Year 2 Drug Table - ST
description
Transcript of Year 2 Drug Table - ST
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 1
Directly Acting Cholinomimetics
AcetylcholineDegraded by Ach-
esterase and recycled
Stimulates muscarinic and nicotinic receptors
None – stimulates all autonomic ganglia General Muscarinic:
Salivation,↑bronchial + GI secretions,
blurred vision,sweating,
hypotension,bradycardia.
Bethanecolt½=3-4hrs
limited access to brain
Muscarinic agonist, especially M3(glands)
↑Bladder emptying + GI motility
Pilocarpinet½=3-4hrs
not Ach-esterase substrate
Muscarinic partial agonist Glaucoma (local admin)Pupil
constriction aids fluid drainage
Indirectly acting Cholinomimetics
Anticholinesterase
Physostigminet½=30minsANS>NMJ
Reversible AChE inhibitor. Block active site with
carbamyl group.Reactivated by hydrolysis
Glaucoma (local), Atropine poisoning
Low: ↑Muscarinic
effectsModerate: ↑ANS
General MuscarinicHigher doses - ↑all ANS,
depolarising blockNeostigmine Myasthenia gravis
Ecothiopate (organo-
phosphorous compounds)
Irreversible AChE inhibitor. Phosphorylates enzyme
(stable)
Glaucoma (local)
[Insecticides]SLUDGE BBB
Excitation, convulsions, unconsciousness, resp
depression, death.Antidote: Pralidoxin BBB
Cholinoceptor Antagonists
Trimetaphan IV Nicotinic ion channel blockers (incomplete, use dependent)
[Ganglion Blocking]
To induce hypotension during surgery
Hypotension, vasodilation,
↓Renin secretion.
↓↓ ANS function. Death due to targeting skeletal muscle.↓ Secretions, pupil dilation, ↓GI tone, bronchodilationHexamethonium Anti-hypertensive
(not in use)
Atropine I.V. after MI Muscarinic antagonistParkinson’s disease,
IBS, MI (↓motility+secretions)
Cholinergic balance in basal
ganglia
Mild doses – agitation, ↓sweating, ↓secretions,
Cylopegia, CNS disturbance, drowsiness, mydriasis,
constipation at high dosesPoisoning: Hyperactivity ->
CNS depression.Hot, Dry, Blind, Mad:
Treat with anticholinesterase
Hyoscine(Anti-emetic)
Transdermal patch, oral, I.V.
Muscarinic antagonist. Acts at vestibular nucleus, NST,
vomiting centre.
Anaesthetic premedication,
prevents motion sickness (not during)
Sedation at mild doses,
bronchodilation
Tropicamide Local Muscarinic antagonist Examination of retina Pupil dilationIpratropium
bromide Inhalation Muscarinic antagonist Asthma, obstructive airway disease Bronchodilation
Neuromuscular blocking drugs
(non-depolarising)
Tubocurarine
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.
Relaxation of skeletal muscle during surgery. ↓ need for anaesthetic and permits artificial
ventilation.
Flaccid paralysis – eye muscles,
face, limbs, diaphragm
Hypotension (↓TPR, histamine release), reflex
tachycardia, bronchospasm, excessive secretions, apnoea – must assist respiration. Can
be reversed by anti AChE
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 2
(non-depolarising) Atracurium Duration – 15-60m
Spon Decompose See above See above Histamine: Bronchospasm, Excessive Secretion + HypoT
Depolarising Neuromuscular
BlockersSuxamethonium
Not broken down by AChE.
Hydrolysed by Pseudo-
cholinesterases. DOA – 3-7mins
AChR agonist. 2 ACh molecules.
Steady influx of Na+ means inactivation remains closed,
as potential cannot fall below threshold.
Brief procedures – tracheal intubation,
dislocations.Flaccid paralysis Muscle pain, loss of K+,
bradycardia
SNS Agonists(sympatho-mimetics)
Direct
Adrenaline
I.V., I.M., localPoor oral
absorption.DOA – mins –
quickly degraded
Non-selective (α<β)
Anaphylactic shock, COPD, heart block
management, spinal anaesthesia, prolong
DOA of local anaesthesia, glaucoma
Bronchodilation, suppression of mediators, ↑HR + contractility,
↑TPR, vasoconstriction
Secretions: ↓ mucus, thickerCVS: cold extremities
tachycardia, palpitations, arrhythmias, stroke &
pulmonary oedemaMuscle: Tremor
PhenylephrineResistant to
COMT, not MAO.Usually local admin
Selective α1 agonistVasoconstrictor, mydriatic, nasal decongestant
Pupil dilation, restricts blood to prevent mucus
production
CVS effects
Clonidine Oral, I.V.Selective α2 agonist
↓Sympathetic tone by pre-synaptic NA inhibition
Hypertension, migraine↓Sympathetic outflow from brainstem
IsoprenalineResistant to
Uptake 1 and MAO. t½=2hrs I.V.
Selective β1+β2 agonist
Heart block, cardiogeneic shock,
acute heart failure, MI (No longer for asthma)
Reflex tachycardia, dysrhythmias
Dobutaminet½=2min, rapid
COMT degradation. I.V.
Selective β1 agonistHeart block,
cardiogeneic shock, acute heart failure, MI
No reflex tachycardia
SalbutamolResistant to
COMT, MAO, Uptake 1. I.V., oral,
inhalation
Selective β2 agonist
AsthmaThreatened
uncomplicated premature labour
Bronchodilation, inhibition of mediators
Reflex tachycardia, tremor.Caution in cardiac patients,
hyperthyroidism and diabetics
SNS Agonists(sympatho-mimetics)Indirect
Tyramine
In cheese, wine, soy sauce.
Extensive 1st pass metabolism, short half life. No BBB
Weak non-selective agonistCompetitive Uptake1 inhibitorMAO Competitor. Displaces NA from vesicles into cytosol
causing NA leak from cell.
- -Hypertensive crisis
“Cheese Reaction” when taking MOA inhibiting drugs
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 3
Indirect sympatho-mimetic,
Drug of abuse,Local
Anaesthetic
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.
Uptake 1 inhibitor.Prevents NA reuptake
therefore ↑ Synaptic Activity
Prevents re-uptake of Dopamine in NAcc.
Blocks voltage gated Na+
channels.
Local anaesthetic in ophthalmology.
Do not co-administer with Adrenaline
Euphoria, excitement, ↑motor activity, tachycardia,
vasoconstriction, ↑BP, HR, platelet activation, tremors,
convulsions, resp depression (medullary centres), death
SNS Antagonists
Propranolol β1+β2 antagonist Anxiety
Hypertension, Arrhythmias, Angina,
Glaucoma
↓CO, + BP during exercise Bronchoconstriction,
Cardiac Failure, Hypoglycaemia
Fatigue, Cold Extremities, Bad Dreams
Atenolol Not for Asthmatics β1 antagonist↓CO, effect on airways only in
high doses
Labetolol β1+α1 antagonist ↓TPR, no change in CO
Phentolamine α1+α2 antagonist Not used ↓BP, TPR, reflex ↑CO/HR
↑ NA release due to α2 blockade, reflex tachycardia,
↑ GI motility, diarrhoea
Prazosin Doxazosin α1 antagonist Hypertension
↓BP/, ↓CO, VD dramatic
hypotension, ↓LDL and ↑HDL
Postural hypotension
False Transmitters Methyldopa
Not degraded by MAO. Doesn’t cross placenta
Taken up by NA neurones, forms false transmitter. Less active on α1, more active on α2. Accumulates in neurone.
Hypertension(in pregnancy)
Renal blood flow well maintained – good in renal
failure.
Dry mouth, postural hypotension, sexual dysfunction, sedationHepatitis-like damage.
Drugs affecting rennin –
angiotensin – aldosterone
system
Enalapril, Captopril
Inhibit ACE, prevent conversion of angiotensin I to
angiotensin II
Hypertension, heart failure, post-MI,
diabetic nephropathy, renal insufficiency.
Prevent vasoconstriction→↓TPR→↓BP
Hypotension, dry cough, angioedema, hyperkalaemia,
renal failure
Losartan Non-competitive antagonist of Angiotensin 1 receptors.
Hypertension. Patients with heart failure that cannot tolerate ACEIs
Less extensive than ACE inhibitors
Aliskiren Inhibits Enzyme (Renin) Experimental
Calcium Verapamil Phenylakylamine Inhibit opening of L-type Angina, Hypertension, ↓ HR (AV) and AV block, bradycardia, heart
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 4
channel Antagonists
calcium channels. Causes arterial vasodilatation
SVT, atrial fibrillation contractility. failure, constipationDiltiazem Benzothiazepine Angina, Hypertension ↓ cardiac
workloadFlushing, headaches,
hypotension, ankle oedemaAmlodipine Dihydropyridines Hypertension
Βeta-Blocker Atenolol No longer 1st lineHypertensive β1 Antagonist
Angina, Cardiac dysrhthmias, HF, Thyrotoxicosis,
Glaucoma, Mirgane
-ve Chronotropic & inotropic
Control/Correct Dysrhythmia
Bronchoconstriction, heart block, bradycardia, fatigue,
cold extremities, nightmares, hypoglycaemia in diabetics
Organic Nitrates
Glyceryl Trinitrate
Extensive 1st pass metabolism. t½=30mins,
sublingual, oral.Latter 2 longer transdermally.
Release NO→venodilation ↓venous return. Weak
antiplatelet, coronary artery VDAngina
Improve myocardial
oxygen demand
Hypotension, headache, flushing,
Tolerance – Eccentric dosing.Nicorandil
Isosorbide Mononitrate
Opens K+ channels→ arterial dilation. Also NO donor.
Anti-arrhythmics
Adenosine t½ = 20-30sI.V.
Acts on A1 receptors to slow conduction through AV node
Terminate SVT, safer than verapamil
Chest pain, SoB, dizziness, nausea.
AmiodaroneDronedarone
t½ = 10-100daysD: Less toxic but
less effectiveComplex ion channel blocker SVTs and ventricular
tachyarrhythmias.
Accumulates in skin, lungs, thyroid. Photosensitive skin
rash, pulmonary fibrosis.
Digoxin
(Cardiac Glycosides)
t½=40hrs
Inhibit Na+/K+ pump. ↑intracellular Na+ →↑Ca2+ via
Na+/Ca Exchange → +ve inotropic effect.
Central Vagal Stimulation ->-ve chronotropic
Atrial fibrillation, relief of symptoms in heart
failure.
↓Ventricular rate,
↑contractility. Slows
conduction through AVn
Amiodarone and verapamil ↓digoxin excretion and tissue
binding. Immune antibody available for toxicity.AV block and ectopic
pacemaker.
IvabradineCI: post-MI, sick sinus syndrome;
cardiogenic shock;
Blocks If channel – Na/K channel in sinoatrial node
Angina (w/ normal sinus rhythm) Slows HR Bradycardia, 1 degree Heart
block, Ventricular & SVA
Cardiac IntropesDobutamine β1 selective agonist Positive Inotroic:
↑ Force of ContractionsMilrinone Phosphodiesterase Inhibitor:
Prevents cGMP breakdownDecrease chronic heart
failure survival rate
α-blockers + sympatholytics
DoxazosinPrazosin Competitive α1 antagonist Postural Hypotension
Phenoxybenzamine Irreversible α1 antagonist Pheochromocytoma (w/ β-blockers) Tachycardia
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 5
Centrally Acting Sympatholytics
Clonidine α2 adrenceptor agonist Hypertension ↓ Sym outflow from BrainMononidine Imadazoline agonist
Vasoconstrictor Sumitriptan5HT1D agonist.
Vasoconstriction of large arteries, inhibits trigeminal
nerve transmission.
Migraine AttacksCoronary vasoconstriction – do not use in patients with
coronary disease.
Drugs of abuse
Cannabis
Inhalation 50%Oral 10-15% ↑½-
2hr duration t½=7days (remains
in fat tissues). Metabolised in liver – active metabolite 11-hydroxy-THC.
Enterohepatic cycling. 25% urine,
65% Bile
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.
Abuse
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
Cocaine
IV. Oral. Nasal. Inhalation
t½=20-90minPlasma/Liver
Choliensterase
Ecgonine Methyl Ester, Benzoylecgonine
Inhibits reuptake of dopamine in NAcc
VC, ↑ Sym, ↑ HR, ↓ Cerebral
Blood flow + hyper-pyrexia in CNS -> Epilsepy
Euphoria/Disphoria, Heightened Energy,
Insomnia, Restlessness, Talkative, Violence, Anorexia
Nicotine
Inhalation 20% absorbed.
Distributes rapidly in tissues.
Elimination t½=2-3hrs. Metabolised in liver to cotinine.
Nicotinic receptor agonist. Sympathetic activation via
peripheral receptors or directly on brain.
Binds to nicotinic receptors on dendrites of VTA
neurones →↑ firing rate.
-
CVS: ↑Sym : ↑ HR, BP, SV, vasoconstriction, blood coagulation, LDL, VLDL, FFA, risk of atherosclerosis, MI, CVD, stroke. ↓ oxygen
carrying capacity HDLMetabolic: ↑metabolic rate, ACTH, cortisol,
↓appetiteNeurological: ↓risk of Parkinson’s & Alzheimer’s
DisulfiramAcetaldehyde
dehydrogenase inhibitor. Causes build up of
acetaldehyde.
Aversion therapy for recovering alcoholics.
Acetaldehyde build up: flushing,
tachycardia, panic, distress.
None when alcohol not present.
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 6
Drugs of abuse Alcohol
Oral. 20% stomach, 80% SI.
Substantial 1stPM – saturation kinetics. 90% metabolised,
10% excreted unchanged by
lungs. 85% metabolised in liver, 15% Gut
↑ 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.
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.
Anticoagulants
Warfarin
Oral, absorbed quickly. Delayed
Effect for 12-16hrs. t½=4-5days.
99.99% Plasma protein bound,
hepatic metabolism by CYP450.
Inhibits the activation of vitamin K → Prevents
synthesis of clotting factors II, VII, IX, X.
Prevention/ treatment of DVT, PE, prevent
clotting during haemodialysis/ bypass
surgery.
Anticoagulant
Haemorrhage, teratogenicity. Drug interactions with:
Drugs inhibiting/ inducing CYP450
Drugs which displace warfarin from albumin
Drugs inhibiting platelet function
Heparin
LMWH
Poor oral absorption. Given S.C./ I.V. short t½. Saturation kinetics. LMWH has longer
t½ and no saturation kinetics.
Activated antithrombin III which inhibits factor Xa and thrombin by active serine
binding.
LMWH has less action on thrombin
Bleeding, thrombocytopenia, osteoporosis,
hypersensitivity.Reversal by protamine I.V.,
binds to give inactive complex.
Antiplatelet agents
Aspirin(also NSAID)
Oral, highly plasma protein bound
Irreversible COX-1 (and slight COX-2) inhibitor. Acetylates active site. Prevents TXA2
and PGE2 production.
Prevention of high risk cardiovascular patients. Analgesic, antipyretic,
anti-inflammatory
Analgesic, antipyretic, anti-inflammatory, antiplatelet.
GI sensitivity (ulceration, bleeding, perforation). ↓Creatinine clearance,
↑bleeding time, BronchoC
ClopidogrelOral. Peak plasma conc at 4hrs, effect
delayed 4 days.
Pro-drug inhibits fibrinogen binding to GpIIb/IIIa
receptors.
Aspirin sensitive patients
Prevents platelet
aggregation
Bleeding, GI haemorrhage, diarrhoea, rash, rarely
neutropenia.
Abciximab
I.V. Binds rapidly to platelets and cleared with
platelets. t½=24-48hrs.
Antagonist of GpIIb/IIIa receptor (monoclonal
antibody)
Acute Coronary Syndromes, with
heparin and aspirin to prevent ischaemia in
unstable angina.
Bleeding, immunogenic.
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 7
Fibrinolytics
StreptokinaseI.V. 30-60 min
infusion
t½=12-18mins
Binds to plasminogen and activates - conformational Acute MI - ↓mortality
(additive with aspirin), acute thrombotic stroke (3hrs), DVT, PE arterial
thromboembolism
Break down clot
Bleeding, GI haemorrhage, stroke. Allergy
AlteplaseRecombinant tPA – works
better on plasminogen bound to fibrin than soluble → clot sensitive. Activates Plasmin
Bleeding, GI haemorrhage, stroke. Not antigenic
Statins SimvastatinPravastatin Oral
HMG-CoA reductase inhibitors. ↓cholesterol
production in the liver. ↑ LDL receptors on hepatocytes →
↓ LDL in blood.
Patients with high cholesterol, blood
pressure, diabetes or MI.
↓Total cholesterol,
LDL, TGs. ↑HDL
RARE: Myalgia, muscle cramps, myopathy,
rhabdomyolysis, acute renal failure
Not for Pregenant Women.
Fibrate BenzafibrateGemfibrozil
Ligand for PPAR-α -> ↑lipoprotein lipase activity First Line for high TG ↓10% LDL ↑10%
HDL ↓30%TG
MiscNicotinic Acid ↓VLDL release -> ↓ 30-50% TG. ↓ 10-20% Cholesterol + ↑HDL A number of UE
Ezetimibe Glucuronidation Activiated
Inhibits cholesterol absorption Combination Therapy
Diuretics
MannitolPharmacologically inert. Filtered by glomerulus, not
reabsorbed. ↑osmolarity of tubular fluid →↓water reabsorption
Prevent acute renal failure (given in clinical setting due to ↑osmol)
↑Urine volumeElectrolyte imbalance
(hypernatraemia: nausea, vomiting, Pul Oe) ↑ECF vol
AcetazolamineInhibit intra+extracellular carbonic anhydrase. ↓
HCO3 reabsorption →Na++H2O reabsorption ↓.↑Na+
delivery to DCT→↑K+ loss.
Used in glaucoma, metabolic alkalosis, &
renal stones.
↑Urine volume, and ↑K+,Na+ and HCO3 excretion.
K+ loss, metabolic acidosis.
Frusemide(Loop diuretic)
Oral, onset 1hr, DOA 4-6hrs.
Tubular secretion, ~50% metabolised.
Inhibitor of Na+/2Cl-/K+ pump.(Triple Transporter in Asc Limb). Dilutes interstitium →↓concentrating power of
collecting duct.
Acute pulmonary oedema, oedema due
to heart failure, renal or hepatic disease. Hypercalcaemia/ hyperkalaemia.
↑ Urine volume~15-
30%, ↑Na+, K+, Cl-, Ca2+, Mg2+
excretion.
Metabolic alkalosis, hypovolaemia, hypotension,
hypokalaemia.
Bendrofluazide(Thiazide)
Oral, onset 1-2hrs, DOA 8-12hrs.
Tubular secretion.
Inhibitors of Na+/Cl- pump at DCT, →↑Na+ delivery to collecting duct →↓water
reabsorption. ↑K+ loss due to compensation for Na+
Congestive heart failure, hypertension, nephrogenic diabetes
insipidus!?, severe resistant oedema.
↑Urine volume 5-10%.
↑Na+,K+,Cl-,Mg2+
excretion. ↓Ca2+
excretion.
K+ loss, diabetes mellitus (interferes with insulin secretion), metabolic
alkalosis.
Amiloride(Potassium
Sparing Diuretics)
Poor orally. Onset 6hrs. DOA 24hrs.
Excreted unchanged.
Blocks Na+ channel in Na+/K+
exchange mechanism. ↑Na+
and ↓K+ loss.
With other diuretics to prevent K+ loss
↑urine vol 5%. ↑Na+,H+, uric
acid loss.
Hyperkalaemia, metabolic acidosis.
Spironolactone Oral, onset/DOA – Aldosterone antagonist. Heart failure, ↑urine vol 5%. Hyperkalaemia,
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 8
days. Filtered by glomerulus.
Blocks Na+/K+ exchanger in DCT. ↑K+ retention.
hypertension to prevent K+ loss with diuretics.
↑Na+,H+, uric acid loss.
gynaecomastia, menstrual disorders, testicular atrophy.
Anti-emetics(see also anti-muscarinics:
Hyoscine)
PromethazineOral. Onset in 1-2hrs, peak effect 4hrs, DOA 24hrs.
Competitive antagonist of H1>muscarinic>D2 receptors.
Acts centrally at NST, vestibular nucleus and
vomiting centres
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.
Metoclopramide
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.
OndansetronOral, well
absorbed, excreted in urine.
5HT3 receptor antagonist. Blocks visceral afferents and
CTZ.
Chemotherapy (cisplatin), radiation sickness and post-
operatively.
Prevents nausea & vomiting
associated with toxins and pain
Headache, flushing and warmth, constipation.
Gastric and duodenal ulcers
Antibiotics e.g. Metronidazole
Targets anaerobic bacteria and protozoa Elimination of
Helicobacter pylori as part of triple therapy.
Metronidazole interferes with alcohol metabolism
Amoxycillin Broad spectrum
Clarithromycin Inhibits bacterial tRNA translocation
Gastric and duodenal ulcers:
PPIsOmeprazole
Oral. DOA 2-3days. Enteric coated for slow
release.
Irreversible inhibitor of H+/K+
pump. Weak base that accumulates in canaliculi and
is activated by acid.
Triple therapy for ulcers, GORD.
↓acid secretion by 90% Rare
H2 antagonists Cimetidine Oral, well absorbed.
Histamine receptor antagonists
Triple therapy for ulcers, GORD
↓acid secretion by 60%
Rare. Likely relapse after withdrawal. CYP450 inhibitorRanitidine
Gastric and duodenal ulcers:Cytoprotective
drugs
Bismuth chelate Strong negative charge in low pH. Binds to positive
charge groups to form gel-like complex. Limits H+
and pepsin getting to ulcer.
Triple therapy, resistant cases
↑PGs, mucus, HCO3 secretion. ↓ Helicobacter
pylori
Constipation↓Absorption of drugs and
nutrientsSucralfate
Misoprostal PG agonist (analogue of PGE1)
Co-prescribed with oral NSAIDs
Maintains mucus barrier, ↓acid secretion
Diarrhoea, abdominal cramps, uterine contractions.
Do not give in pregnancyAnt-Acids Ant-Acids Neutralises acid, ↑ gastric Non-ulcer dyspepsia
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 9
Al3+ & Mg2+ pH, ↓ Pepsin activity Reduce duodenal ulcer
Respiratory Drugs
(Salbutamol & ipratropium)
Aminophylline Oral, I.V.
Phosphodiesterase inhibitor. Prevents breakdown on
cAMP → prolonged smooth muscle relaxation.
AsthmaRelaxation of
airway smooth muscle.
Salmeterol Long-acting 12hrsPowder Inhalation β2 receptor agonist Asthma. COPD Longer than
Salbutamol
NSAIDs(Aspirin)
Ibuprofen Oral Reversible COX-1 and COX-2 inhibitor.
Analgesic, anti-inflammatory,
antipyretic
GI sensitivity (ulceration, bleeding, perforation). ↓Creatinine clearance,
bronchoconstriction (lower incidence than aspirin)
CelecoxibSelective 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 long-term.
Anti-inflammatory
↑ Risk cardiovascular events and MI.
Other analgesic ParacetamolOral. Conjugated with glutathione in
liver.
Not fully known. Restricted to nervous tissue. May inhibit
COX during conversion (peroxidation) of PGG2 to
PGH2
Mild-moderate pain relief
Analgesic, antipyretic
glutathione depletion → build up of N-acetyl-p-
benzoquinoneimine → oxidation of hepatic enzymes
→ liver failure. Treat with acetylcysteine or oral
methionine (oxidises their thiol groups instead)
Opiates
MorphineOral 40-50%
absorption~30minsMetabolised in
liver, excret urine.
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. Euphoria: μ receptors inhibit GABA neurones in
Pain relief, anti-tussive Analgesic
Respiratory depression nausea and vomiting ↓ GI motility pupil constriction histamine release
(itching, urticaria, rarely hypotension)
Dependence and withdrawal
CodeineOral. 5-10% converted to
morphine in liver.
Heroin
Oral 50-100% absorption, I.V. Metabolised by
plasma esterases. Excreted in urine.
Euphoria
More lipid soluble → brain faster. Quickly metabolised → more addictive
Fentanyl Oral, buccal, Very lipid
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 10
intranasal, dermal, 50-100%
absorption. Metabolised in liver
– oxidation. Excreted in urine.
VTA →↑ Dopamine in NAcc Cough: inhibit cough
centre, and afferents from larynx
Resp depression: μ2
receptors inhibit central chemoreceptors in medulla Nausea: μ receptors
soluble. Oxidised
metabolites may be active
Methadone t½=24hrs Wean heroin addicts
Most lipid soluble →
dissipates into fat very quickly.
Opioid antagonists Naloxone I.V. high dose,
short acting Opioid receptor antagonist Treatment of opiate overdose
Precipitates withdrawal symptoms
IBD
Glucocorticoids
Prednisolone Intracellular GC receptor agonist. Positive TFs for anti-
inflammatory proteins or negative TFs for
inflammatory proteins. ↓influx inflammatory cells. ↓antigen
presentation, cell proliferation
Reduces need for surgery. Treats severe
active disease
↓ vasodilation, swelling, cell recruitment +
tissue damage
Osteoporosis, ↑gastric ulceration, suppression HPA axis, diabetes, hypertension,
infection, Cushing’s syndrome
Fluticasone Tapered dose
BudesonideTopical admin –
fluid or foam enemas (high
1stPM)
IBD
Amino-salicylates
Sulfasalazine
Suppositories, enemas, pH
dependent release capsules (SI), slow release
microsphere (small and large bowel)
↓Eicosanoids, free radicals, cytokines, leukocyte
infiltration. Broken down to sulfapyridine and 5-ASA by
gut flora.
Maintenance of remission (no
immunosuppressive actions) Effective in
UC, not Crohn’s
Anti-inflammatory
Caused by sulfapyridine
Mesalazine 5-ASA molecule alone FewOlsalazine 2 5-ASA molecules linked
IBDImmuno-
suppressants
AzathioprinePro-drug, activated
by flora. Metabolised by
Xanthine oxidase
Active component is purine analogue →interferes with DNA synth →prevents cell
division.Enhances T-cell apoptosis
Maintenance of remission in Crohn’s.
Also somewhat effective in UC
↓Antibody + cell immune
responses, infiltration,
proliferation
Bone marrow suppression. Do not administer with
xanthine oxidase inhibitors (allopurinol) → blood
disordersInfliximab I.V. (now also S.C.)
t½=9daysMonoclonal anti-TNF
antibody. ↓activation of TNF Crohn’s disease –
people with refractory ↓cytokines, leukocyte
↑TB, infections, septicaemia, malignancy, demyelinating
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 11
receptors, inactivates TNF bound to receptors. Inhibits
inflammatory responses downstream
disease and fistulae. Most effect in young or
colonic CD
infiltration. ↑T-cell apoptosis, complement lysis of TNF-
expressing cells
disease, heart failure. Can be immunogenic – given with
azathioprine. Only in clinical setting due to anaphylaxis
GABA related drugs
(Sodium Valporate, VIgabatrin)
Muscinol GABAA agonist: Cl- hyperpolarisation -> IPSP
Baclofen
GABAB agonist. Mimics presyn action of GABA (Gs proteins) to 1.↓Ca2+ influx and ↓NT release from excitatory
neurones 2. ↑K+ conductance ->
Hyperpolarisation
Spinal cord muscle relaxant,
Spasmolytic for stroke, MS patients
↓Tone from upper motor
neurones
Bicuculline Competitive GABAA
antagonistNone, used
experimentally Convulsant
PhaclofenSaclofen
Competitive GABAB
Antagonists
Barbiturates
Phenobarbitone 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
Non-selective CNS
depressant, other membrane
effects also
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
Amobarbital t½=20-25hrsSedative/hypnotic, severe intractable
insomnia
Thiopentone General anaesthetic
Benzodiazepine Diazepam Oral, I.V. for status epilepticus. Protein
Bind to BZ subunit of GABAA
receptor. Enhance GABA Anti-convulsant, anti-
spastic, anxiolytic (long “Remove
anxiety without Sedation, confusion, ataxia.
Potentiate other CNS
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 12
bound. Wide distn. Metabolised in
liver. Excreted in urine
t½=32hrs. Metabolised to Temazepam
linkage between GABA, GABA modulin and BZ
subunits, ↑GABA binding to GABA subunit (reciprocated
effect).→ ↑Frequency of channel
openings
acting)Wide safety margin.
Don’t depress respiration or induce
liver enzymes.
impairing mental or physical
activity”
depressants. Tissue tolerance occurs.
Dependence and withdrawal less intense than BARBs.
↑In plasma if used with other highly protein bound drugs.
If overdose -> rousible sleep, give I.V. flumazenil
(competitive BZ antagonist)
Temazepamt½=8hrs.
Metabolised to Oxazepam
Sedatives, hypnotics (short acting)
Reduce mental/physical activity/ induce
sleepOxazepam t½=8hrs.
Other hypnotics Chloral HydrateMetabolised in liver to trichloroethanol
(active component)
Unknown. May be related to alcohol
Wide margin of safety with children and
elderly
In hospitals as hypnotic Few
Other anxiolytics
Propanolol Improves physical symptoms “Stage Fright”: Tachycardia β1, Tremor β2
Buspirone Slow onset (days/weeks) 5-HT1A receptor agonist. Anxiolytic
Fewer than benzodiazepines (especially sedative ones). Possible future alternative
Anti-parkinsonian
L-DOPABroken down by
DD, 95% in periphery
Precursor to dopamine. Dopa-decarboxylase
converts to Dopamine in nerve terminal
Treats hypokinesia, rigidity, tremor ↑ Dopamine
Acute: Nausea and vomiting, hypotension, psychological effects (schizophrenia-like)Chronic: Dyskinesias, on-off
effects. ↓ Effectiveness.
Carbidopa (w/ L-DOPA: Sinamet) Inhibitor of peripheral DD Given with L-DOPA to
prevent periphery bd↑half life of L-DOPA & ↓ UE
[[Madopar – L-DOPA + Benserazide]]
Domperidone Peripherally acting Dopamine receptor antagonist
Given with L-DOPA to prevent nausea
Prevents CTZ stimulation -
Bromocriptine(Pergolide, Ropinerol)
Doesn’t require conversion – used
when there are fewer neurones
Dopamine receptor agonists
Longer DOA than L-DOPA, more sustained,
fewer dyskinesias. Given with L-DOPA
↑ Stimulation of Dopamine receptors
Confusion, dizziness, nausea, vomiting,
hallucinations, constipation, headache, dyskinesias
Deprenyl (Selegiline)Resagiline
(R – promotes anti-apoptosis genes –
Early Trials)
Selective MAO-B inhibitor. Inhibits breakdown of
dopamine only in dopaminergic areas of CNS
Early stages of disease, or with L-
DOPA (↓required dose, ↓side effects)
↑DopamineNausea, vomiting,
hypotension, confusion, agitation
Entacapone Peripherally acting COMT inhibitors, prevent breakdown of dopamine. ↓Required dose of ↑Dopamine in
CNS.→
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 13
COMT in periphery converts L-DOPA→3-0-MD, which
compete for same mechanism to cross BBB.
L-DOPA. More potent than MAO inhibitors
↑bio-availability of L-DOPATolcapone CNS and
peripheral
Neuroleptics(typical)
Phenothiazine - Chlorpromazin
eDelayed effect, take weeks to work. Initially ↑dopamine
synthesis and receptors. ↓Over
time
D2 Dopamine-like receptor antagonists. Most block many
other receptor types (5-HT)Schizophrenia. Treat
positive but not negative symptoms
(due to D1 Dopamine deficit)
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
Haloperidol
Neuroleptics(atypical)
Sulpiride
ClozapineRelatively non-selective
between D1 and D2, but high affinity for D4
General Anaesthetics(inhalation)
Nitrous oxide Rapidly eliminated Brain ↔ Blood ↔ Alveoli. All very lipid soluble, so slow into blood, fast into brain
↓NMDA (glutamate) receptor function To maintain
anaesthesia(IV Propofol maintained
by Enflurane gas)
Loss of consciousness, suppression of
reflex responsesAmnesia, analgesia
Difficult to induce anaesthesia, less potent than
I.V. anaesthetics.
Halothane Potentiate GABAA and glycine receptor function. No
subunit selectivity. Inhibit nicotinic Ach receptors
Enflurane
General Anaesthetics(Intravenous)
EtomidateMetabolised in
liver. No excretion from lungs
Bind somewhere on GABAA
receptor and ↑activity. More effective on β subunits. β3 in spinal cord→ suppression of reflexes, α5 hippocampus→
amnesia
To induce anaesthesia. Suppress coughing,
airway excitation. More potent than inhalation
anaesthetics
Loss of consciousness, suppression of
reflex responsesAmnesia, analgesia
Difficult to control when in the bloodstream. Elimination slower than from lungsPropofol
Local Anaesthetics
(Cocaine)Lidocaine
t½= 2hrs Well absorbed from
mucous membranes (any
ROA) 70% protein bound. Hepatic
dealkylation
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
Surface anaesthetic, minor surgery, limb
surgery, dental surgery, spinal anaesthesia,
epidural.
↓Generation and conduction of
a.p.s.Selective for small, non-myelinated
fibres
CNS: stimulation, restlessness, confusion, tremor (paradoxical, may block inhibitory systems)
CVS: myocardial depression, vasodilation, ↓BP
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 14
Cytotoxic Drugs1. AlkylatingAgents
2. Anti-metabolites
3. Cytotoxic antibiotics
4. Plant alkaloids
5. Misc
Cyclo-phosphamide
(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
Cancer, immunosuppressants
at lower doses
Intra/inter-chain links interfere
with transcription/
replication
Myelotoxicity (↓leukocytes, ↑infections)
↓healing ↓growth in children Sterility Teratogenicity Hair loss Nausea and vomiting.
Methotrexate Folate antagonist. Prevents purine synthesis
Stops cells dividing
FluorouracilPyramidine Analogue –
interferes with 2’-deoxythymidylate synthesis
Azathioprine Purine AnalogueActinomycin D (Dactinomycin)
Interferes w/ topoisomerase II Transcription
Bleomycin I.V.Causes fragmentation of
DNA chains. Acts on non-dividing cells. Metal chelating
Kills cells
Doxorubicin Inhibits topoisomerase II, preventing DNA/ RNA synth
Stops cells dividing
Vincristine[Vinca Alkaloid] NOT I.T.
Bind to tubulin, prevents Spindle Formation. Arrests
mitosis at metaphase
Etoposide [A Podophyllotoxin]Inhibits topoisomerase II,
preventing DNA synthesis. Inhibits mitochondrial function
Hydroxyurea Inhibits ribonucleotides reductase
Cisplatin Causes guanine inter-strand links
Procarbazine Activated by CYP450
MAO inhibitor. Inhibits DNA/RNA synthesis and interferes with mitosis at
interphase. Alkylates N7 + O6 of Guanaine
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 15
Antibacterial Drugs affecting
Folate
Sulpha-methoxazole
Sulphonamides
Oral, readily absorbed.
Peak plasma conc 4-6hrs
Structural analogue of P-aminobenzoic acid.
Competitive inhibitor of dihydropteroate (enzyme of
folic acid synthesis)
Sequential BlockersCo-trimoxazole
UTI and Resp TISynergistic effects
Pneumocystis carinii in AIDS patients
Mild – nausea, vomiting, headache.
Severe – hepatitis, hypersensitivity, bone marrow suppression
TrimethoprimTetrahydrofolate
production inhibitor
Oral, fully absorbed. ↑concs
in lungs and kidney. ⅔ each
drug protein bound
Folate antagonist. Inhibits dihydrofolate reductase in
bacteria(See Methrotrexate –
Cancer)
Nausea, vomiting, skin rashes
Hypersensitivity to Sulphonamide
Antibacterial affecting
Peptidoglycan Synthesis
β-lactamPenicillin
Widely distributed in body fluids.
Crosses placenta. Only crosses BBB when meninges
inflamed. 90% renal tubular
secretion
Irreversible inhibitors of a trans-peptidation enzyme that cross-links peptide chains to form peptidoglycan cell wall
Resistance by β-lactamases (give with
inhibitors e.g. clavulanic acid)
Also ↓permeability of cell membrane and altered binding sites
BactericidalHypersensitivity – skin
rashes, fever, anaphylactic shock. GI disturbances.
Cephalosporins Cephalexin (O)Cefuroxine (P)Cefotaxime (P)
Some oral, most I.M./ I.V. Widely
distributed in body fluids. Cross
placenta + BBB. Mostly renal
tubular secretion
β-lactam antibioticInhibits transpeptidase
Resistance greater than penicillins. Altered
binding sites, ↓penetration
Bacterial meningitis
Bactericidal
Hypersensitivity, similar to penicillin.
Nephrotoxicity, alcohol intolerance.
Diarrhoea if oral.
Antibacterial affecting Protein
Synethesis
Tetracyclines Oral (sometimes parenterally).
Chelate metal irons → ↓absorption with
foods. Enter most body fluids. Excretion
from bile (Doxycycline all
bile) + renal filtration
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
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 Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 16
Antibacterial affecting Protein
Synethesis
Chloram-phenicol
t½ = 2hrs Oral. Widely distributed
in tissues and fluids. Crosses BBB. 30-50% protein bound. Metabolised in
liver. 10% renally excreted
unchanged
Inhibits protein synthesis. Binds to 50S ribosome
subunit, inhibits transpeptidation.
Gram+ and -.Resistance due to
enzyme production. Plasmid mediated.
Bacteriostatic
Hypersensitivity. GI disturbances.
Pancytopenia (Bone marrow suppression),
Grey baby syndrome – vomiting, diarrhoea, flaccidity,
low temp + ash grey –>40% mortality.
GentamicinAminoglycoside
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
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)
Requires active transport enter, which Chloramphenicol
can block.
Progressive Ototoxicity, Reversible nephrotoxicity
Loading Doses.
Anti-mycobacterial
agents
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
Slow metabolisers have a better therapeutic response
(t ½ = 3hr vs 1.5hr)
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
Infrequent (<4%), skin eruptions,
fever, GI disturbances
PyrazinamideOral, widely
distributed, crosses BBB. Excreted by
glomerular filtration
Inactive at pH7, tuberculostatic at low pH.
Effective against intracellular organisms in acidic phagolysosomes
BacteriostaticArthralgia,
GI disturbances, Malaise + fever
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 17
Antifungal agents
Nystatin No absorption across mucus membranes
Binds to cell membrane, forms a pore →ion channel, interferes with permeability
and transport. Greater avidity for ergosterol(fungi, protozoa)
Infections of skin and GI tract
Rare. Nausea, vomiting,
rash
MiconazoleI.V. infusion if
systemic. Oral if GI. Short half life
Blocks ergosterol synthesis by enzyme inhibition →
altered fluidity, interfering with enzymes on membrane
Stops cell division,
prevents hyphae formation
Infrequent, GI disturbances,
pruritis, blood dyscrasias
Antiviral agents
Acyclovir
Oral, I.V., topical. 20% GI absorption. Widely distributed, ½ crosses BBB.
Excreted by filtration+ secretion
Converted to monophosphate by viral TK, then to
triphosphate by host TK. This is viral DNA pol substrate and
is a chain terminator
Herpes simplex, also CMV
Resistance due to change in viral TK
Minimal. Local inflammation in I.V.
infusion, nausea,
headache.
Zidovudine
Oral, 1stPM gives 60-80%
bioavailability. Also I.V. Crosses BBB. Metabolised with
glucuronide in liver. 20% excreted
unchanged in urine
Trhymidine analogue ->Reverse transcriptase
inhibitor. Similar to acyclovir.
Triphosphate form terminates chain.
Enters cells by passive diffusion
Patients with HIV/AIDSResistance due to
progressive accumulating mutations in reverse transcriptase
↓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
Anti-convulsants
Phenytoin
t½=12-40hrs. Hepatic oxidation,
hydroxylation. Renal excretion.
Saturation kinetics. 70-90% protein
boundVoltage gated Na+ channel
blocker
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
Carbamazepine
t½=36hrs (↓with chronic treatment). Hepatic oxidation, conjugation. Can
auto-induce
Partial and secondary generalised seizures
Rash, hepatitis, nephritis, ataxia, dizziness, sedation, diplopia, Vit K def, depression, impotence, osteomalacia, hyponatraemia
Hepatic enzyme inducer
Class of Drug Name Pharmacokinetics MOA Clinical Use Major Effects Side Effects ST 18
Anti-convulsants
Sodium Valporate
t½=4-12hrs. Hepatic oxidation,
conjugation
Enhance GABA mediated inhibition (possibly inhibits
GABA metabolism)
Wide spectrum, partial or generalised seizures
Hepatic toxicity (young), pancreatitis, drowsiness, encephalopathy, tremor,
blood dyscrasias, hair loss, weight gain, PCOS
Potent CYP450 inhibitor
Vigabatrin t½=6-8hrs, but longer DOA
GABA-T inhibitor – prolongs action of GABA inhibition
Little, some infantile spasms
Visual field defects (retinopathy) ~40%. No CYP450 involvement
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
Well tolerated, rash, headache, blood dyscrasia, ataxia, diplopia, dizziness, sedation, insomnia, mood disturbance. No CYP450
involvement
Anti-Convul Drug Effect on Anti-convulsants Drug Effect of Drug on X
Phenytoin
Amiodorone, Isoniazid Phenytoin Metabolism Inhibitor → ↑PHT Warfarin Induces CYP450 -> ↓ [warfin]. Monitor INR closely.
Aspirin Displaces phenytoin from protein bound -> only use near safn
AEDs (Lamotrigine) corticosteroids, cyclosporin Induces CYP450 -> ↓ [conc].
Valproate Displaces protein bound & inhibits metabolism → easy toxicity
Oral Conceptative w/ oestrogen ↓ Efficacy (50ug eostradiol req)
Carbamazepine
PHT, PB Induces metabolismAEDs (PHT, VPA, LTG) Reduce levels of othersVPA
LTGInhibits epoxide-hydrolase →
4x (VGA) ↑ CBZ-epoxideMacrolide antibiotics
(Erythomycin) Inhibits metabolism x2-3 CBZ OCP Inform patients
Ca2+ Channel blockers (Diltiazene / Verapamil) ↑ 2x CBZ (Nifedipine -> no effect) Warfarin ↓ [Warfarin]
Fluoxetine May ↑CBZ levels
Valproate
Hepatic Enzyme Inducerse.g. PHT, PB, CBZ ↓ [Valproate] AED ↑ [PHT, PB, LTG]
Antacids May impair absorptionCarbamzepine ↑ CBZ-epoxideSome NSAIDs, Aspirin,
phenylbutazone Displaces VPA from albumin -> Toxicity