Finals Drugs List Flashcards
Antacids:
Drugs
MOA
Indications
Side effects
- Aluminium hydroxide and magnesium hydroxide
- Calcium carbonate and magnesium carbonate
MOA: Buffer gastric acid to raise pH
Indications:
- Dyspepsia/heartburn
- Acid reflux
Side effects:
- Nausea
- Aluminium can cause constipation
- Magnesium can cause diarrhoea
Antacids and alginates:
Drugs
MOA
Indications
Side effects
- Sodium alginate with sodium bicarbonate
Anionic polysaccharides that form viscous gel upon binding with water which floats on top of stomach contents, reducing reflux symptoms & protecting oesophageal mucosa
Also increases viscosity of stomach contents to reduce acid reflux.
Indications:
- Gastric reflux/ reflux oesophagitis
Side effects:
- Abdominal distension
H2 receptor antagonists:
Drugs
MoA
Indications
Side effects
- Ranitidine
- Cimetidine
- Famotidine
- Nizatidine
Competitive inhibition of histamine actions at gastric H2 histamine receptors in parietal cells to decrease acid secretion by up to 90%
Indications:
- Stomach ulcers
- Reflux oesophagitis
Side effects:
- Dizziness
- Cimeditine inhibits many cytochrome P450 enzymes
Proton-pump inhibitors:
Drugs
MOA
Indications
Side effects/interactions
- Lansoprazole
- Omeprazole
Irreversible inhibition of H+/K+ ATPase pump in gastric parietal cells =decreased basal and stimulated acid secretion:
- From the circulation, the pro-drug (lipophilic) traverses the parietal cell and enters the canaliculus.
- In acidic canaliculus, drug is activated and trapped.
- Drug binds to H+/K+-ATPase, irreversibly inactivating it.
- For acid secretion to resume, new pump molecules have to be synthesized (2-3 days)
Indications:
- Stomach and duodenal ulcers
- GORD and reflux oesophagitis
Side effects:
- Headache
- Diarrhoea
- Warfarin interaction
Pancreatic enzymes:
Drugs
MOA
Indication
Side effects
- Pancreatin
Restoration of pancreatic enzymes in deficiency.
Indication:
- Pancreatic insufficiency:
- Cystic fibrosis
- Pancreatitis
Side effects:
- Abdominal distension
- Constipation
Bulk laxatives:
Drugs
MOA
Indications
Side effects
- Methylcellulose
- Isphagula husk
Polysaccharide polymers not broken down by normal process of digestion. Retain water in the GI lumen, softening and increasing faecal bulk and promote increased motility. Act in 1-3 days.
Indications:
- Constipation and IBS
Side effects:
- Rare
What classes of drugs are used to treat disorders of acid secretion?
- Antacids and alginates
- Histamine H2-receptor antagonists
- Proton pump inhibitors
Faecal Softeners:
Drugs
MOA
Indications
Side effects
- Docusate
- Arachis oil
Stimulates water & electrolyte secretion into intestinal lumen; lower surface tension at oil-water interface allowing water and fat to enter stool cause it to soften. Act 3-5 days
Indications:
- Constipation
- Fissures
- Piles
Side effects:
- Rare
Osmotic laxatives:
Drugs
Macrogol
Lactulose
Magnesium sulphate and magnesium hydroxide
Lactulose
MOA
Indications
Side effects/interactions
Lactulose (osmotic laxative)
Semi-synthetic disaccharide of fructose and galactose- mimicks undigested lactose
Colonic bacteria convert it to its two component monosaccharides which are poorly absorbed. Fermentation yields lactic acid and acetic acid which function as osmotic laxatives.
Acts within 1-3 days
Indications:
- Chronic constipation
- Hepatic encephalopathy
- Negating the constipating effects of opioids.
Side effects/interactions:
- Stomach cramps
- Interacts with antiepileptics
Macrogol
MOA
Indications
Side effects
Macrogol (osmotic laxative)
Inert polymers of ethylene glycol. Sequester fluid in the bowel
Uses:
- Treatment of faecal impaction in children
- Long-term management of chronic constipation
Side effects/interactions:
- Stomach cramps
- Interaction with anti-epileptics
Magnesium sulphate and magnesium hydroxide
MOA
Indications
Side effects/interactions
Magnesium sulphate and magnesium hydroxide (osmotic laxatives)
Potent, rapid action (1-2 Bowel prep prior to procedure)
Indications:
- Bowel prep prior to procedure
Side effects
- Stomach cramps
- Interacts with antiepileptics
Stimulant laxatives
Drugs
MOA
Indications
Side effects
Bisacodyl
Stimulates rectal mucosa, resulting in mass movements and defaecation in 15-30 minutes Only short courses should be used
Indications:
- Constipation
- Opioid related constipation
Side effects:
- Nausea
Senna
Passes unchanged into colon, where bacterial action releases free anthracene derivatives. Anthracene derivatives are absorbed and have a direct on myenteric plexus to increase intestinal motility (stronger muscle contractions)
Indications:
- Constipation
Side effects:
- Nausea
Picosulfate
Same as Senna, used to relieve constipation and also as bowel prep for surgery.
Which 4 classes of drugs are purgatives?
- Bulk laxatives
- Osmotic laxatives
- Faecal softeners
- Stimulant purgatives
Opioid anti-motility agents
Drugs
MOA
Side effects
Indications
- Loperamide
- Codeine
Agonist for μ-opioid receptors in myenteric plexus; increases tone and rhythmic (haustral) contractions of the colon but diminishes propulsive activity. Blocks intestinal muscarinic receptors.
Indications:
- Diarrhoea (acute, uncomplicated, used in adults)
Side effects:
- Constipation
- Flatulence
- Abdo cramps
- Dizziness
- Paralytic ileus can occur
Paracetamol antidote
MoA
Indication
Side effects
- N-Acetylcysteine (Or Acetylcysteine)
MoA: Restores and maintains hepatic intracellular glutathione required for paracetamol detoxification.
Indication: Paracetamol overdose
Side effects:
- Oral inflammation
Benzodiazepine for alcohol withdrawal
MoA
Indications
Side effects
Chlordiazepoxide (Librium)
MoA: Potentiation of GABAA receptors
Indications: severe alcohol misuse and withdrawal
Side effects:
- Drowsiness
- Dizziness
Non-benzodiazepine hypnotic (for alcohol withdrawal)
MoA
Indications
Side effects
- Clomethiazole
MoA: GABA mimetic- GABAA receptor agonist
Indications: alcohol withdrawal and severe alcohol misuse
Side effects:
- Nasal congestion
Substance abuse treatment for alcohol rehabilitation
MoA
Indications
Side effects
- Acamprosate
MoA:GABA mimetic- GABAA receptor agonist, possible NMDA receptor antagonist.
Indications: severe alcohol misuse
Side effects: diarrhoea, nausea
Loop diuretics
Drugs
MOA
Indications
Side effects/interactions
- Furosemide
- Inhibits Na+/K+/2Cl- transporter (competes with Cl- binding) reducing NaCl reabsorption in the thick ascending LoH therefore decreased water absorption.
- Causes decreased osmotic concentration in the medulla therefore decreased ADH mediated H20 absorption.
- Increased delivery of NaCl to the DCT causes increased Na+ uptake by principal cells, causing loss of K+ and H+.
- Reduce calcium and magnesium absorption
Bind to plasma proteins, not filtered, but secreted directly into PCT so effective in renal impairment.
Indications:
- Peripheral oedema
- Acute pulmonary oedema
- Resistant HTN
- Left ventricular heart failure
Side effects/interactions:
- Nausea
- Hypotension
- Dizziness
- Hypovolaemia
- Hyponatraemia/hypokalaemia
- Ototoxicity (high doses)
- Interacts with NSAIDs and ACE-inhibitors
Thiazide and thiazide-like diuretics
Drugs
MOA
Indications
Side effects/interactions
- Indapamide
- Bendroflumethiazide
- Chlortalidone
- Hydrochlorothiazide
Inhibits Na+/Cl- co-transporter in early DCT (compete with Cl- binding) so increasing Na+ in lumen therefore water. Decreased sodium and chloride reabsorption.
Vasodilate by potassium channel activation
Filtered and secreted so not useful in renal impairment
Indications:
- Hypertension
- Peripheral oedema
- Congestive HF
Side effects/interactions:
- Weak/moderate diuresis,
- Hyponatraemia/hypokalaemia
- Increased plasma uric acid (gout)
- Erectile dysfunction
- Hyperglycaemia
- Raised cholesterol
- Interacts with digoxin and NSAIDs
Potassium sparing diuretics: aldosterone antagonists
Drugs
MOA
Indications
Side effects/interactions
- Spironolactone
- Eplenerone
Aldosterone antagonist binds to mineralocorticoid receptor in the late DCT/cortical collecting tubule. Prevents synthesis of ENaC and Na+/K+ATPase activation therefore reduced K+ secretion into the lumen (K+ retained) and reduced Na+ reabsorption and accompanying water.
Indications:
- Oedema
- Congestive heart failure
- Ascites caused by liver cirrhosis
- Hyperaldosteronism (Conn’s syndrome)
- Resistant HTN, in combination with loop/thiazide diuretics to prevent K+ loss.
Side effects/interactions:
- Interacts with NSAIDs and ACE-inhibitors
- Hyperkalaemia
- Gynaecomastia (more with spironolactone than eplerenone)
Potassium sparing diuretics: ENaC antagonists
Drugs
MOA
Indications
Side effects/interactions
- Amiloride
Blockade of sodium reabsorption via ENaC channel (competes for Na binding site) therefore decreases luminal permeability to Na+. Causes reduced K+ secretion into the lumen, therefore K+ retained.
Used in combination to prevent K+ loss from use of loop/thiazide diuretics
Indications:
- Oedema
- Congestive HF
Side Effects:
- Hyperkalaemia
Osmotic diuretics
Drugs
MOA
Indications
Side effects/interactions
- Mannitol
Increases osmolality of glomerular filtrate preventing water reabsorption in the PCT and descending LoH
Indications:
- Raised intraocular pressure
- Cerebral oedema
Side effects:
- Hypotension
Why do loop and thiazide diuretics cause hypokalaemia?
Why may alkalosis also occur alongside this?
They increase delivery of NaCl to the distal nephron and decrease blood volume.
This increases K+ secretion by:
- Increasing tubular flow rate (K+ washes away creating high concentration gradient)
- Increases activity of Na+/K+ATPase via increased Na+ therefore more K+ is secreted out of the cells
- Activation of RAAS from decreased blood volume = increased aldosterone therefore more Na+ reabsorption in kidneys = more K+ secreted.
May also cause alkalosis as it can stimulate intercalated cells to secrete H+ so more acid is lost in urine.
Carbonic anhydrase inhibitors
Drugs
MOA
Indications
Side effects/interactions
- Acetazolamide
Reduces aqueous humour volume by preventing renal absorption of bicarbonate:
Inhibit carbonic anhydrase in the PCT, preventing it from converting carbonic acid to water and CO2, therefore blocking the absorption of HCO3- and the accompanying sodium and water.
Indications:
- Raised intra ocular pressure: open and closed angle glaucoma
Side effects/interactions:
- Paraesthesias
ACE-Inhibitors
Drugs
MOA
Indications
Side effects/interactions
- Ramipril
- Captopril
- Perindopril
- Lisinopril
Inhibits angiotensin converting enzyme, preventing it from converting angiotensin I to angiotensin II. This prevents it from inducing contraction in vascular smooth muscle and increasing BP.
Indications:
- Hypertension
- T1 Diabetic nephropathy
- Congestive heart failure
- Post MI
- Secondary stroke prevention
Side effects/interactions:
- Cough (through inhibited breakdown of bradykinin in the lungs)
- Hyperkalaemia (potassium retained by blocking RAAS)
- Hypotension
- Angioedema
- Decreased GFR as angiotensin normally constricts efferent arterioles
- Caution in renal artery stenosis- can precipitate kidney failure
- Interacts with NSAIDs and Lithium
Angiotensin II receptor blockers
Drugs
MoA
Indications
Side effects/interactions
- Losartan
- Valsartan
- Irbesartan
- Candesartan
Blockade of cell signalling induced by angiotensin II. Binds to type 1 angiotensin II receptors preventing the direct vasoconstriction effects of ATII and its action in the RAAS system (release of aldosterone)
Indications:
- Hypertension
- T2 diabetic nephropathy
- CHF
- LV hypertrophy
- ACE-i intolerance
Side effects/interactions:
- Hypotension
- Fatigue
- Hyperkalaemia
- Myalgia
- Raised CPK
- Other diuretics- avoid
Direct Renin Inhibitor
MoA
Indications
Side Effects
- Aliskiren
MoA: Direct inhibition renin enzymatic function and of angiotensin I generation
Indications: Hypertension
Side effects: diarrhoea, cough
Neprilysin inhibitors
Drugs
MoA
Indications
Side effects/interactions
- Sacubitril (in combination with Valsartan)
Inhibits the breakdown of natriuretic peptide
Indications:
- Heart failure with reduced ejection fraction
Side effects/interactions:
- Hypotension
- Hypoglycaemia
Beta adrenergic receptor antagonists (B-blockers)
Drugs
MoA
Indications
Side effects/interactions
- Bisoprolol (B1 selective)
- Atenolol (B1 selective)
- Metoprolol (B1 selective)
- Labetalol (B1, B2 and A1 selective)
- Propranolol (B1 and B2)
Competitive inhibitors of adrenaline and noradrenaline at beta-adrenergic receptors, inhibit sympathetic stimulation of heart muscle.(B1 antagonists selective for cardiomyocytes and contractility) by inhibiting cAMP cascade (PKA etc) which in cardiomyocytes drives contraction (opposite to bronchiolar smooth muscle)
- Negative inotropes and chronotropes.
- Reduce workload of the heart relieving oxygen demand. (reduced heart rate = reduced cardiomyocyte contractility)
Indications:
- Hypertension
- Stable angina
Side effects/interactions:
- Bradycardia
- Bronchospasm
- Dizziness (hypotension)
- Constipation
- Fatigue
- Interacts with NSAIDs and digoxin
Contraindicated in asthmatic patients
Alpha 1 adrenergic receptor blockers (A-blockers)
Drugs
MoA
Indications
Side effects/interactions
- Doxazosin
Selective alpha1 adrenergic receptor blocker in the bladder neck, urethra and prostate. Prevents sympathetic neurons from initiating smooth muscle contraction, causing relaxation which allows urinary flow.
Vasodilator, decreases total peripheral resistance by inhibiting the postsynaptic alpha-1 receptors on vascular smooth muscle.
Indications:
- Hypertension
- BPH
- Urinary retention
Side effects/interactions:
- Dizziness
- Headache
- Nausea
- Dry mouth
- Constipation
- Anxiety
- Back pain
- Coughing
- Dyspnoea
- Fatigue
- Myalgia
- Paraesthesia
- Vertigo
- Not to be given with hypotensive drugs
Alpha 2 adrenergic agonist
MoA
Indications
Side Effects
- Clonidine
MoA: Stimulation of alpha-2 receptors, driving vasodilation
Indications: acute hypertension
Side effects: Constipation, dry mouth
Calcium channel blockers
Drugs
MoA
Indications
Side effects/interactions
- Amlodipine
- Nifedipine
- Diltiazem
- Verapamil
Prevent opening of L-type voltage-gated calcium channels reducing influx of Ca2+ into cells.
Reduced intracellular calcium has vasodilator effect on resistance vessels = reduced afterload. Causes dilation of coronary arteries increasing blood flow.
Do not act on veins.
Indications:
- Hypertension
- Stable angina
Side effects/interactions:
- Oedema
- Ankle swelling
- Palpitations
- Not to be given with beta blockers or digoxin
Calcium channel blockers: Verapamil
MoA
Indications
Side effects
Mostly works on cardiac muscle. Slows Ca entry during phases 2 and 3 of cardiac action potential.
- Moderate reduction in SVR by peripheral vasodilation
- Moderate coronary vasodilation
- Moderate decrease in cardiac contractility
- Large reduction in heart rate
- Mild reduction in stroke volume
(Mild decrease in BP)
Indications: HTN, tachyarrhythmias (esp re-entry and atrial origin)
Side effects:
- Heart failure
- Heart block (esp when used with a B blocker)
- Peripheral oedema
- Constipation
- Facial flushing
- Headaches
Calcium channel blockers: Diltiazem
MoA
Indications
Side effects
Affects cardiac smooth muscle
- Mild reduction in SVR through peripheral vasodilation
- Moderate coronary vasodilation (useful for angina)
- Moderate slowing of AV node- antiarrhythmic
- Mild reduction in HR and stroke volume
Mild decrease in BP
Indications: HTN, arrhythmia, angina
Side effects:
- Facial flushing
- Headaches
- Peripheral oedema
- Heart failure
- Heart block
Calcium channel blockers: dihydropyridines
Drugs
MoA
Indications
Side effects
Amlodipine and Nifedipine
- Large reduction in SVR by peripheral vasodilation
- Moderat cardiac vasodilation
- Mild decreased cardiac contractility
- Moderate reflex increase in sympathetic tone
- Mild slowing of AV node conduction
- High increase in HR (compensatory from drop in BP)
- Moderate natriuresis and diuresis
Indications: HTN
Side effects:
- Marked facial flushing
- Headaches
- Peripheral oedema
- Polyuria (exacerbate prostatism)
Selective I (f) Current inhibitors
MoA
Indications
Side Effects
- Ivabradine
MoA: Inhibition of cardiac I(f) current in the sinoatrial node
Indications:
- Angina with normal sinus rhythm
- Heart failure
Side effects: bradycardia
Nitrates
Drugs
MoA
Indications
Side effects/interactions
- Glyceryl trinitrate
- Isosorbide mononitrate
Metabolised to release NO which diffuses into cell and stimulates soluble guanylate cyclase.
Increases cGMP in vascular smooth muscle cells:
- Drives dephosphorylation of myosin light chains via activation of MLC phosphatase.
- Inhibits influx of Ca2+ into smooth muscle cytoplasm causing relaxation.
Works on vascular smooth muscle of arteries and veins:
- Venodilation: reduces cardiac preload (capacitance)
- Arteriodilation: coronary artery vasodilation increases blood flow to myocardium
- Moderate arteriolar dilation: reduces cardiac afterload
Indications:
- Acute angina pectoris
- Heart failure
Side effects/interactions:
- Hypotension
- Headache
- Caution with other antihypertensives
Sympathomimetics
Drugs
MoA
Indications
Side effects/interactions
- Adrenaline (alpha and beta)
- Noradrenaline (alpha)
- Dobutamine (beta)
Adrenergic stimulation increases inotropy.
Adrenaline: Binds and stimulates cardiomyocyte B1-adrenergic receptors. Used in cardiac arrest to drive cardiac muscle contraction and restore heart function. Positive inotrope and chronotrope.
Indications:
- Cardiac arrest
- Cardiogenic shock
Side effects/indications:
- Arrhythmia
Anti-platelet drugs
Drugs
MoA
Indications
Side effects/interactions
Aspirin
Blocks the enzyme action of platelet COX enzyme which is required for the synthesis of thromboxane A2 (TXA2).
Reduced TXA2 synthesis results in inhibition of platelet activation and thrombus formation.
Indications:
- NSTEMI
- Stable angina
- Acute ischaemic stroke
Side effects: GI bleeding, caution with other anticoagulants
Clopidogrel, Prasugrel, Ticagrelor
ADP receptor blocker: binds to and block the function of ADP receptors on platelet surfaces, inhibiting platelet activation and subsequent thrombus formation.
Indications:
- Secondary prevention for CVD
Side effects/interactions:
- Gastrointestinal irritation and bleeding
- Not to be given with anticoagulants
Anticoagulants: coumarin
Drugs
MoA
Indications
Side effects/interactions
- Warfarin
Inhibition of epoxide reductase which results in inhibition of vitamin K pathway and vitamin K-dependent coagulation factors (VII, IX, X and prothrombin/FII) (1972)
Indications:
- Prophylaxis and treatment of VTE
- Prophylaxis of stroke from AF
Side effects/interactions
- Abnormal bleeding
- Drug interactions: NSAIDs, diuretics and others
Anticoagulants: direct thrombin inhibitors
Drugs
MoA
Indications
- Dabigatran
Competitive, reversible direct inhibition of thrombin proteolytic function
Indications:
- Prophylaxis of VTE post surgery
Side effects:
- Bleeding
- Abnormal bruising
Anticoagulants: FXa inhibitors
Drugs
MoA
Indications
Side effects/interactions
- Apixaban
- Edoxaban
- Rivaroxaban
Inhibition of factor Xa in the coagulation cascade
Indications:
- Prophylaxis of stroke from AF
- VTE
Side effects/interactions:
- Abnormal bleeding
Anticoagulants: heparins
Drugs
MoA
Indications
Side effects/interactions
- Dalteparin (LMWH)
- Tinzaparin (LMWH)
- Enoxaparin (LMWH)
- Unfractionated heparins
Inactivation of thrombin and factor Xa by reversibly binding to and increasing activation of anti-thrombin III.
Indications:
- Prophylaxis of VTE and P.E
- Treatment of existing clots (higher dose)
Side effects/interactions:
- Abnormal bleeding
Thrombolytics/fibrinolytics
Drugs
MoA
Indications
Side effects/interactions
- Alteplase
- Urokinase
- Streptokinase
Activates plasminogen to plasmin for proteolytic breakdown of fibrin and fibrinogen to restore blood flow
Indications:
- Myocardial infarction
- Ischaemic stroke
Side effects:
- Arrhythmias
- Bleeding
- Ecchysmosis
- Hypotension
- Streptokinase can only be used once as an immune response is generated, memory B cells produce anti-streptokinase ABs.
HMG-CoA reductase inhibitors
Drugs
MoA
Indications
Side effects/interactions
- Simvastatin
- Atorvastatin
Inhibiton of malevolate pathway needed for cholesterol synthesis.
Inhibit HMG-CoA Reductase (HMGCR) enzyme which reduces circulating cholesterol by:
- Reducing intrinsic production of cholesterol
- Promoting uptake of excess cholesterol by liver.
Indications:
- Treatment of HF without affecting BP
- Hypercholesterolaemia
- Risk of CVD and stroke
Side effects/interactions:
- Myalgia
- Interacts with verapamil and macrolides
Class I antiarrhythmics: Sodium Channel Blockers
Drugs
MoA
Indications
Side effects/interactions
Class 1a:
- Disopyramide
- Quinidine
Class 1b:
- Lidocaine
Class 1c:
- Flecainide
- Propafenone
Voltage-sensitive sodium channel blockade. Prolongs QT interval and increases QRS duration.
Indications:
- Class 1a: Ventricular and supraventricular arrhythmias
- Class 1b: CPR (given IV)
- Class 1c: Paroxysmal atrial fibrillation and ventricular ectopic beats “pill in pocket”
Side effects/interactions:
- Oedema
Class II anti-arrythmics: beta blockers
Drugs
MoA
Indications
Side effects/interactions
- Atenolol
- Bisoprolol
- Metoprolol
- Sotalol
Beta-adrenergic receptor blockade reducing adrenergic effects on inotropy and chronotropy.
Sotalol also has K+ channel blocker activity
Indications:
- Prophylaxis of paroxysmal atrial tachycardia or fibrillation
Side effects/interactions:
- Hypotension
- Bradycardia
- Bronchospasm
- Not to be given with NSAIDs or digoxin
Class III anti-arrhythmics: potassium channel blockers
Drugs
MoA
Indications
Side effects/interactions
- Amiodarone
- Dronedarone
- Sotalol (also has some beta blocker activity)
Potassium channel blockade, also evidence of beta blocker and calcium channel blocker properties – prolong QT interval.
Indications:
- Supraventricular, nodal and ventricular tachyarrhythmias, atrial fibrillation
- CPR (given IV)
Side effects/interactions:
- Nausea
- Vomiting
Class IV antiarrhythmics: calcium channel blockers
Drugs
MoA
Indications
Side effects/interactions
- Verapamil
- Diltiazem
Cardiac calcium channel blockade- reduction of action potential and cardiac output.
Indications:
- Supraventricular tachycardia (esp paroxysmal SVT)
Side effects/interactions:
- Constipation (diltiazem)
- Hypotension (verapamil)
Cardiac glycosides
Drugs
MoA
Indications
Side effects/indications
- Digoxin
Reduces contractility of AV node.
Indications:
- Atrial fibrillation
- Congestive heart failure
Side effects/interactions:
- Fatigue
- Nausea
Adenosine
MoA
Indications
Side effects/interactions
- Adenosine
Activates adenosine receptors which cause hyperpolarisation.
Slows conduction through AV node.
Indications:
- Supraventricular tachycardia
Side effects/interactions:
- Nausea
- Contraindicated in obstructive airway disease
Anti-cholinergic (emergency)
Drugs
MoA
Indications
Side effects/interactions
- Atropine
Blockade of vagal (parasympathetic) muscarinic acetylcholine receptors in the SA and AV nodes.
Indications:
- Bradycardia (emergency)
Side effects/interactions:
- Urinary retention
- Dry mouth
- Dilated pupils
Magnesium sulfate
MoA
Indications
Side effects/interactions
- IV Mg sulfate
Unclear – possible alteration of Na+, K+ and Ca2+ ion balance via ion channels and transporters.
Indications:
- Emergency arrhythmia
- Emergency asthma
Side effects/interactions:
- Electrolyte irregularities
Beta2 adrenergic agonists
Drugs
MoA
Indications
Side effects/interactions
- Salbutamol (short acting)
- Terbutaline (short acting)
- Salmeterol (long acting)
- Formoterol (long acting)
Cellular target: Bronchiolar smooth muscle cells
Molecular target: Stimulation of B2-adrenergic receptors
- Activation of B2AR activates G-protein
- Increases activation of adenylate cyclase
- Adenylate cyclase converts ATP to cAMP
- Increased cAMP activates protein kinase A which:
- Drives Ca2+ into intracellular storage vesicles away from cytoplasm.
- Reduces activity of myosin light chain kinase = reduced muscle contraction
- Dephosphorylation of myosin light chain = reduced muscle contraction
- Reduced cytoplasmic Ca2+ levels reduce smooth muscle contraction resulting in bronchodilation.
Indications:
- Asthma
- Reversible airway obstruction
Side effects/interactions:
- Tachycardia
- Tremor
- Cardiac arrhythmias
- Interacts with diuretics
Anti-muscarinics (anti-cholinergics)
Drugs
MoA
Indications
Side effects/interactions
- Ipratropium (short acting)
- Tiotropium (long acting)
- Aclidinium (long acting)
Blocks M3 muscarinic acetylcholine receptors preventing stimulating effects of ACh:
- Inhibits activation of G-protein therefore inhibits activation of phospholipase C enzyme (PLC)
- PLC therefore cannot release calcium from intracellular stores
- Cytoplasmic Ca2+ levels do not rise therefore bronchiolar smooth muscle contraction does not increase (inhibits bronchoconstriction)
- =Bronchiolar relaxation
Indications:
- Acute asthma
- Bronchospasm in COPD
Side effects/interactions:
- Dry mouth
- Constipation
Methylxanthines
Drugs
MoA
Indications
Side effects/interactions
- Aminophylline
- Theophylline
Inhibit phosphodiesterase enzymes (PDE) preventing it from inhibiting CAMP.
CAMP levels maintained therefore protein kinase A enzyme activated which stores intracellular Ca2+ into storage vesicles.
Reduced cytoplasmic Ca2+ results in less smooth muscle contraction so less bronchoconstriction
Indications:
- Acute asthma
- Reversible airways obstruction
Side effects/interactions:
- Headache
- Nausea
- Cardiac arrhythmias
- Seizures
- Interacts with antidepressants and salbutamol
Glucocorticoids
Drugs
MoA
Indications
Side effects/interactions
- Beclomethasone
- Prednisolone
- Hydrocortisone
- Fluticasone
Targets immune cells of the lungs: macrophages, T-lymphocytes, eosinophils.
Activates glucocorticoid receptors which interact with selected nuclear DNA sequences and influences the expression of genes:
- Repression of pro-inflammatory mediators: IL-3, IL-5, Th2 cytokines
- Expression of anti-inflammatory products: secreted leukocyte peptidase inhibitor (SLPI), Lipcortin-1 and upregulation of B2 adrenoceptors.
Indications:
- Asthma
- Allergic rhinitis
- Suppression of inflammatory diseases (RA, SLE, Crohn’s, UC)
Side effects/interactions:
- Cough
- Hyperglycaemia
- Muscle wasting
- Thinning skin
- Osteoporosis
- Increased risk of infection, esp throat infection with inhalers
- Moon face (facial swelling)
- Interacts with aspirin
Leukotriene antagonists
Drugs
MoA
Indications
Side effects/interactions
- Montekulast
- Zafirlukast
Blockade of leukotriene receptors.
Leukotrienes released from mast cell upon activation, normally binds to CysLT1 leukotriene receptor to:
- Stimulate bronchiolar smooth muscle constriction
- Bind to and recruit immune cells such as eosinophils by guiding eosinophil chemotaxis.
Leukotriene receptor antagonists block CysLT1 receptors on smooth muscle and eosinophils blocking the above effects.
Indications:
- Asthma
- Allergic rhinitis
- (used as a preventor)
Side effects/interactions:
- Abdominal pain
- Interacts with phenobarbital
Mucolytic drugs
MoA
Indications
Side effects/interactions
- Dornase alfa
Synthetic DNAse 1 – breakdown Cystic fibrosis of extracellular DNA to reduce sputum viscosity.
Indications:
- Cystic fibrosis
Side effects: GI bleeding
- Carbocisteine
MoA: Cleavage of mucus glycoproteinsto reduce sputum viscosity
Indications: cystic fibrosis
Side effects: GI bleeding
Synthetic Dopamine Agonists
Drugs
MoA
Indications
Side effects/interactions
- Pramipexole
- Ropinirole
- Rotigotine
Synthetic dopamine, act on dopamine receptors (primarily D2) to replace lost dopamine
Less overall improvement than levodopa, more psychiatric side effects.
Indications:
- Parkinson’s disease
- Esp younger patients to delay the need for levodopa
- First line for initial treatment
- Can be used with levodopa in later stages
Side effects/interactions:
- Psychiatric symptoms (due to action on mesocortical and mesolimbic pathways)
- Confusion, agitation
- Nausea and vomiting
- Sudden onset sleep/ drowsiness
- On-off effects
- Hypotension
- Tachycardia
- Interacts with MAOIs
Levodopa
MoA
Indications
Side effects/interactions
Dopamine precursor: crosses blood brain barrier and is metabolised into dopamine to replace that lost. Works on dopamine receptors to restore activity in the nigrostriatal pathway.
Indications:
- Parkinson’s disease (use as late as possible)
Side effects/interactions:
- Psychiatric symptoms (due to action on mesocortical and mesolimbic pathways)
- Confusion, agitation
- Nausea and vomiting
- Sudden onset sleep/ drowsiness
- On-off effects
- Hypotension
- Interacts with MAOIs
- Tachycardia
Monoamineoxidase-B (MAOI-B) inhibitors
Drugs
MoA
Indications
Side effects/interactions
- Selegiline
- Rasagiline
Inhibition of levodopa breakdown in the CNS by monoamineoxidase-B meaning more is available to be converted into dopamine.
Indications:
- Parkinson’s disease
- Use alongside levodopa
Side effects: arrhythmias
Dopa-decarboxylase inhibitors
Drugs
MoA
Indications
- Carbidopa
- Benserazide
Prevents the breakdown of levodopa in the periphery by dopa-decarboxylase enzyme allowing more to cross the blood brain barrier and be converted into dopamine.
Indications:
- Parkinson’s disease
- Use in conjunction with levodopa
Side effects:
- Confusion
- Agitation
Catechol-o-methyl transferase (COM-T) inhibitors
Drugs
MoA
Indications
Side effects/interactions
- Entacapone
- Tolcapone
Prevents breakdown of levodopa in the CNS by Catechol-O-methyltransferase (COM-T) so more is available to be converted to dopamine.
Indications:
- Parkinson’s disease
- Use alongside levodopa
Side effects/interactions:
- Nausea
- Vomiting
Anticholinergics
Drugs
MoA
Indications
Side effects/interactions
- Orphenadrine
- Procyclidine
- Trihexphenadyl
Inhibits cholinergic fibres from the striatum to the globus pallidus that moderate GABAergic cells and prevents them from inhibiting the direct pathway and increase effects of the indirect pathway.
Indications:
- Parkinson’s disease (iatrogenic)
- Muscle rigidity
- Negate the side effects of anti-psychotics
Side effects/interactions:
- Can reduce the absorption of levodopa
- Dry mouth
- Constipation
Dopamine depleting drugs
MoA
Indications
Side effects/interactions
- Tetrabenazine
Inhibits VMAT2 (vesicular monoamine transporter) within basal ganglia, preventing transport of dopamine into presynaptic vesicles therefore less released into the synaptic cleft.
Indications:
- Huntington’s chorea
Side effects/interactions:
- Affects all monoamines: 5-HT and NA
- Can cause depression
- Parkinsonism
- Anxiety
Selective Serotonin Re-uptake Inhibitors (SSRIs)
Drugs
MoA
Indications
Side effects/interactions
- Sertraline
- Citalopram
- Fluoxetine
- Paroxetine
Inhibition of 5-HT reuptake pump in synaptic cleft.
Indications:
- Depression
- Generalised anxiety disorder
Side effects/interactions:
- Slow onset, can increase depressive symptoms initially
- Nausea
- Insomnia, early waking, vivid dreams
- Sexual dysfunction
- Increased bleeding
- Serotonin syndrome (increased 5-HT levels)- Emergency
- Interacts with NSAIDs and lithium
Reversible inhibitors of monoamine oxidase type A (RIMA)
Drugs
MoA
Indications
Side effects/interactions
- Moclobemide
Increases 5-HT and noradrenaline levels by reversibly inhibiting enzymatic breakdown by monoamine oxidase A.
Indications:
- Depression
Side effects/interactions:
- Tachycardia
- Also affects dopamine levels
- DO NOT USE WITH TCAs/SSRIs
- Interacts with cheese (contains tyramine)
- Postural hypotension
- Restlessness
- Convulsions
- Sleep disorders
Tricyclic antidepressants (TCAs)
Drugs
MoA
Indications
Side effects/interactions
- Amitryptiline
- Nortryptiline
- Dosulepin
5 main actions:
- Therapeutic effects:
- 5HT reuptake inhibitor
- Noradrenaline reuptake inhibitor
- Side effect causing:
- A1 adrenoceptor antagonist
- Postural hypotension
- H1 receptor antagonist:
- Sedation
- M1 receptor antagonist
- Cardiac dysrhythmia
- Prolonged QT interval
- A1 adrenoceptor antagonist
Indications:
- Depression
Other side effects:
- Confusion
- Mania