitors: interactions
- Potassium-elevating drugs
- NSAIDs (↑ risk of nephrotoxicity)
Ramipril: prescription
- PO
- 1.25mg OD for HF or CKD
- 2.5mg OD for other indications
- Titrate up to 10mg OD
- First dose before bed (↓ hypotension symptoms)
5α-reductase inhibitor: common indications (2) (e.g. finasteride)
- Second-line intervention for BPH
- Improve LUTS ∴ ↓ need for surgery
- Androgenetic alopecia (MPB)
5α-reductase inhibitors: mechanism of action
↓ size of prostate
- Inhibits conversion of testosterone → active dihydrotestosterone
- Dihydrotestosterone stimulates prostatic growth
Why is an α-blocker first line for BPH instead of 5α-reductase inhibitors?
5α-reductase inhibitors take months to have an effect
5α-reductase inhibitors: adverse effects
Adverse effects related to anti-androgen action;
- Impotence (transient)
- ↓ libido (transient)
- Gynaecomastia
- ↑ hair growth
- Breast cancer
5α-reductase inhibitors: contraindications
Pregnancy
- Exposure (either by handling tablets or through semen of man using these drugs) can cause abnormal genitalia development of a male foetus
Finasteride: prescription
- Usually 5mg PO OD for BPH Tx
- Follow-up 3-6m after first prescription, then review every 6-12m after
α-blockers: common indications (2)
- First-line for BPH
2. Add-on Tx in resistant HTN
α-blockers: mechanism of action
- Highly selective for α1-adrenoreceptors, which are found in smooth muscles (particularly blood vessels, bladder neck and prostate)
- Stimulation ⇒ contraction
- Blockade ⇒ relaxation ∴ vasodilation (⇒ ↓BP) and ↓ resistance of bladder outflow
α-blockers: examples
- Doxazosin
- Tamsulosin
- Alfuzosin
α-blockers: adverse effects
- Postural hypotension
- Dizziness
- Syncope
α-blockers: contraindications
Existing postural hypotension
α-blockers: interactions
Other antihypertensive drugs (⇒ extra BP-lowering effects, but this might be the desired effect)
Doxazosin: prescription
- Licensed for BPH and HTN
- Start at 1mg PO OD, and increase at 1-2w intervals until clinically effective
- Take at bedtime (to avoid BP lowering symptoms)
- Monitor from pt’s LUTS
Tamsulosin: prescription
- Licensed for BPH only
- 400mcg PO OD
- Monitor by pt’s LUTS
Acetylcholinesterase inhibitors: examples
- Donepezil
- Rivastigmine
Acetylcholinesterase inhibitors: common indications
- Mild-moderate Alzheimer’s
2. Mild-moderate dementia in Parkinson’s (rivastigmine)
Acetylcholinesterase inhibitors: mechanism of action
- ACh is an essential neurotransmitter involved in learning and memory
- Alzheimer’s and Parkinson’s results in ↓ cholinergic activity in the brain
- Inhibitors prevent the breakdown of ACh, making it more available for cognitive function
Acetylcholinesterase inhibitors: adverse effects
- N,V&D (caused by ↑ cholinergic activity in PNS)
- Exacerbation of asthma/COPD Sx
- Worsening of tremor in pts with Parkinson’s (rivastigmine)
Less common, but serious;
- Peptic ulcers
- Bleeding
- Bradycardia
- Heart block
- Hallucinations
- Altered/aggressive behaviour
Acetylcholinesterase inhibitors: contraindications
Use with caution;
- Asthma/COPD
- People at risk of peptic ulcer development
Absolute;
- Heart block
- Sick sinus syndrome
Acetylcholinesterase inhibitors: interactions
- NSAIDs and corticosteroids ⇒ ↑ risk of peptic ulcers
- Antipsychotics ⇒ ↑ risk of neuroleptic malignant syndrome
- Rate-limiting medications ⇒ bradycardia and/or heart block
Donepezil: prescription
- Start at 5mg
- Titrate up after 2-4w
- Reassess for treatment efficacy at 3m
- Take before bed
- Available as tablet, capsule, or liquid
- Explain to pt/caregivers that it is not a cure for dementia
Rivastigmine: prescription
- Start at 1.5mg 12-hrly
- Titrate up after 2-4w
- Reassess for treatment efficacy at 3m
- Available as tablet, capsule, or liquid OR
- Available as a patch for pts with swallowing difficulties
- Explain to pt/caregivers that it is not a cure for dementia
Acetylcysteine: indications (2)
- Antidote to paracetamol poisoning
2. ↓ viscosity of respiratory secretions (mucolytic) for inpatients
Acetylcysteine: mechanism of action
- Paracetamol OD overwhelms glutathione protein responsible for ‘mopping up’ hepatotoxic metabolite, NAPQI
- Excess NAPQI is ∴ free to cause liver damage
- Acetylcysteine replenishes body’s supply of glutathione
- Breaks disulphide bonds in mucus ⇒ mucolytic activity
Acetylcysteine: adverse effects
Anaphylactoid rx (if administered IV)
- Different to anaphylaxis as there is no IgE involvement
- ∴ once rx has settled (by stopping infusion + giving antihistamine ± bronchodilator) it is safe to restart at a lower rate of infusion
Bronchospasm (if nebulised)
- Manage by giving a bronchodilator (e.g. salbutamol) immediately beforehand
Acetylcysteine: prescription for paracetamol poisoning
Weight-adjusted dose as IV infusion with 3 components over 21hrs
Acetylcysteine: prescription for respiratory secretions
2.5-5mL of acetylcysteine 10% solution by nebuliser every 6hrs
Activated charcoal: indications (2)
- Single dose to ↓ absorption of certain poisons in gut
- Multiple dose to ↑ elimination of certain poisons
Certain poisons include (weakly ionic, hydrophobic);
- Benzodiazepines
- Methotrexate
Activated charcoal: mechanism of action
- Poisonous molecules are adsorbed onto the surface of the charcoal as they pass through the gut ⇒ ↓ absorption into circulation
- If molecules are likely to diffuse back into the gut, multiple doses are used to maintain a steep concentration gradient and eliminate the poison (‘gut dialysis’)
Activated charcoal: adverse effects
- Black stools
- Vomiting
- Aspiration ⇒ pneumonitis, bronchospasm, airway obstruction
- Intestinal obstruction
Activated charcoal: contraindications
- Pts with ↓ level of consciousness unless airway is protected with endotracheal intubation
- Persistent vomiting (caution, ↑ risk of aspiration)
- Reduced gut motility (caution, ↑ risk of obstruction)
Activated charcoal: single dose prescription
- Used for patients presenting within 1hr of ingestion of poison
- Prescribe on the ‘once-only’ section of drug chart
- 50mg orally (or nasogastric tube if intubated)
Activated charcoal: multiple dose prescription
- 50mg PO every 4hrs
- Consider prescribing with an antiemetic and a laxative
Adenosine: indication
First-line diagnostic and therapeutic agent for supraventricular tachycardia (SVT)
Adenosine: mechanism of action
- Agonist of adenosine receptors on cell surfaces
- In the heart ⇒ ↓ frequency of spontaneous depolarisations (automaticity) and ↑ resistance to depolarisation (refractoriness)
- ∴ slows sinus rate and conduction velocity and ↑ AVN refractoriness
- ↑ refractoriness in AVN breaks re-entry circuit (cause of SVT) ⇒ allows normal depolarisations from SAN to resume control of HR - CARDIOVERSION
- Half-life in plasma is <10s - it is rapidly taken up by RBCs
Adenosine: adverse effects
- Bradycardia
- Asystole
- ‘Sinking’ feeling in chest + breathlessness + sense of ‘impending doom’
Only lasts for <10s
Adenosine: contraindications
Absolute (any pt who will not tolerate its transient bradycardic effects);
- Hypotension
- Coronary ischaemia
- Decompensated HF
- Asthma (induces bronchospasm)
Relative;
- COPD (induces bronchospasm)
- Heart transplant recipients
Adenosine: important interactions
Dypyridamole
- Antiplatelet that blocks cellular uptake of adenosine
- Prolongs and potentiates adenosine’s effects ∴ dose of adenosine should be halved
Theophylline/aminophylline
- Competitive antagonists ∴ ↓ effect
- Require higher dose of adenosine
Adenosine: prescription
- IV
- Written in the ‘once-only’ section of drug chart
- Start at 6mg IV
- If 6mg ineffective ⇒ 12mg IV may be given
- If using a central line, halve the dose (i.e. 3mg)
- Resuscitation facilities should be on hand
- Important that adenosine reaches heart ASAP to avoid peripheral uptake ∴ use a large-bore cannula, sited as proximally as possible (i.e. ACF)
- Administer as rapid injection then immediately flush
- MUST have a continuous cardiac rhythm strip recorded when administered
Adrenaline: indications (3)
- Cardiac arrest
- Anaphylaxis
- Local vasoconstriction (injected directly into tissue to stop bleeding, i.e. mucosal bleeding during endoscopy)
Adrenaline: mechanism of action
- Potent agonist of α1, α2, β1, and β2 adrenoreceptors
- Vasoconstriction of vessels to skin, mucosa, and abdominal viscera (α1)
- ↑ HR, force of contraction, and myocardial excitability (β1)
- Vasodilation of vessels supplying heart and muscles (β2)
- ∴ redirects blood away from non-essential organs and towards the heart
- Bronchodilatation and suppression of inflammatory mediator release from mast cells (β2)
Adrenaline: adverse effects
- Adrenaline-induced hypertension (following cardiac arrest)
- If given to conscious patients ⇒ anxiety, tremor, headache, and palpitations
- Angina, MI, arrhythmias
Adrenaline: warnings
Absolute;
- As an anaesthetic-adrenaline preparation in areas supplied by end-artery (⇒ necrosis)
Relative;
- Caution as a vasoconstrictor in pts with heart disease
Adrenaline: interactions
Β-blockers - adrenaline may induce widespread vasoconstriction because α1 vasoconstriction is not opposed by β2 vasodilatation
Adrenaline: prescription for cardiac arrest with shockable rhythm (e.g. VF, pulseless VT)
- Administer first, prescribe later (when life-threatening situation)
- 1mg IV after THIRD shock, and every 3-5mins thereafter
- Pre-filled syringe containing 1:10,000 (1mg in 10mL) solution, then flush
Adrenaline: prescription for cardiac arrest without shockable rhythm (systole, PEA)
- 1mg IV as soon as IV access is available
- Then every 3-5mins thereafter
- Pre-filled syringe containing 1:10,000 (1mg in 10mL) solution, then flush
Adrenaline: prescription in anaphylaxis
- 500mcg IM, repeated after 5mins if necessary
- 0.5mL of 1:1000 (1mg in 1mL) solution
- Inject into anterolateral aspect of thigh halfway between knee and hip
Aldosterone antagonists: examples
- Spironolactone
- Eplerenone
Aldosterone antagonists: indications (3)
- Ascites and oedema due to liver cirrhosis
- Chronic HF
- Primary hyperaldosteronism
Aldosterone antagonists: mechanisms of action
- Aldosterone causes ↑ activity of Na+ channels
- ⇒ ↑ reabsorption of sodium + H20 ⇒ ↑BP + ↑K+ excretion
- Antagonists inhibit aldosterone by competitively binding to receptors
- ⇒ ↑ Na+ + H20 excretion and ↑ K+ retention
Aldosterone antagonists: adverse effects
- Hyperkalaemia ⇒ muscle weakness, arrhythmias, cardiac arrest
- Spironolactone ⇒ gynaecomastia
- Liver impairment and jaundice
- Stevens-Johnsons syndrome ⇒ bullous skin eruption
Aldosterone antagonists: contraindications
Absolute;
- Severe renal impairment
- Hyperkalaemia
- Addison’s disease
Relative;
- Pregnant or lactating women (teratogenic)
Aldosterone antagonists: interactions
Potassium-elevating drugs (e.g. ACE-inhibitors and ARBs)
- Can still use but requires monitoring
Spironolactone: prescription
- PO OD
- Higher doses for ascites vs. HF
- 100mg daily (ascites)
- 25mg daily (HF)
- Taken with food
- Tell men about the possibility of growth and tenderness of breast tissue + impotence
- Monitor efficacy based on clinical findings (e.g. ↓ ascites or BP)
- Monitor safety by checking renal function and serum K+
Spironolactone is used for all indications, eplerenone is only used for HF
Alginates and antacids: examples
- Gaviscon (R)
- Peptic (R)
Alginates and antacids: indications (2)
- GORD
2. Dyspepsia
Alginates and antacids: mechanisms of action
- Compounds of alginates + antacids (e.g. sodium bicarbonate)
- Antacids - buffer stomach acid
- Alginates - increase viscosity of stomach contents ⇒ ↓ reflux of acid into oesophagus
- Drugs form a ‘raft’ which blocks contents from the gastro-oesophageal junction
Alginates and antacids: adverse effects
- Magnesium salts ⇒ diarrhoea
- Aluminium salts ⇒ constipation
Alginates and antacids: contraindications
Relative:
- Compound alginates should not be given to infants with thickened milk preparations ⇒ excessively viscous stomach contents ⇒ bloating + discomfort
- Patients with fluid overload or hyperkalaemia (e.g. renal failure)
Alginates and antacids: interactions
- Alginates bind to other drugs to ↓ absorption
- Antacids ↓ serum conc. of many drugs
- Should take 2hrs after/before taking the following drugs;
- ACE-inhibitors
- Cephalosporins, ciprofloxacin, tetracyclines
- Bisphosphonates
- Digoxin
- Levothyroxine
- PPIs
Gaviscon / Peptac: prescribing
- Oral suspensions or chewable tablets
- Usually PRN
- Caution in diabetics as they can have sucrose in
Allopurinol: indications
- Gout
- Renal stones
- Hyperuricaemia and tumour lysis syndrome
Allopurinol: mechanism of action
- Xanthine oxidase inhibitor
- Xanthine oxidase metabolises xanthine → uric acid
- Inhibitor ↓ plasma uric acid ⇒ ↓ precipitation in joints/kidneys
Allopurinol: adverse effects
- Trigger or worsen an acute gout attack (when starting)
- Skin rash
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Allopurinol hypersensitivity syndrome
Allopurinol: contraindications
Absolute;
- Current acute gout attack
- Recurrent skin rash
- Signs of severe hypersensitivity to allopurinol
Relative;
- Renal impairment (lower dose)
- Hepatic impairment (lower dose)
Allopurinol: interactions
- Azathioprine (↑ risk of toxicity, as azathioprine active metabolite is metabolised by xanthine oxidase)
- ACE-inhibitors or thiazides (↑ risk of hypersensitivity rx)
- Amoxicillin (↑ risk of skin rash)
Allopurinol: prescription
- PO
- Start at low dose (e.g. 100mg OD)
- Titrate up according to serum uric acid conc.
- Usual maintenance = 200-600mg OD
- Prescribe NSAID when first starting for gout to avoid triggering an attack
- Encourage good hydration, take after meals
- If used for cancer treatment, start before chemotherapy
Aminoglycosides: examples
- Gentamicin
- Amikacin
- Neomycin
Aminoglycosides: indications (5)
- Severe sepsis
- Pylonephritis and complicated UTI
- Biliary and other intraabdominal sepsis
- Endocarditis
- Bacterial skin, eye, or external ear infections (topical)
Aminoglycosides: spectrum of activity
- Against G-ve aerobic bacteriaa
- Inactive against streptococci and anaerobes, so combine with penicillin/metronidazole when organism is unknown
Aminoglycosides: mechanism of action
- Bind irreversibly to bacterial ribosomes ⇒ inhibit protein synthesis
- Bactericidal
- Enter bacteria via oxygen-dependent transport system (hence ineffective with anaerobes and strep as they don’t have these)
- Penicillins weaken cell walls, so can enhance aminoglycoside activity by ↑ bacterial intake
Aminoglycosides: adverse effects
- Nephrotoxicity (PC: ↓ urine output + ↑ serum Cr and urea) - reversible
- Ototoxicity (PC: hearing loss, tinnitus, vertigo) - irreversible
Aminoglycosides accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells ⇒ apoptosis ⇒ death
Aminoglycosides: contraindications
Relative;
- Neonates
- Elderly patients
- Renal impairment
- Myasthenia gravis
Aminoglycosides: interactions
- Loop diuretics and vancomycin (⇒ ototoxicity)
- Ciclosporin, Pl chemotherapy, cephalosporins, and vancomycin (⇒ nephrotoxicity)
Aminoglycosides: prescription
- Given parenterally (IV for severe infection)
- Dose calculated from patient’s weight and renal function
- Dose is usually 5mg/kg (normal renal function) or 3mg/kg (renal impairment)
- Dose interval time is determined by drug level monitoring → subsequent doses only given when plasma conc. has fallen to a safe level (usually 24hr - 48hrs)
How do you calculate the dose of aminoglycosides in obese patients?
Adjusted body weight = [ideal body weight] + 0.4 x ([actual body weight] - [ideal body weight])
- Adipose tissue contains more fat than water
- Aminoglycosides are distributed through WATER not fat, and therefore extra weight in obesity complicates dosing
- Calculate dose by using adjusted body weight
Aminoglycosides: preparation and administration
Diluted and infused slowly to prevent exposure of ear to high conc. bolus
Aminosalicylates: examples
- Mesalazine
- Sulfasalazine
Aminosalicylates: indications (2)
- Ulcerative colitis (mesalazine)
- Rheumatoid arthritis (sulfasalazine)
Aminosalicylates: mechanism of action
- Release 5-aminosalicylic acid (5-ASA)
- Anti-inflam and immunosuppressive effects
- Acts topically on gut (not systemically)
- Prepared in a way that active molecules are only released in the colon
Aminosalicylates: adverse effects
- GI upset
- Headache
- Blood abnormalities (R) - leucopenia, thrombocytopenia
- Renal impairment
- Oligospermia (reversible) - sulfasalazine
- Serious hypersensitivity reaction - sulfasalazine
Mesalazine causes fewer SFx than sulfasalazine
Aminosalicylates: contraindications
Absolute:
- Aspirin hypersensitivity (both salicylates)
Aminosalicylates: interactions
- PPIs (increase gastric pH ⇒ tablets are broken down prematurely, i.e. not the colon)
- Lactulose (lowers stool pH ⇒ prevents 5-ASA release in colon)
Mesalazine: prescription
- For mild-moderate rectal/rectosigmoidal UC ⇒ mesalazine enema or suppository
- In an acute attack, take once or 12hrly for 4-6w to induce remission
- If disease is more proximal or pt doesn’t want rectal administration, use oral formulation
Aminosalicylates: monitoring
Efficacy:
- Pt’s symptoms for UC
- Disease activity scores and measurement of acute phase reactant conc. (CRP, ESR) for RA
Safety:
- Renal function (for oral mesalazine)
- FBC and liver profile (for sulfasalazine)
Amiodarone: indications
Tachyarrhythmias (inc. AF, atrial flutter, SVT, VT, and VF)
Amiodarone: mechanism of action
- Blockade of sodium, calcium, and potassium channels in myocardial cells
- Antagonism of α and β adrenergic receptors in myocardial cells
- ↓ spontaneous depolarisation (automaticity), slow conduction velocity, and ↑ refractoriness
Amiodarone: adverse effects
Acute use:
- Hypotension (IV, though probably effect of solvent)
Chronic use:
- Pneumonitis
- Bradycardia
- AV block
- Hepatitis
- Skin photosensitivity
- Grey discolouration of skin
- Thyroid abnormalities (amIODarone - contains iodine)
- Phlebitis (if chronic peripheral administration)
Amiodarone: contraindications
Relative:
- Severe hypotension
- Heart block
- Active thyroid disease
Amiodarone: interactions
LOADS, but notably…
- Digoxin
- Diltiazem
- Verapamil
- Grapefruit juice
Amiodarone: prescribing
- Always requires senior involvement
Cardiac arrest:
- Given immediately after 3rd shock in ALS algorithm in shockable arrest
- 300mg IV, followed by 20mL of 0.9% sodium chloride/5% glucose as a flush
- Administer first, prescribe later
Angiotensin receptor blockers (ARBs): examples
- Losartan
- Candesartan
- Irbesartan
When should you use ARBs?
Used when ACE-i are not tolerated (usually because of the cough)
Also preferred in black people of African or Caribbean origin
ARBs: prescription
- PO
- Lower starting dose in HF
- e.g. 12.5mg OD in HF or 50mg OD for other indications
- Titrate up over a period of weeks
SSRIs: examples
- Citalopram
- Fluoxetine
- Sertraline
- Escitalopram
SSRIs: indications (3)
- Moderate-severe depression (or mild if psychological Tx haven’t worked)
- Panic disorder
- OCD
SSRIs: mechanisms of action
Inhibit neuronal reuptake of 5-HT ⇒ ↑ availability for neurotransmission
SSRIs: adverse effects
- GI upset
- Change in appetite and weight
- Hypersensitivity reactions
- Hyponatraemia ⇒ confusion + ↓ consciousness
- ↑ suicidal thoughts and behaviour
- ↓ seizure threshold(?)
- Prolong QT interval (citalopram particularly) ⇒ arrhythmias
- ↑ risk of bleeding
- Serotonin syndrome ⇒ autonomic hyperactivity + altered mental state + neuromuscular excitement
- Sudden withdrawal ⇒ GI upset, neurological and influenza-like symptoms, sleep disturbance
SSRIs: contraindications
Relative:
- Epilepsy (↑ risk of SFx)
- Peptic ulcer disease (↑ risk of SFx)
- Young people (↑ risk of self-harm and suicidality)
- Hepatic impairment (↓ dose)
SSRIs: important interactions
Absolute:
- MAOIs
- Serotonergic drugs (e.g. tramadol)
Relative:
- NSAIDs (use gastroprotection due to ↑ risk of bleeding)
- Anticoagulants
- Other drugs that prolong the QT interval (e.g. antipsychotics)
Citalopram: prescription
- PO
- Start low and titrate up until good response
- Start with 20mg OD
Tricyclic antidepressants and other related drugs: examples
- Amitriptyline
- Lofepramime
TCAs: indications (2)
- Second line for moderate-severe depression
- Neuropathic pain (unlicensed)
TCAs: mechanisms of action
- Inhibit neuronal reuptake of 5-HT and noradrenaline
- Block a wide array of receptors (hence why they have a lot of adverse effects)
TCAs: adverse effects
Antimuscarinic receptor blockade:
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
H1 and α1 receptor blockade:
- Sedation
- Hypotension
Cardiac adverse effects (multiple mechanisms):
- Arrhythmias
- ECG changes
Cerebral adverse effects:
- Convulsions
- Hallucinations
- Mania
Dopamine receptor blockade:
- Breast changes
- Sexual dysfunction
- EPSEs (tremor, dyskinesia)
Overdose:
- Hypotension
- Arrhythmias
- Convulsions
- Coma
- Respiratory failure
Sudden withdrawal:
- GI upset
- Neurological and influenza-like symptoms
- Sleep disturbance
TCAs: contraindications
Relative:
- Elderly (↑ risk of SFx)
- Epilepsy (↑ risk of SFx)
- Cardiovascular disease (↑ risk of SFx)
- Prostatic hypertrophy (worsening of urinary retention)
- Constipation (worsening symptoms)
- Glaucoma (worsening of symptoms)
TCAs: interactions
Absolute:
- MAOIs
TCAs: prescription for depression
- Reserved for use only when other options have failed
- Prescribe a small quantity for people at risk of attempting suicide by OD
- e.g. amitriptyline 75mg OD
TCAs: prescription for neuropathic pain
Amitriptyline 10mg at night = starting dose
Venlafaxine and mirtazapine: indications
- Major depression (where SSRIs are ineffective)
2. GAD (venlafaxine)
Venlafaxine: mechanism of action
- SNRI
- ↑ availability of monoamines for neurotransmission
- Weaker antagonist of muscarinic and histamine receptors than TCAs ⇒ ↓ antimuscarinic SFx than TCAs
Mirtazapine: mechanism of action
- Antagonist of inhibitory pre-synaptic α2-adrenoreceptors
- ↑ availability of monoamines for neurotransmission
- Potent antagonist of histamine receptors (but not muscarinic) ⇒ ↓ antimuscarinic SFx, but DOES cause sedation
Venlafaxine and mirtazapine: adverse effects
- GI upset
- Neurological effects
- Hyponatraemia (R)
- Serotonin syndrome (R)
- ↑ suicidality
- Prolonged QT interval (venlafaxine)
- ↑ risk of ventricular arrhythmias (venlafaxine)
- Same withdrawal symptoms as other antidepressants, but venlafaxine causes much worse Sx
Venlafaxine and mirtazapine: contraindications
Relative:
- Elderly (↑ SFx)
- Hepatic and renal impairment (↓ dose)
- Arrhythmias (venlafaxine)
Venlafaxine and mirtazapine: prescription
- PO
- Low starting dose and titrate up
Venlafaxine:
- Start with 37.5mg PO 12-hrly
- Maximum 375mg OD
Mirtazapine:
- Start with 15mg PO OD
- Maximum 45mg OD
- Take at night to minimise/benefit from sedative effects
Antiemetics (dopamine D2-receptor antagonists): examples
- Metoclopramide
- Domperidone
Antiemetics (dopamine D2-receptor antagonists): indications
- Prophylaxis and treatment of N&V
- Particularly used with ↓ gut motility associated N&V
Antiemetics (dopamine D2-receptor antagonists): mechanism of action
- Many stimuli trigger N&V
- Various pathways converge on ‘vomiting centre’ in medulla, which receives input from many systems (e.g. chemoreceptor trigger zone, vestibular system, solitary tract nucleus, etc.)
- D2 receptor is the MAIN receptor in the chemoreceptor trigger zone (CTZ)
- Receptors detect emetogenic substances in blood
- D2-receptor antagonists ∴ are used to counteract nausea from CTZ stimulation
- Dopamine also promotes relaxation of the stomach and LOS and inhibits gasproduodenal coordination
- D2-receptor antagonists ∴ have prokinetic effect ⇒ ↑ gastric emptying
Antiemetics (dopamine D2-receptor antagonists): adverse effects
- Diarrhoea
- EPSEs, usually acute dystonic reaction (e.g. oculogyric crisis) (metoclopramide only, domperidone does not cross the BBB)
- QT-interval prolongation (domperidone)
- Arrhythmias (domperidone)
Antiemetics (dopamine D2-receptor antagonists): contraindications
Absolute:
- Neonates
- Cardiac conduction abnormalities (domperidone)
- Perforation
Relative:
- Children (at ↑ risk of SFx)
- Young adults (at ↑ risk of SFx)
- Severe hepatic impairment (domperidone)
- Intestinal obstruction
- Parkinson’s disease (metoclopramide, domperidone is fine as it doesn’t cross the BBB)
Antiemetics (dopamine D2-receptor antagonists): interactions
Absolute:
- Dopaminergic agents for Parkinson’s disease (will antagonise effects)
- Drugs that prolong the QT interval (domperidone)
- Drugs that inhibit CYP450
Relative:
- Antipsychotics
