Case 7

Asthma
August 2, 2013 Talanquines, Daryl Talplacido, April Cherisse Tan, Joseph Tan, Katherine

Scenario
CD, 52 yo, female Chief Complaint: severe wheezing, shortness of breath and coughing HPI: serious motor vehicle accident 10 weeks ago; frequent asthma attacks for the past 2 months; post traumatic seizure 2 weeks after the accident

Past Medical History: - Periodic asthma attacks since early 20s - Mild CHF (3 years) Family History: -Mother (deceased at age 62) CHF -Father (deceased at age 59) kidney failure secondary to hypertension

Social History: - Caffeine use: 4 cups of coffee and 4 diet colas per day Medication History: - Theophylline SR capsules, 300mg PO BID - Albuterol inhaler, 2 puffs PRN - Phenytoin SR capsules - Hydrochlorothiazide tablets, 50mg PO BID - Enalapril tablets, 5mg PO BID

Allergies: NKDA Physical Examination: GEN: pale, well-developed, anxious-appearing woman VS: ED admission: BP 171/94, RR 31, HR 122, T 38.5C, Wt 61kg, Ht 161cm Current: BP 142/79, HR 80, RR 18, T 38.3C HEENT: PERRLA, oral cavity without lesions, TM without signs of inflammation; no nystagmus noted; positive for AV nicking

COR: no murmurs, normal S1 and S2 CHEST: bilateral expiratory wheezing ABD: nontender, non distended, no masses GU: unremarkable EXT: 1+ ankle edema on right, no bruising, normal pulses NEURO: Ox3; CN intact

Laboratory result

Theophylline: 62 ug/mL Phenytoin: 17 ug/mL Pulmonary Function Tests: FEV1 1.8; FVC 3.0; FEV1/FVC: 60% Initial Peak Flow: 75/min 2nd reading (1hr after treatment): 102/min ECG: Voltage changes consistent with LVH Chest X-ray: blunting of the right and left costophrenic angles

Problem List
1) 2) 3) 4) Asthma Theophylline toxicity Congestive Heart Failure Seizure disorder

Asthma
Problem 1
Talplacido, April Cherisse A.

Problem 1: Asthma
Objectives: 1) To be able to define Asthma and review its pathogenesis and its pathophysiology 2) To be able to enumerate its clinical manifestations and establish the basis for the disease 3) To be able to come up with a treatment objective and give the nonpharmacological and pharmacological approach 4) To be able to prescribe a drug suitable to the patients profile

What is Asthma?
Chronic inflammatory disorder of the airways. trachea to the terminal bronchioles Many cells are involved: - T-lymphocytes, eosinophils, mast cells, macrophages, and neutrophils

Major etiologic factors: predisposition to type I hypersensitivity acute and chronic airway inflammation bronchial hyper responsiveness

Triggers: Cold air Dust mites Pollens

smoke chemical fumes pets molds emotions heavy exercises

Types of Asthma
1. 2. 3. 4. Atopic Asthma Non-Atopic Asthma Drug-induced Asthma Occupational Asthma

Clinical Manifestations
Recurrent episodes of: Wheezing Dyspnea Chest tightness Cough

Diagnosing Asthma
History and PE Measurements of lung function Spirometry measures airflow limitation and its reversibility An increase in FEV1 of 12% and 200 ml after administration of a bronchodilator indicates reversible airflow limitation consistent with asthma. Peak Expiratory Flow (PEF) measurements An improvement of 60 L/min (or 20% of pre-bronchodilator PEF) after inhalation of a bronchodilator.

Bases for diagnosis

Chief complaint: Severe wheezing Shortness of breath Cough HPI: frequent asthma attacks for the past 2 months PMH: Periodic asthma attacks since early 20s Medication History: Theophylline SR capsules, 300mg PO BID Albuterol inhaler, 2 puffs PRN

Bases for diagnosis

PE: GEN: pale, well-developed, anxiousappearing woman VS: ED admission: RR 31, HR 122 Current: HR 80, RR 18, CHEST: bilateral expiratory wheezing

Bases for diagnosis

Pulmonary Function Tests: FEV1 1.8; FVC 3.0; FEV1/FVC: 60% Initial Peak Flow: 75/min 2nd reading (1hr after treatment): 102/min

Therapeutic Goals
prevent chronic asthma symptoms and asthma exacerbations maintain normal activity levels normal or near normal lung function experience no or minimal side effects patient satisfaction with asthma care.

Four interrelated components of therapy are required to achieve and maintain control of asthma: Develop patient/doctor partnership Identify and reduce exposure to risk factors Assess, treat and monitor asthma Manage asthma exacerbations

Non-pharmacologic Approach
In the hospital Evaluate symptoms and, as much as possible, peak flow. Assess oxygen saturation; do ABG Initiate supportive care

Non-pharmacologic Approach
On follow up Develop patient-doctor partnership for the patient to learn to: Identify risk factors/triggers Understand the difference between controller and reliever medications Take medications correctly Monitor their status using symptoms and, if relevant, PEF Recognize signs and to take action when asthma is worsening Seek medical advice as appropriate Reduce exposure to risk factors

Pharmacologic Approach
Relievers - Reverse airflow obstruction - Quickly relieve accompanying symptoms

Controllers - Preventers - Achieves and keeps persistent asthma under control

Reliever
Short-acting beta-2 agonist Anti-cholinergics Short-acting theophylline

Efficacy

+++

++

Suitability

+++

++

Safety

++

+++

Cost

+++

++

P drug: Short-acting beta-2 agonist (Salbutamol)

Controller
Budesonide Budesonide + Formoterol Fluticasone propionate

Efficacy

++

+++

++

Suitability

+++

+++

+++

Safety

+++

++

+++

Cost

+++

++

P drug: Budesonide

THEOPHYLLINE TOXICITIES
Katherine Mae Tan

THEOPHYLLINE toxicities
Salient Features: 4 cups of coffee and diet colas per day Anxious appearing woman HR 122; RR 31 ; T= 38.5 (ED)

THEOPHYLLINE LEVELS 62ug/ml

THEOPHYLLINE toxicities
K+ (3.5-5.0mEq/L) 4.9 mEq/L normal

Ca 2+(8.8 10.3mg) 2.23mEq (8.9mg)

normal

PO43+ (2.5-4.5 mg) 0.872 (2.7mg)

normal

Mg2+(1.6 2.4 0.65 mEq)

Glucose (60110mg /dl) 6.1 mmol/l(110mg/dl)

decrease
normal

OBJECTIVE
1. Relieve the patient symptoms related to Theophylline toxicity

OBJECTIVE
1. Relieve the patient symptoms related to Theophylline toxicity 2. Monitor serum concentration level and reduce or eliminated the toxicity level of Theophylline

OBJECTIVE
1. Relieve the patient symptoms related to Theophylline toxicity 2. Monitor serum concentration level and reduce or eliminated the toxicity level of Theophylline 3. To educated patient on proper use of asthma medication to prevent further complications

OBJECTIVEs
1. Relieve the patient symptoms related to Theophylline toxicity 2. Monitor serum concentration level and reduce or eliminated the toxicity level of Theophylline 3. To educated patient on proper use of asthma medication to prevent further complications 4. Reduce morbidity and mortality

Theophylline
One of the methylxanthine drugs (includes caffeine, theobromide)

Theophylline
One of the methyxanthine drugs (includes caffeine, theobromide) White ,odorless, crystalline powder with bitter taste Bronchodilator relieves airflow obstruction MOA : inhibit the cyclic nucleotide PDE high concentration of cAMP (smooth muscle relaxation)

Theophylline
One of the methyxanthine drugs (includes caffeine, theobromide) White ,odorless, crystalline powder with bitter taste MOA : inhibit the cyclic nucleotide PDE high concentration of Intracellular cAMP PKA activated (bronchodilation) : inhibition of cell surface receptors for non specific adenosine

Theophylline
Adenosine blockade reduces histamine release and indirectly reverse bronchospasm. ANTI INFLAMMATORY Inhibit the synthesis and secretion of inflammatory mediators from mast cells and basophils

Theophylline
Adenosine blockade reduces histamine release and indirectly reverse bronchospasm ANTI INFLAMMATORY Inhibit the synthesis and secretion of inflammatory mediators from mast cells and basophils Increases the IL-10

Theophylline
ANTI INFLAMMATORY Inhibit the synthesis and secretion of inflammatory mediators from mast cells and basophils Increases the IL-10 Promote apoptosis in Eosinophils and neutrophils perpuate chronic inflammation in asthma and COPD

Theophylline
ANTI INFLAMMATORY Inhibit the synthesis and secretion of inflammatory mediators from mast cells and basophils Increases the IL-10 Promote apoptosis in Eosinophils and neutrophils perpuate chronic inflammation in asthma and COPD Activates histone deacetylase Smokers,increase oxidative stress

Theophylline
Therapeutic serum levels :10-20 mcg/ml Toxic dose >20mcg/ml

THEOPHYLLINE
INDICATIONS COPD ASTHMA INFANT APNEA - Additional drug for uncontrolled asthma Nebulizer Antibiotic (if with bacterial infections) Steroids

THEOPHYLLINE
Precautions of administration of theophylline : RISK FACTOR Elderly CHF Liver Disease hypoalbuminemia Dose MUST be decreased and MONITOR CLOSELY!

THEOPHYLLINE
PHARMACODYNAMICS: CNS :

1.mild cortical arousal with increase alertness and deferral of fatigue 2. insomnia 3. HIGH DOSES: medullary stimulation and convulsions 4. Primary SE: nervousness and tremor

THEOPHYLLINE
PHARMACODYNAMICS: CVS :

1.Positive INOTROPIC and CHRONOTROPIC effects 2. ARRHYTHMIAS 3. Slight tachycardias and INCREASE CO 4. Rises PVR an BP

THEOPHYLLINE
PHARMACODYNAMICS: Lungs:

1. Increase the force of contraction of diaphragmatic muscle enhancement of calcium uptake through adenosine-mediated channel (increase RR) 2. Bronchodilation (5 to 20mcg)

THEOPHYLLINE
PHARMACODYNAMICS: GIT : stimulate gastric secretion and digestive enzymes KIDNEYS : Weak diuretics SKELETAL MUSCLES : improve contractility SMOOTH MUSCLES : inhibit the antigen-induced release of histamine from lung tissue

THEOPHYLLINE
PHARMACOKINETICS:

orally and parental administration distributed into all body compartments cross the placenta and pass into BM,CSF Bioavailabity 100% metabolized by liver (CYP1A2; CYP3A4) Unchanged in urine (5-15%) 40% -50% protein bound Usual dose: 3-4 mg/kg q 6 hrs

THEOPHYLLINE
T1/2 : 3.5 hrs children;

8 to 9 hrs adult 4 to 5 hrs smoker 12 hours CHF class III,elderly 24 hours CHF class IIIIV, hepatic impairment

THEOPHYLLINE
INCREASE HALF-LIFE (decrease clearance) Elderly .3rd trimester pregnancy Erythromycin, cimetidine, fluoroquinolones hypothyroidism Cirrhosis CHF Acute Pulmonary edema, pneumonia,influenza infections COPD Obesity High CHO, low protein High levels of methylxanthines (caffeine) DOSE DUMPING

THEOPHYLLINE
Decrease half life (increase CLEARANCE) PHENYTOIN, PHENOBARBITAL, rifampin barbiturates OC Smoking; marijauna Low CHO ; high CHON diet Hyperthyroidism Parenteral nutriotion Charcoal-broiled beef

Theophylline toxicity
Acute overdose >10mg/kg Chronic overdose (repeated doses that are excessive) Generalized seizure Life threatening cardiac arrhythmias Death Seizures, hypotension and dysryhtmias occurs ~ 80 mcg/ml

Clinical Manifestation of THEOPHYLLINE toxicity

1. HA 2. Palpitation 3. Dizziness 4. N&V 5. Hypotension

6. 7. 8. 9. 10.

Tachycardia Severe restlessness Agitation Fatal arrhyhtmias FOCAL AND GENERALIZED SEIZURES 11. sudden DEATH

THEOPHYLLINE
Electrolytes Hypokalemia Hyperglycemia Hypercalcemia Hypophosphatemia HYPOMAGNESEMIA

NON-PHARMACOLOGIC
STOP or WITHDRAW treatment Endotracheal intubation Hemoperfusion most effective Gastric lavage WBI Polyethylene glycol ECG monitoring ACTIVATED CHARCOAL mainstay treatment of theophylline toxicities ; block the absorption

0.5 g/kg up to 20 g

Repeat once every 1 to 2 hours after first dose

Immediately measure upon admission

2 to 4 hours later

Every 4 hours until serum level reach <20mcg/ml

Pharmacologic
Medications for nausea and vomiting: Ondansetron (Zofran) Metoclopramide (Reglan) Prochlorperazine (Compazine)

Pharmacologic
Medications to control seizures: Diazepam (Valium) Lorazepam (Ativan) Midazolam (Versed) Phenobarbital (Barbita, Luminal) Medication to support abnormally low blood pressure: Phenylephrine (Neo-Synephrine) Norepinephrine (Levophed) Hemoperfusion or hemodialysis: Filtering the blood, in order to remove theophylline form the bloodstream

Cardiac Arrhytmias
Abnormal automaticity and abnormal conduction Not a normal sinus rhythm Tachycardia >100bpm Bradycardia <60 bpm

Non-pharmacological
Remove precipitating factors Fever Anxiety Theophylline Monitor ECG closely.

Mag-Ox (MgO) Efficacy Safety +++ ++

Slow-Mag Mag(Mgla (MgCl) ctate) ++ + ++ + ++ +

Suitability +++ Cost +++ (14.00)

++(14-16) ++ (14-16)

Magnesium Oxide
cause hypotension depression myocardial conductivity bradyarrythmias. suppress the neuromuscular transmission diarrhea and nausea. Eliminated: renally and focally Duration 4 to 6 hours PO 140 mg (caps) 3 to 4 times/day or 400mg to 840 mg/day ) tabs

Katherine Mae A. Tan , M.D. Room 808, Right WING, MEDICAL ARTS BLDG CHINESE GENERAL HOSPITAL Tel no. 808-8888 Name : _____________________ AGE : ___________________ DATE:_____________ Address: _______________________________ Sex : _______

Magnesium Oxide (140 mg) Dispense 42 tablets

Sig . Take one tablet three times daily for 14 days Return after 14 days for check up.

Katherine Mae A. TAN, MD Lic no. 88888888 PTR no. 88888888

Acetaminophen Efficacy Safety Suitability Cost ++ +++ +++ +++ (Tylenol 6.00)

Ibuprofen +++ ++ ++ ++ (Advil ~8.00)

P-drug Acetaminophen
Anti-pyretic and analgesic Weak COX1 and COX2 inhibitor Well absorbed Peak blood concentration: 30 to 60 mins Metabolized : hepatic microsomal enzyme Excretion unchanged <5% T1/2 : 2-3 hours Adverse Effects: hepatic toxicity Treatment for OD : N-acetylcysteine Dosage : 325- 500 mg tid

Katherine Mae A. Tan , M.D. Room 808, Right WING, MEDICAL ARTS BLDG CHINESE GENERAL HOSPITAL Tel no. 808-8888 Name : _____________________ AGE : ___________________ DATE:_____________ Address: _______________________________ Sex : _______

Paracetamol (500mg)

Sig . Take one tablet every 6 hours until temperature below 37 0C

Katherine Mae A. TAN, MD Lic no. 88888888 PTR no. 88888888

Congestive Heart Failure

Basis
PMH Family/ Social history - Diagnosed mild CHF 3 yrs ago -father died of kidney failure - Na restricted secondary to diet hypertension - Hydrochlorthiazi -mother died of de CHF - Enalapril

Physical exam
General survey: Pale VS on admission BP: 171/94 RR: 31 HR: 122 Extremity 1+ ankle edema on right

ECG - Voltage changes consistent with LVH CXR - Blunting of the right and left costophrenic angles

HEART FAILURE
Inability of the heart to pump an adequate amount of blood to the bodys needs CONGESTIVE HEART FAILURE refers to the state in which abnormal circulatory congestion exists a result of heart failure

 A disorder in which the heart loses its ability to pump blood efficiently throughout the body Affects Cardiac Output SV X HR

End result: Cardiac Output

Intrinsic Pump Failure 1. 2. 3. 4. 5. Myocarditis Ischemic Heart Disease Cardiomyopathies Metabolic disorders Arrhythmia

Impaired filling of chambers a) Cardiac tamponade b) Constrictive pericarditis.

Etiology
Increased workload on the heart Increased pressure load a) Hypertension b) Chronic lung disease a) b) c) d) Increased volume load Valvular insufficiency Severe anaemia Thyrotoxicosis Arteriovenus shunts

Pathophysiology of compensatory mechanisms in cardiac failure

Heart Failure

Compensatory Mechanisms

Activation of norepinephrine atrial natrouretic peptide Tachycardia

Activation of renin-angiotensinaldosteron mechanism Na+ and water retention

Myocardial contractility Cardiac workload Cell Stretching

Further stress on myocardium

Compensatory Hypertrophy and dilatation

Further Heart Failure

May lead to

New york heart association functional classification

TREATMENT OBJECTIVES
Increased Cardiac Contractility Alleviate Fluid Retention Prevent Disease Progression

NON-PHARMACOLOGIC TREATMENT
Light exercise Avoid heavy labor or exhaustive sports Monitor weight Na restriction

Alleviate Fluid retention

Diuretics - Reduce salt and water retention reduce ventricular preload - Reduction in venous pressure reduction of edema and its symptoms - Reduction of cardiac size Improved efficiency of pump action

Pharmacologic therapy ( Alleviate Fluid Retention)

Name: C.D. Add: Valenzuela 52 Rx: Furosemide 20mg

Date: Aug. 2, 2013 Sex: Female Age:

#30 tab
Sig. Take 1 tab once a day
Joseph Ivan B. Tan, MD Lic. No.: 123456 PTR No.: 9876

NOTE
Monitor Urine Output . Monitor for Fluid and Electrolytes Imbalances .

Pharmacologic Treatment ( Preventing Disease Progression)

2013 Add: Valenzuela Female Age: 52

Sex:

Rx:

Losartan
#30 tab

Sig. Take 1 tab once a day

Joseph Ivan B. Tan, MD

Lic. No.:
123456 PTR No.:

9876

Digoxin
Inhibits Na/k ATPase increase of intracellular Na concentration increase Ca influx causing stronger systolic contraction

Name: C.D. 15,2011 Add: Valenzuela 64

Rx

Date: July
Sex: female Age:

Digoxin (Lanoxin) 0.25mg/ml amp

#14

Sig. Give 0.5ml every 6 hours per day for one week. Joseph Ivan B. Tan, MD Lic. No.: 123456 PTR No.: 9876

NOTE
Monitor Digoxin level and look for digitalis intoxication ( Anorexia, Nausea and Vomiting ) then give Digitoxin Ab (Fab fragments) for treatment Monitor Potassium Level

SEIZURES
By: Daryl O. Talanquines

Definition
A seizure (latin sacire, to take possession of)

EPILEPSY Vs. SEIZURES

A condition in which a person has reccurent seizure due to a chronic underlying process A clinical phenomenon rather than a single disease entity 2 or more unprovoke seizures

CLASSIFICATION OF SEIZURES
This system is based on: CLIN. FEATURES EEG FINDINGS Other potentially distinctive features not included: ETIOLOGY CELLULAR SUBSTRATE

Absence Seizures or petit mal

Typical
LOSS OF POSTURAL CONTROL (clinically & elektrophysiologically) LOSS OF CONSCIOUSNESS few seconds RETURNS TO NORMAL (w/o Post tictal Confusion)

Atypical
LOSS OF POSTURAL CONTROL

LOSS OF CONSCIOUSNESS minutes

(+) SEIZURE , MOTOR

GENERAL TONIC-CLONIC SEIZURES or grand mal

It is the MAIN SEIZURE TYPE of all persons with epilepsy MOST COMMON SEIZURE TYPE from Metabolic derrangements MOST FREQUENTLY encountered clinically

ATONIC SEIZURES
SHORT SEIZURE AS Quick HEAD DROP or NODDING MOVEMENT Collapse

LONG SEIZURE AS

TONIC SEIZURES

Sudden but brief muscle contraction that may involve 1 or more body parts Associated with:

Myoclonic SEIZURES
Brief shock like jerks or contractions
Multiple EEG spikes

In COMPARISON....
FOCAL ORIGIN 1 Cerebral hemisphere (medial temporal) (Inferior frontal ) GENERALIZED 1 Cerebral hemisphere - but rapidly distributed across both cerebral hemisphere via neuronal network Brain Structure Abnormality plus.. cellular abn. biochem abn.

ASSOTIATED WITH

Brain Structure Abnormality

EEG

Non localizing EEG EEG depend on type Normal , but may show epileptiform spikes/sharp waves

EEG
FOCAL SEIZURE GENERALIZED

Unclassifiable Seizures
Example: Epileptic Spasm
Common in INFANTS

CAUSES
Persistently High fever Penetrating Head Trauma

Exogenous factor (toxic drugs/metabolic)

Age /genetics

Clinical syndromes of idiopathic epilepsy associated with identified gene mutation

Clinical syndrome with numeroues mendellian disorders in which seizures are 1 part of the PHENOTYPE.

DRUGS KNOWN TO CAUSE SEIZURES

DIAGNOSTICS

TREATMENT
If the sole cause of a seizure is a metabolic disturbance treat METABOLIC DISTURBANCE If the apparent cause of a seizure was a medication (e.g., theophylline) or illicit drug use (e.g., cocaine), then appropriate therapy is avoidance of the drug NO NEED FOR ANTI EPILEPTIC If confirmed with subsequent seizures occur in the absence of these precipitants... HISTORY, TYPE of Seizure, TREAT

TREATMENT

TREATMENT OF FOCAL SEIZURES

CLASS : GENERIC : BRAND : EFFICACY SUITABILITY SAFETY COST MISCELLANEOUS LAMOTRIGINE ( Lamictal) HYDANTOIN PHENYTOIN (Dilantin) IMINOSTILBENES CARBAMAZEPINE (Carbatrol)

+++

+++

+++

+++
++ ++ 39.00

+++
+ +++ 30.65

+++
+ --

LAMOTRIGINE
MOA: Indication: Toxicity: Focal Seizures Myoclonic Seizures dizziness diplopia nausea & vomiting 24 hours 100 300 mg adults

Well absorbed Half life: Dosage:

LAMOTRIGINE
LAMOTRIGINE ( Lamictal) ADULT dose PEDIA dose ORAL CHEWABLE 25, 150, 200 mg 2, 5, 25 mg 100 to300mg / day 75 to 100 mg/ day

Signa: to be taken twice a day (oral) Signa: to be taken 3x a day (chewable) Drug Interactions with Valproate causes increase by two fold

Daryl O. Talanquines MD Fatima medical center 930-29-55 ______________________________________________________ Patients name: JS Date: Aug 1, 2013 Address: Quezon city Age: 52 y/o

Rx

Lamotrigine 50mg tablet (Lamictal) #14 tablets

Sig: Take one tablet twice a day for 2 weeks. And return for follow up check

_______________________ License No: 61969 PRT No: 69619

Refferences.......