Protriptyline
Encyclopedia
Protriptyline is a tricyclic antidepressant
(TCA), specifically a secondary amine, indicated for the treatment of depression and ADHD
. Unique among the TCAs, protriptyline tends to be energizing
instead of sedating
, and is sometimes used for narcolepsy
to achieve a wakefulness-promoting
effect.
TCAs including protriptyline are also used to reduce the incidence of recurring headaches such as migraine, and for other types of chronic pain. This drug can also be used for sleep apnea treatment along with a carbonic anhydrase inhibitor.
and depression .Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder
, obsessive-compulsive disorder
, attention-deficit/hyperactivity disorder, enuresis
,eating disorders such as bulimia nervosa
, cocaine dependency, and the depressive phase of bipolar disorder
(manic-depressive) disorder. It has also been used to support smoking cessation programs.
derivative, has a molecular weight of 299.84. It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline hydrochloride is supplied as 5 mg or 10 mg tablets. Inactive ingredients are anhydrous lactose, colloidal silicon dioxide, magnesium stearate
, and microcrystalline cellulose
.
and serotonin
(5-HT) in the brain. Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine
. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug.
Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting
the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex
and hippocampus
. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid
systems in the CNS
via an indirect serotonergic
route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.
.
In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed. Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention
.
, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them.
A common problem with tricyclic antidepressants is sedation
(drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most people, sedation decreases or disappears entirely with time, but, until then, patients taking protriptyline should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when protriptyline is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take protriptyline in combination with these substances. Protriptyline may increase the possibility of having seizures .
Protriptyline may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.
When Protriptyline is used to treat the depressive component of schizophrenia
, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of Protriptyline or to use a major tranquilizing drug concurrently.
(convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.
; stroke; heart block; arrhythmias; hypotension
, particularly orthostatic hypotension
; hypertension
; tachycardia
; palpitation
.
Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania
; exacerbation of psychosis; insomnia
, panic, and nightmares.
Neurological: Seizures; incoordination; ataxia
; tremors; peripheral neuropathy
; numbness, tingling, and paresthesias of extremities; extrapyramidal
symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate ADH
(antidiuretic hormone) secretion;tinnitus
; alteration in EEG
patterns.
Anticholinergic
: Paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure
, mydriasis
; dry mouth and rarely associated sublingual adentitis.
Allergic: Drug fever; petechiae, skin rash, urticaria
, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue).
Hematologic: Agranulocytosis
; bone marrow depression; leukopenia
;thrombocytopenia
; purpura
; eosinophilia
.
Gastrointestinal: Nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis
; abdominal cramps; black tongue.
Endocrine: Impotence, increased or decreased libido: gynecomastia
in the male; breast enlargement and galactorrhea
in the female; testicular swelling; elevation or depression of blood sugar levels.
Other: Jaundice
(simulating obstructive); altered liver function; parotid swelling; alopecia
; flushing; weight gain or loss; urinary frequency, nocturia
; perspiration.
Critical manifestations of overdosage include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor
, drowsiness, muscle rigidity, vomiting, hypothermia
, hyperpyrexia.
Studies on the disposition of radioactive Protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually.
Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours. The rate of excretion was slow. Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
(TCA), specifically a secondary amine, indicated for the treatment of depression and ADHD
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
. Unique among the TCAs, protriptyline tends to be energizing
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
instead of sedating
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
, and is sometimes used for narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
to achieve a wakefulness-promoting
Wakefulness-promoting agent
A wakefulness-promoting agent is a type of psychoactive drug which improves wakefulness and alertness, and reduces tiredness, drowsiness, and the need for sleep. They are often used in the treatment of hypersomnia and narcolepsy...
effect.
TCAs including protriptyline are also used to reduce the incidence of recurring headaches such as migraine, and for other types of chronic pain. This drug can also be used for sleep apnea treatment along with a carbonic anhydrase inhibitor.
Purpose
Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxietyAnxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
and depression .Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
, attention-deficit/hyperactivity disorder, enuresis
Enuresis
Enuresis refers to an inability to control urination. Use of the term is usually limited to describing individuals old enough to be expected to exercise such control.Types of enuresis include:* Nocturnal enuresis* Diurnal enuresis...
,eating disorders such as bulimia nervosa
Bulimia nervosa
Bulimia nervosa is an eating disorder characterized by binge eating and purging or consuming a large amount of food in a short amount of time, followed by an attempt to rid oneself of the food consumed, usually by purging and/or by laxative, diuretics or excessive exercise. Bulimia nervosa is...
, cocaine dependency, and the depressive phase of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
(manic-depressive) disorder. It has also been used to support smoking cessation programs.
Description
Protriptyline hydrochloride, a dibenzocyclohepteneDibenzocycloheptene
Dibenzocycloheptene is a chemical compound featuring two benzene rings bound to a cycloheptene group.Various tricyclic antidepressants contain the dibenzocycloheptene moiety in their chemical structures, including amineptine, amitriptyline, amitriptylinoxide, butriptyline, demexiptiline,...
derivative, has a molecular weight of 299.84. It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline hydrochloride is supplied as 5 mg or 10 mg tablets. Inactive ingredients are anhydrous lactose, colloidal silicon dioxide, magnesium stearate
Magnesium stearate
Magnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula . It is a salt containing two equivalents of stearate and one magnesium cation...
, and microcrystalline cellulose
Microcrystalline cellulose
Microcrystalline cellulose is a term for refined wood pulp and is used as a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production. The most common form is used in vitamin supplements or tablets...
.
Mechanism Of Action
Protriptyline acts by decreasing the reuptake of norepinephrineNorepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5-HT) in the brain. Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug.
Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting
Reuptake inhibitor
A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...
the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
and hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
systems in the CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
via an indirect serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...
route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.
Withdrawal
Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaiseMalaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
.
Recommended dosage
Protriptyline is available as 5-mg and 10-mg tablets. Doses range from 15 to 40 mg per day and can be taken in one daily dose or divided into up to four doses daily. Some people with severe depression may require up to 60 mg per day.In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed. Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
.
Precautions
Like all tricyclic antidepressants, protriptyline should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy (enlarged prostate gland), urinary retention, and glaucomaGlaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them.
A common problem with tricyclic antidepressants is sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
(drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most people, sedation decreases or disappears entirely with time, but, until then, patients taking protriptyline should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when protriptyline is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take protriptyline in combination with these substances. Protriptyline may increase the possibility of having seizures .
Protriptyline may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.
When Protriptyline is used to treat the depressive component of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of Protriptyline or to use a major tranquilizing drug concurrently.
Side effects
Protriptyline shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, decreased coordination, anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal problems. Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizureSeizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
(convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.
Adverse Reactions
Cardiovascular: Myocardial infarctionMyocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
; stroke; heart block; arrhythmias; hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, particularly orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
; hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
; tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
; palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
.
Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...
; exacerbation of psychosis; insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, panic, and nightmares.
Neurological: Seizures; incoordination; ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
; tremors; peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
; numbness, tingling, and paresthesias of extremities; extrapyramidal
Extrapyramidal
Extrapyramidal can refer to:* Extrapyramidal system* Extrapyramidal symptoms...
symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate ADH
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(antidiuretic hormone) secretion;tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
; alteration in EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
patterns.
Anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
: Paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure
Intraocular pressure
Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...
, mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
; dry mouth and rarely associated sublingual adentitis.
Allergic: Drug fever; petechiae, skin rash, urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue).
Hematologic: Agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
; bone marrow depression; leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
;thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
; purpura
Purpura
Purpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure. They are caused by bleeding underneath the skin...
; eosinophilia
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
.
Gastrointestinal: Nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis
Stomatitis
Stomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth...
; abdominal cramps; black tongue.
Endocrine: Impotence, increased or decreased libido: gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
in the male; breast enlargement and galactorrhea
Galactorrhea
Galactorrhea or galactorrhoea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.Contemporary Maternal-Newborn Nursing Care defines galactorrhea as "nipple discharge." -Causes:...
in the female; testicular swelling; elevation or depression of blood sugar levels.
Other: Jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(simulating obstructive); altered liver function; parotid swelling; alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
; flushing; weight gain or loss; urinary frequency, nocturia
Nocturia
Nocturia , also called nycturia , is the need to get up in the night to urinate, thus interrupting sleep. Its occurrence is more frequent in pregnant women and in the elderly...
; perspiration.
Overdosage
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible.Critical manifestations of overdosage include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor
Stupor
Stupor is the lack of critical cognitive function and level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain. This is often mistaken for delirium and treated with Haldol and or other anti-psychotic drugs...
, drowsiness, muscle rigidity, vomiting, hypothermia
Hypothermia
Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...
, hyperpyrexia.
Metabolism
Metabolic studies indicate that Protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues. Relatively low plasma levels are found after administration, and only a small amount of unchanged drug is excreted in the urine of dogs and rabbits. Preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation probably takes place in the liver. It penetrates the brain rapidly in mice and rats, and moreover that which is present in the brain is almost all unchanged drug.Studies on the disposition of radioactive Protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually.
Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours. The rate of excretion was slow. Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.
See also
- Tricyclic antidepressantTricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...