CLINICAL PHARMACY PHARM D by RAMSHA TAREEN

1. ANTI HISTAMINE DRUG
ABUSE
GROUP NO 3

2. ANTI HISTAMINE
 A drug that reduces or eliminates the effects mediated
by the chemical histamine
 Histamine is released by your body during an allergic
reaction and acts on a specific histamine receptor
 True antihistamines are only the agents that produce
a therapeutic effect that is mediated by negative
modulation of histamine receptors (other agents may
have antihistaminergic action but are not true
antihistamines)
 The term antihistamine only refers to H1 receptor
antagonists (actually inverse agonists)
 Antihistamines compete with histamine for binding
sites at the receptors. Antihistamine cannot remove
the histamine if it is already bound

3. WHAT IS AN ALLERGY?
 Allergies are caused by a hypersensitivity reaction
of the antibody class IgE (which are located on
mast cells in the tissues and basophils in the
blood)
 When an allergen is encountered, it binds to IgE,
which excessively activates the mast cells or
basophils, leading them to release massive
amounts of histamines.
 These histamines lead to inflammatory responses
ranging from runny nose to anaphylactic shock
 If both parents have allergies, you have a 70% of
having them, if only one parent does, you have a
48% chance (American Academy of Asthma,
Allergies and Immunology, Spring 2003).

4. ALLERGIES
 Histamine is distributed in
Mast Cells in all peripheral
tissues of the body and
basophils, which circulate in
the blood
MAST CELL STRUCTURE OF HISTAMINE
 When it is released, histamine
causes inflammation by
increasing vasodilation, capillary
permeability, causing smooth
muscle contraction, mucus
secretion, and parasympathetic
nerve stimulation

5. TYPES OF HISTAMINE
RECEPTORS

6. CLINICAL USE OF
ANTIHISTAMINE
 Allergic rhinitis (common cold)
 Allergic conjunctivitis (pink eye)
 Allergic dermatological conditions
 Urticaria (hives)
 Angioedema (swelling of the skin)
 Pruritus (atopic dermatitis, insect bites)
 Anaphylactic reactions (severe allergies)
 Nausea and vomiting (first generation H1-
antihistamines)
 Sedation (first generation H1-antihistamines)

7. STRUCTURAL CLASS OF ANTI
HISTAMINE
 Alkylamines (eg, brompheniramine,
chlorpheniramine, dexchlorpheniramine,
pheniramine, triprolidine)
 Ethanolamines (eg, carbinoxamine, clemastine,
dimenhydrinate, diphenhydramine, doxylamine)
 Ethylenediamines (eg, pyrilamine, tripelennamine)
 Phenothiazines (eg, methdilazine, promethazine,
trimeprazine)
 Piperidines (eg, cyproheptadine, fexofenadine,
loratadine), terfenadine and astemizole have been
recalled from the US market
 Piperazines (eg, cetirizine, cyclizine, hydroxyzine,
levocetirizine, meclizine)

8. TYPES OF ANTI HISTAMINE

9. TYPES OF ANTI HISTAMINE
 Most people assume
antihistamines are of no
concern because of their easy
access in over-the-counter
allergy, cough, and cold
medicines and sleep aids.
According to a 2010 review in
Allergy, the older, (first
generation), sedating
antihistamines, developed in
the 1940s to 1950s, penetrate
the central nervous system
(CNS). This is what gives them
a potential for abuse and
addiction.
 second and third
generation
antihistamines are non-
sedating or minimally
sedating and cause less
drowsiness than the first
generation drugs. This is
because they have
limited penetration into
the brain. They also have
fewer side effects
because they only bind
to selected receptors.
SEDATING NON SEDATING

10. TYPES OF ANTI HISTAMINE
 Abuse of the Drugs
 The older, sedating
antihistamines
include:
 Diphenhydramine
(Benadryl)
 Chlorpheniramine
(Chlor-Trimeton)
 Promethazine
 Addiction to the
newer antihistamines
which include:
 Loratadine (Claritin)
 Fexofenadine
(Allegra)
 Cetirizine (Zyrtec)
 Clemastine (Tavist)
 Desloratadine
(Clarinex)
SEDATING NON SEDATING

11. SIGN OF ABUSE

12. SIGN OF ABUSE FOR SEDATING
ANTI HISTAMINE
 Based on the review in the Journal of Child and Adolescent
Psychopharmacology, with overuse of diphenhydramine, after
a while classic signs of abuse or addiction can develop:
 Tolerance and the need to take increasing doses of
diphenhydramine to maintain the desired CNS effects
happens in a few days.
 Physical dependence, because of withdrawal symptoms if
you don't take the drug, can lead to seeking the drug to
relieve the symptoms.
 Addiction behaviors, such as compulsive drug seeking
despite adverse side effects and consequences, occur
because of a chemical and psychological dependence on the
medicine.

13. WITH DRAWL SYMPTOMS
 After abusing diphenhydramine or other sedative
antihistamines if you suddenly stop taking them,
withdrawal symptoms that indicate that you have
physical dependence include:
 Insomnia
 Irritability
 Restlessness
 Sweating
 Abdominal cramps
 Diarrhea
 Runny nose

14. ADVERSE EFFECTS

15. ADVERSE EFFECTS
 Light-headedness
 Loss of coordination
 Dry nose, throat, and mouth
 Blurred vision
 Spatial and mental disorientation
 Drowsiness
 Gastrointestinal upset like nausea, vomiting, constipation, diarrhea, or urinary
retention
 Loss of appetite
 Temporary erectile dysfunction in men
 Visual and aural distortions
 Muscle relaxation
 Nervousness and insomnia
 Mild to moderate hallucinatory experiences
 An increased appreciation of music.

16. PRECAUTIONS

17. ANTI HISTAMINE
PRECAUTIONS
 Before taking an antihistamine, tell your doctor about all
medical conditions you have, especially:
 Diabetes
 An overactive thyroid (hyperthyroidism)
 Heart disease
 High blood pressure
 Glaucoma
 Epilepsy (seizure disorder)
 An enlarged prostate or trouble urinating.
 pregnancy

18. LIST OF OVER THE COUNTER
DRUG ABUSE
Class/therapeutic group Medication example
Antihistamines Diphenhydramine and coricidin
Cough medicines42 Cough medicines containing
dextromethorphan
Codeine-containing products Compound analgesics (codeine with
ibuprofen or paracetamol) and cough
medicines
Analgesics Aspirin and acetaminophen
Laxatives (oral and rectal) Sodium phosphate laxatives and
laxatives containing bisacodyl
Decongestants Pseudoephedrine

19. OVER DOSE

20. OVER DOSE EFFECTS
 Drowsiness
 Dilated pupils
 Flushed, dry skin
 Fever
 Hallucinations
 Delirium
 Convulsions
 Hyperthermia

21. TOXICTY AND ITS MECHANISM

22. TOXICITY
 Acute intoxication with antihistamines
results in symptoms very similar to those
of anticholinergic poisoning. H2 receptor
blockers (cimetidine, ranitidine, and
famotidine) inhibit gastric acid secretion
but otherwise share no effects with H1
agents, do not produce significant
intoxication.

23. MECHANISM OF TOXICITY
 SEDATING ANTI HISTAMINE
 1. piper dines class of anti histamine
(Cyproheptadine)
 is known to block serotonin receptors as do the
recently discovered compounds that have dual H3
antagonist and serotonin reuptake Inhibition
properties
 phenothiazine class of antihistamines
(promethazine)
 They have alpha-adrenergic blocking activity and may
cause hypotension. H1 receptors have been found on
sebocytes, and the use of H1 blockers in the
management of acne may have a future role. There is
no current clinical use for H3- and H4-receptor
antagonists.

24. Cont…..
 Ethanolamines class of antihistamine(Doxylamine)
 exposure has been associated with rhabdomyolysis. The
mechanism of its toxicity is unknown, but doxylamine may have a
direct toxic effect on muscle, possibly thorough injury to the
sarcolemma.
 Fexofenadine, loratadine, desloratadine, astemizole,
cetirizine, and levocetirizine are peripherally selective H1-
receptor antagonists. Desloratadine is the most potent of
these. They have a distinct advantage because they bind
much more selectively to peripheral H1 receptors and have a
lower binding affinity for the cholinergic and alpha-adrenergic
receptor sites than other antihistamines. This group of
antihistamines is popular because specificity for the
peripheral histamine receptor site eliminates many adverse
effects, including central nervous system (CNS) depression,
blurred vision, dry mouth, and tachycardia. These
medications are commonly used in the treatment of allergic
rhinitis and chronic idiopathic urticaria

25. Cont….
 Some of the first-generation H1-receptor blockers
( diphenhydramine, clemastine, promethazine)
are also potent competitive inhibitors of
muscarinic receptors and may cause
anticholinergic syndrome (eg, sinus tachycardia,
dry skin, dry mucous membranes, dilated pupils,
ileus, urinary retention, agitated delirium). H1-
receptor blockers may disrupt cortical
neurotransmission and block fast sodium
channels. These effects can exacerbate sedation,
but they also can result in seizure activity. Sodium
channel blockade in the cardiac cells can cause
conduction delays manifested by widening of the
QRS interval and dysrhythmias

26. Cont…..
 Piperazines class of anti histamine(Levocetirizine)
 which is the L-enantiomer of cetirizine (cetirizine and levocetirizine are
both metabolic derivatives of hydroxyzine) has not been associated with
torsades de pointes in volunteer and animal studies. See the image
below.
 NON SEDATING ANTI HISTAMINE
 Two nonsedating antihistamines, terfenadine and astemizole, are known
to inhibit the potassium rectifier currents (HERG1K), which slows
repolarization. This is manifested clinically as prolongation of the QT
interval and torsades de pointes. Astemizole and terfenadine have been
removed from the US market. Terfenadine has been replaced by
fexofenadine, which is the pharmacologically active metabolite of
terfenadine. Fexofenadine has only been reported to potentially lead to
one case of QT prolongation progressing to ventricular tachycardia and
degenerating into ventricular fibrillation.[8] However, this particular case
may have had additional risk factors that may have contributed or been
responsible for such an effect.

27. ROLE OF PHARMACIST

28. TARGET LOCATIONS PHARMACIST-INITIATED
STRATEGIES
IN A PHARMACY • Refusing sales
• Contacting other pharmacies to
warn them of the suspicions of a
customer who may be abusing a
product
• Claiming products were not in
stock
• Prevent supplies by hiding
medicines
• Supplying only limited amounts
PATIENT INVOLVEMENT • Counseling customers about the
abuse potential of products
• Raising awareness of Internet-
based support groups among
patients by advising them
• Providing information leaflets
PHYSICIAN INVOLVEMENT AND
OTHER SERVICES
• Working on general practitioner
engagement/consultation
• Providing referral to doctors
ROLE OF PHARMACIST IN CONTROLLING
TOXICTY