Download acetylcholine

Jamie Manuell
Year 2
Pharmacology &
Therapeutics
Drugs and the
Autonomic Nervous
System
Cholinomimetics
Directly Acting
acetylcholine
Class
Directly acting cholinomimetic
MOA
Neurotransmitter. Acts on
muscarinic or nicotinic
receptors. in Autonomic NS
Indications
Side Effects
Other
Bethanecol
Class
Directly acting cholinomimetic
Parasympathomimetic
MOA
Choline ester, selective for
muscarinic receptors, then M3.
Not acted on by
acetylcholinesterase so long
lasting. They increase detrussor
muscle contraction, by stimulating
post synaptic receptors
Indications
Gut and Bladder stimulation
postoperatively
Side effects
Bronchoconstriction / secretion,
salivation
Other
Pilocarpine
Class
Directly acting cholinomimetics,
i.e. muscarinic agonist
MOA
Alkaloid, selective for muscarinic
receptors. Causes constriction of
the constrictor pupillae muscles of
the iris, allowing aqueous humour
to drain into trabecular meshwork.
Indications
Given to treat glaucoma (by
causing pupil constriction and
therefore aiding drainage)
Side Effects
Eye irritation, headache and
browache, blurred vision,
hypersalivation, may exacerbate
asthma.
Other
Not with acute iritis, anterior
uvetis
Cholinomimetics
Indirectly Acting
Neostigmine
Class
Intermediate lasting
Anticholinesterase
MOA
Inhibits acetylcholinesterase by
addition of a Carbamyl group to
the enzyme and so increases the
amount of ACh in the synaptic
cleft.
Indications
Used IV to reverse the effects of
non depolarising blockers. Shows
some selectivity for the NMJ
Side Effects
Other
Despite selectivity, atropine is
sometimes co-administered to
block muscarinic effects of the
drug.
Physostigmine
Class
Intermediate acting
anticholinesterase.
MOA
Inhibit AChE so increasing
amount of ACh in the synaptic
cleft. Shows selectivity for the
postganglionic parasympathetic
junction.
Indications
Used to constrict the pupil, and
contract the ciliary muscle in
glaucoma.
Side Effects
Initial excitation, followed by
depression, followed by
respiratory depression and
unconsciousness.
Other
Tertiary amine, so can cross the
blood/brain barrier. Central
effects can be combated by
atropine.
Ecothiapate
Class
Long lasting anticholinesterase.
Organophosphorous compound.
MOA
Irreversible inhibitor of AChE, so
increasing ACh duration of action
in synaptic cleft. Inhibit enzyme
by phosphorylation. Enhance
muscarinic activity. Moderate
dose affects all autonomic ganglia,
high doses causes depolarising
block at ganglia.
Indications
Treatment of glaucoma
Side Effects
Bradycardia, breathing problems,
depolarizing neuromuscular block,
central effects, and possible death
form peripheral nerve
demyelination.
Other
Phosphorylated enzyme is stable,
so new enzymes have to be
produced to regain function.
Cholinoceptor Antagonists
Muscarinic Antagonists
Atropine
Class
Non selective Muscarinic
cholinoceptor Antagonist
MOA
Bind to receptor, but has no
intrinsic activity, effect therefor
depends on previous level of
supplied tone by the agonist.
Indications
Reduces gastrointestinal motility,
cardiac arrest, prevent salivation,
bronchial secretions, protect heart
from arrhythmias, particularly
those caused by neuromuscular
blockers.
Side Effects
Dry mouth and skin, raised body
temperature, dilatation of pupil,
relaxation of ciliary msucle (no
accomodation) urinary retention,
irritability and hyperactivity
Other
Different tissues have different
levels of responsiveness. Salivary,
sweat, bronchial>parietal cells
production of gastric acid. Treat
poisoning with anticholinesterase
drugs
The one from the belladonna
alkaloids, found in deadly
nightshade.
Hyoscine
(Scopoloamine)
Class
Muscarinic Receptor Antagonist,
antiemetic
MOA
Binds to receptor making it
inaccessible for ACh to activate
receptor. Emetic actions in vest.
Nuclei, NTS, vomiting centre, to
block VC’s activation.
Indications
Used to prevent bronchial
secretions and salivations.protect
heart from arrhythmias,
particularly those caused by
neuromuscular blockers.
Prevention of motion sickness,
parkinson’s disease.
Side Effects
Dry mouth and skin, raised body
temperature, dilatation of pupil,
relaxation of ciliary msucle (no
accomodation) urinary retention,
irritability and hyperactivity.
Drowsiness, slow gut movement.
Other
Different tissues have different
levels of responsiveness. Salivary,
sweat, bronchial>parietal cells
production of gastric acid.
Tropicamide
Class
Non-selective Muscarinic
cholinoceptor Antagonist
MOA
Indications
Motion sickness, to dilate the pupil
to view the retina.
Side Effects
Low exocrine secretions, initial
drop in HR followed by
tachycardia. Initial excitation,
then depression, amnesia,
tranquility, OD – Coma,
respiratory depression, death
Other
Ipratropium
Bromide
Class
Muscarinic Receptor Antagonist,
parasympatholytic
MOA
Inhaled, blocks action of
acetylcholine.
Indications
Used in bronchodilation. For
asthma and obstructive airways
disease.
Side Effects
Systemic effects of blocking
muscarinic cholinoceptors.
Other
Cholinoceptor Antagonists
Nicotinic Antagonists
Trimetapham
Class
Short lasting Nicotinic
cholinoceptor Antagonist (also
known as ganglion blockade)
MOA
Blocks transmission at all
autonomic ganglia
(parasympathetic and
sympathetic).
Indications
Used clinically to provide 2-3
minutes of hypotension in surgery
Side Effects
Drop BP, Impaired postural
reflexes, reduced renin secretion,
decreased GI motility, impotence,
impaired bladder emptying,
inhibition of all glands, dilated
pupils, poor eye reflex, far vision.
Other
They Do Not block transmission at
nicotinic receptors in the skeletal
NMJ. Actions depend on the
prevailing autonomic tone to the
target organ.
Hexamethonium
Class
Nicotinic Receptor Antagonist
MOA
Blocks transmission at all
autonomic ganglia
(parasympathetic and
sympathetic).
Indications
No longer used clinically
Side Effects
Drop BP, Impaired postural
reflexes, reduced renin secretion,
decreased GI motility, impotence,
impaired bladder emptying,
inhibition of all glands, dilated
pupils, poor eye reflex, far vision.
Other
Non Depolarising
Neuromuscular Blockers
Tubocurarine
Class
Non depolarising Neuromuscular
Blockers
Competitive
MOA
Competitive neuromuscular
blocking drug, bind to the
nicAChR but don’t activate it,
therefore cause neuromuscular
block. 80-90% must be blocked
for its actions to take place.
Indications
Surgery to stop reflexes.
Side Effects
Partial ganglion block, mild
histamine release, rare
hypersensitivity
Other
Atracurium
Class
Non-depolarising Neuromuscular
blockers
MOA
Like tubocurarine, but with shorter
duration of action. Competitive
neuromuscular blocking drug, bind
to the nicAChR but don’t activate
it, therefore cause neuromuscular
block. 80-90% must be blocked
for its actions to take place.
Indications
preventing reflexes in surgery
Side Effects
Reduction in BP, bronchospasm,
tachycardia and apnoea.
Other
Depolarising Neuromuscular
Blockers
Suxamethonium
Class
Depolarising neuromuscular
blockers, causing phase 1 block.
MOA
Binding to and exciting
postsynaptic nAChR, but for a
long period of time (mins vs ms
for ACh). Eventually, APs can no
longer be produced because
voltage sensitive Na channels have
been inactivated – get flaccid
paralysis.
Indications
Only one used clinically because
of its rapid onset and short
duration of action (4 minutes)
Side Effects
Initial spasms, resulting in
postoperative muscle pain.
Muscarinic receptor activation
resulting in bradycardia.
(prevented by administering
atropine). Potassium release from
muscle giving elevated potassium
levels.
Other
Some people with funny AChE
may suffer NMB for hours. In
myasthenia gravis don’t do
anything because already have v
few receptors on end plate.
Adrenoceptor Agonists
Directly Acting
Adrenaline
Class
Non selective α&β adrenoceptor
agonist
MOA
Binds to and excites the α&β
adrenoceptors, giving its actions.
Indications
Side Effects
Other
Acute anaphylactic reactions –
inhibits mediators of immune
response. Cardiac stimulant in
heart block, prolongs action of
local anaesthetics
(vasoconstrictor). Maintain bp
during spinal anaesthesia.
Decrease blood flow for use in
glaucoma.
Tachycardia, arrhythmia,
hypertension, cerebral
haemorrhage, pulmonary oedema,
low mucus secretions, tremor due
to skeletal muscle effects.
Salbutamol
Class
Β2 selective Adrenoceptor Agonist
MOA
Stimulates B2 receptors in the SM
of the lungs and bronchi, inhibits
the release of bronchoconstrictor
substances from mast cells.
Relative resistance to MAO and
COMT
Indications
Ventolin (asthma inhaler), uterine
relaxation (if premature labour)
Side Effects
Arrhythmias, tachycardia,
vasodilation
Other
Given by aerosol so limited
systemic effects.
Dobutamine
Class
Positive Chronotrope, Beta 1
adrenoceptor agonist
MOA
β1 adrenoreceptors are linked to
adenyl cyclase and their activation
leads to increased cAMP levels,
which leads to and increase in
intracellular calcium and so to an
increased cardiac force of
contraction.
Indications
CCF, all shocks, cardiomyopathy,
cardiac surgery.
Side Effects
Tachycardia and hypertension
Other
Not to be given to tachyarrhythmic
patients.
Isoprenaline
Class
Non selective beta Adrenoceptor
Agonist
MOA
Simple agonist
Indications
Treatment of heart block,
Side Effects
Reflex tachycardia, dysrhythmias.
Other
Less susceptible to uptake 1 and
MAO than adrenaline.
Phenylephrine
Class
Selective for a1 receptors
MOA
Simple agonist (Relatively
resistant to COMT but not
MAO)
Indications
Nasal decongestant (Drops/PO)
Myadriatic (Eye Drops)
Vasoconstrictor (IV)
Side
Effects
Hypertension
Other
Clonidine
Class
Alpha 2 selective Adrenoceptor
Agonist.
MOA
Reduces sympathetic tone via
central brainstem action within
baroreceptor pathway, to reduce
sympathetic outflow.
Indications
Hypertension and migraine.
Side Effects
Drowsiness, hypotension
Other
Ephedrine
Class
Indirectly acting Adrenoceptor
Agonist. (promote NA release)
MOA
Taken in by uptake 1 and displace
NA from the vesicles. Also inhibit
MAO, so displaced NA can
continue to have a sympathetic
effect. Potentiate actions of NA.
Indications
When you need more
sympathomimetic. Useful in
restoring blood pressure and tissue
perfusion in cases of shock.
Decongestant (vasoconstriction of
nasal BVs)
Side Effects
Tachycardia, arrhythmias, dry
mouth, cold extremities, anxiety…
other α & β stimulation issues.
Other
Watch out for neglecting ither
things such as kidney.
Adrenoceptor agonists
Indirectly Acting
Cocaine
Class
Sympathetic enhancer
MOA
Strongly inhibits the reuptake of
catecholamines at NAergic
neurons and thus strongly
enhances sympathetic activity.
Indications
Abuse. Occaisionally used as a
topical anaesthetic by ear, nose
and throat specialists.
Side Effects
Toxic psychosis, cardiac
arrhythmias, hypertension, and
stroke. Psychological dependence,
but no real physical dependence.
Chronically produces paranoid
psychosis, vasoconstriction, tissue
anoxia at sites of injection,
damage to fetal brain. Withdrawl
causes a ↓ in motor performance,
restorable on provision of the
drug.
Tyramine
Class
Weak agonist
Monoamine compound
derived from the amino acid
Tyrosine
MOA
Tyramine competes with
catecholamines for uptake 1,
displaces NA from storage
vesicles into cytosol, this leaks
into the synapse and stimulates
postsynaptic adrenoceptors,
also competes for sites on MAO
Indications
Found in the diet (Cheeses)
Side
Effects
When MAO is inhibited
(Antidepressants – Phenelzine)
indigestion of food containing
tyramine may result in a
hypertensive crisis (Cheese
Reaction)
Adrenoceptor Antagonist
Propranolol
Class
MOA
Non selective beta adrenoceptor
antagonist. Anxiolytics.
Acts by antagonism at βadrenoceptors so that excessive
catecholamine release does not
produce the usual sympathetic
responses.
Indications
Hypertension, angina, arrhythmias,
good at alleviating signs of
sympathetic arousal, such as
palpitations, tremor, sweating and
diarrhoea. Also useful in socially
anxious people or musicians with
stage fright.
Side Effects
Bradycardia, heart failure,
bronchospasm, peripheral
vasoconstriction
Other
Not in people with asthma or heart
failure.
Atenolol
Class
Negative chronotrope and
inotropes, beta blocker, beta 1
selective
MOA
Competitive antagonist for beta 1
adrenoceptor so reduces
sympathetic innervation of the
heart. Lowers tachycardia and
force of contraction.
Indications
Given after MI, hypertension,
prophylaxis, anti-arrhythmia,
thyrotoxicosis, glaucoma and
anxiety
Side Effects
Bronchospasm, bradycardia, heart
block, hypotension
Other
At high doses loses selectivity, so
caution for asthmatics. Not in
bradycardia, hypotension, AV
block, and CCF
Labetalol
Class
Alpha/beta blocker Adrenoceptor
antagonist
MOA
Lowers BP by a reduction of
peripheral resistance. This is via
blockade of α1 in blood vessels
and β1 effects on neurotransmitter
renin release. No change in HR or
CO
Indications
Hypertension
Side Effects
Postural hypotension
Other
Phentolamine
Class
Non selective α antagonist.
MOA
Causes vasodilation and a fall in
BP due to blockade of α1/2
receptors.
Indications
hypertension
Side Effects
Increased GI motility, so diarrhoea
a common problem.
Other
Blockade o f α receptors tend to
increase noradrenaline release
(enhances the reflex tachycardia
seen with any bp lowering agent)
Doxazosin
Class
MOA
α1 adrenoceptor antagonist.
Cause inhibition of α1 adrenoceptor
mediated vasoconstriction, so
reducingPVR and venous pressure.
Also lower LDL, VLDL, and TGA,
and increase HDL, reducing risk of
CAD
Indications
Hypertension, (esp with CCF),
prostate hyperplasia (reduced
bladder and prostate resistance) and
CAD.
Side Effects
Postural hypotension, dizziness,
headache and fatigue, weakness
palpitations, and nausea.
Other
False Transmitters
Methyldopa
Class
False transmitter, antihypertensive
agent
MOA
Taken up by NAergic neurons,
where decarboxylated and
hydroxylated to form α methyl
NA. Not metabolised by MAO, so
shunts NA from synaptic vesicles.
Release as NA but less active that
NA on post α1 receptors, so less
vasoconstriction, and more active
on presynaptic α2 receptor.
Stimulates vasopressor centre to
inhibit sympathetic outflow.
Indications
Renal blood flow well maintained
so a good hypertensive in patients
with renal insufficiency. Good in
pregnancy as has no adverse
effects on foetus.
Side Effects
Dry mouth, sedation, postural
hypotension, male sexual
dysfunction, liver looks like
hepatitis. Orthostatic hypotension.
Other
Drugs and the Heart &
Vasculature
Positive Chronotropes
Digoxin
Class
Positive Chronotrope (cardiac
glycoside)
MOA
These act by inhibiting the
membrane Na+/K+ ATPase pump.
This raises intracellular Na,
decreasing Na gradient, meaning
less Ca is pumped out in the
Ca/Na exchanger. Ca levels
increase, and so does force of
contraction. Stimulation of vagus
shorten atrial AP. They decrease
HR, and reduce AV conductance
for use in arrhythmias.
Indications
Heart failure and superventricular
arrhythmias.
Side Effects
At high doses they raise Sym
stimulation causing arrhythmias
and heart block. Nausea,
vomitting, visual disturbances, ab
pain, diarrhoea.
Other
Contraindications are heart block
and hypokalaemia. Narrow
therapeutic window. In toxicity,
potassium supps and antiarrhythmics given.
Dobutamine
Class
Positive Chronotrope, Beta 1
adrenoceptor agonist
MOA
β1 adrenoreceptors are linked to
adenyl cyclase and their activation
leads to increased cAMP levels,
which leads to and increase in
intracellular calcium and so to an
increased cardiac force of
contraction.
Indications
CCF, all shocks, cardiomyopathy,
cardiac surgery.
Side Effects
Tachycardia and hypertension
Other
Not to be given to tachyarrhythmic
patients.
Milrinone
Class
Positive chronotrope,
Phosphodiesterase II inhibitor
MOA
Phosphodiesterase is responsible
for the degradation of cAMP.
Inhibiting this raises cAMP levels,
so contractility and vasodilation
Indications
Severe acute heart failure, resistant
to other drugs.
Side Effects
Nausea, vomiting, arrhythmias,
liver dysfunction, abdo pain,
hypersensitivity.
Other
Developed to get around adverse
effects with cardiac glycosides.
Negative Chrono and Inotropes
Atenolol
Class
Negative chronotrope and
inotropes, beta blocker, beta 1
selective
MOA
Competitive antagonist for beta 1
adrenoceptor so reduces
sympathetic innervation of the
heart. Lowers tachycardia and
force of contraction.
Indications
Given after MI, hypertension,
prophylaxis, anti-arrhythmia,
thyrotoxicosis, glaucoma and
anxiety
Side Effects
Bronchospasm, bradycardia, heart
block, hypotension
Other
At high doses loses selectivity, so
caution for asthmatics. Not in
bradycardia, hypotension, AV
block, and CCF
Diltiazem
Class
Negative chronotrope and
inotrope, rate limiting calcium
channel blocker
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Verapamil
Class
Negative chronotropes and
inotrope, Rate limiting calcium
channel blockers
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Drugs reducing Preload &
Afterload
Ramipril /
Enalapril
Class
Ace Inhibitor to reduce preload
and afterload
MOA
These work by preventing
angiotensin I to Angiotensin II,
meaning that the ATI receptors in
the arterioles and in the adrenal
cortex are not triggered, resulting
in increased water and sodium
excretion in the kidney
Indications
Indications are in CVD, such as
hypertension, post MI, Diabetic
neuropathy, Progressive renal
insufficiency, patients at high risk
of CVD.
Side Effects
Adverse effects are hypotension,
dry cough and angioedema.
Other
Not in pregnancy, renovascular
disease, aortic stenosis
Captopril
Class
Ace inhibitor
MOA
These work by preventing
angiotensin I to Angiotensin II,
meaning that the ATI receptors in
the aterioles and in the adrenal
cortex are not triggered, resulting
in increased water and sodium
excretion in the kidney
Indications
Indications are in CVD, such as
hypertension, post MI, Diabetic
neuropathy & nephropathy,
Progressive renal insufficiency,
patients at high risk of CVD.
Side Effects
Adverse effects are hypotension,
dry cough and angioedema.
Other
Not in pregnancy, renovascular
disease, aortic stenosis
Losartan
Class
Angiotensin receptor blocker
MOA
Cause inhibition at the angitensin
II receptor, resulting in
vasodilation with reduction in
PVR.
Indications
Hypertension
Side Effects
Cough, orthostatic hypotension,
dizzyness, headache, fatigue,
hyperkalaemia and rash.
Other
Contraindications in breastfeeding,
pregnancy. Caution in renal artery
stenosis and aortic stenosis.
Nicorandil
Class
Organic nitrate (reducing preload
and afterload). Potassium channel
activator
MOA
Activates potassium channels of
vascular SM. Potassium flows out
of the cells causing
hyperpolarisation. This inhibits
the influx of calcium, so inhibits
contraction – hence vasodilation.
Indications
Prophylaxis of angina
Side Effects
Headache, cutaneous vasodilation,
nausea and vomiting
Other
Cardiogenic shock, left ventricular
failure, hypotension.
Bendrafluazide
Class
Thiazide diuretic
MOA
These act on the early distal
tubule. They inhibit the Na/Cl
cotransporter in the luminal
membrane. They increase
secretion of K and protons into the
collecting ducts, but decrease Ca
excretion.
Indications
Hypertension, oedema 2ndary to
CCF, liver disease, or nephrotic
syndrome. Sometimes for
prophylaxis of calcium containing
renal stones.
Side Effects
Hypokalaemia, hyperuricaemia,
hyponatraemia, hypercalcaemia,
and metabolic acidosis.
Other
Shouldn’t be used in those taking
cardiac glycosides, or diabetes
mellitus (as may cause
hyperglycaemia). Or in
hypokalaemia, hyponatraemia, or
hypercalcaemia.
Spironalactone
Class
Aldosterone antagonist.
MOA
Inhibits the sodium retaining
effects of aldosterone.
Indications
It is useful in heart failure and
resistant cases of hypertension.
Side Effects
Can cause hyperkalaemia due to
sodium retention, and steroid like
side effects like gynaecomastia,
menstrual disorders, and testicular
atrophy.
Other
Due to +ve feedback, more
aldosterone may be produced,
increasing unwanted side effects.
Doesn’t prevent aldosterone
production.
Drugs to control or correct
Dysrhythmias
Amiodarone
Class
Wide spectrum anti-arrhythmic,
potassium channel blockers.
MOA
These are potassium channel
blockers which prolong cardiac
action potential duration, and the
refractory period. It also blocks
sodium and calcium channels, and
blocks β and α adrenoceptors.
Indications
For ventricular and
supraventricular arrhythmias.
Side Effects
Can cause arrhythmias, thyroid
dysfunction, liver damage,
pulmonary disorders,
photosensitivity and neuropathy.
Other
Not to be given to those with AV
block, sinus bradycardia, or
thyroid dysfunction
Diltiazem
Class
Negative chronotrope and
inotrope, rate limiting calcium
channel blocker
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Verapamil
Class
Negative chronotropes and
inotrope, Rate limiting calcium
channel blockers
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Digoxin
Class
Positive Chronotrope (cardiac
glycoside)
MOA
These act by inhibiting the
membrane Na+/K+ ATPase pump.
This raises intracellular Na,
decreasing Na gradient, meaning
less Ca is pumped out in the
Ca/Na exchanger. Ca levels
increase, and so does force of
contraction. Stimulation of vagus
shorten atrial AP. They decrease
HR, and reduce AV conductance
for use in arrhythmias.
Indications
Heart failure and superventricular
arrhythmias.
Side Effects
At high doses they raise Sym
stimulation causing arrhythmias
and heart block. Nausea,
vomitting, visual disturbances, ab
pain, diarrhoea.
Other
Contraindications are heart block
and hypokalaemia. Narrow
therapeutic window. In toxicity,
potassium supps and antiarrhythmics given.
Atenolol
Class
Negative chronotrope and
inotropes, beta blocker, beta 1
selective
MOA
Competitive antagonist for beta 1
adrenoceptor so reduces
sympathetic innervation of the
heart. Lowers tachycardia and
force of contraction.
Indications
Given after MI, hypertension,
prophylaxis, anti-arrhythmia,
thyrotoxicosis, glaucoma and
anxiety
Side Effects
Bronchospasm, bradycardia, heart
block, hypotension
Other
At high doses loses selectivity, so
caution for asthmatics. Not in
bradycardia, hypotension, AV
block, and CCF
Coronary Vasodilators
Diltiazem
Class
Negative chronotrope and
inotrope, rate limiting calcium
channel blocker
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Verapamil
Class
Negative chronotropes and
inotrope, Rate limiting calcium
channel blockers
MOA
These bind to and inhibit opening
of the L-type calcium channels.
This causes arterial vasodilation,
so reducing cardiac workload. Has
–ve chronotropic and inotropic
effects
Indications
Indications are prophylaxis and
treatment of angina and
hypertension. Verapamil and
diltiazem are given for
supraventricular arrhythmias
Side Effects
can cause flushing, headaches,
hypotension, ankle swelling, CCF,
heart block, constipation
Other
Not to be given to patients in
cardiogenic shock, severe heart
failure, those taking beta-blockers,
and severe bradycardia.
Glyceryl
Trinitrate
Class
Organic Nitrates
MOA
Release NO which activates
Guanylate cyclase causing
more cGMP and more Ca
storage in the SR, hence
Venodilation which reduces
preload and therefore SV and
CO, also coronary vessel vaso-d
Indications
Angina
Side
Effects
Venodilation causes Postural
hypotension, dizziness, syncope
and reflex tachy. Arterial
dilation causes throbbing
headaches and flushing
Other
Minoxidil
Class
K+ channel opener
MOA
Potent vasodilator acting on
arteries and arterioles by opening
potassium channels in SM and
causing hyperpolarisation.
Indications
Used in hypertension control in
pregnancy
Side Effects
In the absence of β blockade it
causes reflex tachycardia.
Other
Doxazosin
Class
MOA
α1 adrenoceptor antagonist.
Cause inhibition of α1 adrenoceptor
mediated vasoconstriction, so
reducingPVR and venous pressure.
Also lower LDL, VLDL, and TGA,
and increase HDL, reducing risk of
CAD
Indications
Hypertension, (esp with CCF),
prostate hyperplasia (reduced
bladder and prostate resistance) and
CAD.
Side Effects
Postural hypotension, dizziness,
headache and fatigue, weakness
palpitations, and nausea.
Other
Vasoconstrictors
Sumitriptan
Class
Agonist at 5HT1D receptors
MOA
Causes vasoconstriction at some
large arteries and inhibits
trigeminal nerve transmission,
Indications
Used to treat migraine attacks
Side Effects
Sensation of tingling, heat, chest
tightness
Other
Contraindicated in patients with
CAD as it causes coronary
vasoconstriction, hepatic
impairment, pregnancy and
breastfeeding.
Anti-Thrombotic &
Anticoagulants
Thrombolytics (Fibrinolytics)
Streptokinase
Class
Tissue plasminogen activator
MOA
This forms a complex with and
activates plasminogen into
plasmin, a fibrinolytic enzyme
Indications
Life threatening venous
thrombosis, pulmonary embolism,
arterial thromboembolism, and
acute MI.
Side Effects
Nausea, vomiting and bleeding.
Derived form streptococcus,
therefore antigenic. Repeated
administration could result in
anaphylaxis.
Other
Not for use in recent haemorrhage,
trauma, surgery or any form of
Cerebrovascular disease.
Alteplase
Class
Tissue type plasminogen activator
MOA
Binds with and activates
plasminogen into plasmin, which
breaks down fibrin in a clot.
Indications
Useful as a fibrinolytic if the
antigenic streptokinase has already
been administered once, as it is
non antigenic. MI, Pulmonary
embolism
Side Effects
Nausea, vomiting, and bleeding
Other
Same as streptokinase, ie any
patient who has recently suffered a
trauma likely to have required clot
formation.
Anticoagulants
Warfarin
Class
Vitamin K antagonist
MOA
Vitamin K is vital in the post
transcriptional γ-carboxylation of
glutamic acid residues of
prothrombin (factor II) and
clotting factors VII, IX, and X by
the liver. This stops clotting
cascade
Indications
Warfarin can be used in treatment
of DVT and pulmonary embolism,
prophylaxis of embolisation in
atrial fibrillation and rheumatic
disease and in patients with
prosthetic heart valves
Side Effects
haemorrhage
Other
Warfarin only affects new factors
so takes 72 hrs to take effect.
Should not be used in Cerebral
thrombosis, peripheral arterial
occlusion, peptic ulcers,
hypertension, pregnancy
Heparin
Class
Anticoagulant
MOA
Heparins work by activating
antithrombin III, which inactivates
thrombin and factor X. It also
inhibits platelet aggregation
Indications
Heparin and LMWH given in
thrombosis and pulmonary
embolism, MI, prophylaxis against
PO DVT and pulmonary embolism
in high risk patients.
Side Effects
haemorrhage
Other
Action is immediate so can be
used in emergency. Should not be
used in haemophilia,
thrombocytopenia, or peptic
ulcers.
Anti-Platelet Drugs
Aspirin
Class
Cyclo-oxygennase
inhibitor.acetylates the active site.
MOA
This inhibits the COX enzymes,
which in turn inhibit production of
thromboxane A2, preventing
platelet aggregation. Also inhibits
PGE2, making it an analgesic.
COX-2 is proinflammatory.
Indications
In overdose can uncouple
oxidative phosphorylation, causing
metabolic acidosis.
Side Effects
Stomach ulcers,
bronchoconstriction. Arachidonic
acid either forms PGs with COX,
or Leukotrienes with
lipoxygenase. LT4 is a powerful
bronchoconstrictor, more produced
if COX inhibited. Asthmatics
vulnerable. Reduced creatinine
clearance, possible nephritis. Bad
because effects COX-1 200 fold
more than COX-2.
Other
Effects vary according to dose.
Asthmatics can’t take them.
Aspirin also displaces wafarin
from plasma causing bleeding, as
warfarin normally 5% unbound.
Clopidigrel
Class
Anti platelet aggregation drug.
MOA
Clopidogrel inhibits activation of
the IIb/IIIa receptor on the surface
of platelets, required for
aggregation to occur.
Indications
Used if patient truly allergic to
aspirin. Secondary prevention of
CVD.
Side Effects
Haemorrhage, ab discomfort,
nausea and vomiting.
Other
Abciximab
Class
Glycoprotein IIb/IIIa inhibitor
MOA
It is an antibody fragment
antagonist of the glycoprotein
IIb/IIIa receptor on platelets. This
prevents aggregation.
Indications
Used if problems with other ones.
Ischaemic cardiac complications in
open heart surgery. Short term
prevention of MI in unstable
angina.
Side Effects
Haeorrhage, nausea, vomiting
hypotension.
Other
Single administration because it is
antigenic, potential anaphylaxis if
second administration
Statins
Simvastatin
Class
HMG-CoA Reductase Inhibitor
MOA
Catalyses the enzyme that is the
rate limiting step in Cholesterol
synthesis in the Liver, the fall in
circulating Cholesterol then
causes up regulation of LDL
receptors on hepatocytes cell
surfaces, also reduces
circulating VLDL’s and TG’s
Indications
Hyperlipidaemia
Side
Effects
GI upsets
CNS effects (Dizziness, blurred
vision, headache)
Cause of abnormal LFT’s
Myalgia if used with Fimbrates
Other
Stabilizes atherosclerotic
plaques and reduces
inflammatory cell migration
into plaques
NSAIDS
Aspirin
Class
Cyclo-oxygennase
inhibitor.acetylates the active site.
MOA
This inhibits the COX enzymes,
which in turn inhibit production of
thromboxane A2, preventing
platelet aggregation. Also inhibits
PGE2, making it an analgesic.
COX-2 is proinflammatory.
Indications
In overdose can uncouple
oxidative phosphorylation, causing
metabolic acidosis.
Side Effects
Stomach ulcers,
bronchoconstriction. Arachidonic
acid either forms PGs with COX,
or Leukotrienes with
lipoxygenase. LT4 is a powerful
bronchoconstrictor, more produced
if COX inhibited. Asthmatics
vulnerable. Reduced creatinine
clearance, possible nephritis. Bad
because effects COX-1 200 fold
more than COX-2.
Other
Effects vary according to dose.
Asthmatics can’t take them.
Aspirin also displaces wafarin
from plasma causing bleeding, as
warfarin normally 5% unbound.
Ibuprofen
Class
NSAID, COX-2 antagonist
MOA
Works as a competitive substrate
for the COX-2 enzyme, preventing
the arachidonic acid conversion by
COX-2 into prostaglandins, and
prostacyclins.
Indications
Mainly for high risk GI patients
who would get stomach ulcers
from Aspirin. Drug of choice for
inflammatory joint disease
Side Effects
Very few
Other
Celecoxib
Class
This is a selective COX-2 inhibitor
MOA
Selective but expensive COX-2
inhibitor. Used for high risk GI as
no COX-1 side effects. Also less
effect on nephrotoxicity.
Indications
High risk GI anti-inflammatory
Side Effects
Other
Contraindicated in Inflammatory
bowel disease.
Diuretics
Mannitol
Class
An osmotic diuretic.
MOA
Freely filtered at the glomerulus,
but only partially reabsorbed.
Means that water leaves tubule
under osmosis, and more sodium
is excreted, and there is less free
reabsorption of water.
Indications
Raised intracranial and intrtaocular
pressure.
Side Effects
Chills and Fever
Other
Contraindicated in congestive
cardiac failure, and pulmonary
oedema.
Acetazolamide
Class
Carbonic anhydrase inhibitor.
Weak diuretics
MOA
Acts in the proximal tubule to
prevent the usual removal of Na+
and HCO3-, water follows.
Prescence of Na+ in the distal
tubule also increases excretion of
K+.
Indications
Not normally used as diuretics but
of value in the treatment of
glaucoma.
Side Effects
Loss of carbonate can result in
metabolic acidosis.
Other
Frusemide
Class
Loop diuretic – powerful diuretic
MOA
Act on thick ascending segment of
the L of H. Inhibit the Na+, K+,
2Cl- cotransporter in the luminal
membrane. This dilutes the
medullary interstitium and reduces
the concentrating power in the
collecting duct. ↑ delivery of Na to
distal tubule activates Na/K
exchanger. Gives ↑ urine, ↑
excretion of Na, K, Cl, Ca, Mg
Indications
Acute pulmonary oedema, oedema
due to heart failure, liver disease,
renal disease, hypercalcaemia,
hyperkalaemia, Acute renal failure
Side
Effects
Metabolic acidosis, hypokalaemia,
loss of Ca, Mg, hypovolaemia,
hypotension, nausea, deafness,
allergies.
Other
Bendrofluazide
Class
Thiazide
MOA
Inhibition of Na and Cl
reabsorption in the early distal
tubule. ↑ solute ↓ reabsorption of
water, ↑ volume, Na, K, Cl, and
Mg. Reduced loss of Ca. Also
vasodilation and ↓ insulin
production due to opening of K
channels.
Indications
Congestive Heart failure,
hypertension, Idiopathic
hypercalcaemia, nephrogenic
diabetes insipidus
Side Effects
Hypokalaemia, alkalosis,
hypperglycaemia, uric acid
retention (gout). Allergies,
hyponatraemia.
Other
Spironalactone
Class
Aldosterone antagonists,
potassium sparing diuretic.
MOA
This is a competitive antagonist at
aldosterone receptors, ↓ Na
reabsorption, and ↓ potassium and
proton secretion. Mild diuresis,
excretion of 2-3% of Na.
Indications
Heart failure and resistant cases of
hypertension
Side Effects
Hyperkalaemia due to sodium
retention, and steroid like effects
like gynaecomastia, menstrual
disorders, and testicular atrophy.
Other
Amiloride
Class
Potassium sparing diuretic,
Sodium Channel Blocker, distal
tubule
MOA
These block sodium reabsorption
by the principal cells, thus
reducing the potential difference
across the cell, and ↓ potassium
secretion
Indications
With K losing diuretics to prevent
K loss. Primary and secondary
hyperkalaemia.
Side Effects
Better tolerated than
spironalactone. Hyperkalaemia,
hyponatraemia, GI disturbances.
Other
Anti-Emetics
Promethazine
(Remember
Promet-h-azine)
Class
Anti-emetic (phenothiazine
derivative) H1>M>D2
MOA
Acts as a competitive antagonist at
histaminergic (H1), cholinergic
(M), and dopaminergic receptors.
(Mostly H1). It acts centrally
(Labyrinth, NTS, vomiting centre)
to block activation of the vomiting
centre.
Indications
Motion sickness (prophylaxis),
labyrinth disorders (ie Meniere’s
disease), morning sickness, pre
and post operatively. Sedative and
anti muscarinic actions are also
useful.
Side Effects
Dizziness, fatigue, Tinnitus,
sedation, Excitation in excess,
convulsions, Antimuscarinic side
effects.
Other
Metoclopramide
(Remember
metoclopromi-d-e)
Class
Anti-emetic. Receptor antagonist.
D2>>H1>>M
MOA
Acts on D2 receptors, especially
centrally at the central trigger
Zone. Acts in the GI tract ↑ in SM
motility, ↑ in Gastric emptying.
Indications
Nausea and vomiting associated
with uraemia, radiation sickness,
GI disorders, Cancer
chemotherapy like cisplatin.
Side Effects
Drowsiness, dizziness, anxiety,
extrapyramidal reactions, no antipsychotic reactions unlike other D
antagonists.
Other
Competes with other drugs.
Adsorption and effectiveness of
digoxin is ↓. Accelerate GI may
cause nutrient deficiency.
Hyoscine
(Scopolamine)
Class
Muscarinic Receptor Antagonist,
antiemetic
MOA
Binds to receptor making it
inaccessible for ACh to activate
receptor. Emetic actions in vest.
Nuclei, NTS, vomiting centre, to
block VC’s activation.
Indications
Used to prevent bronchial
secretions and salivations.protect
heart from arrhythmias,
particularly those caused by
neuromuscular blockers.
Prevention of motion sickness,
parkinson’s disease.
Side Effects
Dry mouth and skin, raised body
temperature, dilatation of pupil,
relaxation of ciliary msucle (no
accomodation) urinary retention,
irritability and hyperactivity.
Drowsiness, slow gut movement.
Other
Different tissues have different
levels of responsiveness. Salivary,
sweat, bronchial>parietal cells
production of gastric acid.
Ondansetron
(Remember
ondan-s-etron)
Class
Anti emetic, 5HT3 (Serotonin)
receptor antagonist.
MOA
Blocks 5HT3 receptors in visceral
afferents and central trigger zone
Indications
Anti emetic in chemotherapy
induced vomiting, especially
cisplatin. Radiotherapy induced
sickness, PO nausea and vomiting.
Side Effects
Headache, sensation of flushing
and warmth, increased large bowel
transit time (constipation) due to
5HT3 receptor block.
Other
Drugs used for Gastric
& Duodenal Ulcers
Antimicrobials
Metronidazole
Class
Antiprotozoal and antibacterial
against anaerobic bacteria.
Antibiotic to eliminate
helicobacter pylori – bactericidal.
MOA
Metabolised to an intermediate
that inhibits bacterial DNA
synthesis and degrades existing
DNA. Selective because
intermediate form is not produced
in mammalian cells.
Indications
Helicobacter pylori eradication in
peptic ulcer sufferers.
Side Effects
Mild headache and GI disturbance.
ADRs with alcohol
Other
Not to pregnant women
Amoxycillin
Class
Broad spectrum Penicillin
antibiotic.
MOA
Inihibit bacterial wall synthesis.
They bind to penicillin binding
proteins. This results in inhibition
of peptide crosslinking within the
cell wall, and indirect activation of
autolytic enzymes, resultant lysis.
Indications
Broad spectrum so loads of
applications. Used in eradication
of helicobacter pylori in peptic
ulceration.
Side Effects
Specific and safe but possible
hypersensitivity reactions inc.
rashes and anaphylaxis. Diarrhoea
common, neurotoxicity at ↑ CSF
levels.
Other
Not for known hypersensitivity
sufferers. Resistance can be due to
microbial production of a βlactamase enzyme which breaks
the β-lactam ring of penicillins.
Clarithromycin
Class
Macrolide.
Bactericidal/bacteriostatic.
MOA
They bind to the bacterial
ribosome, preventing the
translocation movement of the
ribosome along mRNA. Inhibits
translocation of bacterial tRNA.
Indications
Good against gram +ve bacteria
and spirochaetes. Haemophilus
influenzae, mycobacterium avium
cellulare, and helicobacter pylori.
Side Effects
GI disturbance
Other
Resistance due to alteration of
binding site of ribosome.
Inhibitors of Gastric Acid
Secretion
Omeprazole
Class
Proton pump inhibitor in Peptic
ulceration.
MOA
Prodrug converted in acidic pH to
sulphonamide, which binds
covalently to the suphydryl groups
on H+/K+ATPase responsible for
gastric acid secretion.
Inihibit acid secretion by >90%.
Is a weak base so attracted to
acidic areas like cannaliculi of
parietal cells. Prevents widespread
actions.
Indications
Peptic ulceration, reflux
oesophagitis, H2 receptor
antagonist resistant patients.
Side Effects
GI upset, nausea, headaches.
Potential gastric atrophy
Other
Cimetidine
ranitidine
Class
H2 receptor antagonists.
MOA
Block actions of histamine on
parietal cells
Indications
First line treatment of GORD and
peptic ulcer disease.
Side Effects
Dizziness, fatigue, gynaecomastia,
and rash
Other
Less effective than PPIs at healing
ulcers (60% ↓ in acid secretion).
Inhibits p450 enzymes, so not to
be administered with warfarin,
phenytoin, and theophylline.
Cytoprotective Drugs
Sucralfate
Class
Polymer containing aluminium
hydroxide and sucrose octasulphate. Cytoprotective drugs.
MOA
It acquires a strong negaitve
charge in acidic environment.
Binds to +ve proteins forming a
protective gel over the ulcer, not
allowing peptins or acids to
damage. ↑ mucus, PGs and HCO3, ↓ helicobacter pylori.
Indications
Peptic ulcer.
Side Effects
Can cause constipation and may ↓
absorption of many other drugs (ie
antibiotics) through stomach wall.
Other
Bizmuth chelate
Class
Polymer structure as with
sucralfate
MOA
Forms protective gel over ulcer
Indications
Peptic ulcer disease
Side Effects
Constipation, ↓ absorption of other
drugs through wall.
Other
Misoprostol
Class
PGE1 analogue
MOA
Mimics actions of PGE1 which
stimulates mucus secretions in the
gastroduadenal lining.
Indications
Peptic ulcer disease
Side Effects
Diarrhoea, uterine contractions, ab
cramps.
Other
May be co prescribed with
NSAIDs to counteract their anti
PG effect chronically and prevent
peptic ulcers.
Drugs for
Inflammatory Bowel
Disease
Glucocorticoids
Hydrocortisone
Class
Natural glucocorticoid with some
mineralocorticoid actions.
MOA
Move into cells where they
activate glucocorticoid receptors.
These receptors are translocated to
the DNA where they cause
transcription of corticosteriod
responsive genes. These have
diverse effects on target tissues.
See prednisolone. Can also turn
off genes (reduced antigen
presentation, reduced production
of adhesion molecules, COX, NO,
cytokines such as IL-1 and TNFα)
Indications
IBD (crohn’s, Ulcerative colitis),
Anti-inflammatory,
immunosuppression
Side Effects
Cushing like appearance. See
separate slide. Adrenal
suppression and atrophy.
Other
Withdraw slowly to avoid adrenal
insufficiency crisis. Normal
markers of infection suppressed so
must be aware.
prednisolone
Class
Synthetic glucocorticoid. Antiinflammatory,
immunosuppressant.
MOA
These induce lipocortin which
inhibits the conversion of
membrane phosphilipid to
arachidonic acid by phospholipase
A2. Leukotrienes and prostanoids
are therefore not produced,
suppressing inflammation and
chemotaxis of immune agents.
Indications
Side Effects
Other
IBD (crohn’s, UC)
As for hydrocortisone.
Budesonide
Class
Synthetic glucocorticoid. Antiinflammatory,
immunosuppressant.
MOA
Budesonide in comparison with
prednisolone has been
associated with fewer bone
density losses and unlike other
corticosteroids has little
influence on the hypothalamicpituitary-adrenal axis which
also limit the need of tapering
before discontinuation. Overall,
it has a lower incidence of
systemic manifestations than
similar medications.
Indications
Side
Effects
Other
IBD (crohn’s, UC)
As for hydrocortisone.
Aminosalicylates
Sulfasalazine
Class
Aminosalicylate
MOA
Broken down in the gut to 5-ASA.
These scavenge free radicals.
Fewer anti-inflammatory actions
and no immunosuppressive ones.
AI actions are ↓ inflammatory
cytokine production, ↓ PG and LT,
↓ leukocyte infiltration. Activated
by gut flora from moiety.
Indications
Maintain remission and prevent
relapse of inflammatory bowel
conditions
Side Effects
Sulfaphrindine (non active part of
sulfasalazine) reaponsible for
Nausea, vomiting, headache and
rashes., hypospermia, anorexia
Other
Not to people with renal
impairment, or salicylate
intolerance
Mesalazine
Class
Aminosalicylate (5-ASA)
MOA
Same as sulfasalazine, but without
nasty side effects.
Indications
Inflammatory bowel syndrome.
Side Effects
Few, no sulfapyridine to worry
about.
Other
Immunosupressants
Azothioprine
Class
Immunosuppressive
MOA
Activated by gut flora to 6
metcaptopurine, a purine analogue,
interferes with DNA synthesis.
Inihibits cell replication, cell and
antibody mediated immune
reponses, lymphocyte proliferation,
mononuclear cell infiltration,
synthesis of antibodies.
Indications
Inflammatory bowel syndrome.
Used to maintain remission in CD
Side
Effects
Other
More effective than other
immunosuppressives so can get
away with fewer GCs. Not good in
gout treatment because it is
metabolised by Xanthine Oxidase
(target of gout treatment).
Anti-TNFα
Imfliximab
Class
MOA
Indications
Side Effects
Other
Crohn’s is a type 1 autoimmune
response. TNF-α plays an
important role in pathogenesis.
Anti reduces activation of antiTNFα receptors in the gut.
Promotes apoptosis of activated Tcells.
Inflammatory bowel disease and
other Th1 mediated AI diseases
↑ incidence of extra pulmonary
TB. Worsening of heart failure,
can be immunogenic, specialist
use.
1 IV every 8 weeks
Drugs used in
Respiratory Disease
Salbutamol
Class
Β2 selective Adrenoceptor Agonist
MOA
Stimulates B2 receptors in the SM
of the lungs and bronchi, inhibits
the release of bronchoconstrictor
substances from mast cells.
Relative resistance to MAO and
COMT
Indications
Ventolin (asthma inhaler), uterine
relaxation (if premature labour)
Side Effects
Arrhythmias, tachycardia,
vasodilation
Other
Given by aerosol so limited
systemic effects.
salmeterol
Class
MOA
β-2 receptor agonist
Stmiulation of β2 receptors in the
airway SM leads to rise in
intracellular cAMP levels and SM
relaxation. Also prevent mast cell
activation. This has potent β2
effects but limited β1 actions, so
fewer cardiac side effects.
Indications
Alone to treat mild asthma and
bronchospasm, but more often
with corticosteroids
Side Effects
Fine tremor, tachycardia and
hypokalaemia after high doses.
Other
Not in hyperthyroidism, CVD,
arrhythmias.
aminophylline
Class
Phosphodiesterase inhibitor
MOA
Acts by raising the cAMP levels
(which relaxes SM), by inhibiting
phosphodiesterase, the enzyme
responsible for converting cAMP
to AMP. Aminophylline is the IV
xanthine used in severe asthma
attacks.
Indications
Status asthmaticus
Side Effects
Nausea, vomiting, tremor,
insomnia, and tachycardia.
Other
Not often used because PDE exists
everywhere in the body, cAMP is
very common. Not for use in
CVD, hypertension, hepatic
impairment, have many drug
interactions.
Ipratropium
Bromide
Class
Muscarinic Receptor Antagonist,
parasympatholytic
MOA
Inhaled, blocks action of
acetylcholine.
Indications
Used in bronchodilation. For
asthma and obstructive airways
disease.
Side Effects
Systemic effects of blocking
muscarinic cholinoceptors.
Other
Drugs of Abuse
Opiates
Morphine
Class
Strong opioid analgesic
MOA
Acts on opiate receptors. These
exist in the dorsal horn relay
neurones, descending inhibitory
NA fibres from the brainstem, and
descending seratonergic fibres
from the brainstem, all of which
block sensory information from
travelling in the dorsal column,
leading to analgesia.
Indications
Drug of choice for severe pain in
terminal care.
Side Effects
Drowsiness and sedation – initial
excitement followed by sedation
and coma (in OD). ↓ in sensitivity
of resp centre to CO2 leading to
shallow and slow respiration,
tolerance and dependence,
suppression of cough (antitussive),
vomiting due to CTZ stimulation,
pupillary constriction due to
stimulation of parasympathetic 3rd
CN nucleus, hypotension and ↓
CO, due to reduced hypothalamic
sympathetic outflow.
Bronchospasm, flushing and
arteriolar dilation due to histamine
release.
Heroin
(dimorphine)
Class
Opioid drug of abuse, sometimes
analgesic
MOA
Acts on opioid receptors. Twice
as potent as morphine owing to its
greater penetration of the BBB,
metabolised to morphine in the
body.
Indications
Severe pain, post operative, MI
and acute pulmonary oedema. Not
used as much as morphine due to
added euphoria and dependence.
Side Effects
Causes less nausea and
hypotension than morphine, but
more euphoria.
Other
codeine
Class
Weak opioid analgesic
MOA
Acts on opioid receptors. Only
1/12 analgesic potency of
morphine.
Indications
Mild to moderate pain, Antitussive and anti diarrhoeal effects
(taking advantage of side effects).
Side Effects
Nausea and constipation
Other
methadone
Class
Long acting opioid analgesic.
MOA
Acts on opioid receptors.
Withdrawl symptoms are more
prolonged but less intense than
withdrawl from heroin.
Indications
Weaning opioid addicts from their
addiction
Side Effects
As opioid general ADRs, but not
too marked.
Other
Opiate Receptor Antagonists
Naloxone
Class
Opiate receptor antagonist
MOA
Acts as a competitive inhibitor at
opiate receptors.
Indications
Used in heroin or other opioid
overdose IV, along with
respiratory support.
Side Effects
Other
Reuptake Inhibitors
Cocaine
Class
Sympathetic enhancer
MOA
Strongly inhibits the reuptake of
catecholamines at NAergic
neurons and thus strongly
enhances sympathetic activity.
Indications
Abuse. Occaisionally used as a
topical anaesthetic by ear, nose
and throat specialists.
Side Effects
Toxic psychosis, cardiac
arrhythmias, hypertension, and
stroke. Psychological dependence,
but no real physical dependence.
Chronically produces paranoid
psychosis, vasoconstriction, tissue
anoxia at sites of injection,
damage to fetal brain. Withdrawl
causes a ↓ in motor performance,
restorable on provision of the
drug.
MethyleneDio
xyMethAmpet
amine
(ecstasy)
Class
Serotonin (5-hydroxytryptamine)
reuptake inhibitor
MOA
Release of monoamines, inhibition
of monoamine uptake. Especially
acts on serotonergic neurons,
potentiating 5-HT.
Indications
Drug of abuse
Side Effects
Stimulant and hallucinogenic
properties, euphoria, arousal, and
perceptual disturbances are
common. Feelings of euphoric
empathy so that social barriers are
reduced. Withdrawl like
amphetamines. Toxicity results in
hyperthermia, exhaustion,
dehydration. Seratonergic
neurodegeneration chronically.
Alcohol
Ethanol
Class
Alcohol
MOA
Acts as a volatile anaesthetic agent
producing general CNS
depression. Cellular mechanisms
involve inhibiting calcium entry,
and so reducing NT release, as
well as potentiation of GABA
transmission.
Indications
Antidote to methanol poisoning.
Side Effects
Physical and psychological
dependence occur. Withdrawl
hangover. Late stage involves
delirium, tremor, hallucinations,
and confusion. Acute toxicity
causes ataxia, nystagmus, coma,
resp. depression, and death.
Chronically causes
neurodegeneration (worsened by
vit deficiency), dementia, liver
damage, pancreatitis, and
accompanying depression. ↓
vasopressin secretion causing
diuresis and delayed parturition at
term due to inhibitory effects at
the hypothalamus. Action at ant.
Pit. Causes ACTH production
leading to adrenal steroid
production. This leads to
feminisation in males. Helped by
enhanced testosterone inactivation
in the liver.
Ethanol Aversion Therapy
Disulfiram
Class
MOA
Inhibits action of Acetaldehyde
dehydrogenase and so inhibits
conversion of Acetaldehyde to
Acetic acid
Indications
Ethanol aversion therapy
Wanted
Side Effects
flushing of the skin, accelerated
heart rate, shortness of breath,
nausea, vomiting, throbbing
headache, visual disturbance,
mental confusion, postural fainting
and circulatory collapse
Other
Antimicrobial Drugs
Drugs which interfere with the
synthesis / action of Folate
Sulfamethoxazole
Class
Sulfonamide – anti folate
MOA
Folate necessary to make DNA.
Man has uptake processes, bacteria
have to produce theirs, and need paminobenzoic acid. Sulfonamide
is an analogue of this, meaning it
isn’t produced, so bacteria can’t
replicate. Bacterostatic, then host
system can erradicate infection.
Indications
Not used much except in cotrimoxazole.
Side Effects
Nausea &vomiting, headache,
mental depression. Potential
severe: hepatitis, hypersensitivity,
bone marrow suppression.
Other
Widespread resistance to these
drugs.
Trimethoprim
Class
Folate antagonist.
MOA
Inhibits Dihydrofolate reductase,
an enzyme which is more sensitive
in bacteria to interference. DNA is
stopped from replicating.
Indications
Urinary and respiratory tract
infections.
Side Effects
Nausea & vomiting, skin rashes,
hypersensitivity
Other
Co-trimoxazole
Class
Folate buggerer – sequential
blockade. (actually trimethoprim
and sulfamethoxazole)
MOA
Trimethoprim blocks
dihydrofolate reductase in bacteria,
blocking cell replication.
Sulfamethoxazole affects folate
synthesis (earlier in same
pathway). They potentiate one
another, meaning that1/10th the
dose is needed.
Indications
Infections with pneumocystis
carinii, which causes pneumonia in
AIDS patients. Used in high
doses.
Side Effects
Combination of effects from
trimethoprim and
sulfamethoxazole.
Other
Drugs which interfere with the
synthesis of Peptidoglycan
Penicillins
Class
β-lactam antibiotics. Cell wall
targetting
MOA
Has a thiazolidine ring linked to a
β-lactam ring. Prevents
transpeptidisation. Antibiotic
bonds to normal peptidoglycan
which then can’t join with others
to form a lattice. Bacterium open
to osmotic pressures so lyses.
Indications
Do not cross BBB.
Side Effects
Hypersensitivity (antigenic), skin
rashes and fever but can be
anaphylactic shock. Can also
interfere with gut flora causing GI
disturbance.
Other
Amidaze and β-lactamases can
destroy the anti-biotic, normal
defence mechanism. Using a βlactamase inhibitor (clavulanic
acid) normally gets round this
problem. Other resistance stems
from impermeability of the outer
membrane, and modified penicillin
binding sites.
cefotaxime
Class
Cephalosporin. Peptidoglycan
targetting.
MOA
Like penicillins targets the
peptidoglycan synthesis. Can
combine two or more
synergistically which target
different binding sites to ↑
efficiency.
Indications
Meningitis due to G-ve intestinal
bacteria
Side Effects
Hypersensitivity as seen in
penicillins. Nephrotoxicity,
alcohol intolerance, diarrhoea.
Other
Nearly all gram –ve bacteria
possess β-lactamase, very effective
against cephalosporins.
Drugs which affect Bacterial
Protein Synthesis
tetracyclin
Class
Broad spectrum antibiotics
MOA
Inhibit bacterial protein synthesis.
Actively transported into bacteria
where they interfere with protein
synthesis. Competes with tRNA
for the binding site, doesn’t kill,
just stops growth.
Indications
Side Effects
Form an insoluble complex with
metal ions, so work best without
food. GI disturbances common,
because chelate calcium can stain
teeth and lead to bone deformities.
Some (doxycycline) produce
sensitivity to sunlight.
Other
Resistance based around
tetracyclines being transported out
of the cell, but also on alterations
of the target, the bacterial
ribosome.
chloramphenicol
Class
Broad spectrum ribosome binding.
MOA
Inhibits protein synthesis by
reversibly binding to the 50S
subunit of the ribosome and
inhibiting transpeptidation
(formation of peptide bonds).
Both bactericidal and
bacteriostatic
Indications
Broad spectrum. V. toxix so
reserved for life threatening
infections such as typhoid fever
and meningitis.
Side Effects
Depression of the bone marrow
leading to pancytopenia. Not in
babies because inadequate
excretion can result in grey baby
syndrome (40% mortality).
Other
Not to pregnant women or
neonates. Resistance due to
choloramphenicol acetyltransferase, plasmid mediated so
resistance easily transferred
gentamicin
Class
Aminoglycosides
MOA
Inhibit bacterial protein synthesis
by binding to the 30S subunit of
the ribosome, causing an alteration
in codon:anticodon recognition.
mRNA is read wrong, so faulty
proteins produced. Transported in
by O2 dependent active transport
which chloramphenicol can block.
Indications
Streptococcus lysteria or
pseudomonas. Mostly gram-ve,
some +ve. Polar so not absorbed –
IV or IM. Not cross BBB.
[Tissue] can become toxic.
Side Effects
Other
Ototoxicity – destruction of cells
in the vestibular and cochlear
regions. Damage to kidney
tubules (so can’t be excreted –
viscious circle)
Not good anaerobically. Enhanced
by cell wall disrupting agents.
Resistance due to conformational
binding changes, failure of
penetration, or inactivation by
microbial enzymes.
Anti-Mycobacterial Agents
isoniazid
Class
Antimycobacterial agent.
MOA
Passes freely into mammalian cells
and inhibits synthesis of mycolic
acids, important constituents of the
cell wall peculiar to mycobacteria.
Indications
Mycobacterium (leprosy and
tuberculosis). After phagocytosis,
both can survive inside the
macrophage.
Side Effects
Rare skin eruptions, fever, GI
disturbances.
Other
rifampicin
Class
Antimycobacterial agent
MOA
Binds to and inhibits DNAdependent RNA polymerase in
prokaryotic but not eukaryotic
cells. One of best anti-tuberculosis
agents known. Active against
most gram +ve and some gram-ve.
Indications
Antimycobacterium, mostly
tuberculosis.
Side Effects
Rare side effects including skin
eruptions, fever and GI
disturbances.
Other
pyrazinamide
Class
Anti-mycobacterial. Related to
nicotinamide
MOA
Inactive at neutral pH but active in
acidic pH. Effective once agent
has been phagocytosed, as acidic
in phagolysosomes. Involves
metabolism of drug inside
bacterium to produce a toxic
product, pyrazinoic acid.
Indications
Anti-mycobacterial (tuberculosis,
leprosy
Side Effects
Hepatotoxicity, and raised plasma
urate levels can lead to arthralgia
and gout.
Other
Resistance can be rapid.
Antifungal Agents
nystatin
Class
Polyene macrolide
MOA
Acts by forming a transmembrane
ion channel in fungal cells,
affecting permeability and
transport functions. Not absorbed
so used in GI tract or on skin.
Affects fungi and some protozoa,
mild mammalian effects, not at all
to bacteria. Selective due to
ergosterol rather than cholesterol
in mammal membranes.
Indications
skin or GI infections.
Side Effects
Rare. Some GI disturbance in
high dose, v. rare rash.
Other
miconazole
Class
Broad spectrum anti mycotic of
the azole group.
MOA
Azoles block the synthesis of
ergosterol by interating with the
enzyme needed to convert
lanosterol to ergosterol. This
alters the fluidity of the membrane
which interferes with action of
membrane associated enzymes.
Also prevents the transformation
of yeast cells into hyphae, the
invasive and pathogenic form of
the parasite.
Indications
Orally for GI, IV for systemic
fungal infections
Side Effects
Rare, some GI disturbance, also
pruritus, blood dyscrasias.
Other
Anti-Viral Agents
acyclovir
Class
Nucleic acid synthesis inhibitor.
A guanosine derivative.
MOA
Acyclovir is converted to the
monophosphate form by
thymidine kinase – the virus’s own
kinase is more effective at
converting it than the host cell’s
own kinase, and then converted to
the active triphosphate. Therefore
it is only activated in infected
cells. It is used as a guanine
substitute, which prevents DNA
synthesis.
Indications
Herpes simplex virus
Side Effects
Minimal. Local inflammation
around injection site if extravasion
occurs (alkaline solution so
irritant). Renal dysfunction
reported. Nausea and headache.
Other
Resistance due to changes in viral
genes coding for thymidine kinase
or DNA polymerase, and acyclovir
resistant form have caused
pneumonia and encephalitis in
immunocompromised patients.
Zidovudine
(AZT)
Class
Analogue of thymidine, reverse
transcriptase inhibitor.
MOA
Active inhibitor of reverse
transcriptase. Phosphorylated to the
triphosphate form, where it competes
with cellular triphosphates, essential
for formation of proviral DNA by viral
reverse transcriptase (viral RNA
dependent DNA polymerase). It is
incorporated into the growing DNA
strand which results in chain
termination.
Indications
In retroviruses such as HIV virus.
Reduces risk of transmission from
mothers, reduces chance of
opportunistic infection, HIV associated
dementia etc.
Side Effects
Anaemia and neutropenia,
abnormalities of liver function and
myopathy, GI disturbances, confusion,
anxiety, depression, rash.
Other
Mammal α-DNA polymerase is
resistant but mitochondrial γ-DNA
polymerase is susceptible. Resistance
is due to changing a.a. in the viral
reverse transcriptase, so it is a
constantly moving target.. Also ↓
phosphoylation of zidovudine to its
active form, ↑ in viral load, and
increased virulence of the pathogen.
Anxiolytics
Diazepam
Class
Benzodiazepine (long acting,
32hrs)
MOA
Benzodiazepines potentiate the
action of GABA by binding to a
site on GABAA receptors,
increasing their affinity for
GABA. This results in an
increased opening fluctuations of
these ligand gated Cl- channels,
thus increasing the inhibitory
effects on postsynaptic firing.
Indications
Short term relief of severe anxiety
and severe insomnia, preoperative
sedation, status epilepticus, and
acute alcohol withdrawl.
Side Effects
Drowsiness, ataxia, reduced
psychomotor performance,
dependence after 4-6 weeks. If
taken in combination with alcohol,
fatal respiratory depression can
result. OD treated with flumazenil
Other
Not be given to people with
bronchopulmonary disease, and
have combination effects with
other depressants such as alcohol,
barbiturates, and antihistamines.
oxazepam
Class
Benzodiazepine (short acting,
8hrs)
MOA
Acts to potentiate effects of
GABA, by binding to GABAA
receptors and increasing their
affinity for GABA, therefore
increasing the frequency with
which Cl- is allowed into the cell
and ↑ the inhibitory effect on the
postsynaptic cell.
Indications
Short term relief of severe anxiety
and insomnia, preop sedation,
statuss epilepticus, and acute
alcohol withdrawl.
Side Effects
Other
Drowsiness, ataxia, and ↓
psychomotor performance are
seen. Dependence develops after
4-6 weeks, fatal respiratory
depression if taken in combination
with alcohol (or other CNS
depressants)
Buspirone
Class
Anxiolytic, Azapirones, act on 5HT (serotonergic) receptors
MOA
In the raphe nucleus, dendrites of
the serotonergic neurones have
autoreceptors (5-HT1A)which ↓ the
firing of 5-HT neurons.
Azapirones act as partial agonists
at these receptors.
Indications
Short term relief of general anxiety
disorder.
Side Effects
Nervousness, dizziness, headache
and light headedness. Does not
cause sedation or cognitive
impairment, doesn’t potentiate
alcohol, and only has a minimal
risk of dependence.
Other
Not in epileptics. Effects evolve
over 1-3 weeks.
Sedatives / Hypnotics
Temazepam
Class
Short lasting benzodiazepine
MOA
Potentiates the effects of GABA
by binding to a site on GABAA
receptors, ↑ their affinity for
GABA, ↑ amount of Cl- entering
the cell and so inhibiting the firing
of the neurone.
Indications
Given in short term relief of severe
anxiety and insomnia, preop
sedation, status epilepticus, and
acute alcohol withdrawl.
Side Effects
Other
Drowsiness, ataxia, and ↓
psychomotor performance are
seen. Dependence develops after
4-6 weeks, fatal respiratory
depression if taken in combination
with alcohol (or other CNS
depressants)
amobarbital
Class
barbiturates
MOA
These prolong the time Clchannels are opened at GABA
receptors whereas benzodiazepines
↑ the firing frequency.
Indications
Sedation, reduction of anxiety.
Not used now
Side Effects
More depressant than
benzodiazepines as they ↑ Clconductance directly, decreasing
the neurones sensitivity to
excitatory transmitters.
Other
Chloral hydrate
Class
Hypnotic
MOA
Chloral hydrate is metabolised to
trichloroethanol, which I an
effective hypnotic. Cheap but no
advantage over newer
benzodiazepines.
Indications
Previously popular hypnotic for
children, but worse than
benzodiazepines and children
shoudn’t be sedated anyway.
Side Effects
Gastric irritation
Other
Anticonvulsants
Phenytoin
Class
MOA
Sodium channel inhibitors, anti
epileptic / arrhythmic.
Bind preferentially to the closed Na+
channels, preventing them from
opening, and so preventing
depolarisation. In a seizure, the number
of channels susceptible to blockade is
higher, meaning that normal
transmission is relatively unaffected.
Indications
Seizures, except absence seizures
Side Effects
Dosage effects: Affect
cerebellovestibular system, leading to
ataxia, blurred vision, and hyperactivity.
Acute toxicity leads to sedation and
confusion.
Non dosage effects: collagen effects
such as gum hypertrophy, coarsening of
facial features, allergic reactions (rash,
hepatitis, lymphadenopathy),
haematological effects (megaloblastic
anaemia), hirsutism, teratogenic effects
(congenital malformations)
Other
This drug is liver saturable – will build
up in system until effects become
marked suddenly, like beer.
Fosphenytoin is a water soluble prodrug.
Carbamazepine
Class
Na+ channel blockers
MOA
Inhibits fast Na+ channels involved
in neuronal excitation. Prevents
excessive depolarisation
Indications
Seizure suppression
Side Effects
Limited to NS – ataxia,
nystagmus, dysarthia, vertigo, and
sedation.
Other
Sodium
valproate
Class
anticonvulsant
MOA
Like phenytoin causes use
dependent block of voltage gated
Na+ channels. Also Inhibit
GABA metabolism by GABA
transaminase
Indications
All forms of epilepsy
Side Effects
GI upset, liver failure.
Other
Hepatic toxicity exacerbated when
used with other anti-convulsants.
First line for many types of seizure
syndromes.
vigbatrin
Class
Anti convulsant
MOA
Inhibit GABA metabolism by
irreversible inhibition of GABA
transaminase.
Indications
Tough epilepsy
Side Effects
Drowsiness, dizziness, depression,
and visual hallucinations
Other
Side effect of hallucinations, so
not in people with history of
psychosis. New drug used in
conjunction with other therapies.
Lamotrigine
Class
Anti epileptic
MOA
Acts by effect on sodium channels,
and inhibiting release of excitatory
amino acids.
Indications
Monotherapy and treatment of
partial and generalised tonic clonic
seizures. Neuralgic pain (nerve
root pain) (by stabilising neurones
involved, limiting activation)
Side Effects
Rashes, fever, malaise,
drowsiness, hepatic dysfunction
Other
Not in hepatic impairment
Anaesthetics
Local Anaesthetics
Cocaine
(Ester)
Class
Local anaesthetic
MOA
Blocks Na+ channels. Also
prevents the uptake of NA at the
synapse.
Indications
Ear, nose and throat surgeons
Side Effects
Does not cause CNS depression
like the other local anaesthetics
because it causes euphoria through
long lasting chatecolamine action.
Other
Procaine
Class
Local anaestheic.
MOA
Basically a synthetic derivative of
cocaine. Causes sodium channel
block
Indications
Seldom used because of its CNS
side effects
Side Effects
Causes CNS depression the worst
out of all the local anaesthetics.
Resp depression, myocardial
depression and vasodilation, visual
disturbances and twitching.
Other
Lidocaine
(lignocaine)
Class
Local anaesthetic
Amide
MOA
Indications
Widely used in all applications,
EMLA
Side Effects
Caused by leaking into the
circultion. Restlessness, tremor,
confusion, agitation, CNS
depression.
Other
Bupivicaine
Class
Local anaesthetic
MOA
Slow onset, long lasting local
anaesthetic, with moderate tissue
penetration.
Indications
Epidural and spinal anaesthesia
Side Effects
Systemic problems as with the
others.
Other
General Anaesthetics
Nitrous Oxide
Class
Inhalational GA
MOA
Blockade of NMDA type
Glutamate receptors
Indications
Rapid control of depth of
anaesthesia
Side Effects
Other
Halothane
& Enflurane
Class
Inhalational GA
MOA
Potentiate GABAa receptor (and
Glycine receptors in the spinal
cord to educe reflexes), inhibition
of nicotinic Ach receptors &
facilitate TREK (backround leak
of Potassium due to channel
opening leading to reduced
neuronal activity)
Indications
Side Effects
Other
Propofol &
Etomidate
Class
IV GA
MOA
Potetiates the action of GABAa
receptors, most effective when Beta
subunits of the GABAa receptor
complex predominate, anaesthesia
from depression of Thalamocortical
neurones and influence on the
reticular activating system, amnesia
from depression of the synaptic
transmission at the Hippocampus
and Amygdala
Indications
Side Effects
Other
Usual GA
Cocktails
• Loss of Consciousness (Induction by IV
GA – Propofol)
• Supression of Reflexes (Maintainance
with Enflurane)
• Analgesia (Fentanyl)
• Muscle Relaxation (Suxamethonium)
• Amnesia (Midazolam – BDZ)
Anti-Parkinsonian Drugs
L-dopa
Class
Exogenous precursor to
Dopamine
MOA
Allows the remaining (30% or
lower) DA-ergic neurones to
function by having more of a
reservoir of DA to use
Indications
Treats rigidity & tremor
Start with low dose of the drug
and increase dose until
maximum benefit without side
effects
Effectiveness of L-DOPA
declines with time!
Side
Effects
Acute (N&V, Hypotension and a
Schizophrenic like syndrome)
Other
To prevent N&V formulations of
L-DOPA have been created with
a peripheral DOPA
decarboxylase inhibitor
Sinamet (+ Carbidopa)
Madopar (+Benserazide)
Chronic (Dyskinesias and
On/Off fluctuations)
bromocriptine
Class
DA2 receptor agonist.
MOA
Simple Agonist, no need of
functioning DA-ergic neurones as
in L-DOPA therapy
Indications
Acromegaly,, Benign breast
tumour relief, Acromegaly,
Parkinson’s, prolactinoma
Side Effects
Nausea, vomiting, ab cramps,
psychomotor excitation,
dyskinesias, postural hypotension,
vasospasm in fingers and toes
Other
Caution in Raynauds disease
where vasospasm in fingers and
toes happens already.
Deprenyl
(Selegiline)
Class
Selective for MAO-B,
predominates in dopaminergic
areas of CNS. Actions are without
peripheral side effects of noneselective MAO-I’s
MOA
Increases available DA
Indications
Can be given alone in the early
stages of the disease.
Or in combination with L-DOPA,
reduce the dose of L-DOPA by 3050%
Side Effects
Side effects are rare - hypotension,
nausea/vomiting, confusion and
agitation.
Other
Entacapone
Class
Peripheral and CNS COMT
inhibitor
MOA
CNS - Prevents breakdown of
dopamine in the brain
Peripheral - COMT in the
periphery converts L-DOPA to
3-0-methyl-DOPA (3-0MD). 3OMD and L-DOPA compete
for same transport system into
the brain. COMT inhibitors
stop 3-OMD formation thus
increasing the bioavailability of
L-DOPA, Thus more L-DOPA
converted to dopamine in the
CNS. Reduce L-DOPA dosage!
Indications
Side
Effects
Other
Neuroleptic Drugs
chlorpromazine
Class
Typical antipsychotic
MOA
CNS Antagonist against D2, Ach
and H
Indications
Acute and Chronic Psychoses,
Schizophrenia and the manic phase
in Bipolar disorder
Side Effects
Less incidence of extra pyramidal
disorders in contrast to the more
potent neuroleptics (Haloperidol)
most SE from the drugs Anti Ach
activity (sedation, dry mouth,
constipation, urinary retention)
Other
haloperidol
Class
Typical antipsychotic
MOA
CNS Strong Antagonist against
D2 (and to a lesser extent Ach
& H)
Indications
Schizophrenia
Side
Effects
Extrapyramidal symptoms like
acute dyskinesias (Too much
Ach), Tardive Dyskinesia
(Upregulation of DA receptors),
Parkinsonian like syndrome and
possible increase in Prolactin
levels
Other
Can be used as an anti emetic
sulpiride
Class
Selective CNS D2 receptor
Antagonist
MOA
Simple antagonist
Indications
Schizophrenia
Side
Effects
Extrapyramidal symptoms like
acute dyskinesias (Too much
Ach), Tardive Dyskinesia
(Upregulation of DA receptors),
Parkinsonian like syndrome and
definite increase in Prolactin
levels (Breast Cancer?)
Other
clozapine
Class
Atypical antipsychotic
MOA
CNS Antagonist against D2,
Ach, H & 5HT (Hence
Atypical)
Indications
Schizophrenia
Side
Effects
Agranulocytosis and
myocarditis it may rarely lower
seizure threshold, cause
leukopenia, cause hepatic
dysfunction, weight gain and be
associated with type II diabetes.
More common side effects are
predominantly anticholinergic
in nature, with dry mouth,
sedation and constipation
Other
Cytotoxic Drugs
cyclophosphamide
Class
Alkylating agent
MOA
Highly reactive molecules that
bind irreversibly to cell
macromolecules causing intra
and inter chain cross links
(Notably DNA / RNA) binding
sites N7 of G, N1 & N3 of A
and N3 of C
Indications
Chemotherapy (&
immunosupression at lower
doses)
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
methotrexate
Class
Antimetabolite
MOA
Folate antagonist and so
reduces the synthesis of Purine
nucleotides (Reduction of the
enzyme DHFR)
Indications
Chemotherapy (&
immunosupression at lower
doses)
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
Azathioprine
Class
Antimetabolite
MOA
Purine analogue, inhibit Purine
synthesis and is incorperated
into DNA itself
Indications
Chemotherapy (&
immunosupression at lower
doses)
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
bleomycin
Class
Cytotoxic Antibiotic
MOA
Causes fragmentation of DNA
chains and can act on non
dividing cells. Bleomycin is a
metal chelating glycopeptide
antibiotic which uses Iron ions
to create ROS which then cause
DNA damage
Indications
Chemotherapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
doxorubicin
Class
Cytotoxic Antibiotic
MOA
Topoisomerase II inhibitor and
in such creates DNA strand
breaks
Indications
Chemotherapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
vincristine
Class
Vinca Alkaloid
MOA
Spindle Poisons and exert there
actions by binding to tubulin
causing depolymerisation of
microtubules and therefore
producing metaphase arrest
Indications
Chemothrapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
etoposide
Class
Podophyllotoxin
MOA
Topoisomerase II inhibitor,
prevents DNA replication and
causes strand breaks
Indications
Chemotherapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
procarbazine
Class
Miscellaneous anticancer drug
(MAO-I)
MOA
Inhibition of incorporation of
Thymidine and adenine into
DNA
Indications
Chemotherapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V
Other
cisplatin
Class
Miscellaneous anticancer drug
(Platinum Compound)
MOA
After dissociation of a Cl- from
the drug this generates a
reactive complex that cross
links between G units in DNA
(Similar to alkylating agents)
Indications
Chemotherapy
Side
Effects
General toxic side effects
Myelosupression
Impaired wound healing
Depression of Growth
Sterility
Teratogenicity
Loss of Hair
N&V (WORST SIDE
EFFECT!)
Other
goserelin
Class
GnRH agonists.
MOA
Blocks oestrogen production,
constant bombardment of the
adenohypophesis with the GnRH
agonist causes down regulation of
the GnRH receptors
Indications
Breast cancer in pre menopausal
women.
Side Effects
Other
Can also block oestrogen actions
using enzymatic inhibition, or just
inhibit the actions of oestrogen
within the tumour cell.
Drugs for Endocrine
Disorders
tamoxifen
Class
Estradiol analogue – antioestrogen
MOA
Works by acting as a competitive
inhibitor at the ER on the breast
cell tumours. This stops the effect
and holds the cell at the G1 phase.
Indications
Endocrine treatment of choice for
postmenopausal women
Side Effects
Other
Ferrous
sulphate
Class
Oral iron compound
MOA
Ingested and solves iron deficiency
Indications
Iron deficiency anaemia
Side Effects
none
Other
cabergoline
Class
DA2 receptor agonist with some
DA1 actions.
MOA
Indications
Hyperprolactinaemia. Not as good
as bromocriptine but side effects
are less pronounced and it is
longer lasting.
Side Effects
Other
Mutual antagonists with antipsychotics. Sympathomimetic
toxicity is increased. Exacerbates
effects of alcohol.
Octreotide
Class
Somatostatin analogue
MOA
Imitates actions of somatostatin by
inhibiting production of Growth
hormone.
Indications
Acromegaly – short term treatment
before pituitary surgery.
Side Effects
Other
Ethinyloestradiol
&
medroxyprogesterone
Class
TSH & LH replacement therapy
MOA
Replaces actions of progesterone
and oestrogen.
Indications
Hormone replacement in cases
where gonadotrophins are no
longer produced in pan
hypopituitarism
Side Effects
Other
Terlipressin
Class
V1 receptor agonist.
MOA
Acts at V1 receptors as an agonist
casuing an increase in IP3/DAG
and so causing vasoconstriction,
platelet aggregation, hepatic
glycogenolysis, ↑ vWF and Factor
VIII, ↑ ACTH and so cortisol.
Indications
Stopping bleeding from
oesophageal varices, prolongs the
actions of local anaesthetics.
Side Effects
Other
Desmopressin
Class
V2 receptor agonist
MOA
Imitates actions of vasopressin in
the distal collecting duct as an anti
diuretic
Indications
Given in central diabetes insipidus.
Has no effect with nephrogenic
diabetes. Thiazides used for
nephrogenic diabetes insipidus.
Side Effects
Other
Lithium &
dimethylchlor
otetracycline
Class
Inhibitors of vasopressin action on
the distal tubule
MOA
Prevents anti-diuretic actions of
excessive vasopressin
Indications
Excessive vasopressin production.
Side Effects
Other
Levothyroxine
Class
Thyroxine analogue
MOA
Acts to raise metabolism in tissues
– replacing T4
Indications
hypothyroidism
Side Effects
Other
Liothyronine
Class
T3 analogue – tri-iodothyronine
MOA
Replacement of T3. binds to
intracellular receptor where I tis
transported to the DNA and causes
transcription of tissue specific
DNA regulated effects, ie raising
BMR, sesnsitising tissue to
sympathetic stimuli etc.
Indications
Hypothyroidism. At birth to
prevent cretinism
Side Effects
Other
Protirelin
Class
Thyrotrophin releasing hormone
analogue
MOA
Stimulates release of thyroxine
from the thyroid gland
Indications
Used in stimulation tests of the
thyroid to test function.
Side Effects
Other
Metformin
Class
Insulin sensitiser (Biguanide)
MOA
Requires endogenous insulin
production. Works by decreasing
glucose output by the liver and
increasing its uptake by liver and
peripheral cells.
Indications
Type 2 Diabetes mellitus in fat
people whose diet control hasn’t
worked properly
Side Effects
Lactic acidosis, ↓ vitamin B12
absorption. Nausea and vomiting,
headache, anorexia.
Other
Not in renal insufficiency or
hepatic impairment.
Glibenclamide
Class
Sulphonurea
MOA
These block ATP dependent
potassium channels in the
membranes of the pancreatic β
cells, causing depolarisation,
calcium influx, and insulin release.
Indications
Type II Diabetes Mellitus where
there is still β cell activity in the
pancreas
Side Effects
Potential hypoglycaemia in people
with renal or hepatic insufficiency.
Other
Contraindications in people with
ketoacidosis
Rosiglitazone
Class
Thiazolidinediones. Insulin
sensitisers
MOA
Work by reducing peripheral
insulin resistance, leading to a
reduction in plasma glucose
Indications
Uncontrolled Type II DM
Side Effects
Weight Gain, potential liver
failure.
Other
Must only be used in combination
with a sulphonylarea or
metformin.
Acarbose
Class
α glucosidase inhibitor
MOA
Inibits the breakdown of
oligosaccharides (starch and
sucrose), therefore delays CHO
absorption. This reduces the –
CHO peaks a bit like metformin.
Indications
Useful in the obese diabetic
patient.
Side Effects
GI gas
Other
Not in pregnancy, breastfeeding,
bowel problems.
carbimazole
Class
Thiourylenes – also includes
propylthiouracil
MOA
Blocks thyroperoxidase which is
responsible for the production of
thyroglobulin and T3 & T4
synthesis. May also ↓ antibody
production in Grave’s disease and
↓ the conversion of T4 to T3 in
peripheral tissues.
Indications
Hyperthyroidism
Side Effects
Hypothyroidism
Other
Iodide
Class
Anion inhibitor
MOA
Inhibit the conversion of T4 to T3,
of organification and of hormone
secretion. They also reduce the
size and vascularity of the gland
Indications
Hyperthyroidism
Side Effects
Allergic responses
Other
Radioiodine
Class
Anti hyperthyroid
MOA
Selectively taken up by the thyroid
gland where it has very local
cytotoxic effects due to β particles.
The γ particles pass straight out.
Can destroy the over producing
thyroid follicular cells.
Indications
Low dose test of thyroid function,
high dose, hyperthyroidism or
thyroid tumours.
Side Effects
Not in children or pregnancy
Other
Miscellaneous Drug
Information
SYMPathetic
α1
located postsynaptically, Their activation
causes SM contraction (except in non sphincter
GI), glycogenolysis in the liver, and potassium
release from the liver & salivary glands. Gprotein linked, & by increase in 2 nd messengers.
α2
Located most pre, but post on hepatocytes,
platelets and BV SM. Activation of pre inhibits
NA release and provides end product negative
feedback. Activation of post causes BV
constriction & platelet aggregation. G-protein
linked & by decrease in 2nd messengers.
β1
Mostly postsynaptic in the heart, platelets and
non sphincter GI. Activation causes rise in rate
and force of contraction of the heart, relaxation
of GI, platelet aggregation, rise in NA, lipolysis
in Fat, amylase secretion from salivary glands.
G-protein and rise in 2nd messenger cAMP.
β2
Located post, SM relaxation, glycogenolysis in
liver, inhibition of histamine from mast cells,
tremor in skeletal muscle. G-protein and and
increase in cAMP.
Parasympathetic
M1
Neuroparietal normally found in the CNS,
peripheral neurons, and gastric parietal cells.
Effects are excitatory, depolarizing membranes
through a decrease in K conductance.
Activation causes central excitation and gastric
acid secretion, transduction through G-proteins
and Increase in 2nd messengers.
M2
Neurocardiac are found in the heart and on
peripheral neurons. Effects are inhibitory
raising K conductance(<rate), and inhibiting
calcium channels(<force). G-protein
transduction with decrease of 2nd messengers.
M3
Smooth muscle-glandular found in obvious.
Excitatory by increasing Na conductance.
Causes SM contraction and secretions such as
saliva and sweat. G-proteins and increase in 2nd
messengers. Also on vascular epitelium,
activation of which causes EDRF (NO).
M4
Eye. Causes constriction of the pupil and
accomodation for near vision. Transduction is
via G-proteins and a decrease in 2nd messenger.
Multiple drug
therapies
Helicobacter
pylori
Metronidazole/amoxycillin,
clarithromycin, Omeprazole
Tuberculosis
1st phase of 2 months:
isoniazid, rifampicin,
pyrazinamide (+ethambutol if
resistant)
2nd phase of 4 months:
Isoniazid and rifampicin
Histamine
H1
Histamine in hypersensitivity reaction.
•Capillary and venous dilation (systemic
hypotension
•↑ vascular permeability (oedema)
•Contraction of SM (bronchial and GI
contraction)
•↑ mucus secretion by goblet cells
H2
Regulation of gastric acid secretion.
-H2 receptors respond to histamine secreted from
enterochromaffin like cells that are adjacent to
the parietal cells.
-Negative feedback if on mast cells and
basophils.
-Increases vasopermeability & dilation and
stimulates exocrine glands.
H3
Neurotransmission. Not sure what. Possible
presynaptic inhibition of NT release in the CNS
and autonomic NS? Role in pain perception?
Vasopressin
Receptors
V1
Vascular smooth muscle (prevention of blood
loss from oesophageal varices), non vascular
smooth muscle, anterior pituitary, Liver,
platelets (Stimulation of factor VIII and von
Willbrandt factor), Brain and CNS
V2
Kidney (distal collecting duct), CNS
Glucocorticoid
SE
osteoporosis
↑ osteoclast activity, ↓
osteoblast activity
Gastric ulceration
↓ PG production in
stomach (lipocortin ↓
arachidonic acid.)
Suppression of HPA
-ve feedback on pit. &
hypothalamus
hypertension
Na+ Cl-, water retention; ↑
adrenoceptors hence ↑
response.
infection
Immunosupression
Skin thinning
↓ connective tissue, ↓
tissue turnover and repair
Muscle wasting &
buffalo hump
↓ storage of glucose in
muscle, leads to an ↑ in
fat deposition.
Cataracts & glaucoma