Positive symptoms- delusions, auditory hallucinations

Negative symptoms- social withdrawal, depressed

Positive symptoms are symptoms of stimulation- drug depressant
Negative symptoms- those of depression- stimulant
Positive symptoms are associated with dopamine- dopamine hypothesis-> too much
dopamine causing repetitive behavior
Serotonin has a role in negative symptoms
Block dopamine and raise serotonin
Improve serotonin transmission – 5HT2
In the mesolimbic- balance between dopamine and serotonin
Blockade of 5HT2, improve dopamine because of this balance
Atypical antipsychotics
Dopamine agonist- pimozide Tourette syndrome
Side effects of antipsychotics- dopamine blockade- dyskinesias- extrapyramidal
symptoms- hours of initiation of treatment (pseudoparkinsoniasm)
Resting tremor, rigidity, dystonia

Haloperidol to manage his schizophrenia- after taking for one week he has acute
onset of oromandibular dystonias
Acute dystonic reactions are treated with anticholinergic agents. The most
commonly used agents are benztropine and trihexyphenidyl
Anticholinergic drugs cause a host of common side effects- dry eyes (due to
inhibition of lacrimation), dry mouth (due to inhibition of salivation), constipation
(due to inhibition of GI motility), urinary retention (inhibition of detrusor muscle),
blurred vision ( due to inability to accommodate the lens; cycloplegia)

Bradykinesia (slow movement), rigidity, resting tremor and postural instability

most consistent with Parkinsons disease- which is managed with
levodopa/carbidopa to treat the underlying dopaminergic dysfunction

Carbamazepine- anticonvulsant and mood stabilizer- treatment for trigeminal

neuralgia
Donezepil is an anticholinesterase inhibitor- slow the progression of cognitive
decline in patients with AZ disease

Visual hallucinations occasionally seen in parkinsons disease

Auditory hallucinations and psychosis are consistent with psychiatric disorder such
as schizophrenia which could be treated with an atypical antipsychotic such as
risperidone

D2 receptor antagonist (typical antipsychotic) for his presentation of positive effect

of schizophrenia
These drugs have high potency (FLUPHENAZINE, Haloperidol) with greater effect
on dopamine blockade or low potency (chlorpromazine) with higher muscuranic
antagonism

D2 receptor blockers are associated with EPS (parkinsonism, restless legs, abnormal
muscle tension)
Alpha 1 adrenergic and muscarinic blockage the typical antipsychotics can increase
serum prolactin levels by blockade of dopamine receptors in the tuberoinfundibular
pathway to cause infertility and gynecomastia in males and menstrual irregularities
in women

Amitriptyline- tca that inhibits reuptake of both NE and 5HT

Treat depression, ocd, sleep disorder and chronic pain
They are associated with muscarinic receptor blockade
Alpha one blockade (orthostatic hypotension and reflex tachycardia)
H1 blockade sedation and weight gain
An overdose of tca has serious cardiotoxic potential which is managed via sodium
bicarbonate
Bromocriptine is a D1 and D2 agonist that serves as an adjunct to levodopa
in advanced Parkinson disease in addition to reducing prolactin levels in
prolactinomas. Thus, it can enhance the symptoms of psychosis (vivid
dreams and hallucinations) at high doses.
Clozapine was the first of the atypical antipsychotics, which work to reduce
the negative symptoms of schizophrenia because they have a greater
affinity for 5-HT2 receptor blockade rather than D2 block. Thus, they are not
as strongly associated with EPS as the typical antipsychotics. In the case
of clozapine, there is no tardive dyskinesia because the drug blocks D4
rather than D2 receptor subtypes. D4 are primarily found in mesolimbic
structures. D2 are found in the nigrostriatal pathway. Clozapine, however,
requires biweekly monitoring of leukocytes since a fatal agranulocytosis
can occur.
Lithium is a mood stabilizer used for the treatment of the manic phase of
bipolar disorder. It acts to reduce signaling mechanisms of G protein–
coupled receptors. Lithium is known to block inosine 5’-monophosphatase,
which decreases inositol and Gq-coupled receptor responses. Lithium also
stabilizes the trimeric inactive forms of Gs and Gi proteins, thereby
interfering with cAMP cascades. Because this drug has a narrow
therapeutic index, serum plasma levels should be frequently monitored.
The drug is associated with hypothyroidism, since it can inhibit the
proteolysis reaction involved in hormone release and the effect of TSH
through its Gs-coupled receptor. Patients can complain of increased thirst
and urination with lithium, and the number of aquaporins in the collecting
tubule can be reduced. ADH receptors in the collecting duct are Gs-
coupled.
Valproic acid is a broad-spectrum antiepileptic for the treatment of tonic-
clonic and myoclonic seizures, but also for the manic phase of bipolar
disorder. It has three main relevant mechanisms of action. The blockade of
GABA transaminase prevents degradation of GABA. The inhibition of T-
type calcium channels interferes with thalamic neuron bursts of activity and
explains the use of valproate in absence seizures. Finally, the inhibition of
voltage-gated sodium channels mimics the actions of phenytoin and
carbamazepine, decreasing the conduction of action potentials. This drug
can cause hepatitis as its main toxicity. Therefore, baseline liver function
tests are required before starting and for the duration of treatment.
Alopecia and pancreatitis as well as thrombocytopenia are also important
adverse effects of valproic acid.

psychosis (delusions, visual and auditory hallucinations). Treatment for this

psychiatric disorder includes drugs that block the D2 receptor (typical
antipsychotics) and newer agents, which have a greater affinity for 5HT2
receptors (atypical antipsychotics).
Typical antipsychotics include chlorpromazine, thioridazine, haloperidol,
and fluphenazine, which, by the blockade of dopamine receptors, are very
effective at treating some of the “positive” signs of schizophrenia, such as
those experienced by the patient in this vignette. The typical antipsychotics
are associated with extrapyramidal side effects associated with D2
receptor antagonism. Additional toxicities of the peripheral autonomic
nervous system are common becausethey block muscarinic and alpha-1
adrenergic receptors. Thus, urinary retention, tachycardia, constipation,
and orthostatic hypotension are common. Antagonism of the histamine
blocker produces weight gain and sedation. The picture above represents
an electrocardiogram, with an increased QT interval that is characteristic of
torsade de pointes. This is because thioridazine is most strongly
associated with tachycardia, because this typical antipsychotic is of low
potency with the strongest antimuscarinic potential.

Clozapine was the first atypical antipsychotic, with a higher propensity to

block the 5HT2 rather than the D2 receptor. This class of antipsychotics
has fewer extrapyramidal side effects, with greater action against the
negative symptoms (social withdrawal, depression) of schizophrenia.
Clozapine is associated with fatal agranulocytosis, and for the first 6
months of therapy requires weekly monitoring of leukocyte counts. After
this time period, monitoring should be done every 2 weeks.
Haloperidol is considered to be an antipsychotic of high potency because
the blockade of dopamine at its receptor is the associated with the highest
risk of extrapyramidal effects, including motor restlessness, tremor, rigidity,
bradykinesia, and muscle tension.
Sertraline is a selective serotonin reuptake inhibitor (SSRI), the first-line
treatment for depression, panic, and obsessive-compulsive disorder.
Although these drugs produce fewer side effects of muscarinic, histaminic,
and alpha-1 adrenergic receptor blockade, SSRIs have been observed to
cause impotence in treated males or a dangerous “serotonin syndrome”
when combined with other serotonergic drugs (tricyclic antidepressants,
sumatriptan, phenelzine). 

Calcium channel blockers in general, many anticonvulsants (phenytoin,

valproate, phenobarbital), and cyclosporine are among the drugs that have
been associated with gingival hyperplasia. Serotonin agonists such as
sumatriptan are very effective at aborting the headache because they
block the migraine’s vasodilation phase. However, these drugs should be
limited in treatment because vasoconstriction can induce episodes of
angina in the cardiovascular patient. Therefore, prophylactic drugs for
migraine headache are encouraged.
Although calcium channel blockers are used for hypertension and to
suppress the atrioventricular (AV) node, verapamil is often used as a
prophylactic agent in migraine headache pathogenesis, as it prevents the
vasoconstrictive phase of the headache. These drugs are associated with
gingival hyperplasia

Ergotamine is a partial agonist at alpha 1 and 5HT2 receptors. It is used in

the management of the acute migraine attack due to its vasoconstrictive
action in the CNS. Ergotamine is a partial agonist at alpha 1 and 5HT2
receptors. It is used in the management of the acute migraine attack due to
its vasoconstrictive action in the CNS.

he nonselective beta-adrenergic blocker propranolol is commonly used for

preventing migraines. The proposed mechanism includes the blockade of
vasodilation. In addition, the drug reduces the serotonin release from
platelets, which is the first step in the pathogenesis of migraines

For patients with Alzheimer disease, the main treatment focus is the
increase of cholinergic neurotransmission in the cortex and limbic
structures of the brain. This is accomplished by the inhibitors of
acetylcholinesterase (donepezil, and the newer agents rivastigmine and
galantamine), which increase the levels of acetylcholine in the cortex.
Although these drugs slow the progression of Alzheimer disease, they do
not change the ultimate neurodegeneration associated with this disorder.
The side effects are primarily those associated with excessive muscarinic
stimulation in the periphery and include incontinence, diarrhea, and
excessive sweating and salivation, as well as bradycardia and
bronchospasm.

Alpha1 adrenergic blockers are drugs that inhibit the activation of

phospholipase C, decrease IP3, and inhibit the release of calcium, leading
to smooth muscle relaxation in both the arterioles and bladder. Thus,
prazosin, terazosin, and doxazosin are effective for the treatment of
hypertension (vasodilation) and benign prostatic hypertrophy.

hibitors of catechol-O-methyltransferase (COMT) stop the conversion of

levodopa to 3-O-methyldopa (3OMD), thus preserving dopamine levels
from levodopa in the substantia nigra. This improves the motor function of
the patient with Parkinson disease without the need for a further increase
in levodopa therapy or a “wearing off” effect. The drugs tolcapone and
entacapone are available COMT inhibitors, with entacapone being safer,
with minimal reports of hepatic toxicity.
Monoamine oxidase inhibitors (MAOIs) include phenelzine, which is used
for severe depression and is nonselective for MAO-A and B, and the drug
selegiline, a selective inhibitor of MAO-B. Selegiline is used for the
treatment of Parkinson disease. It inhibits the progression of this disorder
by increasing dopamine levels in the basal ganglia. Selegiline also
decreases the need for an increase in levodopa. Unlike the MAO-A
inhibitor phenelzine, selegiline does not cause hypertensive crisis with
tyramine-containing foods.

patient’s presentation with hyperthermia, rigidity, and autonomic instability

shortly after receiving haloperidol, a typical antipsychotic, is consistent with
neuroleptic malignant syndrome (NMS). In NMS, central D2 dopamine
receptor blockade (due to haloperidol in this case) leads to increased
muscle rigidity and tremor via extrapyramidal pathways. Antipsychotics
should be immediately discontinued, and treatment with dantrolene
considered, along with supportive management.

Cholinergic hyperactivity, as seen in organophosphate poisoning, would

typically present with salivation, lacrimation (tearing), urination, defecation,
GI upset, and emesis (as can be recalled by the acronym “cholinergic
SLUDGE”). 

Alcohol withdrawal is related to dysregulation of GABA receptors; delirium

tremens could present with hyperthermia and diaphoresis, but would
typically develop 24 to 72 hours after alcohol cessation. 
Norepinephrine receptor overactivity could be seen following cocaine
overdose and result in agitation, hyperpyrexia, and cardiovascular
toxicities. However, cocaine would aggravate schizophrenia.

Serotonin syndrome can present with autonomic instability,

encephalopathy, and tremor due to excess serotonergic activity (often
secondary to SSRIs). SSRIs are not used to treat schizophrenia
Rifampin is a bactericidal antibiotic that works by blocking DNA-dependent
RNA polymerase.

This is the mechanism of action for penicillins and cephalosporins. They

bind to PBPs, which then prevents transpeptidation and cross-linking of the
bacterial cell wall. Ceftriaxone, a third-generation cephalosporin, is used
for the treatment of meningococcal meningitis, not for prophylaxis.
Fluoroquinolones are direct nucleic acid synthesis inhibitors that block
topoisomerases II and IV. The fluoroquinolone ciprofloxacin is the second
line for the prophylactic treatment of meningococcal meningitis.
It binds to the p site of the 30s ribosomal subunit. this is the mechanism of
action of aminoglycosides, which have no place in the management or
prophylaxis of meningitis. These antibiotics are often used in combination
with other antibiotics to fight off gram-negative aerobic infections. 

Phencyclidine intoxication- affects the CNS by antagonizing the N-methyl-

D-aspartate receptor thereby blocking the action of glutamate- symptoms
include rage, paranoia, analgesia to pain, hypertension, hyperthermia,
nystagmus and rhabdomyolysis with possible convulsions and death
resulting
Pcp antagonizes the nicotinic acetylcholine receptor and is a partial
agonist of D2 receptor, contributing to the drugs psychotic effects
(classified as dissociative drug)
Similar drug- ketamine is used therapeutically for anesthesia induction
Ondansetron (an antiemetic) is known to antagonize the 5-HT3 receptor.

The patient is experiencing the classic signs of an absence seizure, which

most commonly occurs in the pediatric population. This type of seizure is
categorized by a brief loss of consciousness in which the patient stares
into space, followed by a full recovery. The safest and most effective drug
for absence seizures in the pediatric patient is ethosuximide. This drug
inhibits neuronal T-type calcium channels, which are activated in absence
seizures.
Sodium channel blockers include phenytoin and carbamazepine. These
drugs delay the formation of a new action potential by prolonging the time
that the sodium channel's inactivation gate remains closed. As they cause
CNS depression, these drugs exacerbate absence seizures. Phenytoin
and carbamazepine are first-line drugs for tonic-clonic seizures. Besides
their similar mechanism of action, these sodium channel blockers are
inducers of cytochrome P450, which cause drug interactions by
accelerating the metabolism of concurrent drugs. In addition,
carbamazepine is used to treat both trigeminal neuralgia and bipolar
disorder. Complete blood counts should be done with carbamazepine
therapy because aplastic anemia has been reported. Phenytoin has an
even greater toxicity profile than carbamazepine because it exhibits zero-
order elimination. Megaloblastic anemia, hirsutism, and gingival
hyperplasia are other toxicities associated with phenytoin use.

Glutamate is an excitatory neurotransmitter that activates the N-methyl-D-

aspartate (NMDA) receptor to increase calcium transmission into the
neurons, increasing seizure activity. Valproate is a broad-spectrum
antiepileptic, with several mechanisms of action, including a reduction in
glutamate synthesis. Valproate is effective in treating both tonic-clonic and
myoclonic seizures. Although valproate is used to treat absence seizures
in adults, it can cause hepatotoxicity. This requires careful monitoring of
liver transaminases. Thus, ethosuximide is first line in treating this seizure
type in the pediatric patient.

Benzodiazepines potentiate GABA by increasing the frequency of chloride

channel opening. These drugs are considered primary treatment for acute
anxiety. However, the specific benzodiazepines lorazepam and diazepam
are first-line drugs for status epilepticus when administered IV. This is a
life-threatening emergency in which the patient has a continuous tonic-
clonic seizure without regaining consciousness between each episode. 

Meperidine is a mu receptor analgesic with strong antimuscarinic

pharmacology. It has an active metabolite, normeperidine, an SSRI that
can cause agitation and seizures. This is particularly true in the elderly
patient with renal dysfunction, since drug excretion will be decreased.
Therefore, another analgesic should be given to relieve metastatic
carcinoma pain in this geriatric patient.
Codeine is less potent than morphine as a mu receptor agonist and is
often combined with NSAIDs, aspirin, or acetaminophen for the treatment
of mild to moderate pain. Codeine is also very effective as an antitussive.
Methadone is a mu receptor agonist with a long duration of action. Even
though it can be used for analgesia, the drug is effective for the treatment
of opioid dependence. The long t ½ of methadone prevents the occurrence
of the euphoria and withdrawal symptoms associated with opioid addiction
Pentazocine is a partial agonist that has a greater affinity for the kappa (κ)
receptor and is used as treatment for moderate to severe pain. This drug is
often associated with severe cardiovascular and CNS effects (focusing
difficulty, disturbed dreams, insomnia), but not with seizures.
Alfentanil is a derivative of fentanyl, which is used intravenously as part of
an anesthesia protocol for short-term procedures.

Beta 2 agonist- relaxes the smooth muscle and increases lipolysis

it is Gs coupled
The increased cAMP causes protein kinase to phosphorylate myosin light
chain kinase (MLCK) inactivating it
Lack of phosphorylation of the MLC by kinase prevents interaction with
actin- smooth muscle relaxation
The side effect of vasodilation causes blood pressure to drop and possible
tachycardia

Flumazenil is a benzodiazepine antagonist used to treat situations of

benzodiazepine or zolpidem overdose
Fomepizole is an inhibitor of alcohol dehydrogenase, which prevents the
toxic metabolites produced by an overdose of methanol or ethylene glycol
"antifreeze" poisoning. 
Naloxone is an opioid receptor antagonist. The drug has a short half-life
and must be given repeatedly by intravenous route to counteract the
effects of the opioid. 
Physostigmine is an inhibitor of cholinesterase. It is the antidote for
antimuscarinic drug intoxication.
Sodium bicarbonate is used for trapping "acidic" drugs in the urine, for
enhancement of elimination. Overdoses of aspirin and barbiturates are
often treated by administration of sodium bicarbonate so the remaining
drug can be excreted in the urine.
Nortriptyline is a tricyclic antidepressant that inhibits the reuptake of both
norepinephrine and serotonin. These drugs are effective, but have been
replaced with newer antidepressants because tricyclic antidepressants
block the alpha1, histamine, and muscarinic receptors, which are
associated with significant toxicities. In fact, because these drugs are
considered to have anticholinergic effects, patients with benign prostatic
hypertrophy (BPH) and narrow-angle glaucoma should avoid tricyclic
antidepressants, as they can exacerbate these conditions.
Narrow angle glaucoma- needs a drug that increases the outflow of
aqueous humor at the schlemm canal

Bupropion is an antidepressant with weak inhibition of reuptake of

dopamine, norepinephrine, and serotonin. One benefit of bupropion
compared to other antidepressants is the lack of anticholinergic,
cardiovascular, and sexual side effects. In addition, bupropion reduces the
craving for cigarettes and is used for smoking cessation. This drug should
be used with caution in patients with bulimia or anorexia, since there is a
higher risk of seizures in these patients who are treated with bupropion.

Carbamazepine is a sodium channel blocker used for the treatment of

tonic-clonic seizures, trigeminal neuralgia, and the manic phase of bipolar
disorder. There have been reports of drug interactions with
carbamazepine, since the drug is a known inducer of cytochrome P450.
Carbamazepine is associated with ataxia, drowsiness, and rarely, aplastic
anemia. Therefore, complete blood counts should be routinely taken. 
Lithium is used specifically to treat the manic phase of bipolar disorder.
The proposed mechanism of this "mood stabilizer" is the inhibition of
inositol triphosphate (IP3) formation, which reduces the neuronal response
to neurotransmitters. Patients should be monitored periodically while being
treated with lithium because the drug has a low margin of safety. One
major adverse effect associated with this mood stabilizer is polyuria and
polydipsia, which result from the inability of the kidney to concentrate urine
due to a reduced response to antidiuretic hormone (ADH). In addition,
patients should be advised to report any signs and symptoms of
hypothyroidism because lithium may interfere with the release of hormone
from the thyroid follicle. 
Sertraline is a selective serotonin reuptake inhibitor (SSRI). SSRIs have
largely replaced tricyclic antidepressants for obsessive-compulsive
disorder and depression because they are associated with fewer sedative,
cardiovascular, and autonomic toxicities. This is especially beneficial in the
elderly patient. The main toxicity associated with SSRIs is male sexual
dysfunction.

Lithium is a mood stabilizer used to treat and prevent the manic phase of
bipolar disorder. The drug reduces the formation of the second messenger
molecule inositol (IP3) by inhibiting the enzyme involved in its regeneration,
inosine-5’ monophosphatase. Lithium also stabilizes the trimeric inactive
forms of Gs and Gi proteins, thereby interfering with cAMP-mediated
responses. Finally, lithium is also known to decrease protein kinase
function. These effects are responsible for reducing responsiveness to
neurotransmitters and hormones. Lithium has a narrow therapeutic index,
meaning that the drug’s therapeutic and toxic dosages are very close.
Thus, toxicities are common, which include tremors (managed by beta-
adrenergic receptor blockers), polyuria, and polydipsia (related to Gs-
coupling of ADH receptors). In addition, lithium inhibits the release of T3
and T4 from the colloid (via proteolysis) through inhibition of TSH effects.
TSH receptors are Gs-coupled. Therefore, some patients can experience
the signs and symptoms of hypothyroidism (constipation, fatigue, dry skin,
cold sensation), as described in the vignette above. Patients may need
levothyroxine if clinical therapy is required for the low serum hormone.
Carbamazepine is a sodium channel blocker that is beneficial for the
treatment of partial and tonic-clonic seizures, trigeminal neuralgia, and the
manic phase of bipolar disorder. In addition, it is associated with fewer
adverse effects than lithium while having a faster onset for mania
management. Carbamazepine is associated with drug interactions
because it is a well-known inducer of cytochrome P450. Rare cases of
aplastic anemia have occurred.

Clozapine was the first developed atypical antipsychotic. Atypical

antipsychotics have greater antagonism potential for the 5-HT2 receptor
rather than the D2 receptor. Thus, fewer extrapyramidal effects (dystonia,
akathisia, rigidity, and bradykinesia) are associated with clozapine.
However, patients using the drug require biweekly monitoring of leukocyte
counts, since it is associated with agranulocytosis. Clozapine is approved
for the treatment of schizophrenia (many of the “negative” symptoms) and
is useful for the acute manic episodes associated with bipolar disorder.

Thioridazine is a typical antipsychotic that is used for the management of

the positive symptoms of schizophrenia. Typical antipsychotics are known
for their D2-receptor antagonism. Therefore, extrapyramidal effects are
common, in addition to elevated prolactin levels and hypotension. The
latter effect is due to alpha1 adrenergic blockade. Thioridazine has the
greatest propensity for muscarinic blockade, which minimizes acute
extrapyramidal symptoms but increases the cardiotoxic potential of the
drug. Thioridazine is associated with elevated QT interval and torsades de
pointes. 

Valproate is a broad-spectrum antiepileptic, since it has several

mechanisms: blockade of T-type calcium channels and sodium channels in
addition to a decrease in GABA degradation through GABA transaminase
inhibition. Although this drug is associated with a high risk of teratogenic
effects (spina bifida) and hepatotoxicity, valproate is used as alternative to
lithium for the manic phase of bipolar disorder.

Based on this vignette, the patient has signs and symptoms of serotonin
syndrome. This occurs when two drugs (selective serotonin reuptake
inhibitor, monoamine oxidase inhibitor, St. John’s wort, or serotonin
agonist) that  alter the level of neuronal serotonin are taken
simultaneously, resulting in excess serotonin. This is a dangerous
condition and supportive measures (aborting the seizure, reducing fever,
and blood pressure) should be administered promptly, along with
discontinuation of the medications. In addition, the serotonin antagonist
cyproheptadine has been observed to be useful for this emergency.

Left pupil is found to be constricted relative to the right, and his left eyelid
droops slightly, this patient has traumatic horner syndrome caused by
damage to the sympathetic nerve plexus that runs with the carotid artery
This is the third order neuron in the sympathetic pathway that innervates
the pupil and the muller muscles of the eyelid- NE is not made so
amphetamine nor cocaine make the pupil dilate but phenylephrine is an
alpha 1 agonist, working directly on the receptors of the postsynaptic
smooth mucle

Carbonic anhydrase catalyzes the formation of bicarbonate which is

secreted with other substances that make aqueous humor into the
posterior chamber of the eye- increasing intraocular pressure
Carbonic anhydrase inhibitors such as acetazolamide and dorzolamide are
used to treat acute and chronic glaucoma
Carbonic anhydrase also reabsorbs sodium bicarbonate from the PCT
The use acetazolamide and dorzolamide inhibits bicarbonate reabsorption
leading to the alkalinization of the urine

Loop diuretics inhibit the Na/K+/2Cl- symporter in the thick ascending loop
of Henle (TAL). This group provides the greatest diuresis of all the other
classes of diuretics, and is indicated for pulmonary edema and congestive
heart failure. Electrolyte abnormalities associated with this group of drugs
include hypokalemia, hypomagnesemia, and hypocalcemia. Furosemide
and ethacrynic acid are well-known loop diuretics and have been observed
clinically to cause ototoxicity is some patients. However, ethacrynic acid is
not a sulfonamide and is considered safe in those with hypersensitivity
reactions
The collecting duct is the site of action of aldosterone and antidiuretic
hormone (ADH). Aldosterone increases sodium reabsorption to promote
sodium retention. Spironolactone has been observed to have a lifesaving
effect in patients with congestive heart failure because it blocks
aldosterone to increase sodium and water excretion. Amiloride and
triamterene are weak diuretics that block the sodium channel to prevent
sodium reabsorption. These diuretics are known to cause hyperkalemia,
especially in patients with renal disorders or those taking angiotensin
antagonist medications (lisinopril, losartan).

The descending loop of Henle is one site of action of mannitol, an osmotic

diuretic. In reality, the osmotic effect of mannitol occurs throughout the
tubule. This type of diuretic is used to increase water excretion, rather than
sodium, and because of this effect, mannitol is indicated for the situations
of increased intracranial pressure and to “flush out” nephrotoxicants.
Hyponatremia can result from mannitol because of the extraction of water
from the extracellular fluid.

The thiazide diuretics are sulfonamides that work in the distal tubule to
inhibit the Na+/Cl- symporter, the area of the kidney where sodium and
chloride are reabsorbed. These diuretics are often considered to be first-
line in hypertension and are associated with electrolyte abnormalities,
mainly hypokalemia. In addition, hyperuricemia has been associated with
an increase in gout episodes in affected patients. Thiazide diuretics can
provide some benefit in osteoporosis because calcium is reabsorbed in the
distal tubule with drugs such as hydrochlorothiazide.

The patient is showing signs and symptoms of tricyclic antidepressant

toxicity: mydriasis and hyperthermia from muscarinic blockade; low blood
pressure from α adrenergic blockade; and arrhythmia from sodium channel
blockade. Seizures are also common in overdose. In addition to supportive
treatment, sodium bicarbonate should be administered to ionize the
remaining drug in the body so it can be eliminated faster. Tricyclic
antidepressants inhibit the reuptake of serotonin and norepinephrine and
include drugs such as nortriptyline, amitriptyline, and desipramine

Bupropion inhibits the reuptake of norepinephrine, serotonin, and

dopamine. This antidepressant does not induce sexual side effects and
sedation. It is also used for smoking cessation. Bupropion should not be
used in bulimics since the risk of seizures is higher in these patients.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). These drugs

have replaced tricyclic antidepressants as first line for the treatment of
depression, anxiety, and obsessive-compulsive disorders, since they have
a greater safety profile than tricyclic antidepressants. The main toxicity
associated with SSRIs is sexual dysfunction.

 Phenelzine is an inhibitor of monamine oxidase (MAO). These drugs are

effective in the treatment of depression since the degradation of serotonin,
dopamine, and norepinephrine are inhibited, thus improving mood.
Monoamine oxidase inhibitors are not considered the primary choice for
depression because reports of serious hypertensive crisis can occur
with tyramine-containing foods such as aged cheese and wine.

Venlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI).

Like the tricyclic antidepressants, these drugs inhibit serotonin
and norepinephrine reuptake. However, SNRIs do not share the
same toxicities because there is no blockade of muscarinic, alpha1, and
histamine receptors.

Venlafaxine and duloxetine are known as serotonin and NE reuptake

inhibitors (SNRIs) because they block the reuptake of these
neurotransmitters. Even though, this mechanism is similar to that observed
in tca such as amitriptyline, SNRIs do not block the muscuranic, adrenergic
or histamine receptors.
Therefore, patients with a history of glaucoma, benign prostatic
hypertrophy or cardiovascular problems are able to tolerate these drugs
without specific toxicities associated with receptor antagonism
Snris are indicated for depression, neuropathic pain and gad

Bupropion is a weak inhibitor of the reuptake of dopamine. Since it blockas

nicotine at central cholinergic receptors this drug is also indicated for
smoking cessation in addition to having antidepressant potential

Citalopram is an antidepressant of the selective serotonin reuptake

inhibitor class (SSRI). These drugs are widely used for the treatment of
depression, obsessive-compulsive disorder, and generalized anxiety
disorder. They are considered safer than tricyclic antidepressants but have
minimal activity for norepinephrine reuptake.

Phenelzine inhibits monoamine oxidase (MAOI), which leads to increased

concentrations of dopamine, norepinephrine, and serotonin in the neuron
of the depressed patient. A serious toxicity associated with MAOIs is a
dangerous elevation in blood pressure that occurs after the ingestion of
tyramine-containing foods. Therefore, MAOIs are used to treat individuals
who have a poor response to other antidepressants (SSRIs, SNRIs, etc.).
Trazodone is both an inhibitor of serotonin uptake and a 5HT2A receptor
antagonist. Since the drug antagonizes the histaminic and alpha-
adrenergic receptors, sedation and priapism, arrhythmias, and orthostatic
hypotension are common side effects.

Carbidopa is a peripheral decarboxylase inhibitor that facilitates L-

DOPA entry into the CNS. Entacapone is a catechol-o-
methyltransferase (COMT) inhibitor that prevents the breakdown of L-
DOPA and DA. Paroxetine is an SSRI and inhibits the reuptake of
serotonin.

The patient, a recent immigrant from China presenting with peripheral

neuropathy and anemia, is suffering from vitamin B6 deficiency caused by
use of isoniazid for tuberculosis, which is endemic to China. Isoniazid
causes decreased levels of Vitamin B6, which over time, can cause
peripheral neuropathy and sideroblastic anemia due to impaired
hemoglobin synthesis (B6 is required for the first enzymatic step in heme
synthesis that is catalyzed by D-ALA synthase).

Quinine, an alkaloid derived from the cinchona tree often used to treat
malaria, is known to cause cinchonism, which presents with ringing of the
ears, flushed skin, headache, and visual disturbances.

Risperidone is an atypical antipsychotic that antagonizes dopamine and

serotonin receptors. Side effects include hyperprolactinaemia,
galactorrhea, weight gain, dyslipidemia, and extrapyramidal side effects,
although to a lesser extent than typical antipsychotics.

Rifampin is used orally as short-term monotherapy for the prophylaxis of

N. meningitidis in individuals who have had contact with someone exposed
to these bacteria. This is a broad-spectrum drug that inhibits transcription
and RNA synthesis by binding to DNA-dependent RNA polymerase. In
addition, rifampin is combined with isoniazid, pyrazinamide, and
ethambutol for the treatment of tuberculosis. Monitoring of liver function
tests should be done regularly since the drug is hepatotoxic. In addition,
rifampin has been observed to change secretions of saliva, tears, and
urine to a reddish-orange color. This drug is also a known inducer of
cytochrome P450 (1A2, 2C9, 3A4). Remember rifampin "revs up" P450.
Although rifampin is the current DOC for prophylaxis of Neisseria
meningitidis, ciprofloxacin (in adults), ceftriaxone, minocycline or
spiramycin are accepted alternative.  In particular, ceftriaxone is the choice
prophylaxis in pregnancy.
Chloramphenicol is a broad-spectrum bacteriostatic inhibitor of protein
synthesis that binds to the 50S ribosomal subunit. Although this drug is
associated with "gray baby syndrome" in neonates and aplastic anemia, it
is lipophilic and able to cross the blood brain barrier to treat meningitis
associated with N. meningitidis, S. pneumoniae, and H. influenzae. This is
useful for patients who have hypersensitivity reactions to penicillins and
cephalosporins.

Amphotericin B selectively binds to ergosterol in fungal membranes,

allowing the contents of the cytoplasm to escape from the fungal cell. This
drug is used to treat systemic infections, including fungal meningitis
caused by Cryptococcus in the immunocompromised patient. Amphotericin
causes infusion reactions after intravenous administration and is a highly
nephrotoxic.

All drugs of the beta-lactam inhibitor class (penicillins and cephalosporins)

are bactericidal. These drugs bind to penicillin-binding proteins (PBPs) to
inhibit the transpeptidases responsible for the cross-linking of
peptidoglycans and synthesis of the bacterial cell wall. Third-generation
cephalosporins, mainly ceftriaxone, have a high degree of lipophilicity and
are able to cross the blood-brain barrier. Therefore, these drugs are often
administered intravenously as treatment for patients with bacterial
meningitis
Acyclovir is an inhibitor of viral DNA polymerase and causes chain
termination due to a missing 3’OH group for the attachment of a new
nucleoside. Acyclovir can be administered by intravenous route for the
treatment of viral meningitis caused by herpes simplex (HSV) and
varicella-zoster (VZV) viruses.
The patient is experiencing symptoms of trigeminal neuralgia, which
manifests as intense pain in the facial areas. Carbamazepine is considered
the drug of choice in treatment for this condition. This drug is a sodium
channel blocker, which, when used for epilepsy, inhibits the spread of
abnormal electrical discharges from the seizure to other neurons. While
carbamazepine is associated with CNS effects (ataxia and drowsiness)
and induction of cytochrome P450 enzymes, aplastic anemia and
agranulocytosis have also been reported with this drug. The decrease in
white blood cells can occur with carbamazepine because there is an
inhibition of colony-stimulating factor in the bone marrow. 

Lamotrigine is a sodium channel blocker and inhibitor of the excitatory

neurotransmitter glutamate. This drug is used adjunctively in the treatment
of seizures and can cause CNS depressant effects such as drowsiness.
The main toxicity of lamotrigine is a skin rash that can progress into
Stevens-Johnson syndrome, which is considered to be fatal.

Oxycodone is an opioid drug that acts as an agonist at the mu receptor.

Although these drugs can be used in the management of chronic pain,
there is a concern for tolerance and physical dependence with these
drugs. Therefore, treatment with opioids should be reserved as analgesics
for metastatic cancer and for acute pain caused by surgery or trauma.  

The main use of phenytoin is for the treatment of generalized tonic-clonic

seizures. Like carbamazepine, this drug acts as a sodium channel and is
associated with drug interactions because it is an inducer of cytochrome
P450. Phenytoin exhibits dose-dependent kinetics meaning that at high
concentrations, zero-order kinetics dominate and produce enhanced
toxicity. In addition, folic acid kinetics can be affected by phenytoin
resulting in megaloblastic anemia. 

Drugs that are addictive provide euphoria by activating intrinsic reward

pathways in the brain that involve dopamine. There are four main
dopamine pathways in the brain. The ventral tegmental area sends
projections to the nucleus accumbens that release dopamine. This
pathway is thought to be critical for mediating reward in the brain, and
dopamine receptors become down-regulated with repeated exposure to
the rewarding stimulus. This causes both the initial euphoria and eventual
tolerance that occur to drugs of abuse.  
The nigrostriatal pathway is involved in motor function and is strongly
implicated in the pathology of Parkinson’s disease. This pathway is not
thought to be important for providing internal reward signals in the brain.

The tuberoinfundibular pathway is important for the regulation of prolactin

release. This pathway is not thought to be important for providing internal
reward signals in the brain.

This patient likely has schizophrenia and is displaying psychotic symptoms

(delusions and hallucinations) as well as negative symptoms (social
withdrawal). The potency of both typical and atypical antipsychotic drugs is
strongly correlated with the affinity of these drugs at the D2 receptor.
Atypical antipsychotics also therapeutically interact with other receptors,
such as the 5HT2A receptor, but there is not a strong relationship between
5HT2A receptor affinity and drug potency.

5HT-1D receptors may be important in migraine pathophysiology and that

5HT-3 receptors may be important in nausea and emesis.
early generation typical antipsychotics do block muscarinic receptors,
which is responsible for the dry eyes, dry mouth, constipation, and urinary
retention seen with those drugs.

The patient in this vignette presents with CNS toxoplasmosis, which is

common in those who are immunocompromised (HIV). The standard
therapy for CNS toxoplasmosis consists of pyrimethamine-sulfadiazine and
folinic acid. However, the patient reports a severe reaction to furosemide,
which contains a sulfa group. Hence, pyrimethamine-sulfadiazine is
contraindicated in this patient. Clindamycin is recommended during the
treatment of CNS toxoplasmosis if the patient is allergic to sulfa drugs.
This antibiotic is a protein synthesis inhibitor at the 50S ribosome and is
most associated with pseudomembranous colitis. . The standard therapy
for CNS toxoplasmosis consists of pyrimethamine-sulfadiazine. However,
the patient had reported a severe reaction to furosemide, a loop diuretic,
which contains a sulfa group in its chemical structure.
Sulfamethoxazole/trimethoprim (SMX-TMP) is a prophylactic agent used
against Toxoplasma gondii when the CD4 count falls below 100cells/µl. It
is also used in the treatment of CNS toxoplasmosis, but it contains a sulfa
group and would create a hypersensitivity reaction in this patient.

The patient in this vignette is using transdermal scopolamine, a patch used

over 3 days to prevent motion sickness. The drug inhibits the
neurotransmission of acetylcholine from the inner ear to the vomiting
center in the brain. Like other muscarinic blockers, scopolamine is
associated with dry mucous membranes, pupil dilation, an increase in
atrioventricular (AV) nodal conduction, constipation, and urinary retention.

Drugs that antagonize histamine include antihistamines (H1) and drugs that
inhibit gastric acid secretion from the parietal cells (H2). Drugs of the first-
generation H1 receptor blocker category include diphenhydramine and can
cause sedation because they are able to cross the blood-brain barrier,
unlike the second-generation antihistamines such as fexofenadine,
loratadine, and cetirizine. Sedative antihistamines have strong
anticholinergic potential, which makes them highly effective drugs for the
treatment of motion sickness. But the side effects of drying all secretions,
constipation, and urinary retention are due to the blockade of muscarinic,
not H1 receptors.
Leukotriene receptor blockers include montelukast and zafirlukast. These
drugs inhibit bronchoconstriction and are observed to be effective in
improving pulmonary function, reducing the need for albuterol in the
asthmatic. These drugs are safe and effective in the pediatric population.
The central-acting sympatholytic drugs reduce the outflow of
norepinephrine form the CNS into the circulation by activation of the α2
receptor. These include the antihypertensive drugs, clonidine, and
methyldopa.
Serotonin antagonists (5-HT3) include the antiemetic drug ondansetron,
used to prevent the nausea and vomiting associated with chemotherapy.
The serotonin blockers of the 5-HT2 receptor are used for the treatment of
the negative symptoms of schizophrenia. Thus, clozapine is often referred
to as an “atypical” antipsychotic.
The patient in this vignette is experiencing signs and symptoms of opioid
(heroin, morphine, codeine) withdrawal. Aside from the administration of
supportive treatment and drugs, like clonidine (a central acting alpha2
agonist), for the management of elevated blood pressure and heart rate,
methadone suppresses symptoms of withdrawal because it is a long acting
mu receptor agonist, which prevents drug craving in the opioid addict,
without significant euphoria or reinforcing effects.  In addition, methadone
can be used in an outpatient setting as it is appropriate to manage pain in
opioid dependent patients. 

Chlordiazepoxide is a long-action benzodiazepine that is used to suppress

the acute manifestations of alcohol withdrawal, often referred to as delirium
tremens (delusions, tremors, and seizures). After several weeks, this
benzodiazepine can be slowly withdrawn. 
Flumazenil is used to counteract the effects of benzodiazepines after an
accidental or intentional overdose because it is a competitive receptor
antagonist of this class of GABAergic drugs.
Naloxone is administered intravenously in situations of opioid overdose
because it is a mu receptor antagonist. Since this drug has a short half-life,
it must be given continuously to prevent the likelihood of the patient
developing respiratory depression, the most serious effect of opioid
agonists.

. Pentazocine is considered a partial opioid agonist because it activates

both the μ (weakly) and the κ receptors. Thus, the liability of dependence
and respiratory depression is reduced with these agents. However, these
drugs can precipitate withdrawal in a patient who is dependent on a full
opioid agonist such as heroin or morphine.
Primidone is metabolized into phenobarbital and phenylethylmalonamide
(PEMA), which contribute to its activity for partial and generalized tonic-
clonic seizures. Phenobarbital potentiates GABA by increasing the
duration of chloride channel opening to allow inward flux of this ion and
ultimately, hyperpolarization. These drugs can cause drowsiness,
dizziness, and cognitive impairment. Respiratory depression occurs in
overdose situations.

Carbamazepine is indicated for tonic-clonic seizures, trigeminal neuralgia,

and bipolar disorder. The drug acts to delay the formation of a new action
potential by prolonging the time the sodium channel's inactivation gate
remains closed. Carbamazepine is an inducer of cytochrome P450, and
drug interactions by the acceleration of concurrent drug metabolism is
expected. Because carbamazepine therapy has been associated with
aplastic anemia, frequent white blood cell counts should be performed.
Benzodiazepines, such as lorazepam and diazepam, are used
intravenously or rectally as first-line therapy for patients with status
epilepticus. These drugs potentiate GABA by increasing the frequency of
chloride channel opening. 
Valproate is effective in treating both tonic-clonic and myoclonic seizures,
since it has several mechanisms of actions, including sodium and T-type
calcium channel blockade, and a decrease in GABA degradation and
glutamate synthesis. Valproate causes hepatotoxicity and requires careful
monitoring of liver transaminases.
The patient is experiencing depression that has not been responsive to
first-line agents (selective serotonin reuptake inhibitors (SSRIs) or tricyclic
antidepressants (TCAs). Therefore, monoamine oxidase inhibitors (MAOIs)
are the alternative when these former treatments fail. The MAOIs inhibit
the degradation of dopamine, serotonin, and norepinephrine, improving the
treated patient’s mood. These drugs induce hypertensive crisis in those
who consume tyramine-containing foods. Tyramine accumulates in the
cleft when MAO is absent. This displaces norepinephrine into the
circulation, causing the serious elevation in blood pressure.
GABA is an inhibitory transmitter in the nervous system. Most drugs
available to treat anxiety, insomnia, or invoke anesthesia before surgery
potentiate GABA by opening the chloride channel. This includes the
barbiturates, benzodiazepines, and alcohol class depressants.
N-methyl-D-aspartate receptor (also known as the NMDA receptor or
NMDAR) is selective for glutamate, an amino acid that functions as an
excitatory neurotransmitter. Glutamate is involved in long-term potentiation
of memory and is involved in the toxicity resulting from trauma. Blocking
the excitation in neurons is the basis for drugs used to treat Alzheimer
disease (memantine) and seizures (felbamate).
Histamine is involved in regulating the sleep cycle, the production of acid
from the parietal cells of the gut, and is released in allergic responses
where it induces erythema, itching, and inflammation. Although histamine
H1 receptor blockers are frequently used to inhibit the allergic response,
the blockade of this specific receptor in the CNS is responsible for the
drowsiness caused by the first-generation antihistamines
(diphenhydramine) and is the rationale for their use in over-the-counter
sleep aids.

Ketamine is an anesthetic that is related in structure to the illicit drug

phencyclidine (PCP). These drugs block the action of glutamate at the N-
methyl-D-aspartate (NMDA) receptor. The most significant effect of this
drug includes a “dissociative anesthesia,” which is defined as dissociation
from the procedure being done at the time without a total loss of
consciousness. During recovery, the drug induces hallucinations and
delirium. Since the pediatric population has experienced these toxicities to
a lesser extent, ketamine is often used for surgical procedures in the
young patient.

. Fentanyl is a μ receptor agonist indicated for moderate to severe pain,

common in metastatic cancer. It is administered as an anesthetic with the
ability to reduce pain, usually in combination with other anesthetics. Other
drugs with a similar mechanism include the shorter-acting opioids
sufentanil, alfentanil, and remifentanil. These drugs are often used
intravenously as adjuncts for the induction of anesthesia.

Lidocaine is the most widely used local anesthetic of the amide class,
which blocks sodium channels to prevent the propagation of the action
potential. This drug is available as a topical solution, ointment, and
parenteral formulation.
Midazolam is a short-acting benzodiazepine indicated for anesthesia for
diagnostic procedures not needing a high level of analgesia. In patients
who have been given too much midazolam, flumazenil can be
administered to reduce sedation and possible respiratory depression. All
benzodiazepines potentiate GABA by increasing the frequency of chloride
channel opening to induce hyperpolarization.
Thiopental is a barbiturate that acts to enhance GABA by increasing the
duration of chloride channel opening. This drug is often used to induce
anesthesia, but because it is redistributed into muscle and fat tissue, its
effect wears off quickly. However, hangover is common with thiopental
use.

Local anesthetics bind to sodium channels and decrease the permeability

of sodium to the nerves. This leads to a decrease in the action potential.
These drugs specifically block the voltage-dependent fast sodium channel
in its activated state, which is the same mechanism of class Ib
antiarrhythmics. Lidocaine is included in this Ib class. Certain individuals
are susceptible to hypersensitivity reactions with anesthetics. This
happens mainly with ester-type local anesthetics because these drugs are
metabolized to para-aminobenzoic acid (PABA), a compound with allergic
potential. Lidocaine is an amide-type local anesthetic that is safe in
patients with a prior allergic reaction to an ester-type anesthetic. Amide–
type local anesthetics do not have the same hypersensitivity potential
since they are not metabolized to PABA. Other amide-type anesthetics
include bupivacaine, mepivacaine, and ropivacaine.

Chloroprocaine is an ester-type local anesthetic. This drug has low

potency and short duration. Cocaine is an ester-type local anesthetic with
sympathomimetic effects. It has significant vasoconstrictive
potential. Tetracaine is an ester-type local anesthetic with longer duration
of action than procaine.

The patient is experiencing the negative symptoms of schizophrenia

(social withdrawal, lack of motivation, etc.). These schizophrenic
symptoms are best treated with “atypical” antipsychotics—so named
because they have less effect on the dopamine receptor than the “typical”
drugs (haloperidol, fluphenazine). Thus, they have a decreased potential
for extrapyramidal side effects (EPS). Atypical antipsychotics block the
serotonin 5-HT2 receptor. Clozapine is associated with a potentially fatal
decrease in white blood cells (agranulocytosis), and therefore, leukocyte
counts are required to be checked weekly during the first 6 months of
therapy, then biweekly thereafter.
Chlorpromazine is a typical antidepressant considered to be low potency
because it has a higher affinity to antagonize the cholinergic receptor
rather than the D2 receptor. The drug is associated with corneal deposits
and retinopathy.
Haloperidol is a high-potency D2 receptor antagonist indicated for the
positive symptoms of schizophrenia (delusions, hallucinations). The drug
has a potential for causing Parkinson-like effects (rigidity, bradykinesia,
tremor), akathisia (restless legs), tardive dyskinesia (abnormal, involuntary
movements), and dystonia (abnormal muscle tension that affects the
tongue, pharynx, and facial muscles).
Olanzapine is an atypical antipsychotic, similar in mechanism to clozapine,
but with no effect on leukocytes. The drug has been observed to alleviate
both the positive and negative symptoms of schizophrenia, since it has
some dopamine (D2, D3, and D4) receptor blockade. Olanzapine is
associated with sedation and weight gain.
Risperidone is an atypical antipsychotic, with less sedation and a higher
dopaminergic (D2) potential. Therefore, both positive and negative
symptoms of schizophrenia are treated with this formulation.
Pioglitazone is an agonist at the peroxisome proliferator-activated receptor
gamma (PPAR- γ) that increases gene transcription and enhances insulin
sensitivity. These drugs increase the retention of sodium and water,
causing edema. This leads to a higher risk of congestive heart failure in
patients with type 2 diabetes. Currently, pioglitazone has been associated
with an increased risk of pancreatic cancer, which is an effect being
studied. Rosiglitazone is another drug in the thiazolidinedione class, which
has been associated with high cardiac risks.
In the pathogenesis of Parkinson disease, there is a degeneration of
inhibitory dopaminergic neurons and an increase of cholinergic activity.
Anticholinergic drugs such as trihexyphenidyl and benztropine decrease
the activity of cholinergic neurons by acting as antagonists at cholinergic
muscarinic receptors. These drugs are used to reduce tremors and rigidity
in patients treated for Parkinson disease.

Dopamine agonists are useful in the later stages of Parkinson disease,

since the drug effect is not dependent on functional dopaminergic neurons.
The drugs included in this category are bromocriptine, an ergot alkaloid
and an agonist at the D2 receptor. Newer D2 agonists include pramipexole
and ropinirole, which can be used as monotherapy for Parkinson disease. 
Dopamine itself is unable to cross the blood-brain barrier. Therefore,
levodopa is the main treatment used in Parkinson disease, which
increases dopamine neuronal concentrations and is converted to
dopamine by l-aromatic amino acid decarboxylase (AAAD). This corrects
the deficiency of dopamine observed in the Parkinsonian patient.
Selegiline is an inhibitor of the enzyme monoamine oxidase type B (MAO-
B) which breaks down dopamine. This drug reduces the dosage of
levodopa because it increases dopamine levels in the basal ganglia.
Selegiline has been observed to inhibit free radical formation, therefore
stopping the progression of Parkinson disease.

Inhibitors of catechol-O-methyltransferase (COMT) stop the metabolism of

levodopa to its metabolite, 3-O-methyl-dopa (3-OMD). This effect leads to
a higher bioavailability of levodopa and an improvement of motor function
in the Parkinson patient. COMT inhibitors include tolcapone and
entacapone. Although entacapone is limited to peripheral action, it is
associated with a lower incidence of hepatotoxicity than tolcapone.

Alprazolam is a useful short-term benzodiazepine used to relieve the acute

symptoms of a panic attack, until other therapies are implemented. Abrupt
withdrawal of these drugs can increase the occurrence of seizures.
Therefore, alprazolam should be tapered slowly over several weeks to
avoid this toxicity.

Buspirone is a partial agonist at the serotonin 5-HT1A receptor. It is

indicated for the treatment of chronic anxiety, but takes up to 4 weeks to
have a full therapeutic effect.
Diazepam is a drug of the benzodiazepine class, but because of the
formation of active metabolites, has a long duration of action. Therefore,
this drug can be used to prevent seizures and other acute withdrawal
symptoms.
Sertraline is a selective serotonin reuptake inhibitor (SSRI). SSRIs are
used for the treatment of obsessive-compulsive disorder and depression,
and for the long-term treatment of panic disorder. However, acute panic
attacks require treatment with benzodiazepines.

Valproic acid is a broad-spectrum antiepileptic indicated for the treatment

of partial and generalized seizures. Valproic acid is an alternative to lithium
for the management of the manic phase of bipolar disorder.
  Clonidine is an alpha-2 agonist that inhibits sympathetic outflow from the
vasomotor center of the brainstem.  Depression is a side effect of
clonidine.

Sevoflurane is a halogenated inhaled anesthetic with a rapid rate of

induction and recovery. These drugs facilitate gamma-aminobutyric acid
(GABA)-mediated inhibition by increasing potassium efflux and chloride
influx from neurons. Halogenated anesthetics, especially when combined
with succinylcholine and treatment with antipsychotics, can induce
malignant hyperthermia. This dangerous rise of temperature leads to
rhabdomyolysis and renal injury. Malignant hyperthermia is associated with
a gene defect in 60% of all cases, which is related to mutations of the
ryanodine receptor. This toxicity can also result from mutations of the
alpha subunit of the L-type calcium channel. Dantrolene should be
administered promptly to this patient since it binds to this receptor and
inhibits the release of calcium from the sarcoplasmic reticulum.

Ketamine resembles phencyclidine (PCP) in structure and produces a

"dissociative anesthesia" effect that includes delirium and hallucinations.
This drug blocks the action of glutamate on the N-methyl-D-aspartate
(NMDA) receptor. Unlike inhaled anesthetics, ketamine is an injectable that
increases blood pressure, but has a minimal effect on respiratory rate. 

Midazolam is a short-acting benzodiazepine used adjunctively as an

anesthetic for procedures that do not require high-levels of analgesia.
Benzodiazepines increase the frequency of gamma-aminobutyric acid
(GABA)-mediated opening of the chloride channel (hyperpolarization).
Flumazenil is a benzodiazepine receptor antagonist that can reverse the
respiratory depression associated with higher doses of midazolam.

Propofol induces a rapid anesthetic effect with a fast recovery. This drug
produces vasodilation, with subsequent hypotension after IV
administration.
Thiopental is an ultra-short acting barbiturate, which enters the brain
rapidly due to its high lipid solubility. This drug is injected to induce
anesthesia or for short surgical procedures. The effect of thiopental is
limited due to drug redistribution as the drug distributes from the highly
perfused brain to adipose tissue. Thiopental can induce cardiac and
respiratory depression.

Neostigmine acts by reversible inhibition of cholinesterase enzyme,

especially at the neuromuscular junction.  It also increases acetylcholine
at  nicotinic receptors and improves skeletal muscle strength. Neostigmine
acts by reversible inhibition of cholinesterase enzyme in cholinergic
synapses and increases acetylcholine at the muscarinic receptors, but is
not responsible for the therapeutic benefit in myasthenia. Instead, this
results in side effects.

Woman complains of severe bilateral head pain accompanied by nausea

and seeing flashes of light…these episodes occur at least twice a month
and leave her unable to function for the whole day:
Sumatriptan is a selective agonist at the 5-HT1B/1D receptor. These drugs
are analogs of serotonin. In the pathogenesis of migraine headaches, 5-
HT1B/1D-B receptor agonists are very effective at inducing vasoconstriction
because vasodilation induces the throbbing pain experienced in the
migraine attack. Newer agents have been developed (naratriptan,
frovatriptan, and rizatriptan—that have the same mechanism as
sumatriptan, but have enhanced pharmacokinetics and improved
bioavailability. Since 5-HT1B/1D receptor agonists induce vasoconstriction,
these drugs should not be used in patients with uncontrolled hypertension
or coronary artery disease. Although not considered harmful, serotonin
agonists can cause a tingling sensation in various areas of the body.

The atypical antipsychotic clozapine has been associated with

agranulocytosis. Therefore, weekly monitoring of leukocytes is required
with this drug. The sodium channel blocker carbamazepine, which is used
to treat tonic-clonic seizures, bipolar disorder, and trigeminal neuralgia,
has been associated with aplastic anemia. Patients who are treated with
these drugs should be advised to report signs of infection (fever, sore
throat, and malaise) promptly to their physician. CBC!

Elevated intraocular pressure can result from treatment with drugs that
block the muscarinic receptor—tricyclic antidepressants and low potency
antipsychotics, such as chlorpromazine. Drugs that have muscarinic
blockade relax the ciliary muscle and trabecular meshwork, leading to a
decrease in the outflow of aqueous humor. These ocular effects can
complicate therapy in patients treated for narrow angle glaucoma.

Liver function tests should be evaluated before starting treatment with

valproate. Patients treated with valproate should promptly report nausea,
GI discomfort, and yellowing of the eyes or skin to their physician. This
drug is considered to be a broad-spectrum antiepileptic since it has several
mechanisms of action. Valproate is also used as a replacement for lithium
in the treatment of the manic phase of bipolar disorder for patients unable
to tolerate the adverse effects of lithium.

Lithium is used to treat the manic phase of bipolar disorder. This drug
reduces inositol triphosphate (IP3) formation, which reduces the neuronal
response to neurotransmitters. This drug has a low therapeutic index, so
patients treated with lithium should be warned of toxicities. This includes
tremor, skin effects, symptoms of nephrogenic diabetes insipidus, and
hypothyroidism. Lithium has been observed to block the release of thyroid
hormones. Therefore, patients treated with this drug are encouraged to
report symptoms of low thyroid (dry skin, weight gain, constipation, and
bradycardia) to their physician, who should routinely monitor TSH and T4
levels.

Ramelteon is a melatonin receptor agonist, with a similar mechanism as

this endogenous hormone. Melatonin regulates the circadian rhythm and is
released before the onset of sleep to produce drowsiness. Therefore, it is
effective for the treatment of jet lag and in the elderly, who do not secrete
melatonin. Ramelteon is the first drug of its class and does not produce
dependence, unlike the GABA drugs (zolpidem, benzodiazepines). The
drug is available as a noncontrolled prescription.

First-generation antihistamines (diphenhydramine, doxylamine) are

lipophilic enough to cross the blood-brain barrier and cause sedation.
Therefore, these drugs are often formulated as over-the-counter sleep
aids. The anticholinergic effects of these agents contribute to the
constipation, urinary retention, and overall “dryness” that patients
commonly experience.
Flurazepam potentiates GABA by increasing the frequency of chloride
channel opening. This drug is used to treat insomnia by increasing the
duration of sleep, but its long-acting effect is associated with excessive
daytime drowsiness. Flurazepam, like all drugs of the benzodiazepine
class, has the potential for physical dependence and abuse potential.

Phenobarbital is a barbiturate that enhances GABA by increasing the

duration of chloride channel opening. Although these drugs were used
previously for their sedative-hypnotic effects, they have been largely
replaced by benzodiazepines for this indication because an overdose of
barbiturates is associated with a fatal respiratory depression. These drugs
are commonly abused.
Zolpidem and other nonbenzodiazepine GABA mimetics have replaced
both benzodiazepines and barbiturates for insomnia because they have
little effect on REM sleep and have a shorter duration of action, producing
fewer hangover effects. The drugs of this class do target the GABAA
receptor, but only if they contain alpha 1 subunits. These drugs are
considered to be controlled substances.

Young man- chief complaint of severe right-sided headache

The headache began few hours ago and the pain is located around the
right eye
Eye tearing and nasal congestion
No prodrome or aura
Diaphoretic and restless – conjunctival redness with no papilledema or
retinal hemorrhage
Similar episodes before
The patient is suffering from a cluster headache, and prophylaxis with
verapamil and other calcium channel blockers, including nimodipine and
diltiazem, might have prevented the current attack. Cluster headaches, like
migraines, are a vascular headache thought to arise from cerebral artery
vasodilation causing compression of the trigeminal nerve. Patients often
report excruciating pain, with recurrent episodes; hence the modifier
“cluster.” Symptoms include a stabbing unilateral pain, often around the
eye, lacrimation; nasal congestion; and eyelid drooping. There is usually
no aura as in a migraine headache. Acute treatment consists of 100%
oxygen via facemask, triptans, and analgesics. Regular prophylactic use of
verapamil has been shown to reduce the number of cluster headache
attacks. Note: Propranolol, a nonselective beta-blocker, is prophylactically
used to prevent migraine headaches.
Sumatriptan is a 5-HT1d agonist that causes vasoconstriction of cranial
arteries. It is used for acute migraine and cluster headache attacks.

Propranolol is a nonselective beta-adrenoceptor antagonist. It is taken

several hours before anticipated anxiety to stop the sympathomimetic
effects of anxiety (rapid heart rate, sweating, and shaking). These drugs
are neither habit forming nor sedative. However, nonselective beta
antagonists (beta-1 and beta-2) are contraindicated in patients with asthma
or chronic obstructive pulmonary disease because they can exacerbate
bronchial spasm in asthmatics (due to beta 2 blockade). Nonselective beta
antagonists can also induce vasospastic disorders. In diabetics, these
drugs mask symptoms of hypoglycemia, such as tachycardia.
Alprazolam is a short-acting benzodiazepine used primarily for the
treatment of panic disorder. These drugs increase the frequency of
gamma-aminobutyric acid (GABA)–mediated opening of the chloride
channel. Alprazolam has the potential for both sedation and abuse.
Because of these effects, alprazolam is used short term to relieve the
symptoms of anxiety while other therapies, such as buspirone or selective
serotonin reuptake inhibitors (SSRIs) start to have a therapeutic benefit.

Buspirone is a partial agonist of the serotonin (5HT1A) receptor. This drug is

used for the treatment of chronic anxiety and lacks both sedative and
abuse potential. However, because there is a delay of onset for anxiolytic
effect (2 to 4 weeks), Buspirone does not benefit a patient needing
immediate anxiety relief. This drug should be combined with a
benzodiazepine until therapeutic effect is reached.
Sertraline, fluoxetine, and paroxetine are selective serotonin reuptake
inhibitors (SSRIs). These drugs block the reuptake of serotonin by
inhibiting the serotonin transporter (SERT). Although SSRIs are widely
used to treat depression, they are also used in the treatment of panic
attacks and general anxiety disorder. Sertraline would not be the best
option in this instance of situational anxiety because SSRIs take several
weeks to have a full therapeutic effect.

The patient is demonstrating signs of clinical depression: loss of interest in

activities, withdrawal, and fatigue that lasts more than two weeks in
duration. Bupropion is an antidepressant that inhibits the reuptake of
norepinephrine, serotonin, and dopamine at their specific transporters
(NET, SERT, and DAT). The drug is also used clinically to help reduce
craving for cigarettes. Unlike selective serotonin reuptake inhibitors
(SSRIs, citalopram), bupropion is not associated with sexual dysfunction,
especially in male patients. There is also little sedative potential since
there is no histamine receptor blockade.
Tricyclic antidepressants (TCAs) inhibit the reuptake of serotonin and
norepinephrine and include drugs such as amitriptyline, imipramine, and
desipramine. Although these drugs are very effective for the treatment of
depression, TCAs are known to block muscarinic, histaminic, and a1
adrenoceptors. Therefore, toxicities such as drowsiness, dry mouth,
urinary retention, and orthostasis are common with amitriptyline treatment.

The inhibitors of monamine oxidase (MAO) are effective for the treatment
of depression since they increase the neuronal storage of serotonin,
dopamine, and norepinephrine to improve mood. Phenelzine is an inhibitor
of monoamine oxidase (MAOI). These drugs are reserved for patients who
do not respond to other antidepressants because the consumption of
sympathomimetic amines or tyramine-containing foods with MAOIs can
cause a dangerous increase in blood pressure.

Sertraline is one of the selective serotonin reuptake inhibitor s(SSRIs),

which are considered first-line treatments for depression, panic, and
obsessive-compulsive disorders because they have a better safety profile
than tricyclic antidepressants (TCAs). SSRIs are associated with sexual
dysfunction that is correlated with the dosage of the drug. Patients treated
with SSRIs experience an improvement in sexual function when the dose
is lowered or discontinued. This is most common in males. This patient has
experienced this side effect because he was treated with citalopram,
another drug of the SSRI class.

Trazodone is a serotonin antagonist and inhibitor of serotonin neuronal

reuptake. The sedative potential of this drug makes it useful clinically for
the treatment of insomnia. This can be attributed to its ability to block the
H1 receptor. In addition, treatment with trazodone has been associated with
the occurrence of prolonged penile erection known as priapism.

Rifampin is the first-line prophylactic treatment for meningococcal

meningitis. It is a bactericidal drug that works by blocking DNA-dependent
RNA polymerase. Also used to treat tuberculosis, it is synergistic with
isoniazid. It is famous for giving a harmless orange-red color to saliva,
urine, and tears. I also causes a more adverse side effect, hepatotoxicity.
Rifampin also has an effect on the metabolism of other drugs. It is known
as a cytochrome P450 inducer. Cytochrome P450s are a major part of
phase I drug metabolism. In particular, it increases the gene expression of
CYP3A4, so any drugs that are metabolized by this particular cytochrome
may be affected. Inducing cytochrome P450 causes a drug to be
metabolized faster, making less of the drug available to react within the
body. In this case, it may render the OCPs ineffective due to decreased
levels. Other CYP450 inducers include antiseizure drugs such as
barbiturates, phenytoin, carbamazepine, the HIV drugs efavirenz and
nevirapine, chronic ethanol use, St. John's wort, and  glucocorticoids. The
patient should be warned about this side effect in order to avoid any
unplanned pregnancies. 

Examples of drugs that may cause the levels of OCPs to increase (a

CYP3A4 inducer) include the anti-ulcer drug Cimetidine, macrolides (with
the exception of azithromycin), protease inhibitors such as ritonavir, azoles
such as ketoconazole, grapefruit juice, acute alcohol use (as opposed to
chronic, which is an inducer), and calcium channel blockers such as
verapamil and diltiazem. 

The blockade of muscuranic receptors produces dry mouth, constipation,

blurred vision and urinary retention. The TCA are associated with
significant muscuranic receptor blocking action

The drugs which include zolpidem, zaleplon, and eszopiclone are

considered to be "non-benzodiazepines." They have replaced
benzodiazepines to induce sleep. These drugs target the gamma-
aminobutyric acid (GABAA) receptor, similar in mechanism to the
benzodiazepines. However, unlike benzodiazepines, these drugs have
little effect on REM sleep. Their shorter duration of action produce less of a
hangover effect. These drugs are commonly used to treat insomnia,
especially in the elderly.
Although benzodiazepines can be used as sleep aids, newer drugs, such
as zolpidem, have been developed which induce less of a hangover effect.
Benzodiazepines are metabolized to active metabolites. Diazepam is
converted into desmethyldiazepam, which makes this benzodiazepine long
acting. This is especially true in the elderly because since they often have
reduced hepatic function.
Diphenhydramine is a first-generation H1 antagonist used mainly for
allergies. Since the drug crosses the blood-brain barrier, various degrees
of sedation can be produced. This is the main reason for diphenhydramine
being formulated as the active ingredient in several over-the-counter sleep
preparations. Diphenhydramine also blocks the muscarinic receptor
causing atropine-like effects such as urinary retention, dryness,
tachycardia, and blurred vision. Therefore, patients with benign prostatic
hypertrophy (BPH) and glaucoma should be advised against using these
drugs.
Flurazepam is a benzodiazepine used mainly for insomnia. These drugs
can cause drowsiness and hangover the next day. In addition, flurazepam
is a benzodiazepine that produces a metabolite that contributes to its long
duration of action. The elderly are most sensitive to these effects, and
newer drugs such as zolpidem have replaced benzodiazepines for the
treatment of insomnia.
Phenobarbital is a barbiturate used as a sedative-hypnotic before the
development of newer drugs. Barbiturates increase the duration of
gamma-aminobutyric acid (GABA) by keeping the chloride channel open.
This can happen in the absence of gamma-aminobutyric acid (GABA),
which makes an overdose of phenobarbital dangerous since full respiratory
arrest occurs. For insomnia, these drugs also produce hangover, daytime
sedation, and a suppression of REM sleep.  Phenobarbital is used as an
anticonvulsant and can induce drug interactions since it is an inducer of
cytochrome P450. 

Postural hypotension and reflex tachycardia are the side effects at the
initiation of therapy with prazosin. Hence, patients are advised to take it at
bedtime to reduce the postural hypotension. Alpha-1 blockade results in
vasodilation, decreasing blood pressure and causing tachycardia. It also
results in large vein dilation, decreasing preload and causing postural
hypotension

Excessive salivation and bronchospasm are not found with prazosin.

These effects are classically those of muscarinic agonist

Lithium is a mood stabilizer that works by suppressing the formation of

second messengers involved in neurotransmitter signal transduction. This
drug has a low therapeutic index, with high levels of lithium causing
neurotoxicity and cardiac toxicity. Chronic diuretics such as
hydrochlorothiazide decrease the renal excretion of lithium, leading to
increased lithium levels and toxicity. Diuretics do not interfere with the
excretion of the other drug choices.
Bupropion is an antidepressant that is a weak reuptake inhibitor of
dopamine, serotonin, and norepinephrine. The drug has low sedation and
sexual dysfunction potential. Bupropion is also used to reduce the cravings
for tobacco.
Carbamazepine is a sodium channel blocker used for the treatment of
tonic-clonic seizures and for the manic phase of bipolar disorder. It is
associated with aplastic anemia, and, since it is an inducer of cytochrome
P450, drug interactions are common.
Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI)
used for the treatment of depression, generalized anxiety, and diabetic
neuropathic pain. It has a similar mechanism for neurotransmitter reuptake
as tricyclic antidepressants, but without muscarinic, histaminic, or
adrenergic blockade.
Valproate is a broad-spectrum antiepileptic used for the manic phase of
bipolar disorder, especially those that are rapid cyclers. The drug is
associated with fatal hepatitis, so liver function tests should be monitored
regularly in patients treated with valproate

The patient has post-traumatic stress disorder (PTSD), and a trial of

fluoxetine, an SSRI, is indicated. PTSD is a psychological disorder that
may develop after a traumatic event, such as rape, war, or witnessing
death. For the diagnosis of PTSD, the DSM-V requires the presence of a)
exposure to a traumatic event; b) persistent re-experiencing; c) persistent
avoidance and emotional numbing; d) persistent symptoms of increased
arousal; and e) duration of symptoms longer than 1 month. Some
symptoms of hyperarousal include difficulty sleeping, hypervigilance,
anger, difficulty concentrating, and emotional outbursts. If the symptoms
are present for less than a month, a diagnosis of acute stress disorder is
made. The biological mechanisms of PTSD have been linked to increased
activity in the amygdala, decreased cortisol levels, and increased levels of
norepinephrine and epinephrine in the brain. First-line treatments for PTSD
are cognitive behavioral therapy and SSRIs, such as fluoxetine,
paroxetine, or sertraline. Tricyclic antidepressants are not FDA-approved
for PTSD management, but amitriptyline and imipramine have some
efficacy in treating PTSD. Antipsychotics can be used to help mood and
aggression. There is some evidence that propranolol may help to prevent
hyperarousal symptoms.

Lorazepam is a high-potency benzodiazepine helpful in the short-term

treatment of anxiety and insomnia associated with PTSD.
Phenelzine is a monoamine oxidase inhibitor that is uncommonly used in
the treatment of PTSD. It is reserved for patients who do not respond to
conventional antidepressants. isperidone is an atypical antipsychotic that
can be used in PTSD to help manage mood and aggression issues.
Based on presentation, the patient is clinically depressed. Bupropion binds
to specific transporters (NET, SERT, and DAT) to inhibit the reuptake of
the neurotransmitters norepinephrine, serotonin, and dopamine. It is an
antidepressant with no effect on sexual function. In addition, bupropion
acts as a noncompetitive antagonist at nicotinic cholinergic receptors. This
may explain its use in patients trying to quit smoking.
Mirtazapine is approved for depression and is an antagonist of the 5-HT2,
5-HT3, and α2-adrenergic receptors. This results in the release of serotonin
and norepinephrine from neuronal cells. The drug can elevate liver
enzymes, requiring frequent monitoring in the hepatic patient. Because
mirtazapine blocks the H1 receptor, sedation and weight gain can result. 
Nortriptyline is a tricyclic antidepressant (TCA) that inhibits the reuptake of
serotonin and norepinephrine by binding to their respective transporters,
SERT and NET. TCAs are muscarinic, histaminic, and α1 adrenoceptor
antagonists, and produce toxicities associated with this blockade (dry
mucous membranes, constipation, weight gain, sedation, and orthostatic
hypotension).

The serotonin and norepinephrine reuptake inhibitors (SNRIs), such as

venlafaxine are similar in mechanism to the tricyclic antidepressants
(TCAs). However, these drugs do not have the same toxicities as TCAs
because SNRIs are not antagonists at muscarinic, alpha1, and histamine
receptors.

he patient is experiencing the positive symptoms of schizophrenia

(agitation, delusions, and auditory hallucinations), which were treated with
typical antipsychotics of the phenothiazine group, since a retinopathy is
diagnosed as a side effect of the antipsychotic medication. These drugs
exert their action primarily by D2 receptor blockade and include high-
potency drugs (haloperidol, fluphenazine) and low-potency drugs
(chlorpromazine and thioridazine). The low-potency drugs have a greater
potential for histamine, muscarinic, and a1 antagonism. Blockade of the
dopamine receptor causes extrapyramidal side effects (EPS), including
motor restlessness, rigidity, bradykinesia, and dystonia early in treatment.
Tardive dyskinesias occur months or years after typical antipsychotic
treatment, manifesting as abnormal involuntary movements of the mouth
and face. High doses of thioridazine are associated with an increase in the
QT interval, leading to cardiac toxicity and a “brown vision” known as
pigmentary retinopathy.

Clozapine is an antipsychotic of the atypical class that is indicated for the

treatment of the negative symptoms of schizophrenia (social withdrawal,
lack of interest in activities). The drug is a serotonin (5-HT2) blocker and
produces fewer EPS effects than the D2 receptor blockers. Clozapine
requires weekly monitoring of leukocyte counts during the first 6 months of
therapy and biweekly thereafter, since the drug is associated with fatal
agranulocytosis.
Donepezil is a centrally acting cholinesterase inhibitor that is lipophilic
enough to cross the blood-brain barrier to increase the acetylcholine
concentration in the synapse. It is indicated for the treatment of Alzheimer
disease.

Haloperidol is a high-potency D2 receptor blocker and is associated with

one of the highest incidences of EPS effects.

Olanzapine is an analog of clozapine and is effective in treating both the

positive and negative symptoms of schizophrenia, with fewer EPS effects.
The drug is associated with drowsiness and weight gain.

Risperidone is an atypical antipsychotic that effectively treats both negative

and positive symptoms of schizophrenia. Because it has the potential for
histamine, muscarinic, and a1 blockade, orthostatic hypotension, sedation,
and weight gain are common, along with an increase in prolactin levels.
Risperidone increases the QT interval, predisposing the patient to more
cardiotoxic effects.

Lithium is used to treat bipolar disorder, with the greatest effect on the
manic phase. The mechanism of action of this drug is the suppression of
second messengers, mainly IP3, which reduces the response to
neurotransmitters, such as serotonin and norepinephrine. The blood
concentration of lithium should be carefully monitored because the drug
has a low margin of safety. Aside from reports of hypothyroidism, tremor,
and acne, lithium is associated with nephrogenic diabetes insipidus. In this
condition, the kidney does not respond to antidiuretic hormone (ADH). The
patient presents with excessive thirst and a high volume of dilute urine,
due to the absence of aquaporins to reabsorb water from the collecting
tubule. In addition, thiazide diuretics (hydrochlorothiazide, indapamide)
enhance lithium toxicity because the reduced sodium from the urine output
caused by these diuretics decreases the clearance of this bipolar disorder
drug. This leads to an increase in lithium levels and enhanced toxicity.

The tricyclic antidepressant amitriptyline inhibits the reuptake of both

norepinephrine and serotonin by blocking the specific transporters for
these neurotransmitters. Although tricyclics have been replaced by newer
antidepressants with less toxicity, these drugs are effective for the
treatment of depression, panic disorders, and obsessive-compulsive
disorders. The toxicities associated with these drugs are related to
adrenergic, histaminic, and muscarinic receptor blockade. Therefore,
urinary retention is common with tricyclic antidepressants.

Carbamazepine is used for tonic-clonic seizures because it blocks sodium

channels. Although lithium is the primary medication for bipolar disorder,
carbamazepine can be used for patients who are not able to tolerate the
drug’s toxicities. The drug is an inducer of cytochrome P450, so drug
interactions are common. Carbamazepine is associated with ataxia,
drowsiness, and rarely, aplastic anemia.

Chlorpromazine is considered a low-potency, typical antipsychotic of the

phenothiazine class. Although it has D2 blockade, chlorpromazine is
associated with anticholinergic and muscarinic and alpha 1 blockade.
Therefore, toxicities associated with these receptors (dry eyes/mouth,
constipation, urinary retention, and hypotension) should be considered. 

Clozapine is an atypical antipsychotic. These drugs are used to treat the

negative symptoms of schizophrenia, such as withdrawal from life
activities, lack of speech, etc. They do not display the extrapyramidal side
effects associated with D2 blockers because the 5-HT receptor has a
greater affinity with the atypical agents. Clozapine is associated with fatal
agranulocytosis, so weekly complete blood counts should be performed
during treatment with this antipsychotic drug.
Valproate is an antiepileptic and an effective treatment for bipolar disorder
in patients who experience toxicities with lithium. Valproate has several
mechanisms, including inhibition of both sodium and T-type calcium
channels, reduction of glutamate synthesis, and enhanced GABA
concentration. Liver function tests should be performed before and during
therapy with valproate because fatal hepatitis can result. 

The patient likely suffered an embolic stroke due to atrial fibrillation, after a
sudden increase in vitamin K intake interfered with his warfarin therapy.
Warfarin is a therapeutically important anticoagulant that inhibits vitamin K
dependent synthesis of biologically active clotting factors. Patients taking
warfarin need to be strongly cautioned not to dramatically vary their intake
of vitamin K rich foods such as leafy greens and cruciferous vegetables,
since sudden increase or decrease in vitamin K intake can seriously affect
their clotting activity.

Edrophonium is a short-acting reversible cholinesterase inhibitor with a

duration of action < 5 minutes. It is safe for the diagnosis of myasthenia
gravis under supervision in hospital settings  If muscle strength improves
with edrophonium challenge (4/4), the condition is a myasthenic crisis, and
the individual requires acetylcholine action on nicotinic receptors at the
neuromuscular junction.  If the muscle weakness worsens with
edrophonium challenge (1/4), the condition is a cholinergic crisis due to
overdose of a reversible cholinesterase inhibitor like neostigmine.

Myasthenia gravis- complaining of fatigue, difficulty swallowing, exhibition

of droopy eyelids and slurred speech due to skeletal muscle weakness

Atropine is also not used to diagnose or confirm myasthenia gravis, but it is

added to neostigmine to decrease the side effects of the myasthenia
treatment. The autoantibodies of myasthenia gravis do not block
muscarinic receptors, yet the acetylcholinesterase inhibitor increases
acetylcholine at the muscarinic junction as well as the nicotinic ones.

Narrow- or low-therapeutic-index drugs such as warfarin, digoxin, and

lithium produce a  dose-response curve of desired effect that is not well
separated from the dose-response curve of adverse effects. In other
words, the dose required to produce the maximum beneficial effect
increases the likelihood of adverse effects.

The patient in this vignette is experiencing signs and symptoms associated

with migraine headache. There are two phases of migraine headache
pathogenesis. First is the vasoconstrictive phase (prevented by calcium
channel blocker prophylaxis), with the release of serotonin from neurons—
the reason that treatment by nonsteroidal antiinflammatory drugs or
serotonin blockers is effective. Second is the vasodilation phase,
responsible for the “throbbing” pain experienced in migraines. Thus, drugs
that vasoconstrict in the cerebrum, such as 5-HT1D receptor agonists
(sumatriptan) are most effective at terminating the headache. However,
these drugs can vasoconstrict vessels of the cardiovascular system,
causing coronary vasospasm, especially in those with a history of
hypertension and angina. Thus, 5-HT1D receptor agonists should be
avoided in these patient types and should be limited to 2 treatment days
per week in those without underlying cardiac disease.

Although antagonists at the α1 receptor produce vasodilation, they do so by

acting on the smooth muscle of the arterioles and bladder, not in the
cerebral area. Thus, they are not considered effective for migraines, but
are used to treat hypertension and benign prostatic hypertrophy (BPH).
Drugs in this class include prazosin and doxazosin, which induce
orthostatic hypotension, especially if the patient fails to rise slowly, and
reflexive tachycardia, to counteract the significant smooth muscle
relaxation and blood pressure drop.

Since the second phase of migraines does involve vasodilation, β2 receptor

antagonists (propranolol) can be used in migraine prophylaxis to block this
vasodilation. Beta2 receptors, unlike alpha1 receptors, are very numerous in
cerebral vessels. In addition, they reduce serotonin release from platelets.
Nonselective beta-adrenergic blockers mask hypoglycemia and induce
bronchoconstriction. Therefore, patients treated for diabetes or asthma can
experience an exacerbation of these symptoms.

Antiemetics such as prochlorperazine and metoclopramide are antagonists

at the D2 receptor. Although not considered to be involved in the
pathogenesis of migraines, these drugs can treat the nausea and vomiting
experienced by headache patients. These drugs are associated with
extrapyramidal effects (symptoms of parkinsonism: bradykinesia, dystonia,
akathisia, rigidity) because of the dopamine receptor blockade.

Nonsteroidal antiinflammatory drugs (NSAIDs) are reversible inhibitors of

cyclooxygenase that stop the prostaglandins involved in the inflammatory
response. For migraine headache therapy, these drugs (naproxen,
ibuprofen) block some platelet synthesis, which reduces the release of
serotonin responsible for the initial phase of migraine pathogenesis. Taken
chronically, NSAIDs block cytoprotective prostaglandins (PGE2) in the
gastrointestinal tract (GI), causing irritation and, at worst, bleeding.

Blockade of the calcium channel with drugs such as verapamil is used in

migraine prophylaxis because of prevention of the vasoconstrictive phase
of migraine headaches. Verapamil is the calcium channel blocker most
associated with AV nodal suppression (bradycardia; because it is a phase
IV antiarrhythmic), constipation, and gingival hyperplasia, especially when
taken for a long period of time.
The earlier symptoms and signs of this patient (pharyngitis, nasal
discharge, malaise, myalgia, and fever) suggest influenza infection, which
could have been treated with antiviral agents that inhibit uncoating
(amantidine/rimantidine) or viral release (oseltamivir/zanamivir).
Amantadine is an antiviral used to prevent and treat influenza A by
blocking the M2 channel, preventing viral uncoating and a decrease in pH.
The drug also increases the level of dopamine in the substantia nigra,
which is beneficial in patients with early signs and symptoms of Parkinson
disease. However, the increase in dopamine may exacerbate psychiatric
symptoms in schizophrenic patients.

Acyclovir is a viral DNA polymerase inhibitor used for the treatment of

Herpes simplex virus (HSV) and Varicella zoster virus (VZV). These drugs
are incorporated in viral DNA to cause chain termination since there is no
3’OH group for the subsequent nucleoside to bind. Acyclovir is associated
with crystalluria when it is administered intravenously in a dehydrated
patient.

Zanamivir is a nasal spray used for the prophylaxis and treatment of

influenza A and B viruses. It acts to inhibit neuraminidase, which is an
enzyme that cleaves sialic acid from the virus to allow the virus to spread
to a new cell. Patients with asthma who are treated with inhaled zanamivir
can experience increased episodes of bronchospasm.

The patient in this vignette is presenting with generalized tonic-clonic

seizure disorder, since there is an alteration in consciousness. The first-
line treatment for this type of seizure is phenytoin, valproate, or
carbamazepine. Carbamazepine blocks neuronal sodium channels to
reduce action potential propagation and the spread of abnormal electrical
discharges from the seizure focus. The drug is associated with drug
interactions since it is an inducer of cytochrome P450, accelerating its own
metabolism and that of other drugs. In addition to aplastic anemia,
carbamazepine has been observed to increase the risk of Stevens-
Johnson syndrome, especially in patients of East Asian descent. It is
recommended that these patients be tested for the HLA allele B*1502
before this drug is prescribed. It can also be used to treat bipolar disease
and trigeminal neuralgia. It should be noted that other antiseizure
medications, phenytoin (for tonic-clonic seizures) and lamotrigine (an
adjunct therapy for partial and generalized seizures) can have the same
erythema multiforme reaction as carbamazepine.
Status epilepticus is a dangerous seizure type in which the patient does
not regain consciousness, leading to hypoxia and severe brain damage.
Thus, this type of seizure must be terminated with an intravenous or rectal
GABA-minergic agent such as the benzodiazepines diazepam and
lorazepam. These drugs can induce drowsiness, antegrade amnesia, and
physical dependence, which is dependent on duration and dosage of
medication administration.

Ethosuximide produces drowsiness as its main toxicity, with a long half-life.

It is used in children for the treatment of absence seizures (“staring into
space”). Ethosuximide inhibits T-type calcium channels in the neurons.
Topiramate is an adjunct treatment for partial seizures, with several
mechanisms of action including enhancement of GABA and blockade of
both glutamate and the sodium channel. With this drug, toxicity is limited to
the central nervous system (ataxia, drowsiness, and dizziness).

Valproate has several mechanisms that make it useful for the treatment of
tonic-clonic seizures, bipolar disorder, and the prevention of headaches. It
enhances GABA by increasing its synthesis and inhibiting degradation. In
addition, it blocks sodium channels and glutamate synthesis. Although this
drug has minimal CNS effects, unlike other antiseizure drugs, it is
associated with hepatitis, warranting the need of baseline liver tests. The
drug can raise the levels of other drugs, including lamotrigine, which can
make the patient more prone to the skin toxicity associated with
lamotrigine.

Tramadol is a mu receptor agonist and a reuptake inhibitor of serotonin

and norepinephrine, similar to what is experienced with both opioids and
tricyclic antidepressants. Its active metabolite, O-desmethyltramadol, or
M1, is a more potent mu agonist. Since the drug has little dependence
liability and respiratory depression, tramadol is a very effective treatment
for chronic pain. It can be associated with serotonin syndrome.

Buprenorphine is a partial agonist at the mu receptor. It is administered

sublingually, parenterally, or transdermally for opioid detoxification
because it has fewer withdrawal symptoms and a longer duration of action
than methadone. It causes little sedation, hypotension, and respiratory
depression, unlike strong mu receptor agonists.

Fentanyl is a mu receptor agonist that is a hundred times more potent than

morphine. A transdermal preparation of the drug is available for cancer
patients to limit tolerance, while epidural fentanyl is used for anesthesia
induction. Like other mu receptor agonists, fentanyl is associated with
dependence, constricted pupils, constipation, and respiratory depression in
overdose situations.

Methadone is a mu receptor agonist, with less euphoria and a longer

duration (t ½) than morphine. The drug is effective for pain relief, but its
properties make it an ideal treatment for the prevention of the withdrawal
symptoms associated with abusers of heroin and morphine. 

Acute onset of dizziness and gait difficulty, left pupil is very small
compared to the right and the left eyelid is drooping.
Patients voice is hoarse and the patient has lost pain and temperature
sensation in his right and left arm and leg
Occluded blood vessel is a of which branch? Left vertebral artery

This patient is suffering from Wallenberg syndrome, which is caused by a

stroke in the left posterior inferior cerebellar artery. This classic
syndrome is also called "lateral medullary syndrome" because multiple
structures in the lateral medulla are damaged when these strokes occur. 

The syndrome presents with an ipsilateral Horner syndrome (due to

lesion of the descending hypothalamic tract),
a contralateral loss of pain and temperature (due to loss of the
spinothalamic tract),
hoarse voice (due to lesion of the nucleus ambigus of cranial nerves IX
and X),
dizziness (due to vestibular nucleus lesion) and
ataxia (due to lesion of inferior cerebellar peduncle).
The left posterior inferior cerebellar artery is a branch of the left
vertebral artery. 

Ipsilateral weakness in tight closure of the eyelids- the mass indicated is a

tumor of the parotid salivary gland, the main motor branch of the facial
nerve (VII) emerges from the stylomastoid foramen and passes through
the substance of the parotid gland, dividing into multiple branches before
emerging from the gland to provide innervations to the muscles of facial
expression.
Orbicularis oculi a muscle of facial expression acts to close the eyelids
During examination, when both sides of his body are touched
simulateneously he reports that only right side is being touched
When sensory function is tested in either side of separately it appears
intact

The patients presentation is typical of hemispatial neglect, which often

results from a stroke or other injury to the parietal lobe causing deficits in
awareness of and attention to the contralateral side of the body and visual
field.
The patient’s difficulty in recognizing his own symptoms represents
anosognosia, another symptom consistent with parietal lobe dysfunction

the patients presentation is typical of hemispatial neglect, which often

results from a stroke or other injury to the parietal lobe causing deficits in
awareness of and attention to the contralateral side of the body and visual
field.
The patient's presentation is typical of hemispatial neglect, which often
results from a stroke or other injury to the parietal lobe causing deficits in
awareness of and attention to the contralateral side of the body and visual
field. The patient’s difficulty in recognizing his own symptoms
represents anosognosia, another symptom consistent with parietal lobe
dysfunction.

The axons of the ganglionic cells of the inner layer of the retina leave the
eyeball at the optic disc and form the optic nerve, chiasm, and tract to
reach the lateral geniculate nucleus of the thalamus.
The axons of ganglionic cells of the inner layer of the retina leave the
eyeball at the optic disc and form the optic nerve, chiasm, and tract to
reach the lateral geniculate nucleus of the thalamus

The problem is in radial nerve, which can be lesioned in the axilla, spiral
groove or forearm
Lesions in the forearm or spiral groove spare the triceps, which are
involved only in lesions in the axilla
People with diabetes are at particular risk for these kinds of neuropathies,
spontaneously or potentially after compression such as after using
crutches

Forearm or spiral grove spare the triceps

Which only lesions in the axilla
The long thoracic nerve runs near the lateral thoracic artery in the axilla
and can be injured during mastectomy
The long thoracic nerve innervates the serratus anterior muscle and can
cause winged scapula when injured

Taste input from the anterior two thirds of the tongue is relayed by the
facial nerve (CN VII). More precisely, taste sensation first goes from the
anterior two thirds to the lingual nerve, then to the chorda tympani to the
facial nerve, ending up in the nucleus of the tractus solitarius, located in
the upper medulla of the brainstem. The tractus solitarius also receives
taste inputs from the posterior third of the tongue through the
glossopharyngeal nerve and from the epiglottis through the vagus nerve.
Chemosensitive fibers from the aortic and carotid bodies also send their
afferent fibers to the same nucleus.

Taste input from the anterior two thirds of the tongue is relayed by the
facial nerve, taste sensation first goes from the anterior two thirds to the
lingual nerve, then to the chorda tympani to the facial nerve, ending up in
the nucleus of the tractus solitarius located in the upper medulla of the
brainstem
The tractus solitarius also receives taste inputs from the posterior third of
the tongue through the glossopharyngeal nerve and from the epiglottis
through the vagus nerve

Edinger-westphal nucleus involved in parasympathetic information

conveyed by oculomotor nerve (CNIII) – constriction of the pupil and
accommodation of the lens

Chief complaint of headache and facial swelling

Left sided swelling around the eye
Left sided thrombus in the cavernous sinus – ptosis
The patient is suffering from a cavernous sinus thrombosis, and of the
listed physical signs, ptosis would most likely be found. The cavernous
sinus is a paired cavity in the skull that is adjacent to the sella turcica.
Cranial nerves III, IV, V1 of V, V2 of V, VI, and the internal carotid
artery pass through the cavernous sinus and are susceptible to injury
when a thrombus forms.
Cavernous sinus thrombosis can form as a result of either a
hypercoagulable state or, more commonly, an ascending infection from the
face, as the facial vein drains through veins of the orbit and eventually into
the cavernous sinus.
Symptoms of a cavernous sinus thrombosis include headache, periorbital
swelling, photophobia and palsy of the cranial nerves passing through the
sinus.
Palsy of CN III can result in ophthalmoplegia of the extraocular muscles
without affecting lateral rectus or superior oblique muscle function. Since it
also provides somatic efferent innervation to the levator palpebrae muscle,
severe ptosis can be seen on physical exam.
CN IV, the trochlear nerve, innervates the superior oblique muscle; palsy
of this nerve results in diplopia and upward movement of the eye.
Ophthalmic and maxillary branches of CN V, the trigeminal nerve, provide
sensation to the upper half of the face.
CN VI, the abducens nerve, provides somatic efferent innervation to the
lateral rectus muscle; palsy of this nerve results in inability to abduct the
eye.
Complete unilateral blindness would be seen in injury to CN II, the optic
nerve. It does not pass through the cavernous sinus. An enlarging pituitary
adenoma can cause compression of the optic chiasm and resultant visual
field deficits (but not complete blindness).
Deviated uvula can be seen in palsy of CN X, the vagus nerve. 
CN VIII, the vestibulocochlear nerve, is responsible for sensorineural
hearing. It exits the cranium through the internal auditory canal along with
CN VII.

The prior patient was hypovolemic, so low pressure baroreceptors are

activated. Cranial nerves IX and X innervate low and high pressure
baroreceptors- cardiopulmonary and arterial, respectively and the cranial
nerves project to the nucleus tractor solitarius
The nts then projects to gustatory and regulatory centers of the brain- such
as the parabrachial nucleus and hypothalamus to increase thirst, blood
pressure and renal retention of water

The area postrema is a circumventricular organ that lacks the blood brain
barrier. This allows it to respond to factors in the blood such as toxins and
peptides. The ap is not directly innervated by cranial nerves IX and X
which carry the signal from low and high pressure baroreceptors, which
are activated in the patient

The glossopharyngeal nerve provides parasympathetic innervation to the

parotid gland and sensory innervation from the oropharyngeal mucosa,
which forms the sensory side of the gag reflex it also innervates one of the
six muscles (stylopharyngeus) used in swallowing

Sensory input of the 1a fibers from the muscle spindles of the muscles of
mastication have their cell bodies in the mesencephalic nucleus of cnv
located in the dorsal lateral midbrain
The fibers of the mesencephalic nucleus project to the motor nucleus of
CNV in the lateral mid pons
Where they synapse with LMN of the mandibular nerve

CT scan indicates a tumor compressing the jugular foramen. Which of the

following functions would the physician expect to remain normal? Elevation
of the corner of the mouth
A tumor at the jugular foramen would compress cranial IX, X and XI
which pass through the foramen
Tumor of the jugular foramen would compress cn IX, X, XI which pass
through the foramen

A tumor at the jugular foramen would compress cranial nervesCN IX, X, XI

which pass through the foramen
Elevation of the mouth innervated by the seventh cranial nerve
Vocalization and moving the vocal folds are functions of CN X
Laryngeal mucosa- provided by CN X
Vagus nerve innervates five of the six muscles used for swallowing reflex

Middle cerebral artery supplies blood to the motor and sensory cortex
mainly of the contralateral head, trunk, and upper limb
Upper temporal lobe
Genu and posterior limb of the internal capsule
And parts of the of the basal ganglia via lenticulostriate branches of the
mca
Fasciculus cuneatus- touch, proprioception, vibration ----arms
Fasciculus gracilis- touch, proprioception, vibration---- legs
Corticospinal tract- upper motor neurons
Anterolateral system- spinothalamic tract; pain/temperature
Dorsal horn (sensory)
Lateral horn (preganglionic sympathetic neurons)
Ventral horn (lower motor neurons)

The patient has Huntington Disease. Patients often present in their 20s
and 40s with personality changes and movement disorder. The movement
disorder is characterized by chorea and athetosis. Chorea Is characterized
by many rapid movements that are random in nature and can resemble
dancing: athetosis is a series of slow, writhing movements. Cognitive
decline is characteristic of HD. Symptoms of dementia include irritability,
loss of interest, impairment of intellectual and executive functions and
memory disturbances
Psychiatric symptoms such as depression are also frequent

Pathologic findings include severe atrophy of the caudate nucleus (with

loss of GABAergic medium sized spiny neurons) less severe involvement
of putamen and cerebral cortex, dilation of the lateral ventricles apparent
on CT AND mri
Expansion of CAG trinucleotide repeat in a gene on the short arm of
chromosome 4 coding for a protein called huntingtin

Left-sided- hemiplegia
Left Babinski sign
Left lower facial paralysis
So its pure motor and all on the left
The tract that must be affected is the corticospinal tract because he is
showing UMN signs (paralysis, hyperreflexia, Babinski sign) – contralateral
because lesion must be in the brain

Thalamus lesion causes contralateral sensory loss

Lateral frontal lobe controls the arm and the face, whereas the medial
portion controls the legs
Complete facila paralysis- LMN CN VII

Lacunar infarct which commonly involves lenticulostriate vessels, leading

to small cystic areas of infarction
Hypertension and diabetes are risk factors
Pure motor deficit of lacunar infarct- posterior limb and genu of the internal
capsule
Corticospinal fibers originate in the primary motor cortex of the frontal lobe
and descend through the posterior limb of internal capsule – caudal
medulla
Corticobulbar fibers to the facial nucleus originate in the primary motor
cortex of the lateral frontal lobe and descend to the genu of the internal
capsule
A lesion right internal capsule result in left-sided hemiplegia
Lower left facial paralysis is the result of an UMN which is consistent with a
stroke in internal capsule

GBS which once was described as a single disorder, but is now thought to
be collection of clinical syndromes that are characterized by an acute
inflammatory polyradiculoneuropathy leading to weakness and diminished
reflexes.
Demyelinating neuropathy with ascending symmetric weakness with
absent or depressed tendon reflexes
Ventromedial nucleus is thought to be the satiety center- bilateral
destruction leads to hyperphagia, obesity and savage behavior
Stimulation inhibits the urge to eat
Lateral nucleus has the opposite function of the VMN it is the feeding
center
Destruction of the lateral nucleus results in starvation whereas stimulation
of this nucleus induces eating

Werdnig-Hoffman disease- gene that normally turns off perinatal

programmed cell death, so neuronal cell death continues postnatally and
results in denervation of muscle with resultant atrophy
Disease of the anterior ventral horn cells- and is an example of a lower
motor neuron disease
LMN disease- flaccid muscle weakness, hypotonia, loss of voluntary
movement, loss of deep tendon reflexes, fasciculations and fibrillation
potentals seen on the EMG

The patient cannot move either her arms or legs, thus she has bilateral
symptoms
The basilar artery supplies both sides of the ventral and medial pons
The basilar artery is formed by the joining of the 2 vertebral arteries, it
ascends along the ventral midline of the pons and then divides into two
posterior cerebral arteries
This patient has sustained a stroke of a segment of the basilar artery,
leading to a lesion of the ventral pons- descending corticospinal and
corticobulbar fibers are interrupted

True coma- bilateral lesions that damage substantial portions of reticular

formation in upper pons and midbrain
Locked in syndrome can be also caused by central pontine myelinolysis-
damage to pons caused by overly rapid correction of hyponatremia ,
pontine abscess, and pontine tumors

Lateral medulla is known as the PICA syndrome or the Wallenberg

syndrome
Dysphonia, dysarthria, and loss of pain and temperature on the ipsilateral
face and contralateral body, nystagmus and gait

The sagittal sinus thrombosis which is often associated with

hypercoagulable states
Increased frequency during pregnancy and during the first few weeks of
postpartum
Obstruction of the venous drainage can lead to increased ICP, seizures,
parasagittal hemorrhages and infarcts from decreased cerebral perfusion

The right sympathetic trunk lies posterior to the right carotid sheath and
may be injured
Preganglionic sympathetic nerve fibers arising from T1 spinal cord
segment and ascending through the cervical sympathetic chain will be
damaged
Superior cervical ganglion- postganglionic sympathetic neurons that
innervate structures in the head
Dilator pupillae muscle- smooth muscle of the iris that dilates pupil

The patient feels “winded”, and noticed she has trouble breathing when
she runs.
Prominent a wave in the jugular venous pulsation
Thickening of leaflets of the mitral valve, left atrial enlargement and RVH
(right ventricular hypertrophy)
The patient is exhibiting mitral stenosis, patients will typically complain of
dyspnea on exertion with an insidious onset, progressing over years.
Stenotic mitral valve leads to left atrial enlargement, pulmonary
hypertension and eventually right ventricular hypertrophy
Prominent a wave is caused by increase in right atrial pressure, the result
of right ventricular hypertrophy and pulmonary hypertension
Murmur is opening snap followed by a late diastolic rumble
The stenotic mitral valve creates an artificial pressure gradient, requiring
greater pressure to build up in the atrium before the valve can open, and
when this pressure gradient is overcome- the valve opens rapidly causing
the opening snap- the murmur is caused by turbulent flow across the
stenotic orifice

Continuous machine like murmur is heard with a patent ductus arteriosus

and can be heard in young infants and adults with an anomalously patent
ductus
Aortic pressure > pulmonary arterial pressure throughout the cardiac cycle-
so blood flow across the patent ductus arteriosus into the pulmonary
arterial circulation is heard continuously

Crescendo-decresendo systolic ejection murmur is heard in aortic stenosis

An early high pitched blowing diastolic murmur is heard in aortic
regurgitation

Mitral or tricuspid regurgitation- a high pitched blowing holosytolic murmur-

opening snap

Newborn infant begins to breathe immediately after birth, but remains a

blue color despite efforts to provide oxygen.
Misalignment and anterior rightward displacement of the AP septum
The described defect during heart development leads tetralogy of fallot
which consists of pulmonary stenosis, overriding aorta, membranous
septal defect, and hypertrophy of the right ventricular wall
Right to left shunt which bypasses oxygenation within the lungs leading to
cyanosis

Neural crest cell migration to the endocardial cushion is important for atrial
and ventricular septum formation so failure of migration can lead to primum
atrial septal defect
The ductus arteriosus arises distal to the origin of the subclavian artery
and shunts blood during fetal life from the pulmonary trunk to the aorta.
Most of the blood passing through the ductus is systemic, deoxygenated
blood that has returned to the heart through the superior vena cava and
passed through the right ventricle into the pulmonary artery
Ductus arteriorsus does bypass the lungs but deoxygenated blood

The shunting of oxygenated blood from the aorta to the pulmonary artery
occurs with a patent ductus arteriosus

This lower blood volume is present in the capacitance portion of the

vasculature (venous) rather than pressure portion (arterial)
Low-pressure (cardiopulmonary) mechanoreceptors (baroreceptors) are
activated within the walls of the great veins and atria in proportion to the
patients volume status: a hypovolemic patient fires fewer and hypervolemic
patient fires greater APS
Elevated hematocrit- hypovolemic
Low pressure baroreceptors in the vena cava are likely affected
High-pressure (arterial) baroreceptors are located in the aortic arch and
carotid sinuses. High pressure baroreceptors are activated if cardiac
output and systemic blood pressure are low
The patients blood pressure is slightly lower than normal, but is likely
maintained by pressor agents such as angiotensin II and carotid sinus
reflex
However arterial baroreceptors are not most likely receptors to be
activated since volume loss rather than a decrease in BP is main concern

Blood flow can increase due to metabolic vasodilation of arterioles as

much as 20-fold in dynamically exercising skeletal muscle which is a
greater increase than in any other tissue in the body
This tremendous increase in blood flow results almost entirely from the
actions of local vasodilator substances on the muscle arterioles
During high intensity static exercise such as high force weight lifting,
compression of blood vessels actually decreases blood flow because of
vessel compression even though the arterioles are dilated

During high intensity exercise the muscles use ATP more rapidly than it
can be regenerated from ADP and phosphate. A decrease rather than
increase in the ratio of ATP/ADP is implicated in the rapid fatigue of
intensely exercising muscles
Extracellular K + increases and intracellular K+ decreases
During high-intensity static exercise such as weight lifting the blood
vessels are compressed by S.M. thus increasing vascular resistance and
decreasing blood flow
During dynamic, endurance exercise, vascular resistance decreases and
blood flow increases due to metabolic vasodilation of arterioles

Distribution of blood volume in the circulation is directly related to the

compliance and capacitance of the different vessels
The total blood volume of the body is about 5000 mL
Systemic veins distend easily (high compliance) and are large (high
capacitance)
Resting conditions the systemic veins contain about 64% of blood volume
or about 3200 mL
Supine posture at rest is used as the basal state for comparisons, to
reduce gravitational and effects and activation of the baroreflex which
alters smooth muscle tone

The medial umbilical fold is an elevation of the parietal peritoneum that

covers the medial umbilical ligament (the adult remnant of the umbilical
artery)
Paired umbilical arteries arise from the internal iliac arteries
In the fetus the umbilical arteries convey fetal deoxygenated blood to the
placenta
After birth, the distal portion of the umbilical arteries obliterate and their
vestigial remnants are the medial umbilical ligaments
The proximal portion of the umbilical artery remains patent and supplies
the urinary bladder
Allantois remnant is the median umbilical ligament- which contains the
urachus –
Abdominal aorta gives rise to the common iliac arteries which give rise to
external and internal iliac arteries

External iliac arteries become the femoral arteries when they pass deep to
the inguinal ligaments
Hepatic veins receive blood from liver sinusoids which then drain to the
inferior vena cava

VEGF is one of the most important growth and survival factors for
endothelial cells under normal physiologic conditions
VEGF is a heparin binding glycoprotein
Most cells (not endothelial cells) secrete VEGF under hypoxic conditions
The decrease in tissue oxygenation that occurs in muscles during exercise
is a potent stimulus for VEGF production and secretion by the muscle cells
It rises to high levels within an hour after exercising
Repeated bouts of exercise can lead to significant endothelial proliferation
and actual growth of new capillaries in the muscles

Blood pressure leaving the heart is high, typically around 100 mmHg but
when returning to the heart the pressure is very low, usually around 2
mmHg
The reason for this drop in the blood pressure is peripheral vascular
resistance
Change in pressure= cardiac output x total peripheral resistance
This relationship is analogous to electrical circuits in which the equation is
in voltage = current times electrical resistance

to determine change in Pressure we need to calculate the difference

between the blood pressure as it leaves the heart (mean arterial pressure)
and the blood pressure as it returns the heart (right atrial pressure)
Change in pressure = mean arterial pressure – right atrial pressure
As blood moves through the peripheral vasculature its pressure gradually
drops due to peripheral vascular resistance
MAP- RAP = CO X TPR

Cardiac output is equal to the volume of blood ejected from heart during
each systole (SV) multiplied by the number of times heart beats each
minute (Heart rate)
CO= SVXHR
Stroke volume is determined by preload, afterload, and contractility of the
heart
Heart rate is mediated by parasympathetic and sympathetic neural input to
cardiac pacemeakers
Measurements of stroke volume is initial steps in evaluating cardiac
function

The circulatory system is a parallel circuit since blood flow to all organ
branches from the aorta and joins together in the vena cava
The various organs of the body are arranged in parallel and therefore
contribute a parallel resistance to the peripheral circulation
Adding resistances in parallel reduces total resistance of a circuit because
of the manner in which parallel resistances are added
Removing a parallel resistance increases the total resistance
AV anastomosis adds another parallel resistor so total peripheral
resistance and mean arterial pressure drop
Decreasing the number of resistors (occlusion of blood supply to an organ)
increases TPR and MAP
Resistances in parallel- the reciprocal of the total resistance is the sum of
the reciprocals of the individual resistances
The total resistance is always less than any of the individual resistances
Adding a resistance lowers the total resistance and decreases arterial
blood pressure
Decreasing the number of resistances (occlusion of an organs vessels)
increases resistance and arterial blood pressure

Resistance in series:
Major feature is that flow must be equal at all points
If the flow changes it changes equally at all points
The total resistance is the sum of the individual resistances and is
therefore greater than any of the individual resistances
Adding an additional resistance increases the total resistance

The infant has persistent truncus arteriosus which results from a failure of
the conotruncal ridges (which are of neural crest origin) to form the AP
septum
As a consequence the ascending aorta and the pulmonary trunk arise from
a common tube
If this septum fails to form, the single truncus arteriosus will receive blood
from both the right and left ventricles allowing the deoxygenated blood to
be mixed with oxygenated blood, causing CYANOSIS
Since conotruncal ridges also participate in the formation of the
membranous interventricular septum, a ventricular septal defect must also
be present
Right to left shunting of blood occurs resulting in cyanosis

T defects are always cyanotic conditions and include tetralogy of fallot,

transposition of the great arteries and persistent truncus arteriosus

Overriding aorta also produces a R-L shunt and cyanosis because right to
left pressure gradient but it is a feature of TOF not persistent truncus
arteriosus
Patent ductus arterisosu results in blood passing from the aorta to the
pulmonary trunk postnatally. This left to right shunt does not cause
cyanosis
Cyanosis is caused by right to left shunts
Prenatally the ductus arteriosus allows the passage of blood from the PT
to the aorta
After birth when the pressure gradient reverses and the pressure is higher
on the left side of the heart the flow in a pda reverses and becomes a left
to right shunt
Atrial spetal defects allow for left to right shunting of blood postnatally
because of pressure is higher in the left atrium than in the RA
Left to right shunts do not cause cyanosis
Persistent truncus arteriosus results from a failure of the conotruncal
ridges to for the aorticopulmonary septum
Since the conotruncal ridges also participate in the formation of the
membranous interventricular septum a ventricular septal defect will aslo be
evident in patients with this condition
This causes a right to left shunting of blood with resultant cyanosis

The patients physical examination and symptoms are consistet with mild to
moderate dehydration
The baroreceptors mechanism is important for maintaining arterial
pressure when a person sits or stands from a lying position especially
when they are dehydrated
When a person suddenly stands, blood pressure in the brain and upper
body tends to fall, because of gravity
It causes blood to pool in the high compliance veins of the lower
extremities
This causes decreased venous return which also decreases stroke volume
of the heart
Baroreceptors predominantly located on the carotid sinus detect the lower
BP and via the glossopharyngeal nerve (CNIX) send signals to the medulla
which initiates a strong sympathetic response and decreased PS from the
vagus nerves- raising BP to normal
Increase HR, conduction velocity and myocardial contractility
Constriction of nearly all the arterioles in the body which increases tpr
Renal vasculature decreases in renal blood flow
Constriction of large veins increases venous return to the heart by forcing
blood against gravity

Decreasing the number of resistors (occlusion of blood supply to an organ)

increases TPR and MAP
Removing a parallel resistance from a circuit increases total resistance of
the circuit

The patient has pulmonary embolism, the large filling defect in the right of
pulmonary artery and in the superior branch of the left pulmonary artery
More than 90% of the pulmonary emboli originate from the deep veins of
the lower limbs. The only deep vein of the lower limb listed – femoral vein
Venous thrombosis can also form more distally in the popliteal vein
The risk of embolism increases as the clot extends proximally
The basilica and cephalic veins are two superficial veins of the upper limbs
and are the ones most frequently accessed with IV catheters
Brachial vein- is the major deep vein of the upper extremities
Greater saphenous and lesser saphenous veins are the superficial veins of
the lower limbs and do not commonly result in Pulmonary embolism

More than 90% of the pulmonary emboli begin in the deep veins of the
lower limbs
Deep vein thrombosis of the lower extremities generally form in the
popliteal veins and extend proximally
The more proximal the clot the more likely it is to embolize to the lungs

The azygous vein is a major accessory pathway for venous return in

patients with end stage liver disease and critical portal hypertension
The pathway starts at the left gastric vein, which drains into the portal vein
With portal hypertension flow through the left gastric vein reverses and
blood flows into the venous plexus esophageal
Azygous vein is the major outlet for the esophageal venous plexus and
relieves some of the pressure of the esophageal vein (bears the burden in
esophageal varices)
Esophageal varices become engorged variceal rupture can occur
This is major complication of portal hypertension- 50% chance death and
surviviors have recurrence!

All forms of dynamic exercise cause vasodilation in the exercising muscles

due to the metabolic factors produced by the muscles
This decrease in vascular resistance causes an increase in blood flow to
the muscles supplying them with extra oxygen and nutrients
Reduction in vascular resistance increases BP downstream in capillaries
Lactic acid, K+ and adenosine- metabolic factors that lead to vasodilation
during exercise in addition during exercise the vasodilation seen in muscle
tissue is mediated by B2 agonist

Resistance of arterioles is decreased, the pressure falls to a lesser extent

causing the downstream pressures (capillaries) to be elevated- increase in
rate of fluid filtration from capillaries (increased capillary filtration rate
which in turn leads to increase in the flow of lymph from the muscle
The sarcomere length is the longest when the LV is filled to the greatest
extent with blood ( LV volume is greatest, this occurs at the end of diastole,
just before the ventricle contracts) – End diastolic volume
Sarcomeric length is the shortest at the end of the systole (point D) when
the volume of the left ventricle is the lowest (END systolic volume)
When the venous return to the heart increases the end diastolic volume
increases ( preload) and the sarcomere length increases
Maximal force is generated with a sarcomere length of 2.2 micrometer
Increase in sarcomere length improve sthe interdigitation of actin and
myosin filametns and enables the LV to contract with greater force to expel
the extra volume of blood
Stalings law of the heart!

During each cardiac cycle the walls of the ventricle undergo isometric
contraction and relaxation as well as isotonic contraction and relaxation
Muscle contraction is isometric when the muscle length does not change
Isotonic when the muscle length does change with a constant tension on
the muscle

Phase 0 of the cardiac muscle action potential corresponds to the opening

of the voltage-dependent sodium channels causing transient but large
increase in sodium conductance and depolarization
The shape of the QRS complex of ECG is determined by the spread of the
combined phase 0 (depolarization) of all ventricular muscle of the heart

The QT interval, the QRS (Na+ depolarization)

represent the ventricular depolarization
P wave corresponds to atrial depolarization. The mass of atrial tissue is
much smaller than ventricular muscle, so overall gNa is smaller during
atrial depolarization than during ventricular depolarization
The ST interval represents the time interval during which all ventricular
cells are in phase 2 of their AP. Phase 2 is dominated by a high, prolonged
calcium conductance through slow, L-type calcium channels
Sodium channels are inactivated during the plateau phase. The length of
the ST interval corresponds closely to the AP duration in ventricular
muscle
T wave corresponds to ventricular repolarization, this depends on closure
of calcium channels and increased potassium conductance
U wave is found only occasionally in ECGs and is presumed to be due to
the repolarization of papillary m

The QRS complex of an ECG is caused by spreading of ventricular

depolarization. This correlates with phase 0 of the ventricular action
potential and is dominated by massive inward sodium conductance

The glossopharyngeal nerve and the vagus nerve (CN X) carry afferent
information to the medulla from the carotid sinus and aortic arch
baroreceptors respectively
The firing rate of these neurons increases with increasing blood pressure
Therefore, cutting the glossopharyngeal nerve sends a false signal to the
medulla signaling that the animal suddenly had a decrease in blood
pressure
This elicits a baroreceptor reflex resulting in an increase in sympathetic
outflow and a decrease in parasympathetic outflow- hypertension and
tachycardia
The carotid sinus provides a much larger part of the control of blood
pressure than the aortic arch receptors. Depending on the situation,
various numbers are reported, but the carotids are generally credited with
80-90% of the response to hypotension
So even though the afferents from the aortic arch are intact, the loss of
signal from the carotid sinus overwhelms the contradictory information
from the aortic arch
severing the glossopharyngeal nerve sends to the medulla a false signal
that there is a sudden decrease in BP
this elicits a baroreceptor reflex that results in an increase in sympathetic
outflow leading to hypertension and tachycardia

this patient is suffering from a ruptured abdominal aortic aneurysm (AAA)

it is important to realize that the aorta is retroperitoneal and lies directly on
the vertebral bodies
therefore, aortic pathology is usually associated with back pain
thus patients with AAA typically have abdominal pain that radiates to the
back and AAA should be considered differential diagnosis of the acute
abdomen
the history of hypercholesterolemia is further concerning for AAA
rupture of the aneurysm is indicated by this patients hemodynamic
instability- tachycardia and hypotention
physical findings of abdominal aortic aneurysm includes pulsatile
abdominal mass, abdominal bruit and hemodynamic instability

The AV node is in the subendocaridum of the interatrial spetum

The location of the penetrating wound would correspond to the lower part
of the atria (left and right) in the region where the AV node is found
From the av node, the purkinje fibers of the av bundle enter the
interventricular septum to carry impulses to the ventricle
The function of the av node is to retard the conduction of the cardiac
impulses so that ventricular systole occurs after atrial systole
The atrioventricular node is located in the interatrial septum near the
opening of the coronary sinus

This patient has widened pulse pressure secondary to age related

stiffening of large arterial vessels
These large, proximal vessels including the thoracic aorta and its branches
must be able to cushion the high pressure pulsatile blood flow coming from
the heart
Thus a major component of these vessel walls is elastin, which increases
their compliance
Compliance is the ability of a vessel to distend or increase its volume in
response to increasing pressure
With age, the elastic lamina of large vessels breaks down, becoming
calcified and mineralized
Many of these elastin fibers are replaced by collagen which is significantly
less compliant
These changes also known as arteriosclerosis, produce two main side
effects- systolic BP increases because the artery is unable to expand
adequately in response to pulses of blood flow from the heart
During diastole BP stays the same or decreases due to reduced vessel
compliance, volume of blood remaining in the arteries during diastole
decreases because of increased stiffness
Other causes of widened pulse pressure include aortic regurgitation,
patent ductus arteriosus, and exercise
Cardiac output is directly related to MAP
PULSE PRESSURE is directly proportional to stroke volume but not
HEART RATE
Decreases in stroke volume would decrease pulse pressure
A decrease in myocardial contractility would decrease stroke volume and
therefore cause the pulse pressure to decrease
A decrease in stroke volume causes pulse pressure to decrease because
a smaller amount of blood enters the arterial system with each heartbeat
Thus the rise and fall of pressure between systole and diastole is
decreased
his pulse is 110/min and his bP is 90/50 mmHg, the patient is started on
aggressive IV fluids and a swanz-ganz catheter is placed revealing a
pulmonary capillary wedge pressure of 2mmHg and low cardiac output

the patient has decreased cardiac output and increased heart rate. Since
cardiac output = stroke volume x heart rate, this means that stroke volume
has decreased
stroke volume = end diastolic volume – end systolic volume
three factors regulate stroke volume: these are preload, afterload, and
contractility

the primary reason for reduced stroke volume is reduced preload, due to
decreased end diastolic volume

The large difference in blood pressure between his upper and lower limbs
This suggests disease of the aorta distal to the arch, where the vessels
supplying the upper limbs arise
In younger individuals postductal coarctation of the aorta is the most
probable diagnosis
In older individuals severe atherosclerosis of the abdominal aorta, iliac
system and or femoral system is most probable diagnosis
In patients with aortic coarctation, anterograde flow through the stenotic
portion of the aorta is severely limited

Aplastic anemia- disorder of unknown aetiology- anemia, leukopenia,

thrombocytopenia- resulting in aplasia of BM
The exact mechanism in which aplastic anemia occurs is not known
Anemia, leukopenia, thrombocytopenia (pancytopenia)
Anemia- condition in which blood hg is below
Leukopenia- wbcs is reduced
Thrombocytopenia- platelet level is less than normal
Aplasia of Bone marrow- absent or reduced proliferation of stem cells

Secondary- drug idiosyncracy- hypersensitive reaction to drug, in a small

population drug can cause nonimmunological hypersensitive reaction
Low risk group- their risk is very low
High risk group
Chlorpromazine, gold salts, chloramphenicol and antirhematic drugs
Fanconi syndrome- hyperproliferative myeloid stem cells, defective DNA
mechanism, hyploplasia of kidney or bones, esp bones related to thumbs
or bones

Haptoglobin amounts are always decreased because some hemoglobin

escapes into the plasma
In most forms of hemolytic anemia there is reactive hyperplasia of the
mononuclear phagocyte system, which results in splenomegaly

In chronic hemolytic anemia changes in iron metabolism lead to increases

in iron absorption from the gut
HS the primary abnormality resides in one of a group of proteins that form
a meshlike supportive skeleton on the intracellular face of the red cell
membrane
This patient is likely suffering from lead poisoning. His work with ceramics places
him at risk, as lead is used in the making of ceramic pottery. δ-Aminolevulinic
acid dehydratase, the second enzyme in heme biosynthesis, is extremely
sensitive to inhibition by heavy metal ions, including lead. This inhibition leads to
the elevation of δ-aminolevulinic acid seen in lead poisoning and the anemia
caused by insufficient hematopoiesis. Lead also denatures both ferrochelatase
(further blocking the synthesis of heme) and ribonucleases in RBCs (preventing
ribosomal breakdown and causing basophilic stippling). The high ferritin can be
thought of as buildup of iron in the mitochondria (with the disrupted heme
synthesis), leading to increased storage of iron as ferritin. Liver synthesis of
transferrin is decreased in turn, resulting in a lower total iron-binding capacity.
Lead poisoning may also lead to liver dysfunction in general, adding to the
laboratory findings.  Lead poisoning in adults is suggested by microcytic anemia,
coarse basophilic stippling, peripheral neuropathy (eg, wrist drop), and
metaphyseal deposits of lead. In children, the most concerning consequence of
lead poisoning is central nervous system dysfunction, including cerebral edema,
demyelination, behavioral and motor abnormalities, and intellectual disability.
Lead lines, which are indicated by the arrow in the image, are dense
metaphyseal bands in long bones that strongly support the diagnosis of lead
poisoning in children (these lines are only seen in growing bones and will not be
present in adults with lead poisoning.)