Drugs acting on Adrenoreceptors:

Adrenoreceptor effects:

Receptors (G-linked) 1 (GQ) 2 (GI)* 1 (GS) 2 (GS)

2nd messengers IP3 / DAG  c-AMP  c-AMP  c-AMP

 K conduct

1) Smooth m
 Blood vessels contraction contraction (2b) dilation
 Bronchi constriction dilation
 GIT:
- non-sphinct relax relax relax
-
- sphincters constrict
 Bladder:
- Detrussor relax
- Sphincter constrict
 Uterus contract relax
 Seminal ejaculation relax
 Iris contract (= mydriasis)
 Ciliary m relax
2) Skeletal m tremor
Glycogenolysis
3) Heart tachycardia
+ inotropy
+ lusitropy
4) N terminals
- Adrenergic  release  release
- cholinergic release
5) PLT’s aggregation
6) Liver glycogenolysis Glycogenolysis
7) Pancreas  Insulin release
8) Fat lipolysis
9) Mast cells  histamine rel
10) Salivary gl’s K release amylase
11) Kidneys vasoconstrict renin secr

1
Catecholamine synthesis:
l-phenylalanine  l-tyrosine  l-DOPA  dopamine  noradrenaline  adrenaline
    
1 2 3 4 5

phenylalanine = amino acid , l-tyrosine = present in body fluids

Enzymes (1-5 above):
1) hydroxylase (liver)
2) tyrosine hydroxylase: limited distribution, slowest step  rate limiting step, very substrate
specific, under negative feedback from noradrenaline. Also inhibited by alpha-methyltyrosine
(sometimes used in pheochromisitoma)
3) DOPA decarboxylase; non selective, also involved with 5-HT + histamine synthesis
4) Dopamine-beta-hydroxylase: stored in vesicles with NA + ATP, so also released  measure of
sympathetic activity (not re-uptaken or degraded like NA). Non-selective, but restricted to
catecholamine synthesizing cells. Inhibited by disulfiram / copper chelating agents.
5) Phenylethanolamine-N-methyltransferase (  in adrenal medulla)

Noradrenaline storage:
 In vesicles in N-terminals (very little in cytoplasma due to presence of MAO)
 Uptake from cytosol into vesicles inhibited by reserpine (so decreasing amount of available NA)
 Vesicles also contains ATP (co-transmitter + is important for initial rapid phase of smooth m
contraction) and dopamine-beta-hydroxylase
 NA can be displaced from vesicles ( eg by alpha-methylnoradrenaline, a metabolite of methyldopa)

Termination of NA effect:

1) Uptake by nerve terminals: ( = most important). Two types of uptake:

- Uptake-1: neuronal, high affinity for NA, low max rate. Inhibitors: TAD’s, cocaine,
amphetamine, phenoxybenzamine (PBA)
- Uptake-2: non-neuronal, lower affinity for NA, high max rate. NB in termination of
NA. Inhibitors: steroids (part of +’ve effect in asthma), PBA.
2) Degradation: 2 important enzymes; MAO and COMT:
- MAO: intracellular only and converts catecholamines (ca) to corresponding aldehyde.
Aldehyde converted to a carboxylic acid (by aldehyde dehydrogenase) eg
dihydroxymandelic acid for NA. Also metabolises other mono-amines eg 5-HT,
dopamine etc. Two types with different distrib, selectivity and inhibition:
MAO-A: Found in neuronal and extraneuronal cells (liver, GIT, placenta). selective for
NA + 5-HT + dopamine (inhib by moclobemide (Aurorix).
MAO-B: Also neuronal and extraneuronal cells (blood platelets): selective for dopamine
and tyramine. (Inhibited by selegiline which is used in parkinson’s)

- Catecholamine-o-methyltransferase (COMT): Primarily in liver, but important in neurons

intra (NB'st) + extracellular: degrades any catechol containing compounds ( methylates the –OH
group) as well as products of MAO catabolism.

Note: products of MAO + COMT = VMA, HMMA, metanephrine etc (  in phaeo)

2
Drugs acting on adrenoreceptors:
 t1/2 1 2 1 2 Main uses
Agonists (Sympathomimetics):

Direct acting:

Noradrenaline ~ 2min +++ +++ ++ + ICU/ sepsis etc

Adrenaline ~ 2min ++ ++ +++ +++ CPR/anaphylaxis
Isoprenaline ~2 hr 0 0 +++ +++ chemical pacing
Phenylephrine ~3hrs ++ 0 0 0 BP/nasal decongest
Clonidine 12 hr + +++ 0 0 HTN, analg/sedative
Salbutamol 4 hrs 0 0 0 +++ asthma/ prem labour
Salmeterol ~6hrs +++ asthma (sereventR)
Terbutaline 4 hrs 0 0 0 +++ asthma
Dobutamine 2 min +/-* 0 +++ + ICU (CCF )

Indirect acting Sympathomimetic Agents (ISMA’s):

Ephedrine 6 hrs + + +++ ++ BP/nasal decongest
Metaraminol* +++ + ++ 0  BP

Antagonists:

Phenoxibenzamine 12 hr +++ +++ 0 0 Phaeochromocitoma

Phentolamine 2 hr +++ +++ 0 0 Phaeo / HTN crisis
Ergotamine ++(PA) ++ 0 0 migraine
Prazocine 4 hr +++ + HTN, BPH
Doxazosine +++ + 0 0 HTN, BPH
Yohimbine + +++ 0 0
Propranolol 5 hr 0 0 +++ +++ HTN,tremor,thyroid
Atenolol 6-9 hr 0 0 +++ + HTN, IHD
Metoprolol 3 hr 0 0 +++ + HTN, IHD
Alprenolol 2-3 hr 0 0 ++(PA) ++
oxprenolol 2-3 hr 0 0 ++(PA) ++
Labetalol 4 hr + +/- ++ ++ HTN ( PET)
Esmolol 9 min 0 0 +++(PA) HTN, anti-arrhythm
*Note: Dobutamine used as racemic mix: Complex drug…both isomers strong agonists at B1 (inotrope>>chronotrope) and weak
agonists at B2. The (-) isomer has alpha1 agonist effects(offsets B2 vasodilator effects) and the (+) isomer has alpha1 blocking effects.

3
Basic structure of Sympathomimetics:
  All sympathomimetics are derived from beta – phenylethylamine

 Catecholamines all have –OH groups on positions 3 and 4 of the aromatic ring

Salmeterol
 Direct and indirect acting synthetic non-catecholamines:

4
Structure activity relationships (adrenoreceptor acting drugs):
In general, modifying structure of NA, explain the properties of the directly + ISMA’s as
well as the beta-blockers, but not for the alpha-blockers.
 Levo (l) forms = more potent than dextro (d)
 Bulkiness of substituents of N-atom:
- Gives agents more potency as B-agonists ( eg adrenaline, isoprenaline,
salbutamol, salmeterol)
- Less susceptible to MAO and uptake-1
 Extension of the alkyl side-chain (isopropyl substitution on N atom) +
modification of catechol OH groups: Yield potent B-blockers (eg propranolol)
 Methylation of alpha-C atom:
- Increases alpha receptor selectivity (metaraminol)
- Resistance to MAO, but still susceptible to uptake-1 (act as ISMA)
 Hydroxyl groups on C3 + C5 on aromatic ring: = B2 agonist activity
 Removal of beta-C atom OH group:
- Greatly reduces adrenoreceptor interaction ( eg dopamine)
- Most directly acting sympathomimetics + B-blockers retain this OH group, but not all
alpha-blockers.
 Substitution or transfer of catechol OH group: Produces compounds resistant to
COMT, eg salbutamol. Also, usually not substrates for uptake-1.
 Removal of one (metaraminol) or both (ephedrine) catechol OH groups:
- Reduces direct adrenoreceptor activity
- Can still act as indirect sympathomimetic agents (ISMA) as they are substrates for
uptake-1 and so inhibits NA uptake ( eg ephedrine, amphetamine, tyramine)
- Phenylephrine + metaraminol: OH on C3   potency but gives 1 selectivity.

Adrenoreceptor Agonist functions:

 Smooth muscle: 1 constricts (except GIT) = esp blood vessels or skin, renal,
splanchnic, large arteries, veins + arterioles, with less effect on cerebral, coronary +
pulmonary circulations where autoregulation is prominent. 2 also constricts vessels, esp
via circulating ca’s. -effects = relaxation, vasodilatation (esp skeletal), bronchodilatation
(2), uterine relaxation (2).
 Nerve terminals: 2 = inhibitory (1 = weak facilitatory)
 Heart: 1 = + chronotrope, inotrope + lusitrope,  VO2, + arrhythmogenic
 Metabolism: Both  +  (mainly) effects. Main effect = to convert stored energy into
available energy. Effects at liver (+2)   s-Glucose, and at fat (3)   FFA. The
 glucose + FFA enters muscle cells where it is converted into energy via Krebs cycle
(enhanced by 2 effects which inhibits glycogen synthase and accelerates phosphorylase).
Note: There’s also  in substrates for GNG (aa’s, lactate). Note that  in s-glucose by
adrenalin = inhibited by combination of  + -blockers. Also,  Insulin with 2
stimulation of pancreas  cells.
 Other effects: - skeletal m tremor (2), -  Histamine release by MAST cells (2)
- Bronchodilation (2), - mydriasis
-
5
Clinical uses of the adrenoreceptor agonists:
 I) CVS:

 Cardiac arrest: Adrenaline I.V. or E.T.

 Cardiogenic shock: Dobutamine or Dopamine “renal” dose
 Heart block: Isoprenaline (- agonist)
 Hypotension: Metaraminol (direct, ISMA), Ephedrine (direct + ISMA),
Phenylephrine

II) Anaphylaxis:

 Adrenaline s.c./ imi/ i.v.

II) Respiratory System:

 2 agonists in asthma: Salbutamol, salmeterol, terbutaline inhaled.

Salbutamol IV in severe.
 Nasal decongestant (Phenylephrine)

III) Other:

 Inhibition of prem labour: Salbutamol (2)

 Hypertension: 2- agonists; clonidine and methyldopa (converted to
-methylnoradrenaline)
Both give fall in B.P. due to  N.A. release and also central action.
 Prolonging duration of action of local anaesthetics (Adrenaline)

6
Adrenoreceptor Antagonists
 and  selective and also sub-selective (1 + 2 and 1 + 2)

IV) Alpha antagonists:

i. Non-selective

 Phenoxybenzamine: Irreversible competitive

- Antagonist 1 + 2; long half life (12 hours)

- Long half life (12 hours) Also inhibit uptake 1 & 2
- Used in Rx of Pheochromocytoma with - blockers

[Because irreversible, not influenced by  Adrenaline release]

 Phentolamine: Reversible competitive, short acting

 Labetalol: 1 + (2) and 1 + 2; more  selective. Oral : = 1:3

and IV : = 1:7

 Non-selective blockers produce fall in B.P. (vasodilatation) and concomitant 2 –

blockade enhances reflex tachycardia ( N.A. release, and 1 not blocked)
 All sympathetic blockers give  GIT mobility with diarrhea as side effect.

ii. Selective 1- blockers:

 More useful: Drop in B.P. pronounced (vasodilation = large
arteries, veins and arterioles  also  in C.V.P. +  C.O.)
Also a beneficial  LDL +  HDL.
Usually less reflex tachycardia c/f non-selectives because of lack
of 2- blocking effects
E.g. Prazosin: short half life
Doxazosin, terazosin: longer half lives  once daily use

Uses:
- Hypertension
- Urinary retention in B.P.H.

iii. Selective 2- blockers: Yohimbine (Aphrodisiac)

  N.A. release (pre-synaptic 2 block)

 Vasodilation (post-synaptic 2 – some organs) = complex effects
7
Clinical uses of - blockers:

 Hypertension
 1- blockers
 Less reflex tachycardia and arrhythmias and diarrhea
  LDL,  HDL

Esp: longer acting doxazosin and terazosin

 Benign prostatic hypertrophy: relieves urinary retention (1- blockers)

 Pheochromocytoma: Pre-operative. E.g. Phenoxybenzamine (irreversible) +

- blocker (atenolol)
o NB: - blockade must first be established before giving - blocker
[otherwise  H.T. from unopposed 1- effect of adrenaline]

o Also used if inoperable: -Methyltyrosine (tyrosine analogue strongly

inhibits the rate limiting enzyme, Tyrosin hydroxylase.)

8
Beta Blockers (BB):

 Usually, 1- antagonism is more desirable

  Note: certain BB’s show a relative selectivity, not specificity for 1. ( ie 2
blockade can still occur, esp at higher doses).
 The BB’s can be further subdivided into either pure or partial blockers, based on
absence or presence of intrinsic sympathomimetic activity (ISA) respectively.
Partial agonists (pindolol, labetalol) produce less myocardial depression /
bradycardia than drugs without ISA but are unable to preserve ventricular
function.
 Non-selective: Propranolol (1+2, t1/2 4-6 hr), labetalol (1+2 + 1+2, t1/2 4hr)
Alprenolol, oxprenolol (both = partial agonists), carvedilol
 Selective 1: Atenolol ( t1/2 6-9 hr), metoprolol, bisoprolol, sotalol, esmolol ( PA,
t1/2 9 min = due to RBC ChE breakdown)

Clinical usage:

A) Cardiovascular:
1) Antihypertensives:
 Mechanisms:
-  CO ( 1) via  in HR +  SV ( neg inotropy)
-  Renin secretion in kidneys (1)
- Central mechanism ( sympathetic activity)
- Presynaptic 2-blockade (facilitating effect)
 Favourable qualities: less postural hypotension and exercise induced
hypotension, because reflex vasoconstriction preserved (1 effects)
2) Anti-anginal: Myocardial oxygen balance improved, because  in coronary flow
is less than  in myocardial O2 consumption.
3) Anti-dysrhythmic: Class 2 as well as class 3 (sotalol)
4) Post-MI: prevent re-infarction + dysrhythmias.
5) CCF: Once stabilized, slow introduction of BB’s has been shown to be
beneficial.

9
B) Other:
1) Glaucoma: Timolol ( ?  aqueous humor production)
 2) Pheochromocytoma: once alpha- blockade established (help  BP + reflex
tachycardia)
3) Thyrotoxicosis: for symptomatic control until definitive treatment.
4) Anxiety states: symptomatic relief of tremor, palpitations etc.
5) Benign essential tremor: = familial condition
6) Migraine prophylaxis:

C) Peri-operative beta-Blockers:

A lot has been published re the cardiac protective effects of peri-op BB’s. Initial studies
( Mangano ’98) showed dramatic benefit. The earlier studies were criticized though on
methodology. Later, better-controlled studies (Poldermans et al), however confirmed
benefit of peri-op BB (results not as dramatic as Mangano).
Despite the fact that the myocardial depression from volatiles + iv anaesthetics is
additive to that of pure BB’s, the perioperative use does seem to reduce the M+M in
patients with CAD.
There is still controversy re which patients should be routinely given prophylactic
periop BB’s and for how long should it be continued for. Some studies showed long
term benefit even from a single preop dose of a BB.
There is however no doubt that pts already on established B-blockade, should not
miss any of their BB therapy during this critical perioperative period ( the worst time
to subject a pt to BB-withdrawal…). Some authorities suggest increasing BB dosage
during periop period (more evidence needed).
Recent study (POISE), showed increased CVA’s with peri-operative B-Blocker use…

Unwanted effects:

1) Bronchoconstriction: not in normal people (although  FEV1).

NB though to avoid / extreme care in asthmatics.
2) Acute/ decompensated Cardiac failure: In theory should be less with partial
agonists, eg oxprenalol + alprenolol, pindolol + esmolol.
3) Diabetics: Can mask warning signs + symptoms of hypoglycaemia. Also
hypoglycaemia possible (less marked with 1-selective agents, because liver
glucose release is a 2 – response). Note: Lipolysis unaffected = 3
4) Acute withdrawal: rebound hypertension on acute BB withdrawal (due to up-
regulation of beta receptors), which may lead to M+M, especially in
perioperative period…
5) Fatigue +  exercise tolerance:  CO and  muscle blood flow.
6) Cold extremities: NB avoid in Raynauds.
7) Other: bad dreams (central effect, esp lipid soluble ones like propranolol)

10
Contraindications for BB therapy:
  Reactive airways disease (relative CI, individualize)
 AV-block
 Acute systolic cardiac failure
 WPW syndrome (use amiodarone)
 Use with care in combination with other negative chronotropics, eg CCB’s
(BB’s in combination with CCB’s and H2-blockers may result in severe negative
inotropism)

Other drugs affecting noradrenergic neurons:

Achieve their effect(s) via one of following, NA synthesis, storage or release.

A) Drugs affecting NA synthesis:

1) Alpha-methyltyrosine: Inhibits the rate limiting enzyme, tyrosine hydroxylase.
Sometimes used in Mx of inoperable pheochromocytoma.
2) Carbidopa: Inhibits DOPA-decarboxilase. Used as adjunct with L-dopa in
Parkinsonism. It reduces peripheral side-effects of dopamine and NA (from L-
dopa). Does not cross BBB, so does not impair central dopamine production.
3) Methyldopa: (Aldomet)
 Taken up in neuron + transformed to -methylnoradrenaline
 Is not broken down by MAO,   concentration in neuron and displaces
NA from vesicles + broken down by MAO
 Also gets released: poor 1-effects, but agonist at 2 pre-synaptic receptors
with  in NA release (similar to clonidine etc).
 Central effects: - similar to clonidine ( sympathetic outflow, sedation etc)
B) Drugs affecting NA storage:
Reserpine:
 Blocks uptake from cytosol into vesicles NA degraded by MAO 
depletion of NA and  NA transmission. = antihypertensive use
 Non-selective: also inhibits uptake and thus depletion of dopamine and
5-HT in brain   depression 

C) Drugs affecting NA release:

Methods:
 Preventing exocytosis in response to depolarization of the nerve terminal
(Noradrenergic neuron blocking drugs, - see below)
 Causing NA release in absence of nerve terminal depolarization ( ISMA’s)
 Interaction with presynaptic receptors: - enhancing (2, AT1), or
- inhibiting ( 2)
 Increasing ( MAOI) or decreasing (reserpine, methyldopa) available NA stores.

11
Noradrenergic neuron blocking drugs:
  Prevents exocytosis in response to depolarization of nerve terminal. Most
likely mechanism = accumulation in the synaptic vesicles, preventing them
from fusing with membrane in normal way.
 Examples:
- Guanethidine: older drug used in HTN, but too many s/e’s (postural
hypotension, diarrhea, nasal congestion)
- Bretilium: anti-dysrhythmic (unknown mechanism)

Indirect sympathomimetic agents: (ISMA)

 Cause release of NA in absence of nerve terminal depolarization, eg

amphetamine, ephedrine, tyramine
 Principle action: Structurally related to NA, but lack one or both OH-groups on
catechol ring (thus reducing adrenoreceptor affinity). It does resemble NA enough
to be transported into nerve terminals by uptake-1. Inside n-terminal
displacement of NA from vesicles into cytosol. MAO degrades some, but the rest
escapes by facilitated diffusion (non-exocytotic).
 Secondary actions:
- Partly by direct effect on adrenoreceptors (eg metaraminol + ephedrine)
- Partly by inhibiting uptake-1 (amphetamine + ephedrine)
- Partly by inhibiting MAO (leads to  in NA, dopamine and serotonin)
 Thus, their effects are strongly influenced by other drugs that affect NA transmission:
eg: - Reserpine: abolishes their effects
- MAOI’s: strongly potentiates their effects. MAOI’s especially enhances the
effects of tyramine, which is found in certain foods (eg cheese). Tyramine in
food usually destroyed by gut-wall MAO, but  cheese intake in people on
MAOI’s can lead to a hypertensive crisis.
- Uptake-1 inhibitors (eg TAD’s): Prevents uptake of ISMA’s  decrease their
effect.

Effects of the ISMA’s: (reflect actions of NA)

a) Peripheral:
 BP, tachycardia*,  GIT motility, inotropic, bronchodilation, peripheral
vasoconstriction. Effects are generally longer lasting than direct acting drugs.
b) Central: (due to  NA, 5-HT, dopamine, = especially amphetamine)
Euphoria, excitement, wakefulness, loss of appetite, hallucinations / scizophrenia-
like symptoms (esp in high doses). Note: less central effects with ephedrine, but
can cause insomnia + excitement (elderly pts esp).
c) Other: = tolerance = typical of the ISMA’s = due to depletion of releasable stores
of NA and other transmitters  may lead to dependence ( esp amphetamine).

12
 Ephedrine: Natural product of Ephedra plant. Has two chiral centers, thus 4 isomers: the
racemic mixture of 1R,2S and 2R,1S = ephedrine, whereas 1S,2S and 1R,2R =
pseudoephedrine. Lacks OH-groups on catechol ring.
Direct  +  agonist as well as ISMA, as it competes with NA for reuptake   [NA] at
receptor sites. In general terms, ephedrine’s actions are very similar to that of adrenaline, ie
preferentially more beta 1+2 effects, but is less potent and is longer acting.  CO due to 1
effects. Also effective at 2 ( eg bronchodilation) and also indirect -mediated
venoconstriction play NB role in increasing preload and thus CO. Thus iv ephedrine leads to
 HR,  SBP + DBP,  CO, and  coronary flow. It decreases renal + splanchnic flow.
Stimulating effects on CNS ( MAC) and tachyphylaxis can occur with extended use.
Implicated in increased fetal incidence of acidosis with use in obstetrics.
Effects potentiated by MAOI’s and decreased by the TAD’s.
Presentation: Clear fluid, 30mg in 1ml amp; Dose: 3-6mg increments
OBA: 85%; Elimination: mainly excreted unchanged renally

Metaraminol: Synthetic vasopressor with direct effects on  (mainly) and 1 receptors, but
also indirect effects (stimulates release of NA). (Similar to effects of noradrenaline, and as
with ephedrine, = less potent and effects last longer). Can cause a marked  in SBP + DBP
with an accompanied reflex bradycardia.
Onset = minutes, with duration ~ of effect 30 – 90 min (dose dependant)
[Very comparable to the direct acting 1 agonist Phenylephrine, which onset = within a
minute and effects last 15 –20 min depending on dose]
Not implicated with fetal acidosis in obstetric use (neither is Phenylephrine).
Presentation: Clear fluid, 10mg in 1ml; Dose: 0.5-1mg iv increments
45% PPB; Elimination: Hepatic metabolism (not COMT), resistant to MAO

Inhibitors of NA uptake:

Eg TAD, cocaine, amphetamine

Can be either uptake-1 or uptake-2.
- Uptake-1 is NB in abolishing the effects of released and injected NA.
- Uptake-2 is NB in clearance of circulating adrenaline.

 Uptake-1 inhibitors:

 Tricyclic antidepressants (TAD’s):

Main effect is in CNS (high lipid sol), but also has peripheral effects (tachycardia, dry mouth
( atropine-like) + also other peripheral sympathetic effects).
 Cocaine:
An ester local anaesthetic. Sympathetic effects can be peripheral (tachycardia, HTN, arrhythmias) or
central (euphoria, excitement).

 Uptake-2 inhibitors:
Not affected by most of the drugs that inhibit uptake-1.

 Phenoxybenzamine: (inhibits both uptake 1+2)

 Corticosteroids: partly explains some of the beneficial effect in asthma
13
Other drugs with adrenergic effects:

 Phosphodiesterase inhibitors: eg methylxantines (theophyline etc)

They  c-AMP independent of  receptors.
Different subtypes of phosphodiesterase exist. Inhibitors of cardiac subtype
(PDE-3) give  c-AMP intracellular with +’ve inotropic + chronotropic (less)
effects and may also be arrhythmogenic. Eg = amrinone, milrinone and
enoximone. (Some deaths with amrinone, so not used any more)
Milrinone used in ICU in short term Mx of acute decompensated CCF.
Effects = PVR,  PCWP,  SVR, with myocardial VO2 +/- normal.
New, stereoselective drug, levosimendan (calcium sensitiser). Seems to have
better inotropic effect with smaller increase in VO2 than milrinone.
 Glucagon: Positive inotropic effects via action on GS-linked receptors 
 c-AMP. Note: = physiological antagonist of B-blockers.
Side effects = hyperglycaemia + hyperkalaemia.

A classification of positive inotropic drugs:

a) Increased i-Ca++:
Direct: CaCl2 Ca-gluconate
Indirect:
i) Increasing c-AMP: - B1 Agonists: adrenaline, noradrenaline, ephedrine
- Glucagon receptor agonists (Gs): glucagon
- PDE inhibitors:
- Non-selective: methylxantines (theophylline, caffeine)
- Selective (PDE-3): amrinone, milrinone

b) Increased calcium sensitivity: Levosimendan

c) Other: Digoxin: Inhibits 3Na+/2K+ ATPase and thus the secondary active 3Na+/Ca++
exchanger, which leads to an increase in intracellular calcium.

14
Interactions with MAOI’s:

Important:

1) Pethidine: agitation, HTN, seizures, hyperthermia

2) TAD’s: delirium, seizures, HTN, hyperthermia

3) ISMA’s: HTN, seizures, headache, tachycardia, hyperthermia, CVA

4) Tyramine: Hypertensive crisis (“cheese reaction”) – does not occur with

moclobemide.

Lesser importance:

1) Morphine: enhanced depressive effects of morphine

2) Volatiles: enhanced effects of volatiles ( MAC)
3) Phenothiazines: enhanced effects

No effect: Adrenaline, NA + dopamine ( ie the direct acting ones)

Benzo’s, NMBD’s, LA’s

Note: with the newer selective MAO-A inhibitors (moclobemide, = Aurorix), - more
selective antidepressant activity ensue, however, most of the side effects are also due to
MAO-A inhibition. Moclobemide = reversible inhibition, thus shorter acting and does not
interact with tyramine.
 15
Addendum / terminology:

Organic compound: Compound which contains carbon in covalent bond in its

structure

Alkyl: -CH2 groups (eg methyl, ethyl, propyl, butyl)

Alkaloid: Organic compound containing at least one basic nitrogen.

Phenyl ring: Aka Benzene ring = C6-ring structure

Amine: An organic compound derived from ammonia (NH3) where one or more
hydrogens are replaced by organic groups.

Carboxylic acid: (R-COOH) An organic compound that contains a carboxyl group

(COOH) attached to an R-group (R being an alkyl group, ie only containing C and
H).

Amino acid: Organic compound that contains amine and carboxyl groups along with
side chains specific to each amino acid.

Nucleoside: Compound consisting of a nitrogenous base and a 5-C sugar (eg ribose
or deoxyribose)

Nucleotide: Consists of nitrogenous base, 5-C sugar and 1 or more phosphate groups

Common chemical messengers:

 Hormone: Chemical messenger produced by a ductless gland, secreted into
bloodstream and has distant effect(s).
 Autacoid: Chemical messenger produced by tissues and has local effect(s).
 Neurotransmitter: Chemical messenger stored in nerve terminals, secreted
into synaptic cleft and binds with post-synaptic receptor.
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