Class of Drug
Name
Acetylcholine Bethanecol Directly Acting Cholinomimetics Pilocarpine
Pharmacokinetics Degraded by Achesterase and recycled t½=3-4hrs limited access to brain t½=3-4hrs not Ach-esterase substrate
Physostigmine Indirectly acting Cholinomimetics Anticholinesterase
Neostigmine
t½=30mins ANS>NMJ
Ecothiopate (organophosphorous compounds) Trimetaphan
IV
Hexamethonium
Cholinoceptor Antagonists
Neuromuscular blocking drugs (nondepolarising)
MOA
Clinical Use
Stimulates muscarinic and nicotinic receptors
None – stimulates all autonomic ganglia
Muscarinic agonist, especially M3(glands)
↑Bladder emptying + GI motility
Muscarinic partial agonist
Glaucoma (local admin)
Reversible AChE inhibitor. Block active site with carbamyl group. Reactivated by hydrolysis
Glaucoma (local), Atropine poisoning
Irreversible AChE inhibitor. Phosphorylates enzyme (stable)
Glaucoma (local)
Nicotinic ion channel blockers (incomplete, use dependent) [Ganglion Blocking]
Atropine
I.V. after MI
Muscarinic antagonist
Hyoscine (Anti-emetic)
Transdermal patch, oral, I.V.
Muscarinic antagonist. Acts at vestibular nucleus, NST, vomiting centre.
Tropicamide Ipratropium bromide
Local
Muscarinic antagonist
Inhalation
Muscarinic antagonist
I.V. (↑ charged) doesn’t cross BBB/ placenta. Not metabolised. Excreted 70% urine, 30% bile.
Competitive AChR antagonist at NMJ. 70-80% block necessary. Graded block – greater block further away from endplate.
Tubocurarine
Myasthenia gravis
Major Effects
Pupil constriction aids fluid drainage Low: ↑Muscarinic effects Moderate: ↑ANS SLUDGE BBB
[Insecticides] To induce hypotension during surgery Anti-hypertensive (not in use) Parkinson’s disease, IBS, MI (↓motility+secretions) Anaesthetic premedication, prevents motion sickness (not during) Examination of retina Asthma, obstructive airway disease Relaxation of skeletal muscle during surgery. ↓ need for anaesthetic and permits artificial ventilation.
Hypotension, vasodilation, ↓Renin secretion. Cholinergic balance in basal ganglia Sedation at mild doses, bronchodilation Pupil dilation Bronchodilation Flaccid paralysis – eye muscles, face, limbs, diaphragm
Side Effects
ST 1
General Muscarinic: Salivation, ↑bronchial + GI secretions, blurred vision, sweating, hypotension, bradycardia. General Muscarinic Higher doses - ↑all ANS, depolarising block Excitation, convulsions, unconsciousness, resp depression, death. Antidote: Pralidoxin BBB ↓↓ ANS function. Death due to targeting skeletal muscle. ↓ Secretions, pupil dilation, ↓GI tone, bronchodilation Mild doses – agitation, ↓sweating, ↓secretions, Cylopegia, CNS disturbance, drowsiness, mydriasis, constipation at high doses Poisoning: Hyperactivity -> CNS depression. Hot, Dry, Blind, Mad: Treat with anticholinesterase Hypotension (↓TPR, histamine release), reflex tachycardia, bronchospasm, excessive secretions, apnoea – must assist respiration. Can be reversed by anti AChE
Class of Drug
Name
(nondepolarising)
Atracurium
Depolarising Neuromuscular Blockers
SNS Agonists (sympathomimetics) Direct
MOA
Clinical Use
See above
See above
AChR agonist. 2 ACh molecules. Steady influx of Na+ means inactivation remains closed, as potential cannot fall below threshold.
Brief procedures – tracheal intubation, dislocations.
Adrenaline
I.V., I.M., local Poor oral absorption. DOA – mins – quickly degraded
Non-selective (α<β)
Anaphylactic shock, COPD, heart block management, spinal anaesthesia, prolong DOA of local anaesthesia, glaucoma
Phenylephrine
Resistant to COMT, not MAO. Usually local admin
Selective α1 agonist
Vasoconstrictor, mydriatic, nasal decongestant
Clonidine
Oral, I.V.
Selective α2 agonist ↓Sympathetic tone by presynaptic NA inhibition
Hypertension, migraine
Isoprenaline
Resistant to Uptake 1 and MAO. t½=2hrs I.V.
Suxamethonium
Dobutamine
Salbutamol SNS Agonists (sympathomimetics) Indirect
Tyramine
Pharmacokinetics Duration – 15-60m Spon Decompose Not broken down by AChE. Hydrolysed by Pseudocholinesterases. DOA – 3-7mins
t½=2min, rapid COMT degradation. I.V. Resistant to COMT, MAO, Uptake 1. I.V., oral, inhalation In cheese, wine, soy sauce. Extensive 1st pass metabolism, short half life. No BBB
Selective β1+β2 agonist
Selective β1 agonist
Selective β2 agonist Weak non-selective agonist Competitive Uptake1 inhibitor MAO Competitor. Displaces NA from vesicles into cytosol causing NA leak from cell.
Heart block, cardiogeneic shock, acute heart failure, MI (No longer for asthma) Heart block, cardiogeneic shock, acute heart failure, MI Asthma Threatened uncomplicated premature labour -
Major Effects
Side Effects
ST 2
Histamine: Bronchospasm, Excessive Secretion + HypoT
Flaccid paralysis
Bronchodilation, suppression of mediators, ↑HR + contractility, ↑TPR, vasoconstriction Pupil dilation, restricts blood to prevent mucus production ↓Sympathetic outflow from brainstem
Muscle pain, loss of K+, bradycardia Secretions: ↓ mucus, thicker CVS: cold extremities tachycardia, palpitations, arrhythmias, stroke & pulmonary oedema Muscle: Tremor CVS effects
Reflex tachycardia, dysrhythmias No reflex tachycardia Bronchodilation, inhibition of mediators
Reflex tachycardia, tremor. Caution in cardiac patients, hyperthyroidism and diabetics
-
Hypertensive crisis “Cheese Reaction” when taking MOA inhibiting drugs
Class of Drug
Indirect sympathomimetic, Drug of abuse, Local Anaesthetic
Name
Pharmacokinetics
Cocaine
Smoked – absorbed quickly, slow orally, nasally. Well absorbed. Readily crosses BBB. Degraded by plasma + hepatic esterases. 90% protein bound t½=30mins. Excreted in urine.
Propranolol Atenolol SNS Antagonists
Not for Asthmatics
Labetolol
Drugs affecting rennin – angiotensin – aldosterone system Calcium
Prevents re-uptake of Dopamine in NAcc. Blocks voltage gated Na+ channels.
β1 antagonist β1+α1 antagonist α1+α2 antagonist
Prazosin Doxazosin
Methyldopa
Uptake 1 inhibitor. Prevents NA reuptake therefore ↑ Synaptic Activity
β1+β2 antagonist
Phentolamine
False Transmitters
MOA
Not degraded by MAO. Doesn’t cross placenta
Hypertension, Arrhythmias, Angina, Glaucoma Not used
Taken up by NA neurones, forms false transmitter. Less active on α1, more active on α2. Accumulates in neurone.
Hypertension (in pregnancy)
Losartan
Non-competitive antagonist of Angiotensin 1 receptors. Phenylakylamine
Anxiety
Inhibits Enzyme (Renin) Inhibit opening of L-type
Hypertension, heart failure, post-MI, diabetic nephropathy, renal insufficiency. Hypertension. Patients with heart failure that cannot tolerate ACEIs Experimental Angina, Hypertension,
Side Effects
ST 3
Euphoria, excitement, ↑motor activity, tachycardia, vasoconstriction, ↑BP, HR, platelet activation, tremors, convulsions, resp depression (medullary centres), death
Do not co-administer with Adrenaline
Hypertension
Inhibit ACE, prevent conversion of angiotensin I to angiotensin II
Major Effects
Local anaesthetic in ophthalmology.
α1 antagonist
Enalapril, Captopril
Aliskiren Verapamil
Clinical Use
↓CO, + BP during exercise ↓CO, effect on airways only in high doses ↓TPR, no change in CO ↓BP, TPR, reflex ↑CO/HR
Bronchoconstriction, Cardiac Failure, Hypoglycaemia Fatigue, Cold Extremities, Bad Dreams ↑ NA release due to α2 blockade, reflex tachycardia, ↑ GI motility, diarrhoea
↓BP/, ↓CO, VD dramatic hypotension, ↓LDL and ↑HDL Renal blood flow well maintained – good in renal failure.
Dry mouth, postural hypotension, sexual dysfunction, sedation Hepatitis-like damage.
Prevent vasoconstriction →↓TPR→↓BP
Hypotension, dry cough, angioedema, hyperkalaemia, renal failure
Postural hypotension
Less extensive than ACE inhibitors ↓ HR (AV) and
AV block, bradycardia, heart
Class of Drug
channel Antagonists
Βeta-Blocker
Name
Pharmacokinetics
MOA
Diltiazem
Benzothiazepine
calcium channels. Causes arterial vasodilatation
Amlodipine
Dihydropyridines
Atenolol Glyceryl Trinitrate
Organic Nitrates
Nicorandil Isosorbide Mononitrate Adenosine Amiodarone Dronedarone
Anti-arrhythmics
st
No longer 1 line Hypertensive Extensive 1st pass metabolism. t½=30mins, sublingual, oral. Latter 2 longer transdermally. t½ = 20-30s I.V. t½ = 10-100days D: Less toxic but less effective
Ivabradine
α-blockers + sympatholytics
SVT, atrial fibrillation
contractility.
failure, constipation
Angina, Hypertension Hypertension
↓ cardiac workload
Flushing, headaches, hypotension, ankle oedema
Angina, Cardiac dysrhthmias, HF, Thyrotoxicosis, Glaucoma, Mirgane
-ve Chronotropic & inotropic Control/Correct Dysrhythmia
Bronchoconstriction, heart block, bradycardia, fatigue, cold extremities, nightmares, hypoglycaemia in diabetics
Angina
Improve myocardial oxygen demand
Hypotension, headache, flushing, Tolerance – Eccentric dosing. Chest pain, SoB, dizziness, nausea. Accumulates in skin, lungs, thyroid. Photosensitive skin rash, pulmonary fibrosis. Amiodarone and verapamil ↓digoxin excretion and tissue binding. Immune antibody available for toxicity. AV block and ectopic pacemaker.
Release NO→venodilation ↓venous return. Weak antiplatelet, coronary artery VD Opens K+ channels→ arterial dilation. Also NO donor. Acts on A1 receptors to slow conduction through AV node
Terminate SVT, safer than verapamil
Complex ion channel blocker
SVTs and ventricular tachyarrhythmias.
t½=40hrs
Atrial fibrillation, relief of symptoms in heart failure.
↓Ventricular rate, ↑contractility. Slows conduction through AVn
CI: post-MI, sick sinus syndrome; cardiogenic shock;
Blocks If channel – Na/K channel in sinoatrial node
Angina (w/ normal sinus rhythm)
Slows HR
Dobutamine Cardiac Intropes
Major Effects
Inhibit Na+/K+ pump. ↑intracellular Na+ →↑Ca2+ via Na+/Ca Exchange → +ve inotropic effect. Central Vagal Stimulation -> -ve chronotropic
Digoxin (Cardiac Glycosides)
β1 Antagonist
Clinical Use
Milrinone Doxazosin Prazosin Phenoxybenzamine
β1 selective agonist Phosphodiesterase Inhibitor: Prevents cGMP breakdown
Positive Inotroic: ↑ Force of Contractions
Competitive α1 antagonist
Postural Hypotension
Irreversible α1 antagonist
Pheochromocytoma (w/ β-blockers)
Side Effects
ST 4
Bradycardia, 1 degree Heart block, Ventricular & SVA Decrease chronic heart failure survival rate
Tachycardia
Class of Drug
Name
Centrally Acting Sympatholytics
Clonidine Mononidine
Vasoconstrictor
Sumitriptan
Cannabis
Drugs of abuse
Cocaine
Nicotine
Disulfiram
Pharmacokinetics
MOA α2 adrenceptor agonist Imadazoline agonist 5HT1D agonist. Vasoconstriction of large arteries, inhibits trigeminal nerve transmission.
Inhalation 50% Oral 10-15% ↑½2hr duration t½=7days (remains in fat tissues). Metabolised in liver – active metabolite 11-hydroxy-THC. Enterohepatic cycling. 25% urine, 65% Bile IV. Oral. Nasal. Inhalation t½=20-90min Plasma/Liver Choliensterase Inhalation 20% absorbed. Distributes rapidly in tissues. Elimination t½=23hrs. Metabolised in liver to cotinine.
Endogenous cannabinoid receptors (hippocampus, cerebellum, cortex, basal ganglia CB1, immune cells CB2). Anandamide is endogenous agonist. Inhibit GABA interneurones in VTA → disinhibition of dopaminergic projection.
Clinical Use
Major Effects
Hypertension
↓ Sym outflow from Brain
Ecgonine Methyl Ester, Benzoylecgonine Inhibits reuptake of dopamine in NAcc Nicotinic receptor agonist. Sympathetic activation via peripheral receptors or directly on brain. Binds to nicotinic receptors on dendrites of VTA neurones →↑ firing rate.
-
Acetaldehyde dehydrogenase inhibitor. Causes build up of acetaldehyde.
Aversion therapy for recovering alcoholics.
ST 5
Coronary vasoconstriction – do not use in patients with coronary disease.
Migraine Attacks
Abuse
Side Effects
Effects on perception, depression of cognition, slow reaction times, defects in short term memory, ↑ satiety, motor incoordination
Tachycardia, vasodilation → reddening conjunctivae, postural hypotension and fainting, immunosuppressant, respiratory effects (tar, carcinogens), psychosis due to loss of anterior cingulated cortex → loss of inhibition and more primitive actions
VC, ↑ Sym, ↑ Euphoria/Disphoria, HR, ↓ Cerebral Heightened Energy, Blood flow + Insomnia, Restlessness, hyper-pyrexia in Talkative, Violence, Anorexia CNS -> Epilsepy CVS: ↑Sym : ↑ HR, BP, SV, vasoconstriction, blood coagulation, LDL, VLDL, FFA, risk of atherosclerosis, MI, CVD, stroke. ↓ oxygen carrying capacity HDL Metabolic: ↑metabolic rate, ACTH, cortisol, ↓appetite Neurological: ↓risk of Parkinson’s & Alzheimer’s Acetaldehyde build up: None when alcohol not flushing, present. tachycardia, panic, distress.
Class of Drug
Drugs of abuse
Name
Alcohol
Warfarin
Anticoagulants
Heparin LMWH
Aspirin (also NSAID) Antiplatelet agents
Clopidogrel
Abciximab
Pharmacokinetics
MOA
Oral. 20% stomach, 80% SI. Substantial 1stPM – saturation kinetics. 90% metabolised, 10% excreted unchanged by lungs. 85% metabolised in liver, 15% Gut Oral, absorbed quickly. Delayed Effect for 12-16hrs. t½=4-5days. 99.99% Plasma protein bound, hepatic metabolism by CYP450. Poor oral absorption. Given S.C./ I.V. short t½. Saturation kinetics. LMWH has longer t½ and no saturation kinetics.
↑ GABA mediated inhibition (sedative effects) Inhibition on Ca2+ entry → ↓ NT release. Inhibition of NMDA receptor function (memory loss?) Major action on cortex, RAS, corpus callosum, hypothalamus, hippocampus, cerebellum, basal ganglia.
Oral, highly plasma protein bound Oral. Peak plasma conc at 4hrs, effect delayed 4 days. I.V. Binds rapidly to platelets and cleared with platelets. t½=24-48hrs.
Inhibits the activation of vitamin K → Prevents synthesis of clotting factors II, VII, IX, X.
Clinical Use
Major Effects
Antagonist of GpIIb/IIIa receptor (monoclonal antibody)
ST 6
CNS: Depressant, ↓sensory function, concentration, motor function, reaction time, coordination. ↑confidence, euphoria, memory loss. Coma, resp failure. Dementia, degeneration of cerebellum, neuropathy, myopathy, Wernicke-Korsakoff syndrome. CVS: Vasodilation, flushing, ↓Ca2+ entry, ↑prostaglandins, ↓thrombosis risk/ heart disease - ↑HDL, ↓plaque formation, ↓thromboxane, ↓platelet aggregation. Chronic Liver: Fatty Liver -> Hepatitis -> Cirrhosis. Oesophageal Varice. Endo: ↑ACTH, ↓Testosterone -> Feminisation. Foetal Development. Haemorrhage, teratogenicity. Drug interactions with: Prevention/ treatment • Drugs inhibiting/ of DVT, PE, prevent inducing CYP450 clotting during Anticoagulant • Drugs which displace haemodialysis/ bypass warfarin from albumin surgery. • Drugs inhibiting platelet function
Activated antithrombin III which inhibits factor Xa and thrombin by active serine binding. LMWH has less action on thrombin Irreversible COX-1 (and slight COX-2) inhibitor. Acetylates active site. Prevents TXA2 and PGE2 production. Pro-drug inhibits fibrinogen binding to GpIIb/IIIa receptors.
Side Effects
Bleeding, thrombocytopenia, osteoporosis, hypersensitivity. Reversal by protamine I.V., binds to give inactive complex. Prevention of high risk cardiovascular patients. Analgesic, antipyretic, anti-inflammatory Aspirin sensitive patients Acute Coronary Syndromes, with heparin and aspirin to prevent ischaemia in unstable angina.
Analgesic, antipyretic, antiinflammatory, antiplatelet. Prevents platelet aggregation
GI sensitivity (ulceration, bleeding, perforation). ↓Creatinine clearance, ↑bleeding time, BronchoC Bleeding, GI haemorrhage, diarrhoea, rash, rarely neutropenia. Bleeding, immunogenic.
Class of Drug
Name Streptokinase
Fibrinolytics Alteplase
Statins
Fibrate Misc
Simvastatin Pravastatin Benzafibrate Gemfibrozil Nicotinic Acid Ezetimibe
Diuretics Mannitol Acetazolamine
Frusemide (Loop diuretic)
Bendrofluazide (Thiazide) Amiloride (Potassium Sparing Diuretics)
Pharmacokinetics
MOA
Clinical Use
Major Effects
Binds to plasminogen and Acute MI - ↓mortality activates - conformational I.V. 30-60 min (additive with aspirin), Recombinant tPA – works infusion acute thrombotic stroke Break down clot better on plasminogen bound (3hrs), DVT, PE arterial to fibrin than soluble → clot t½=12-18mins thromboembolism sensitive. Activates Plasmin HMG-CoA reductase Patients with high inhibitors. ↓cholesterol ↓Total cholesterol, blood Oral production in the liver. ↑ LDL cholesterol, pressure, diabetes or receptors on hepatocytes → LDL, TGs. ↑HDL MI. ↓ LDL in blood. Ligand for PPAR-α -> ↓10% LDL ↑10% First Line for high TG ↑lipoprotein lipase activity HDL ↓30%TG ↓VLDL release -> ↓ 30-50% TG. ↓ 10-20% Cholesterol + ↑HDL Glucuronidation Inhibits cholesterol Combination Therapy Activiated absorption Pharmacologically inert. Filtered by glomerulus, not Prevent acute renal reabsorbed. ↑osmolarity of tubular fluid →↓water failure (given in clinical ↑Urine volume reabsorption setting due to ↑osmol) Inhibit intra+extracellular carbonic anhydrase. ↓ Used in glaucoma, ↑Urine volume, HCO3 reabsorption →Na++H2O reabsorption ↓.↑Na+ metabolic alkalosis, & and ↑K+,Na+ and delivery to DCT→↑K+ loss. renal stones. HCO3 excretion. Acute pulmonary Inhibitor of Na+/2Cl-/K+ pump. ↑ Urine Oral, onset 1hr, oedema, oedema due (Triple Transporter in Asc volume~15DOA 4-6hrs. to heart failure, renal or Limb). Dilutes interstitium 30%, ↑Na+, K+, Tubular secretion, hepatic disease. →↓concentrating power of Cl-, Ca2+, Mg2+ ~50% metabolised. Hypercalcaemia/ collecting duct. excretion. hyperkalaemia. Inhibitors of Na+/Cl- pump at Congestive heart ↑Urine volume Oral, onset 1-2hrs, DCT, →↑Na+ delivery to failure, hypertension, 5-10%. DOA 8-12hrs. collecting duct →↓water nephrogenic diabetes ↑Na+,K+,Cl-,Mg2+ Tubular secretion. reabsorption. ↑K+ loss due to insipidus!?, severe excretion. ↓Ca2+ + compensation for Na resistant oedema. excretion. + + + Poor orally. Onset Blocks Na channel in Na /K With other diuretics to ↑urine vol 5%. 6hrs. DOA 24hrs. exchange mechanism. ↑Na+ prevent K+ loss ↑Na+,H+, uric + Excreted and ↓K loss. acid loss. unchanged.
Side Effects
ST 7
Bleeding, GI haemorrhage, stroke. Allergy Bleeding, GI haemorrhage, stroke. Not antigenic RARE: Myalgia, muscle cramps, myopathy, rhabdomyolysis, acute renal failure Not for Pregenant Women. A number of UE Electrolyte imbalance (hypernatraemia: nausea, vomiting, Pul Oe) ↑ECF vol K+ loss, metabolic acidosis. Metabolic alkalosis, hypovolaemia, hypotension, hypokalaemia. K+ loss, diabetes mellitus (interferes with insulin secretion), metabolic alkalosis. Hyperkalaemia, metabolic acidosis.
Class of Drug
Anti-emetics (see also antimuscarinics: Hyoscine)
Gastric and duodenal ulcers
Name
Pharmacokinetics
MOA
Clinical Use
Major Effects
Spironolactone
Oral, onset/DOA – days. Filtered by glomerulus.
Aldosterone antagonist. Blocks Na+/K+ exchanger in DCT. ↑K+ retention.
↑urine vol 5%. ↑Na+,H+, uric acid loss.
Hyperkalaemia, gynaecomastia, menstrual disorders, testicular atrophy.
Promethazine
Oral. Onset in 12hrs, peak effect 4hrs, DOA 24hrs.
Competitive antagonist of H1>muscarinic>D2 receptors. Acts centrally at NST, vestibular nucleus and vomiting centres
Heart failure, hypertension to prevent K+ loss with diuretics. Motion sickness, normally prophylactically. Disorders of labyrinth, morning sickness, pre-/post-operatively.
Also relief of allergic symptoms, anaphylaxis, night sedation.
Dizziness, tinnitus, fatigue, sedation (excitation in excess), convulsions, general anti-muscarinic.
Metoclopramid e
Oral, rapid absorption, Extensive 1stPM. I.V. Crosses BBB and placenta.
Dopamine receptor antagonist (D2>>H1>>M). Acts centrally at CTZ.
Nausea & vomiting associated with toxins, e.g. uraemia, radiation sickness, GI disorders, chemotherapy.
↑ GI motility and gastric emptying.
Drowsiness, dizziness, extrapyrimidal reactions (children – Parkinsonian-like) Hyperprolactinaemia. anxiety, ↓bioavailability when co-administered.
Ondansetron
Oral, well absorbed, excreted in urine.
5HT3 receptor antagonist. Blocks visceral afferents and CTZ.
Chemotherapy (cisplatin), radiation sickness and postoperatively.
Prevents nausea & vomiting associated with toxins and pain
Headache, flushing and warmth, constipation.
Oral. DOA 23days. Enteric coated for slow release. Oral, well absorbed.
Targets anaerobic bacteria and protozoa Broad spectrum Inhibits bacterial tRNA translocation Irreversible inhibitor of H+/K+ pump. Weak base that accumulates in canaliculi and is activated by acid. Histamine receptor antagonists
Antibiotics e.g. Metronidazole Amoxycillin Clarithromycin
Gastric and duodenal ulcers: PPIs H2 antagonists Gastric and duodenal ulcers: Cytoprotective drugs
Omeprazole Cimetidine Ranitidine Bismuth chelate Sucralfate Misoprostal
Strong negative charge in low pH. Binds to positive charge groups to form gel-like complex. Limits H+ and pepsin getting to ulcer. PG agonist (analogue of PGE1)
Triple therapy for ulcers, GORD.
↓acid secretion by 90%
Triple therapy for ulcers, GORD
↓acid secretion by 60% ↑PGs, mucus, HCO3 secretion. ↓ Helicobacter pylori Maintains mucus barrier, ↓acid secretion
Co-prescribed with oral NSAIDs
ST 8
Metronidazole interferes with alcohol metabolism
Elimination of Helicobacter pylori as part of triple therapy.
Triple therapy, resistant cases
Side Effects
Rare Rare. Likely relapse after withdrawal. CYP450 inhibitor Constipation ↓Absorption of drugs and nutrients Diarrhoea, abdominal cramps, uterine contractions. Do not give in pregnancy
Class of Drug
Name
Ant-Acids
Ant-Acids Al3+ & Mg2+
Respiratory Drugs (Salbutamol & ipratropium)
Pharmacokinetics
Aminophylline
Oral, I.V.
Salmeterol
Long-acting 12hrs Powder Inhalation
Ibuprofen
Oral
NSAIDs (Aspirin) Celecoxib
Other analgesic
Paracetamol
Opiates Morphine
Codeine Heroin
Oral. Conjugated with glutathione in liver.
Oral 40-50% absorption~30mins Metabolised in liver, excret urine. Oral. 5-10% converted to morphine in liver. Oral 50-100% absorption, I.V. Metabolised by plasma esterases. Excreted in urine.
MOA
Clinical Use
Neutralises acid, ↑ gastric pH, ↓ Pepsin activity Phosphodiesterase inhibitor. Prevents breakdown on cAMP → prolonged smooth muscle relaxation.
Non-ulcer dyspepsia Reduce duodenal ulcer Asthma
Relaxation of airway smooth muscle.
β2 receptor agonist
Asthma. COPD
Longer than Salbutamol
Reversible COX-1 and COX2 inhibitor.
Analgesic, antiinflammatory, antipyretic
Selective reversible COX-2 inhibitor →↓ risk of ulceration (can still inhibit HCL secretion with COX-1)
Patients at high risk of GI side effects, and asthmatics. Those taking NSAIDs longterm.
Not fully known. Restricted to nervous tissue. May inhibit COX during conversion (peroxidation) of PGG2 to PGH2 Bind to μ, κ, δ G-protein receptors. ↑K+ loss & ↓Ca2+ entry. • Analgesia: μ, κ receptors in dorsal horn of spinal cord, ↓pain perception. μ, κ receptors on PAG (actually inhibit GABA interneurones) , ↑ pain tolerance. μ, δ receptors in NRPG to↑ pain tolerance.
Major Effects
Side Effects
ST 9
GI sensitivity (ulceration, bleeding, perforation). ↓Creatinine clearance, bronchoconstriction (lower incidence than aspirin) Antiinflammatory
Mild-moderate pain relief
Analgesic, antipyretic
Pain relief, anti-tussive
Analgesic
Euphoria
More lipid soluble → brain faster. Quickly metabolised → more addictive
↑ Risk cardiovascular events and MI. glutathione depletion → build up of N-acetyl-pbenzoquinoneimine → oxidation of hepatic enzymes → liver failure. Treat with acetylcysteine or oral methionine (oxidises their thiol groups instead) • Respiratory depression • nausea and vomiting • ↓ GI motility • pupil constriction • histamine release (itching, urticaria, rarely hypotension) • Dependence and withdrawal
Class of Drug
Opioid antagonists IBD Glucocorticoids
Name
Pharmacokinetics
Fentanyl
Oral, buccal, intranasal, dermal, 50-100% absorption. Metabolised in liver – oxidation. Excreted in urine.
Methadone
t½=24hrs
Naloxone
I.V. high dose, short acting
Prednisolone Fluticasone Budesonide Sulfasalazine
IBD Aminosalicylates
IBD Immunosuppressants
Mesalazine Olsalazine Azathioprine
Tapered dose Topical admin – fluid or foam enemas (high 1stPM) Suppositories, enemas, pH dependent release capsules (SI), slow release microsphere (small and large bowel) Pro-drug, activated by flora. Metabolised by Xanthine oxidase
MOA
Clinical Use
Major Effects
Side Effects
ST 10
Very lipid soluble. Oxidised metabolites may be active
• Euphoria: μ receptors inhibit GABA neurones in VTA →↑ Dopamine in NAcc • Cough: inhibit cough centre, and afferents from larynx • Resp depression: μ2 receptors inhibit central chemoreceptors in medulla Opioid receptor antagonist Intracellular GC receptor agonist. Positive TFs for antiinflammatory proteins or negative TFs for inflammatory proteins. ↓influx inflammatory cells. ↓antigen presentation, cell proliferation ↓Eicosanoids, free radicals, cytokines, leukocyte infiltration. Broken down to sulfapyridine and 5-ASA by gut flora. 5-ASA molecule alone 2 5-ASA molecules linked Active component is purine analogue →interferes with DNA synth →prevents cell division. Enhances T-cell apoptosis
Wean heroin addicts
Most lipid soluble → dissipates into fat very quickly.
Treatment of opiate overdose Reduces need for surgery. Treats severe active disease
Precipitates withdrawal symptoms ↓ vasodilation, swelling, cell recruitment + tissue damage
Osteoporosis, ↑gastric ulceration, suppression HPA axis, diabetes, hypertension, infection, Cushing’s syndrome Caused by sulfapyridine
Maintenance of remission (no immunosuppressive actions) Effective in UC, not Crohn’s
Antiinflammatory
Maintenance of remission in Crohn’s. Also somewhat effective in UC
↓Antibody + cell immune responses, infiltration, proliferation
Few Bone marrow suppression. Do not administer with xanthine oxidase inhibitors (allopurinol) → blood disorders
Class of Drug
Name
Infliximab
Pharmacokinetics
MOA
Clinical Use
Major Effects
I.V. (now also S.C.) t½=9days
Monoclonal anti-TNF antibody. ↓activation of TNF receptors, inactivates TNF bound to receptors. Inhibits inflammatory responses downstream
Crohn’s disease – people with refractory disease and fistulae. Most effect in young or colonic CD
↓cytokines, leukocyte infiltration. ↑Tcell apoptosis, complement lysis of TNFexpressing cells
Spinal cord muscle relaxant, Spasmolytic for stroke, MS patients
↓Tone from upper motor neurones
None, used experimentally
Convulsant
GABAA agonist: Clhyperpolarisation -> IPSP GABAB agonist. Mimics presyn action of GABA (Gs proteins) to 1.↓Ca2+ influx and ↓NT release from excitatory neurones 2. ↑K+ conductance -> Hyperpolarisation Competitive GABAA antagonist Competitive GABAB Antagonists
Muscinol GABA related drugs
Baclofen
(Sodium Valporate, VIgabatrin) Bicuculline Phaclofen Saclofen Phenobarbitone
Amobarbital Barbiturates
Thiopentone
t½=20-25hrs
Bind to BARB subunit of GABAA receptor. Enhance GABA linkage between GABA, GABA modulin and BZ subunits. ↑GABA binding to GABA subunit (not reciprocated). At high concs, direct opening of Cl- channel. → ↑Duration of channel openings. Also ↓glutamate transmission
Anti-convulsant Sedative/hypnotic, severe intractable insomnia
General anaesthetic
Non-selective CNS depressant, other membrane effects also
Side Effects
ST 11
↑TB, infections, septicaemia, malignancy, demyelinating disease, heart failure. Can be immunogenic – given with azathioprine. Only in clinical setting due to anaphylaxis
Low margin of safety – resp depression, lethal overdose (alkaline diuresis can be used to↑ excretion), ↓REM sleep →hangover effects. Potentiate other CNS depressants, develop tolerance (pharmacokinetic and tissue), dependence and withdrawal (insomnia, anxiety, tremor, convulsions, death) CYP450 inducers
Class of Drug
Name
Diazepam Benzodiazepine
Temazepam Oxazepam Other hypnotics Other anxiolytics
Chloral Hydrate
Pharmacokinetics Oral, I.V. for status epilepticus. Protein bound. Wide distn. Metabolised in liver. Excreted in urine t½=32hrs. Metabolised to Temazepam t½=8hrs. Metabolised to Oxazepam t½=8hrs. Metabolised in liver to trichloroethanol (active component)
Propanolol
MOA
Bind to BZ subunit of GABAA receptor. Enhance GABA linkage between GABA, GABA modulin and BZ subunits, ↑GABA binding to GABA subunit (reciprocated effect). → ↑Frequency of channel openings
Unknown. May be related to alcohol Improves physical symptoms
Clinical Use
Anti-convulsant, antispastic, anxiolytic (long acting) Wide safety margin. Don’t depress respiration or induce liver enzymes.
“Remove anxiety without impairing mental or physical activity”
Sedatives, hypnotics (short acting)
Reduce mental/physical activity/ induce sleep
Slow onset (days/weeks)
5-HT1A receptor agonist.
Anxiolytic
L-DOPA
Broken down by DD, 95% in periphery
Precursor to dopamine. Dopa-decarboxylase converts to Dopamine in nerve terminal
Treats hypokinesia, rigidity, tremor
Carbidopa
(w/ L-DOPA: Sinamet)
Inhibitor of peripheral DD Peripherally acting Dopamine receptor antagonist
Domperidone Bromocriptine (Pergolide, Ropinerol) Deprenyl (Selegiline) Resagiline
Doesn’t require conversion – used when there are fewer neurones (R – promotes antiapoptosis genes – Early Trials)
Dopamine receptor agonists Selective MAO-B inhibitor. Inhibits breakdown of dopamine only in dopaminergic areas of CNS
Given with L-DOPA to prevent periphery bd Given with L-DOPA to prevent nausea Longer DOA than LDOPA, more sustained, fewer dyskinesias. Given with L-DOPA Early stages of disease, or with LDOPA (↓required dose, ↓side effects)
Side Effects
ST 12
Sedation, confusion, ataxia. Potentiate other CNS depressants. Tissue tolerance occurs. Dependence and withdrawal less intense than BARBs. ↑In plasma if used with other highly protein bound drugs.
Wide margin of safety In hospitals as with children and hypnotic elderly “Stage Fright”: Tachycardia β1, Tremor β2
Buspirone
Antiparkinsonian
Major Effects
↑ Dopamine ↑half life of LDOPA & ↓ UE Prevents CTZ stimulation ↑ Stimulation of Dopamine receptors ↑Dopamine
If overdose -> rousible sleep, give I.V. flumazenil (competitive BZ antagonist) Few Fewer than benzodiazepines (especially sedative ones). Possible future alternative Acute: Nausea and vomiting, hypotension, psychological effects (schizophrenia-like) Chronic: Dyskinesias, on-off effects. ↓ Effectiveness. [[Madopar – L-DOPA + Benserazide]] Confusion, dizziness, nausea, vomiting, hallucinations, constipation, headache, dyskinesias Nausea, vomiting, hypotension, confusion, agitation
Class of Drug
Neuroleptics (typical) Neuroleptics (atypical)
Name
Pharmacokinetics
Entacapone
Peripherally acting
Tolcapone
CNS and peripheral
Phenothiazine Chlorpromazin e Haloperidol Sulpiride Clozapine Nitrous oxide
General Anaesthetics (inhalation)
General Anaesthetics (Intravenous)
Local Anaesthetics (Cocaine)
Halothane Enflurane Etomidate Propofol
Lidocaine
Delayed effect, take weeks to work. Initially ↑dopamine synthesis and receptors. ↓Over time Rapidly eliminated Brain ↔ Blood ↔ Alveoli. All very lipid soluble, so slow into blood, fast into brain Metabolised in liver. No excretion from lungs t½= 2hrs Well absorbed from mucous membranes (any ROA) 70% protein bound. Hepatic dealkylation
MOA
Clinical Use
Major Effects
COMT inhibitors, prevent breakdown of dopamine. COMT in periphery converts L-DOPA→3-0-MD, which compete for same mechanism to cross BBB.
↓Required dose of L-DOPA. More potent than MAO inhibitors
↑Dopamine in CNS.→ ↑bio-availability of L-DOPA
D2 Dopamine-like receptor antagonists. Most block many other receptor types (5-HT) Relatively non-selective between D1 and D2, but high affinity for D4 ↓NMDA (glutamate) receptor function Potentiate GABAA and glycine receptor function. No subunit selectivity. Inhibit nicotinic Ach receptors Bind somewhere on GABAA receptor and ↑activity. More effective on β subunits. β3 in spinal cord→ suppression of reflexes, α5 hippocampus→ amnesia Voltage gated Na+ channel blocker. Weak base, crosses connective tissue into nerve, into neurone. Becomes ionised with proton inside neurone, blocks open Na+ channel to prevent Na+ influx
Schizophrenia. Treat positive but not negative symptoms (due to D1 Dopamine deficit) To maintain anaesthesia (IV Propofol maintained by Enflurane gas) To induce anaesthesia. Suppress coughing, airway excitation. More potent than inhalation anaesthetics Surface anaesthetic, minor surgery, limb surgery, dental surgery, spinal anaesthesia, epidural.
Side Effects
ST 13
Anti-emetic (CTZ), anti-histamine (block H1 receptors), acute dyskinesias - reversible on withdrawal, controlled by anticholinergics Tardive dyskinesias (20-30%) – made worse by withdrawal, only overcome by ↑neuroleptic (months or years of treatment). Incidence ↓with atypical neuroleptics. Hyperprolactinaemia, lactation. Anti-muscarinic Loss of consciousness, Difficult to induce suppression of anaesthesia, less potent than reflex responses I.V. anaesthetics. Amnesia, analgesia Loss of consciousness, suppression of Difficult to control when in the reflex responses bloodstream. Elimination Amnesia, slower than from lungs analgesia ↓Generation and CNS: stimulation, conduction of restlessness, confusion, a.p.s. tremor (paradoxical, may Selective for block inhibitory systems) small, nonCVS: myocardial depression, myelinated vasodilation, ↓BP fibres
Class of Drug
Cytotoxic Drugs 1. Alkylating Agents
2. Antimetabolites
Name
Pharmacokinetics
MOA
Cyclophosphamide (mephalon, chloramibucil)
Pro-drug, hydroxylated by CYP450 -> Phosphoramide Mustard + Acrolein
Carbonium ion is reactive group, bind irreversibly to DNA, RNA, proteins. Main target is N7 of guanine, but most have other targets Folate antagonist. Prevents purine synthesis Pyramidine Analogue – interferes with 2’deoxythymidylate synthesis Purine Analogue Interferes w/ topoisomerase II Transcription Causes fragmentation of DNA chains. Acts on nondividing cells. Metal chelating Inhibits topoisomerase II, preventing DNA/ RNA synth Bind to tubulin, prevents Spindle Formation. Arrests mitosis at metaphase Inhibits topoisomerase II, preventing DNA synthesis. Inhibits mitochondrial function Inhibits ribonucleotides reductase Causes guanine inter-strand links MAO inhibitor. Inhibits DNA/RNA synthesis and interferes with mitosis at interphase. Alkylates N7 + O6 of Guanaine
Methotrexate Fluorouracil
3. Cytotoxic antibiotics
Azathioprine Actinomycin D (Dactinomycin) Bleomycin
I.V.
Doxorubicin 4. Plant alkaloids
5. Misc
Vincristine [Vinca Alkaloid]
NOT I.T.
Etoposide
[A Podophyllotoxin]
Hydroxyurea Cisplatin
Procarbazine
Activated by CYP450
Clinical Use
Major Effects
Side Effects
ST 14
Intra/inter-chain links interfere with transcription/ replication
Stops cells dividing
Kills cells Cancer, immunosuppressants at lower doses
Stops cells dividing
• Myelotoxicity (↓leukocytes, ↑infections) • ↓healing • ↓growth in children • Sterility • Teratogenicity • Hair loss • Nausea and vomiting.
Class of Drug
Antibacterial Drugs affecting Folate
Name
Pharmacokinetics
Sulphamethoxazole Sulphonamides
Oral, readily absorbed. Peak plasma conc 4-6hrs
Trimethoprim Tetrahydrofolate production inhibitor
Oral, fully absorbed. ↑concs in lungs and kidney. ⅔ each drug protein bound
β-lactam Penicillin Antibacterial affecting Peptidoglycan Synthesis Cephalosporins
Cephalexin (O) Cefuroxine (P) Cefotaxime (P) Tetracyclines
Antibacterial affecting Protein Synethesis
Widely distributed in body fluids. Crosses placenta. Only crosses BBB when meninges inflamed. 90% renal tubular secretion Some oral, most I.M./ I.V. Widely distributed in body fluids. Cross placenta + BBB. Mostly renal tubular secretion Oral (sometimes parenterally). Chelate metal irons → ↓absorption with foods. Enter most body fluids. Excretion from bile (Doxycycline all bile) + renal filtration
MOA Structural analogue of Paminobenzoic acid. Competitive inhibitor of dihydropteroate (enzyme of folic acid synthesis) Folate antagonist. Inhibits dihydrofolate reductase in bacteria (See Methrotrexate – Cancer)
Irreversible inhibitors of a trans-peptidation enzyme that cross-links peptide chains to form peptidoglycan cell wall
β-lactam antibiotic Inhibits transpeptidase
Clinical Use
Major Effects
UTI and Resp TI Synergistic effects Pneumocystis carinii in AIDS patients
Resistance greater than penicillins. Altered binding sites, ↓penetration
Hypersensitivity to Sulphonamide
Bactericidal
Bactericidal
Bacterial meningitis Actively transported into bacteria. Interrupt protein synthesis. Compete with tRNA for A binding site -> inhibits mRNA-tRNA
Gram+ and -, mycoplasma, rickettsia, chamyldia, some spirochaetes and protozoa. Resistance largely due to efflux
ST 15
Mild – nausea, vomiting, headache. Severe – hepatitis, hypersensitivity, bone marrow suppression Nausea, vomiting, skin rashes
Sequential Blockers Co-trimoxazole
Resistance by βlactamases (give with inhibitors e.g. clavulanic acid) Also ↓permeability of cell membrane and altered binding sites
Side Effects
Hypersensitivity – skin rashes, fever, anaphylactic shock. GI disturbances.
Hypersensitivity, similar to penicillin. Nephrotoxicity, alcohol intolerance. Diarrhoea if oral.
Bacteriostatic
GI disturbances. Can cause bone deformities in children. Do not give when pregnant. Some phototoxicity (Demeclocycline & Minocycline) and vestibular disturbances. High doses give anti-anabolic effect. Do not give if renal function impaired - accumulation
Class of Drug
Name
Antimycobacterial agents
t½ = 2hrs Oral. Widely distributed in tissues and fluids. Crosses BBB. 30-50% protein bound. Metabolised in liver. 10% renally excreted unchanged t½=2hrs. Polar, not absorbed orally. I.M./ I.V. minimal protein binding, doesn’t enter cells, cross placenta or BBB. Excreted by glomerular filtration
MOA
Clinical Use
Major Effects
Gram+ and -. Resistance due to enzyme production. Plasmid mediated.
Bacteriostatic
Inhibit protein synthesis. Bind to 30S subunit, alter codon: anticodon recognition → production of defective proteins
Gram+ and -. Resistance by enzyme inactivation (plasmid mediated). Also failure of penetration, binding site mutations.
Bactericidal (enhanced by agents interfering with cell wall synth)
Isoniazid
Oral, readily absorbed. Widely distributed, crosses BBB. Metabolism involves acetylation
Not fully understood. Passes into mammalian cells – effective against intracellular bacteria. Inhibits mycolicacids (cell wall components)
Tuberculosis and leprosy. Penetrates to necrotic, tuberculous lesions.
Bacteriostatic on resting cells, bactericidal on dividing cells
Rifampicin
Oral, widely distributed. Excreted in bile and urine. Undergoes enterohepatic cycling. Metabolites retain activity
DNA-dependent RNA polymerase inhibitor in prokaryotes. Enters phagocytic cells
Mycobacteria and other Gram + and many gram - species
Pyrazinamide
Oral, widely distributed, crosses BBB. Excreted by glomerular filtration
Inactive at pH7, tuberculostatic at low pH. Effective against intracellular organisms in acidic phagolysosomes
Gentamicin Aminoglycoside
Side Effects
ST 16
Hypersensitivity. GI disturbances. Inhibits protein synthesis. Binds to 50S ribosome subunit, inhibits transpeptidation.
Chloramphenicol
Antibacterial affecting Protein Synethesis
Pharmacokinetics
Pancytopenia (Bone marrow suppression), Grey baby syndrome – vomiting, diarrhoea, flaccidity, low temp + ash grey –> 40% mortality. Requires active transport enter, which Chloramphenicol can block. Progressive Ototoxicity, Reversible nephrotoxicity Loading Doses.
Slow metabolisers have a better therapeutic response (t ½ = 3hr vs 1.5hr)
Infrequent (<4%), skin eruptions, fever, GI disturbances
Bacteriostatic
Arthralgia, GI disturbances, Malaise + fever
Class of Drug
Name
Nystatin Antifungal agents
Pharmacokinetics
No absorption across mucus membranes
Miconazole
I.V. infusion if systemic. Oral if GI. Short half life
Acyclovir
Oral, I.V., topical. 20% GI absorption. Widely distributed, ½ crosses BBB. Excreted by filtration+ secretion
Antiviral agents Zidovudine
Phenytoin Anti-convulsants
Carbamazepine
Oral, 1stPM gives 60-80% bioavailability. Also I.V. Crosses BBB. Metabolised with glucuronide in liver. 20% excreted unchanged in urine t½=12-40hrs. Hepatic oxidation, hydroxylation. Renal excretion. Saturation kinetics. 70-90% protein bound t½=36hrs (↓with chronic treatment). Hepatic oxidation, conjugation. Can auto-induce
MOA Binds to cell membrane, forms a pore →ion channel, interferes with permeability and transport. Greater avidity for ergosterol(fungi, protozoa) Blocks ergosterol synthesis by enzyme inhibition → altered fluidity, interfering with enzymes on membrane Converted to monophosphate by viral TK, then to triphosphate by host TK. This is viral DNA pol substrate and is a chain terminator Trhymidine analogue -> Reverse transcriptase inhibitor. Similar to acyclovir. Triphosphate form terminates chain.
Clinical Use
Major Effects
Stops cell division, prevents hyphae formation
Infrequent, GI disturbances, pruritis, blood dyscrasias Minimal. Local inflammation in I.V. infusion, nausea, headache.
Herpes simplex, also CMV Resistance due to change in viral TK
Enters cells by passive diffusion
ST 17
Rare. Nausea, vomiting, rash
Infections of skin and GI tract
Patients with HIV/AIDS Resistance due to progressive accumulating mutations in reverse transcriptase
Side Effects
↓incidence of opportunistic infection, ↓viral load, ↓risk of transmission from mother to baby Accidental Exposure
Common: Anaemia, Neutropenia Uncommon: GI disturbance, skin rash, insomnia, fever, headache, abnormal liver function, Repeated: Confusion, anxiety, depression, flu-like symptoms
Partial epilepsy and status epilepticus
Rash, vasculitis, fever, hepatitis, ataxia, sedation, gingival hypertrophy, folate deficiency, depression, hirsutism, peripheral neuropathy. CYP450 inducer, easily displaced from proteins
Partial and secondary generalised seizures
Rash, hepatitis, nephritis, ataxia, dizziness, sedation, diplopia, Vit K def, depression, impotence, osteomalacia, hyponatraemia Hepatic enzyme inducer
Voltage gated Na+ channel blocker
Class of Drug
Anti-convulsants
Anti-Convul
Phenytoin
Name
Pharmacokinetics
Valproate
Clinical Use
Major Effects
Side Effects
t½=4-12hrs. Hepatic oxidation, conjugation
Enhance GABA mediated inhibition (possibly inhibits GABA metabolism)
Wide spectrum, partial or generalised seizures
Vigabatrin
t½=6-8hrs, but longer DOA
GABA-T inhibitor – prolongs action of GABA inhibition
Little, some infantile spasms
Lamotrigine
t½=29hrs. Hepatic glucuronidation (no phase 1) t½= ↑by valporate to 60hrs, ↓PHT/CBZ to 15hrs
Voltage gated Na+ channel blocker
Wide spectrum, partial or generalised seizures
Drug
Effect on Anti-convulsants
Drug
Amiodorone, Isoniazid
Phenytoin Metabolism Inhibitor → ↑PHT
Warfarin
Displaces phenytoin from protein bound -> only use near safn Displaces protein bound & inhibits metabolism → easy toxicity Induces metabolism Inhibits epoxide-hydrolase → 4x (VGA) ↑ CBZ-epoxide
AEDs (Lamotrigine) corticosteroids, cyclosporin Oral Conceptative w/ oestrogen AEDs (PHT, VPA, LTG)
Reduce levels of others
Inhibits metabolism x2-3 CBZ
OCP
Inform patients
Warfarin
↓ [Warfarin]
AED
↑ [PHT, PB, LTG]
Carbamzepine
↑ CBZ-epoxide
Aspirin
PHT, PB VPA LTG Macrolide antibiotics (Erythomycin) Ca2+ Channel blockers (Diltiazene / Verapamil) Fluoxetine Hepatic Enzyme Inducers e.g. PHT, PB, CBZ Antacids Some NSAIDs, Aspirin, phenylbutazone
↑ 2x CBZ (Nifedipine -> no effect)
Effect of Drug on X Induces CYP450 -> ↓ [warfin]. Monitor INR closely. Induces CYP450 -> ↓ [conc]. ↓ Efficacy (50ug eostradiol req)
May ↑CBZ levels ↓ [Valproate] May impair absorption Displaces VPA from albumin -> Toxicity
ST 18
Hepatic toxicity (young), pancreatitis, drowsiness, encephalopathy, tremor, blood dyscrasias, hair loss, weight gain, PCOS Potent CYP450 inhibitor Visual field defects (retinopathy) ~40%. No CYP450 involvement Well tolerated, rash, headache, blood dyscrasia, ataxia, diplopia, dizziness, sedation, insomnia, mood disturbance. No CYP450 involvement
Sodium Valporate
Valproate
Carbamazepine
MOA