dm acute & chronic rx

8/9/2019 DM Acute & Chronic Rx

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Treatment of DM Treatment of acute emaergencies

Treatment of uncomplicated DM


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The acute emergencies are:

DKA

Hyperglycemic Hyperosmolar State

Hypoglycemia


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DKA


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Introduction to Diabetic ketoasidosis

(DKA) Is a major medical emergency.

Serious cause of morbidity, principally in type I

diabetes. Occur in Type 2 DM but at a much lower frequency.

Annual incidence: 4.6 to 8 episodes per 1000

patients with DM.


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DKA cont

It is a state of relative insulin deficiency

associated with high blood levels of sugar and

ketones. Dehydration is a very important feature


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Pathogenesishyperglycemia is a result of:

Increased hepatic glycolysis and gluconeogenesis Impaired glucose utilisation by peripheral tissues

There is an in counterregulatory hormones:

Cortisol

Growth hormone

Catecholemines

Glucagon These hormones promote lipolysis & release of

free fatty acids

In the liver, free fatty acids converted to ketones.


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Signs & symptomsusually develop over 24 h

May be the initial presentation in type 1 DM

Classic presentation is :

a history ofPolyuria, Polydipsia, Polyphagia

often prominent Nausea & vomiting

Severe Abdominal pain which can minic acutepancreatitis or other acute abdominal emergencies

A fruity odor (acetone smell) on the patients breathcalled Kussmauls breathing

Hyperglycemia induces an osmotic diuresis thatleads to intravascular volume depletion causingTachycardia/hypotension

Lethargy & CNS depression may evolve into coma


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Precipitating events On a detailed Hx and Examination we can find:

Inadequate/missed insulin administration

Evidence of infection e.g:

Pneumonia

UTIGastroenteritis

Spesis

Infartion (cerabral,MI,mesenteric,peripheral..etc)

Drugs (e.g. cocaine)

Pregnancy

Recent surgery/trauma


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Laboratory Findings

TheC

ardinal Biochemical features of diabeticketoacidosis are:

HY

PERGLY

CEM

IA

HYPERKETONAEMIA

METABOLIC ACIDOSIS

Mmol/l Multiply by 18 = mg/dl


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Investigation plan We will perform the following test:

Blood glucose level on admission by glucometer

FBC

Ketone bodies (B-hydroxybutyrate ) usually measured in urine,but to

avoid false positive,serum or plasma assays for B-hydroxybutyrate

should be preformed.

Serum electrolyte- sodium,potassium,chloride

ABG for; Arterial pH, pCO2,osmolality,Bicarbonate,Anion gap

LFT

CXR

ECG

Ultrasound abdomen

Culture & sensitivity of body fluids as guided by clinical presentation

CT scan of brain can be planned in case of poor response to

treatment to rule out any other cause of coma


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Interpretation of Lab Results 1

Occasionally, the serum glucose is only minimally elevated.

Serum bicarbonate is frequently


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Interpretation of Lab Results 2

Interference by acetoacetate may falsely elevate the serum

creatinine measurement.

Leukocytosis, hypertriglyceridemia,&

hyperlipoproteinemia are commonly found.

The measured serum sodium is reduced as a consequence

of the hyperglycemia NOTE: A normal serum sodium in the setting of DKA

indicates a more profound water deficit.

serum osmolality is mildly to moderately elevated

Osmolality can be calculated by the formula :

[2 (serum sodium + serum potassium) + plasma

glucose (mg/dL)/18 + BUN/2.8]


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Treatment plan

Initial Evaluation

Close Monitoring

Fluid management

Electrolyte Replacement

Insulin Therapy

Resolution & Conversion to home therapiesASAP


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Management 11. Admit to ICU2. ABC of resusitation may be needed

3. Cardiac monitor & Pulse oximeter4. O2 mask/intranasal

5. NG tube if altered mental status

6. Blood sampling & ABG7. Initial bolus of 0.9% N/S replacement of a deficit of ~ 3

5L is carried out over 24hours

8. hourly urine output monitoring with/without

catheterisation

9. For starting insulin infusion, serum potassium should be

maintained > 3.5 mmol/l.

10. NOTE

:Do not administer insulin if K


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Insulin Initial Phase

fast acting insulin iv bolus of 0.1Units/kg or

IM 0.3Units/kg

then

0.1Units/kg/hr via insulin pump.

NOTE: Hyperglycemia improves at a rate of ~ 4.6-5.6

mmol/l/hour, more rapidly in the 1st

-2nd

hours.

Sodium infusion*********


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Insulin Later phase When plasma glucose level reaches 13.9mmol/l

reduce infusion of insulin to 0.05Units/kg/hourand

add 5% dextrose with 0.45% NS.

At this stage fast acting insulin S/C before eachmeal and long actin insulin at night can be added.

NOTE:

Aim is to keep the plasma glucose at 11.1 13.9mmol/l

Normal insulin requirement of the body:

1Unit/kg/day but in DKA a person may require


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Management 3KCl 1g in 0.5L of iv fluid 4/6 hourly according to

fequently monitored serum K level *****

Sodium Bicarbonate is usually not needed in the 1st

48hours

ADA advise to give NaHCO3 with very low pH levels:

pH 6.9 7.0 : 50mmol/l NaHCO3 in 200ml DW

with 10meq/L KCl

pH < 6.9 : 100mmol/l NaHCO3 in 400ml of DW with

20meq/L KCl


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complications Aspiration

may occur due to decreased mental status at

presentation.

Hypoglycemia

Hypokalemia

Iwould like to make a special note that insulin pushes K inside the

cells,so during the treatment,likelyhood ofhypokalemia

increases.Therefore frequent monitoring of K is VERY important.


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Complications of DKA Cerebral edema

An extremely serious complication of DKA, is seenmost frequently in children. Coma ultimately ensue.

Pancreatitis

caused by severe Hypertriglyceridemia

NOTE: Hyperamylasemia of salivary origin is usually

seen.

Serum lipase should be obtained if pancreatitis issuspected.


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Hyperglycemic Hyperosmolar

State


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PathophysiologyHHS is a nonketotic state

The absence of ketosis is not completelyunderstood.

the insulin deficiency is only relative and less severe

than the absolute insulin deficiency of DKA. There are Lower levels of counterregulatory

hormones and free fatty acids than in DKA

Possibly the liver is less capable of ketone bodysynthesis

or insulin/glucagon ratio does not favor

ketogenesis.


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n ca p c ure os y s m ar o

Notably absent are symptoms of nausea, vomiting, and

abdominal pain and the Kussmauls Breathing

Usually several weeks history of : polyuria

weight loss

diminished oral intake

mental confusion

Lethargy

Coma

On Physical examination profound dehydration

tachycardia

and altered mental status.

Often a precipitation event is present as in DKA


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Lab Results Marked hyperglycemia [plasma glucose may be

>55.5 mmol/L (1000 mg/dL)] hyperosmolality (>350 mosmol/L) and

prerenal azotemia

serum sodium may be normal or slightly low

In contrast to DKA, acidosis and ketonemia are

absent or mild

A small anion gap metabolic acidosis may bepresent secondary to increased lactic acid

Moderate ketonuria, if present, is secondary to

starvation


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Treatment of HHS Rx is Mostly same as in DKA except for the fact that

In HHS, fluid losses and dehydration are usually

more pronounced than in DKA due to the longer

duration of the illness.

13 L of 0.9% normal saline over the first 23 h

initially.

The calculated free water deficit (which averages 9

10 L) should be reversed over the next 12 days

(infusion rates of 200300 mL/h of hypotonicsolution) then 5% dextrose)

NOTE : too rapid a reversal of fluid deficit may

worsen neurologic function.


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Hypoglycemia in DM


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Introduction to Hypoglycemia &

Diagnosis

This is the commonest endocrine emergency even

more dangerous than hyperglycemia

brain damage & death can occur in severe

prolonged cases

Diagnosis is based on finding a Plasma glucose


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Hypoglycemia

the commonest cause is insulin or sulfonylurea

treatment with activity,

missed meal,

accidental or non-accidental overdose.


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PathophysiologyThe acute response to hypoglycemia is

counterregulatory effects ofglucagon and

catecholamines

Initial symptoms occur secondary to catecholamine

release

Later on neuroglycopenic symptoms occur from the

direct effects of hypoglycemia on CNS function


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Signs & symptomssymptoms secondary to catecholamine release are :

Sweating

AnxietyHunger

Tremor

Palpitations


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Signs & symptoms

Neuroglycopenic symptoms are : Confusion, drowsiness, seizures, coma.

Rarely focal symptoms can occur,eg:

transient hemiplegia Mutism

personality change

Restlessness and incoherence

may lead to misdiagnosis of alcohol intoxication,

even psychosis or CVA


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nocturnal hypoglycemia

The same characteristic set of symptoms

night sweats

Nightmaresmorning headaches

Accompanies hypoglycemic episodes that

occur during sleep


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Treatment Treat with oral sugar, and a long-acting starch

If cannot swallow:

25-50ml 50% glucose IV (via large vein with 0.9%

saline flush to prevent phlebitis) or

glucagon 1mg IM if no IV access and

monitor plasma glucose level hourly

WARNING :

Rebound hyperglycemia can occur after

hypoglycemia because of the actions ofcounterregulatory hormones (Somogyi

phenomenon), an effect that can be aggravated by

excessive glucose administration.


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Treatment of uncomplicated DM


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LONG-TERMTREATMENT

The goals of therapy for type 1 or type 2 DM are to:

eliminate symptoms related to hyperglycemia

reduce or eliminate the long-term microvascular

and macrovascular complications of DM

Allow the patient to achieve as normal a lifestyle as

possible


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TREATMENT GOALS FOR ADULTS WITH DIABETES


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Symptoms of diabetes usually resolve when theplasma glucose is


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DIET management should begin with Medical

Nutrition Therapy (MNT) We advise a diet that includes fruits,

vegetables, fiber rich foods, and low-fat milk .

It should provide: 1,5002,000 calories with

50% from carbohydrate,

20% from protein

30% from fat

E i


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Exercise increases insulin sensitivity

weight loss should be promoted.

ADA recommends 150 min/week (distributed over at least 3

days) of aerobic physical activity


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When to start drugs?

If the patients glycemic target is not achieved

after 3 to 4 weeks of MNT & exercise regimen,

pharmacologic therapy is indicated.

h l i


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Pharmacologic management

Pharmacologic management of Type 1DM is

only insulin

Pharmacologic management of Type 2 DM

includes both oral glucose lowering agents or/

plus insulin (As Type 2 DM is a progressive

disorder, it ultimately requires multiple

therapeutic agents and often insulin)


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Recap of Drugs


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Oral Hypoglycemic Agents

Based on their mechanisms of action, oral glucose lowering

agents are subdivided into agents those:

Increase insulin secretion ( Insulin Secretagogues)

Reduce glucose production

Decrease glucose absorption from GIT

Increase insulin sensitivity


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Diabetes treatment

Anti-Diabetic medications

Oral hypoglycemic agents

Sulfonylureas

Biguanides Thiazolidinediones

Alpha-glucosidase inhibitors

D-phenylalinine derivatives

Combinations

Insulins


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Insulin Secretagogues (hypoglycemic agents)

1st. Generation:

Chlorpromamide(100-500 mg od)

Gliclazide ( 40- 80mg bd, up to

320mg/day)

2nd. Generation:

Gliblenclamide (5-15 mg bid ac)

Glimepiride (1-6 mg od)

Sulfonylureas Meglitinides

Rapaglinide (0.25 - 4 mg tid/ qid)

Nateglinide


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Sulfonylureas These drugs stimulate insulin secretion by

interacting with the ATP sensitive K+ channel on thebeta cells of pancreas

1st generation sulfonylureas have a longerplasma half-life which causesa greater

incidence of hypoglycemia

2nd generation sulfonylureas are generallypreferred, because they cause much less

hypoglycemia due to their shorter half-life

S lf l


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SulfonylureasAdverse effects : hypoglycemia, weight gain

Contraindications : Type 1 DM, liver or kidney disease,

sulfa allergy

Clinical advantage : Lean patients, with high

blood glucose

Drug interactions

Drugs which can increase hypoglycemic effects of

sulfonylureas: NSAIDs ,Sulfonamides, Warfarin, Beta -

blockers

Drugs which can decrease hypoglycemic effects of

sulfonylureas : Thiazides, Hydantoins, Oral

contraceptives


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Insulin Secretagogues (meglitinides)Mechanism of Action:also interact with the ATP-sensitive K+ channel

and increase insulin secretion from -cell of pancreas.They have

Fast onset of action (


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BIGUANIDES Metformin is the only drug used

Mechanisms of action:

Reduced hepatic gluconeogenesis

Increased glycolysis in peripheral tissues

Reduced absorption of glucose from GIT

Decreased plasma glucagon level. initial starting dose is 500 mg OD/ BID, upto 1000 mg TDS

ADR: diarrhea, anorexia, nausea, and loss of appetite.The major

ADR of metformin is lactic acidosis

Clinical Advantage: No hypoglycemia & No weight gain,henceUseful in OBESE diabetics with not very high Blood Glucose level

Metformin is contraindicated in patients with renal / liver

diseases any form of acidosis, congestive heart failure Use of

contrast radiography (MF stopped 48 hrs before)

GLOCUSI AS INHI I O S


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-GLOCUSIDASE INHIBITORS

Examples: acarbose and miglitol

M.O.A.: Reduction in glucose absorption byinhibiting the enzyme that breaks complex sugars

into simple sugars in the intestinal lumen.

Dose: start with a low dose (25 mg of acarbose ormiglitol) and may be increased over weeks to

months

ADRs: diarrhea, flatulence, abdominal distention

Clinical advantage: Pre-diabetic, obese persons


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Sulfonylureas

Stimulate pancreas to secrete insulin

Glyburide (Diabeta) [Prototype Pro p 393]

Glucotrol (Glipizide)

Diabenese (chlorpropamide)

Adverse reactions

Hypoglycemia

Water retention/edema

Photosensitivity

May need to add insulin in times of stress


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Thiazolidinediones

Increase cellular sensitivity to insulin

Pioglitazone (Actos)

Rosiglitazone (Avandia)

Client should have liver enzymes

checked periodically


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D-Phenylalanine derivatives

Nateglinide (Starlix)

Rapid onset, short half-life

Good for those with rapid post prandial rise in

blood glucose


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Combinations

Glucovance

Glyburide and Metformin

Avandamet

Avandia and Metformin

[come tell me when you run into this question]


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Insulin

Made in beta cells of the pancreas

Moves glucose into cells (thus acts like growthhormone in a way)

Moves potassium into cells (can buy time in

emergencies)


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Insulin preparations (Easy p 390)given ONLY with syringes marked in units

Rapid acting (lispro,

asparte)

Short acting (regular)

Intermediate acting

(NPH)

Long acting Ultralente

[Glargine/Lantus]


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Your learning

Onset of action

Peak (blood glucose will be lowest then)

Duration


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Rapid acting insulin

Lispro (Humolog, Novolog Aspart)

Onset of action

15-30 minutes [may come on in 5 minutes]

Peak of action

1 - 2 hours

Duration

3 4 hours


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Short acting insulins

Regular (clear so can be given IV)

Onset of action

0.5 to 1 hour

Peak of action

2 4 hours

Duration of action

6 8 hours


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Intermediate acting insulins

NPH, Lente (chemicals added. Cloudy)

Onset of action

1 4 hours

Peak of action

4 12 hours

Duration of action

18 24 hours


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Long acting insulins

Ultralente

Onset of action

4 8 hours

Peak of action

18 hours

Duration of action

24 36 hours


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Combination insulins

70/30 (70% NPH and 30% regular)

Humolog 70/30 (Humolog and regular)

Fewer injections

Rotate sites to decrease lipodystrophy


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