ANTITUSSIVES:
Suppress cough, produces symptomatic relief, useful for bothersome sleep, prevent restful sleep cough
MOA: suppress cough centre in medulla (central & peripheral effects)  epithelial tissues heal themselves
Description
Codeine  Low analgesic potency,
high antitussive activity
 Suppress cough center
as agonist at central μ
opioid peptide
receptors
 Semi-synthetic opioid
derived from codeine:
dihydrocodeine &
hydrocodeine
Dextromethropha  Active ingredients in
n many OTCs cold &
cough medicines
 Suppress cough center
at central & peripheral
sigma opioid peptide
receptors & antagonist
at NMDA receptors
 Also acts as a
nonselective serotonin
reuptake inhitor
 Half as potent as
codeine as an
antitussive
Pharmacokinetics
 Good oral bioavailability: 90%
 Methylation of morphine at
carbon-3 ↓ hepatic pass effect
 Cytochrome P450 2D6 convert
codeine (10%)  morphine
 Cytochrome P450 3A4 convert
codeine  norcodeine
 Uridine diphosphate
glucuranosyl transferase
(UDPGT) conjugates codeine,
norcodeine & morphine to the
corresponding 3- and 6-
glucuronides
 O-demethylation 
dextrorphan by CYP3A4
 N-demethylation to 3-
methoxymorphinan by CYP3A4
 Partial conjugation with
glucuronic acid and sulphate
ions
 Traces of the unchanged drugs
are detectable in urine
 Poor metabolisers experience
↑ effects, duration, & side
effects
 CYP450 inhibitor will effect this
drug
Adverse effect Drugs interaction
 Abuse potential, but less than  CYP450 inhibitors ↓ or
morphine completely block the
 Common: drowsiness, conversion of codeine to
constipation morphine
 Uncommon: addiction,  CYP450 inducers
dependence, euphoria, (rifampicin &
itching, nausea, vomiting, dry dexamethasone  ↑
mouth, miosis, hypotension, conversion rate)
depression  Poor metabolisers
 Rare: anaphylaxis, seizure, experience less
respiratory depression morphine effects & side
 Codeine is metabolised to effects
morphine  passed through
breast milk  fatally
depressing the respiration of a
breastfed baby
 Withdrawal symptoms: drug
craving, runny nose, yawning
Pharmacokinetics only:
 Recommended doses: nausea, slight drowsiness, dizziness
 Recreational doses: euphoria, elevated mood, disorientation,
confusion, altered time perception
 Acute OD: hallucinations, disturbance in thinking, senses &
memory, impaired judgment
 Could trigger histamine release  allergic rxn
 Potentiates activity of MAOIs & SSRIs  hypotension &
infrequently come
Noscapine General: Headache, loss of ↑ effects of centrally
Alkaloids from plants of the Papaveraceae family, w/o coordination, dizziness, sedating substances
significant analgesic properties drowsiness, tachycardia, such as alcohols &
Used for its antitussive effects nausea, vomiting hypnotics
Suppress cough center as agonist at central & peripheral May ↑ effect of
sigma opioid peptide receptors & antagonist at β2 receptors warfarin
Menthol General:
 Organic compound derived from peppermint plant
 Anti-irritant or anaesthetic  cooling sensation produces by chemically triggering cold receptors
 Has astringent & antibacterial properties that inhibit bacterial growth & help treat bad breath
 Sore throat medication
 ROA: oral
 Suppress cough reflex & may be prescribed as menthol crystals or in the form of proprietary capsules
 Cough suppression is acute and short-lived
Benzonatate  Chemically related to Procaine, which is local anaesthetic Adverse effects:
 Has both central & peripheral actions Headache, dizziness, pruritis, nasal congestion, burning of
 MOA: exerts antitussive action on stretch or cough receptor in eyes, tightness of chess
lungs (local anaesthetic effect – also has some central effects)
DRUGS AFFECT THE RESPIRATORY TRACT FLUIDS (Expectorant, Mucolytic agents, Surfactants)
EXPECTORANTS

Description Pharmacokinetics Adverse effects Drug interaction

Guaifenesin  OTC expectorant  Rapidly metabolised  Nausea, vomiting, formation of  ↑ absorption &
 Derived from guaiac tree used & excreted in the kidney stones, diarrhea, analgesic effect of
as remedy by American urine constipation paracetamol & aspirin
Indians, found when explorers  Undergoes oxidation  Nausea & vomiting can be ↓ by  ↑ sedative effects of
reach North America in 16th to β-(2- taking guaifenesin w/ meals alcohol, tranquiliser,
century methoxyphenoxy) –  Risk of forming kidney stones sleep-pills, & total
 MOA: ↑ volume & ↓ viscosity lactic acid can be ↓ by maintaining good anaesthetics
of secretions in trachea &  40% of a dose is hydration & ↑ urine pH  ↑ drug effects that ↓
bronchi; stimulates the flow of excreted as this  Rare: severe allergic rxn may muscle tone
respiratory tract secretion metabolite in the occur, inc. rash or swelling of  ↑ effects by lithium or
(allowing ciliary movement to urine w/I 3 hrs the lips or face magnesium
carry the loosened secretions  t1/2 in plasma: 1hr  Dry mouth  ↑ dehydration effects of
upward toward the pharynx) diuretics & laxatives
Ammonium General: Irritant to gastric mucosa  induce nausea & vomiting
chloride  An electrolyte
 Eg: Diphenhydramine expectorant syrup
 MOA: irritate bronchial asthma  production of excess
respiratory tract fluids

MUCOLYTIC AGENTS

Dissolves thick mucus & used to help relieve respiratory difficulties by dissolving various chemical bonds w/i secretions ↓ the viscosity

Inhalational: Acetylcysteine, Tyloxapol

Oral: Acetylcysteine, Bromohexine, Carbocysteine, Methylcysteine

Description Clinical uses Side effects

Acetylcysteine L-cysteine amino acid Asthma, emphysema, bronchitis, Stomatitis (inflammation of mouth &
MOA: contain reactive sulphydryl group  ↓ mucus pneumonia, cystic fibrosis, lips), nausea, vomiting, rhinorrhoea
viscosity & liquefies it  making it easier to cough up respiratory complication after (nasal cavity is filled with mucous
surgery fluid), bronchospasm
Bromhexine Synthetic derivative of vasicine Acute & chronic bronchitis CNS: Headache, tinnitus
MOA: acts at the formative stage of mucus formation in Bronchial asthma GIT: GI disturbances, gastric irritation
 the glands w/i the mucus secreting cells by disrupting the
structure of acid mucopolysaccharide fibers  easier to
expectorate
Ambroxol General: Occasional GIT side effects may
Synthesised from paracetamol & dibromobenzaldehyde occur but it is normally mild
MOA: stimulates synthesis & release of surfactant by type II pneumocytes  promote mucus
clearance

MUCOPROTECTIVE AGENTS / ORAL DEMULCENT

 Protects mucous membrane tissues of the respiratory tract

 MOA: coat the mucous membrane with soothing film  relieve minor pain and inflammation
 Used as common ingredient in cough syrup & throat lozenges
 Example: Pectin, glycerine, honey, propylene glycol, methyl cellulose, herbs that have high content of mucilage
 Throat lozenges
 Small medicated tablets intended to dissolve in mouth
 Have lubricating and soothing effect on irritated tissue of the throat
 May contain benzocaine or dextromethorphan

BRONCHODILATORS

 If cough is d/t bronchospasm, β2 agonists are given

 Relieve cough in patients w/ bronchial hyper reactivity
 Should be used only when an element of bronchoconstriction is present
 Short-acting: albuterol, levalbuterol, ipratropium (inhaler or as a liquid added to a nebulizer)
o Side effects: dry mouth, blurred vision, cough, tremors
 Long-acting bronchodilators: tiotropium, salmeterol, formoterol, arformoterol, indacaterol, aclidinium (inhaler or nebulizer)
o Side effects: dry mouth, dizziness, tremors, runny nose, irritated/scratchy throat, rashes, blurred vision, rapid heart rate