Download Year 2 Drug Table – ST

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.
SNS
Antagonists
Not for Asthmatics
Drugs affecting
rennin –
angiotensin –
aldosterone
system
Prevents re-uptake of
Dopamine in NAcc.
Blocks voltage gated Na+
channels.
β1 antagonist
Clinical Use
Anxiety
β1+α1 antagonist
Phentolamine
α1+α2 antagonist
Not used
Methyldopa
α1 antagonist
Hypertension
Taken up by NA neurones,
forms false transmitter. Less
active on α1, more active on
α2. Accumulates in neurone.
Hypertension
(in pregnancy)
Enalapril,
Captopril
Inhibit ACE, prevent
conversion of angiotensin I to
angiotensin II
Losartan
Non-competitive antagonist
of Angiotensin 1 receptors.
Aliskiren
Inhibits Enzyme (Renin)
Hypertension, heart
failure, post-MI,
diabetic nephropathy,
renal insufficiency.
Hypertension. Patients
with heart failure that
cannot tolerate ACEIs
Experimental
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
Labetolol
Not degraded by
MAO. Doesn’t
cross placenta
Major Effects
Local anaesthetic in
ophthalmology.
Hypertension,
Arrhythmias, Angina,
Glaucoma
Prazosin
Doxazosin
False
Transmitters
Uptake 1 inhibitor.
Prevents NA reuptake
therefore ↑ Synaptic Activity
β1+β2 antagonist
Propranolol
Atenolol
MOA
↓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
Less extensive
than ACE
inhibitors
Postural hypotension
Class of Drug
Calcium
channel
Antagonists
Βeta-Blocker
Name
Pharmacokinetics
Verapamil
Phenylakylamine
Diltiazem
Benzothiazepine
Amlodipine
Dihydropyridines
Atenolol
No longer 1st line
Hypertensive
Glyceryl
Trinitrate
Organic Nitrates
Nicorandil
Isosorbide
Mononitrate
Adenosine
Amiodarone
Dronedarone
Anti-arrhythmics
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
β1 Antagonist
Major Effects
Angina, Hypertension,
SVT, atrial fibrillation
Angina, Hypertension
↓ HR (AV) and
contractility.
AV block, bradycardia, heart
failure, constipation
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
Inhibit opening of L-type
calcium channels. Causes
arterial vasodilatation
Clinical Use
Inhibit Na+/K+ pump.
↑intracellular Na+ →↑Ca2+ via
Na+/Ca Exchange →
+ve inotropic effect.
Central Vagal Stimulation ->
-ve chronotropic
Digoxin
(Cardiac
Glycosides)
MOA
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% ↑½Endogenous cannabinoid
2hr duration
receptors (hippocampus,
t½=7days (remains
cerebellum, cortex, basal
in fat tissues).
ganglia CB1, immune cells
Metabolised in liver
CB2). Anandamide is
– active metabolite
endogenous agonist.
11-hydroxy-THC.
Inhibit GABA interneurones in
Enterohepatic
VTA → disinhibition of
cycling. 25% urine,
dopaminergic projection.
65% Bile
IV. Oral. Nasal.
Ecgonine Methyl Ester,
Inhalation
Benzoylecgonine
t½=20-90min
Inhibits reuptake of dopamine
Plasma/Liver
in NAcc
Choliensterase
Inhalation 20%
Nicotinic receptor agonist.
absorbed.
Sympathetic activation via
Distributes rapidly
peripheral receptors or
in tissues.
directly on brain.
Elimination t½=2Binds to nicotinic receptors
3hrs. Metabolised
on dendrites of VTA
in liver to cotinine.
neurones →↑ firing rate.
Acetaldehyde
dehydrogenase inhibitor.
Causes build up of
acetaldehyde.
Clinical Use
Major Effects
Hypertension
↓ Sym outflow
from Brain
-
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
Mannitol
Acetazolamine
Frusemide
(Loop diuretic)
Diuretics
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+
↑urine vol 5%.
6hrs. DOA 24hrs.
With other diuretics to
exchange mechanism. ↑Na+
↑Na+,H+, uric
Excreted
prevent K+ loss
+
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
Morphine
Opiates
Codeine
Heroin
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.
Oral. Conjugated
with glutathione in
liver.
Not fully known. Restricted to
nervous tissue. May inhibit
COX during conversion
(peroxidation) of PGG2 to
PGH2
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.
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
↑ Risk cardiovascular events
and MI.
Analgesic,
antipyretic
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)
Pain relief, anti-tussive
Analgesic





Euphoria
More lipid
soluble → brain
faster. Quickly
metabolised →
more addictive
Mild-moderate pain
relief

Respiratory depression
nausea and vomiting
↓ GI motility
pupil constriction
histamine release
(itching, urticaria, rarely
hypotension)
Dependence and
withdrawal
Class of Drug
Opioid
antagonists
Name
Pharmacokinetics
MOA
Fentanyl
Oral, buccal,
intranasal, dermal,
50-100%
absorption.
Metabolised in liver
– oxidation.
Excreted in urine.
 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
 Nausea: μ receptors
stimulate CTZ
 Constipation: μ, κ receptors
on ENS ↓gastric emptying,
↑water absorption
 Pupil constriction: μ
receptors stimulate E-W
nucleus.
Methadone
t½=24hrs
Naloxone
I.V. high dose,
short acting
Prednisolone
Fluticasone
IBD
Glucocorticoids
IBD
Aminosalicylates
IBD
Immunosuppressants
Budesonide
Sulfasalazine
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
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
Clinical Use
Major Effects
Side Effects
ST 10
Very lipid
soluble.
Oxidised
metabolites may
be active
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
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
Osteoporosis, ↑gastric
ulceration, suppression HPA
axis, diabetes, hypertension,
infection, Cushing’s
syndrome
Caused by sulfapyridine
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
Antiparkinsonian
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
Major Effects
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
Wide margin of safety
In hospitals as
with children and
hypnotic
elderly
“Stage Fright”: Tachycardia β1, Tremor β2
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
↑ Dopamine
Carbidopa
(w/ L-DOPA:
Sinamet)
Inhibitor of peripheral DD
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)
↑half life of LDOPA & ↓ UE
Prevents CTZ
stimulation
Peripherally acting Dopamine
receptor antagonist
Bromocriptine
(Pergolide,
Ropinerol)
Doesn’t require
conversion – used
when there are
fewer neurones
Dopamine receptor agonists
Deprenyl
(Selegiline)
Resagiline
(R – promotes antiapoptosis genes –
Early Trials)
Selective MAO-B inhibitor.
Inhibits breakdown of
dopamine only in
dopaminergic areas of CNS
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.
Buspirone
Domperidone
Side Effects
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]]
-
↑ Stimulation of
Dopamine
receptors
Confusion, dizziness,
nausea, vomiting,
hallucinations, constipation,
headache, dyskinesias
↑Dopamine
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)
Halothane
Enflurane
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
Etomidate
General
Anaesthetics
(Intravenous)
Local
Anaesthetics
(Cocaine)
Propofol
Lidocaine
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)
Antibacterial
affecting Protein
Synethesis
Tetracyclines
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
Actively transported into
bacteria. Interrupt protein
synthesis. Compete with
tRNA for A binding site ->
inhibits mRNA-tRNA
Clinical Use
Major Effects
UTI and Resp TI
Synergistic effects
Pneumocystis carinii in
AIDS patients
Resistance greater
than penicillins. Altered
binding sites,
↓penetration
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 to
Sulphonamide
Bactericidal
Bactericidal
Hypersensitivity – skin
rashes, fever, anaphylactic
shock. GI disturbances.
Hypersensitivity, similar to
penicillin.
Nephrotoxicity, alcohol
intolerance.
Bacterial meningitis
Diarrhoea if oral.
Gram+ and -,
mycoplasma, rickettsia,
chamyldia, some
spirochaetes and
protozoa. Resistance
largely due to efflux
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.
Bacteriostatic
Do not give if renal function
impaired - accumulation
Class of Drug
Name
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
Antibacterial
affecting Protein
Synethesis
Gentamicin
Aminoglycoside
Side Effects
ST 16
Hypersensitivity.
GI disturbances.
Inhibits protein synthesis.
Binds to 50S ribosome
subunit, inhibits
transpeptidation.
Chloramphenicol
Antimycobacterial
agents
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