what is another term for peak concentration
Cmax
What is another term for trough
Cmin
Maintenance dose formula
dose needed to maintain a steady state concentration
MD = Css x CL MD = Css x Vd x Kel
vd = volume of distribution Css = steady state concentration kel = elimination rate constant
What would be the equation for the steady state concentration if I administered a particular dose at this dosing interval
Css = 1.5(t1/2) x dose
All divided by
Vd x dose interval
volume of distribution
Css = steady state concentration
loading dose equation
Ld= Co x Vd
Co = desired plasma concentration of drug Vd = volume of distribution
is the EC50 =/not= to the ED50?
same thing -
Effective concentration where 50% of max effect
Effective dose where 50% of the max effect
what is the difference between first-order kinetics and zero-order kinetics
in first order - constant fraction of drug is eliminated
This is where you have half-life calculated
in zero order kinetics. There is a constant amount of drug is eliminated. It does not matter how much you give (independent of concentration of drug)
in first order kinetics on a non-log scale, what kind of line?
curved
in first order kinetics on a log scale, what kind of line?
straight
Is ASA a first order kinetic drug or a zero order kinetic drug
zero order
Is Dilantin a first order kinetic drug or a zero order kinetic drug
zero order
on a non-log scale, what kind of line for zero order kinetic drug
straight
on a log scale, what kind of line for zero order kinetic drug
straight
in first order kinetic drugs the rate of drug elimination per hour is _______ on drug concentration.
dependent
The more drug in the body, the more eliminated per hour
in zero order kinetic drugs, the rate of drug elimination per hour is ______ of drug concentration.
independent
the same amount is eliminated per hour regardless of how much drug is in the body
in zero order kinetic drugs Cp decreases ______ with time
linearly
In first order kinetic drugs Cp decreases ______ with time
exponentially
gentamycin
zero order or first order
first order
Vancomycin
zero order or first order
first order
Ethanol
zero order or first order
zero order
phenytoin
zero order or first order
zero order
what is pharmacodynamics
once the drug has arrived to its site of action what is the effect on the body
formula for therapeutic index
IT = LD50/ED50
LD50 = lethal dose in 50 percent
ED - effective dose in 50%
the higher the Therapeutic index, the _____ the drug
safer
2 drugs have the same active ingredients and are identical in strength or concentration, dosage form, route of administration and F (fraction making it - how much of the drug actually makes it to the body)
they have ______
Bioequivalence
Fraction of the drug that makes it to the body
bioavailability (F)
Dosage formulation influences rate of _____
dissolution
where are drugs metbolized
liver
intestines
kidneys
What is the purpose of drug metabolism
to make active (or) inactive metabolites
and to make drug molecules more water soluble for easier elimination
what class of meds are known to significantly inhibit the metabolism of simvastatin because of inhibition of CYP3A4
Protease inhibitors
what meds will increase the levels of Warfarin via (S-warfarin due to CYP2C9)?
Amiodarone
Metronidazole
TMP/SMX
Fluconazole
increases risk of bleeding
Phenytoin brand names
Dilantin
Phenytek
Phenytoin are used for what type of seizures
primary generalized and partial seizures
what type of seizures does Phenytoin known to worsen
Absence
Dosage forms of Phenytoin
PO or IV (NO IM)
side effects for Phenytoin
Increase drugs associated with CYP3A4
Sedation and CNS depression
gingival hyperplasia (also Calcium channel blockers and Cyclosporine)
Hirsutism
coarsening of facial features
hyperglycemia
Hematologic effects
osteoporosis - due to reduction in Vit D
Rash (including DRESS) - drug reaction when eosinophils are high
Megaloblastic anemia - due to reduction in folate (macrocytosis)
Teratogenicity
labs to monitor for Phenytoin
albumin uremia (BUN) TSH Total Phenytoin level Free Phenytoin level
How does Phenytoin work
blocks Na+ channels associated with depolarization, repolarization and membrane stability.
so if you have rapid firing this is to help stop the seizure
cardiac problems in TCA overdose or when you combine TCA with phenytoin
widen QRS
ventricular tachydysrhythmias
cause seizures
if someone has overdosed on TCA, now seizing….what should you avoid
(any tox case with seizures…NEVER give…)
Phenytoin -
blocks NA channels
worsen the seizures and cardiac conduction
what is the prodrug of phenytoin
Fosphenytoin (Cerebyx)
Prodrug of phenytoin is different from phenytoin and can be given by what route
This can be given IM
does not contain propylene glycol
Caution for phenytoin and kinetics
phenytoin will go from first order kinetics to a zero order kinetics at higher doses. overall phenytoin is considered to follow non-linear kinetics
what is the max rate for phenytoin on the IV load and why?
15-20mg/kg rate at no more than 50mg/min due to the presence of propylene glycol causes hypotension and cardiac arrhythmias
Phenytoin dose adjustments are based on ____
levels
Cp < 7mg/L - increase dose by 100mg/d
Cp 7-12 mg/L: increase by 50mg/d
Cp >12 mg/L increase by 30mg/d or less
0.74 mg/kg will increase level by 1 ug/ml assuming you haven’t reached the saturation point
Free fraction is what is pharmacologically ____
active
when you give fosphenytoin IM when can you check a phenytoin level?
IV?
4 hours
2 hours
Phenytoin toxic effects
levels and effect
Total >20mg/L = nystagmus
> 30mg/L = ataxia, increased seizures
> 40mg/L = Lethargy, altered consciousness and coma
drug of choice for trigeminal neuralgia
Carbamazepine
what type of seizures will Carbamazepine treat?
Partial and secondarily generalized tonic-clonic seizures
what type of seizures will Carbamazepine make worse
absence or myoclonic
what type of mental health disorder will Carbamazepine also treat
Mood stabilizer for bipolar disorder (esp mixed or rapid cycling)
other names for Carbamazepine
Tegretol, Tegretol XR
Carbatrol
Epitol
Equetro
Mechanism of Action Carbamazepine
Blocks Na channels
partial agonist at the adenosine A2A and A2B receptors
Therapeutic range for Carbamazepine
4-12 mg/L
Phenytoin (Dilantin) level reference range (total)
10-20mg/L
Can pregnant women take Carbamazepine
no
what genetic problem Carbamazepine
HLA-B 1502 allele - > severe rash (Stevens-Johnson Syndrome or Toxic epidermal necrolysis (TEN) - they need to be sent to the burn ICU - seen mainly in patients of Asian descent (Specifically Han Chinese)
Side effects of Carbamazepine
Leukopenia - caution in pt with Bone marrow suppression
Aplastic anemia and agranulocytosis (BBW)
Hyponatremia - stimulates release of ADH (SIADH)
Drowsiness
Fatigue
Nystagmus
Oxcarbazepine is also called
Oxtellar XR
Trileptal
what drug interaction is important to note for oxcarbazepine
contains ethanol
cannot take with flagyl or antibuse
what drugs mentioned cannot be taken with flagyl or antibuse
Oxcarbazepine (antiepileptic)
ritonavir (HIV)
what is the indication for Oxcarbazepine?
Initial and/or adjunct therapy for partial seizures
MOA Oxcarbazepine
Structurally similar to carbamazepine
NOT a metabolite
Inhibit voltage sensitive Na+ channels and modulates activity of voltage activated calcium channels
pharmacokinetic difference between Oxcarbazepine and Carbamazepine
Oxcarbazepine is not metabolized by CYP450
but it does still induce CYP3A4
Oxcarbazepine and food
IR can be taken without regard to food
XR should be taken on an empty stomach (1 hr before or 2 hrs after food)
Pregnancy risk
Lactation risk
Oxcarbazepine
C
L3
Oxcarbazepine side effects
Headache dizziness nystagmus blurred vision n/v rash hyponatremia
overall lower risk
Eslicarbazepine indications
partial -onset seizures adjunct therapy
MOA Eslicarbazepine
thought to be sodium channel blocker but unknown
Eslicarbazepine pharmacokinetic
Induces CYP3A4
Inhibits CYP2C19 - problem if on plavix
Valproic Acid indications
Complex partial (mono or adjunct therapy)
Status epilepticus
Absence Seizures (alternative option for, not first line)
Bipolar Disorder
Migraine prophylaxis
Migraine abortive therapy
Valproic Acid Brand
Depakene and Stavzor - Caps/syrup
Depakote (enteric coated) - preferred due to the GI side effects
How does Valproic Acid work
Partially blocks Na currents
may increase GABA levels and its effects by inhibiting the degradation of GABA by inhibiting GABA-T enzyme on the brain
Reference range and Tox range for Valproic acid
Ref - 50-125 mg/L or mcg/mL
Toxicity starts between 150-200
Drug interactions with Valproic acid
Lamotrigine (lamictal) - inhibits metabolism - associated with a dose or concentration effect of skin reactions (Steven johnsons)
Phenytoin
phenobarbital
CBZ
Ethosuximide
AZT (zidovudine)
Valproic acid pregnancy and lactation
D - neural tube defects
L2
Side effects of Valproic Acid
GI is the most common - enteric coated will help
weight gain
hepatotoxicity
pancreatitis
tremors
thrombocytopenia
Teratogenicity - due to folate deficiency
Hyperammonemia (NH3) - consider L carnitine therapy (Carnitor) if this happens
- causes encephalopathy
how do you treat hyperammonemia from valproic acid
L carnitine therapy (Carnitor)
drug of choice for absence seizures
Ethosuximide (Zarontin)
mechanism of action for Ethosuximide (Zarontin)
blocks thalamic (T-type) Ca++ channels
reference range for Ethosuximide (Zarontin)
60-100mcg/ml (some go up to 125 mcg/ML
side effects for Ethosuximide (Zarontin)
Gastritis (primary)
fatigue
headache
neurologic (psychotic behavior)
Rash (SJS)
Leukopenia (check CBC periodically)
Lupus like syndrome
phenobarbital (luminal) indications
alternative for partial and generalized tonic clonic seizures
typically used as second line but may be preferred in pregnant women (cat B/D depending on manufacturer)
Avoid in absence seizures - can worsen like phenytoin
MOA phenobarbital (luminal)
enhances GABA via increase in cl channel opening and makes GABA work better
also decreases glutamate mediated excitation on AMPA
at higher concentrations may block Ca channels
herbal medicinals that work on GABA providing anti anxiety
GABA
Valerian root
Kava
phenobarbital (luminal) clinical issues
Inducer of CYP450 and UGT enzymes
main side effect is sedation
develop tolerance
Reference range phenobarbital (luminal)
desired
toxic
desired 15-40mg/L
toxic >50mg/L
Primidone (Mysoline) metabolized to
PEMA (phenylethylmalonamide) by oxidation and phenobarbital
what supplement do pt need if on phenobarbital (luminal)
folic acid
what levels do you monitor for Primidone (Mysoline)
Primidone (8-12 ug/ml) phenobarbital levels (15-30ug/ml)
dose adjustments for Primidone (Mysoline)
renal dose adjustment after CrCl <50ml/min - metabolites can accumulate
metabolism warning for Primidone (Mysoline)
CYP450 inducer
Primidone (Mysoline) side effects
CNS depression Sedation Confusion Suicidal ideations megaloblastic anemia due to lowering of RBC and CSF folate levels
Avoid in pregnancy - crosses placenta and lowers folic acid
Lamotrigine (Lamictal) approved for ….
adjunctive therapy in adults and children > 2 years with
Partial epilepsy refractory to other agents
Lamictal XR approved for once a day add on for primary generalized tonic clonic seizures
Lennox Gastaut (in children) seizures
Bipolar disorder
MOA Lamotrigine (Lamictal)
block voltage sensitive Na+ channels -> inhibition of glutamate and aspartate
what antiepileptic is available in ODT
Lamotrigine (Lamictal)
drug drug interactions Lamotrigine (Lamictal)
Valproate - inhibits Lamotrigine (Lamictal) metabolism. start dose at 25mg qod when added
Carbamazepine: induces Lamotrigine (Lamictal) metabolism
Side effects Lamotrigine (Lamictal)
nausea
diplopia
ataxia
Skin rash - typically occurs in first 8 weeks and can lead to SJS, peds seem to be risk - other risk are doses higher than recommended, rapid dose escalation, giving with valproic acid
Gabapentin (Neurontin) indications
Partial seizures
postherpetic neuralgia
off label diabetic neuropathy
post op pain
restless leg syndrome
hot flashes
MOA GAbapentin
water soluble anticonvulsant that is still able to penetrate BBB. Binds to amino acid carrier protein and elevates GABA levels (does this but not as much)
Binds to subunits of voltage-gated Ca++ channels (primary)
metabolism consideration for gabapentin
renal dosing (CrCl <60)
Pregabalin (Lyrica) indications
partial onset seizures (adjunct)
Pain associated with diabetic neruopathy, post SCI, post herpetic neuralgia, fibromyalgia
MOA Pregabalin (Lyrica)
same as gabapentin but 3 xs more potent (I give less to have same pharm effect)
max dose of Gabapentin vs Pregabalin
3600mg/day
vs
600mg/day
metabolism consideration for Pregabalin (Lyrica)
renal dosing (CrCl <60)
side effects Pregabalin (Lyrica)
edema sedation dizziness blurred vision weight gain
Felbamate (Felbatol) used for
not first line agent
used in Lennox-Gastaut
side effects Felbamate (Felbatol)
Aplastic anemia (within first 6 mos) n/v
Tiagabine (Gabitril) indication
Partial seizures (adjunct)
Mechanism Tiagabine (Gabitril)
enhance activity of GABA by inhibition of neuronal uptake
metabolism considerations Tiagabine (Gabitril)
no renal or hepatic dosing
major substrate of CYP3A4
- clearance increased if used with carbamazepine and phenytoin
side effects Tiagabine (Gabitril)
Dizziness
drowsiness
difficulty concentrating
weakness
Topiramate (Topamax) indications
epilepsy (adjunct and monotherapy)
migraine prophylaxis
essential tremor and cluster headache prophylaxis
MOA Topiramate (Topamax)
inhibit Na channels, enhance GABA and antagonize glutamate receptors
dose difference in Topiramate (Topamax)
renal dose reductions occur for CrCl <70 ml/min instead of 60
drug interactions Topiramate (Topamax)
weak inhibitor of CYP2C19
side effect of Topiramate (Topamax)
weight loss
ataxia
impaired concentration
Acute angle closure glaucoma
Metabolic acidosis due to reduction in bicarbonate
Nephrolithiasis
Hyperammonemia
Pregnancy Cat D
Lacosamide (Vimpat) indications
adjunct partial onset seizures with epilepsy age>17 years (available IV and PO)
dosing considerations Lacosamide (Vimpat)
hepatic disease or CrCl <=30 then max daily dose is 300mg instead of 400
side effects Lacosamide (Vimpat)
increased SI
dizziness
ataxia
DRESS ( drug reaction with eosinophilia and systemic symptoms)
PR interval prolongation
Drug interactions Lacosamide (Vimpat)
Substrate CYP2C19
pregnancy risk Lacosamide (Vimpat)
C
Levetiracetam (Keppra) indications
partial seizures
tonic clonic
myoclonic
status epilepticus (off label)
MOA Levetiracetam (Keppra)
inihibit voltage dependent N type Ca++ channels
Facilitate GABA ergic inhibitory transmission by displacing negative modulators
binding to synaptic vesicle proteins 2A ligand (SV2A) that affect neurotransmitter release
dosing Levetiracetam (Keppra)
reduce dose once CrCl <80mL/min
Side effects of Levetiracetam (Keppra)
behavior problems (shows up in preexisting neuropsychiatric conditions)
weakness
n/v
headache
Brivaracetam (Briviact) works on
partial seizures
Vigabatrin (Sabril) indications
monotherapy for infantile spasms
add on to adults with partial complex seizures refractory to other anticonvulsants
why does Vigabatrin (Sabril) have strict access
toxicity to retina
(irreversible concentric peripheral visual field deficits) associated with retinal dysfunction
SHARE program
requires vision testing baseline and testing every 3 months
MOA Vigabatrin (Sabril)
thought to be related to being an irreversible inhibitor of GABA -T which is responsible for the metabolism of GABA
Vigabatrin (Sabril) drug interactions
Inducer of CYP2C9
can lower levels of phenytoin (Dilantin)
increase clonazepam through unknown mechanism
preg risk C
Zonisamide (Zonegran)indication
adjunct therapy in adults with partial seizures
Mechanism of Zonisamide (Zonegran)
blockade of Na and CA
Side effects Zonisamide (Zonegran)
dizziness and drowsiness
Hyperthermia (heat stroke in children)
Nephrolithiasis (encourage hydration)
drug interaction Zonisamide (Zonegran)
dont take with Sulfonamide allergy
Substrate CYP2C19 and 3A4
Perampanel (Fycompa) indication
Partial seizure and generalized tonic clonic
Perampanel (Fycompa) metabolism
Avoid if CrCl <30ml/min
major substrate of CYP3A4
Black box warning Perampanel (Fycompa)
dose related serious and life threatening psychiatric events - aggression, anger, HI, hostility in the first 6 wks of use
Rufinamide (Banzel) indication
Lennox-Gastaut syndrome
notes on Rufinamide (Banzel)
weak inhibitor of CYP2E1 and weak inducer of CYP3A4
known to cause dose related shortening the QT interval
what drugs inhibit Na channels
anticonvulsant
Carbamazepine Eslicarbazepine Lamotrigine Lacosamide OxCBZ Phenytoin Rufinamide
what drugs increase GABA activity (anticonvulsant)
Benzodiazepine Phenobarbital Primidone Tiagabine Vigabatrin
What anticonvulsant drugs work on synaptic vesicle protein 2A ligand
Brivaracetam
Levetiracetam
what anticonvulsant drugs work on inhibit Na and Ca channels
Zonisamide
what anticonvulsants inhibit Na channels and increase GABA levels
Topiramate
Valproic acid
What anticonvulsants decrease glutamate
Felbamate
Perampanel
non-opioid cox 3 inhibitor
Acetaminophen
max daily dose for tylenol
4,000mg/d however some limit to 3,000mg/d
Iv formulation of tylenol is approved for what age
2 yrs and older
antidote for acetaminophen tox
N-acetylcysteine (mucomyst; acetadote) best if given within 8-10 hrs of APAP ingestion/overdose
what organ does acetaminophen overdose effect
liver
opioid analgesics are all prototypes of
heroin
the net effect of opioid analgesics
a reduction in the ascending pathways for pain stimuli
opioid poisoning symptoms
coma pinpoint pupils respiratory depression (apnea)
Oxygenation vs ventilation
Oxygenating is inhaling (oxygenating)
ventilation is exhaling (blowing off Co2)
symptoms for opioid sedation
confusion with lack of rest from inadequate pain control
change dose
Can consider stimulant in certain patients
Resp depression from opioid overdose - antidote
Narcan
Rapid Sequence intubation
Pre-oxygenation (3-5 min at 100% O2)
cricoid pressure
sedative
paralytic
intubate
post intubation sedation
what drug class for Dexmedetomidine (precedex)
Sedative/hypnotic
selective CNS A-2 agonist
what sedative is used in ICU for weaning off ventilator since it doesn’t depress resp drive
Dexmedetomidine (precedex)
Autoimmune destruction of the beta-cell thereby leading to absolute insulin deficiency
type I DM
A metabolic disorder resulting from the body’s inability to make enough or properly use insulin
Type II DM
when would a hypothyroid pregnant woman need a dose increase
1st trimester
thyroid gland primarily secretes what?
T4
the most potent form of the thyroid hormone on metabolic influence is ____ is primarily derived by ____ being converted to ___ at the tissue level
T3
T4->T3
It takes about _____ weeks for the TSH to reach steady state after changes in the T4/T3
6-7 weeks
TSH low
T4 WNL
subclinical hyperthyroidism
usually asymptomatic
Low TSH
High T4
Overt hyperthyroidism
symptomatic
Very low TSH
Very high T4
thyroid storm
hyperadrenergic state
high TSH
High T4
secondary hyperthyroidism
usually tumor from pituitary
excess thyroid hormone with thyroid storm being the more extreme presentation of hyperthyroidism
thyrotoxicosis
what herb can cause increase TSH secretions via thyroiditis
St. Johns Wort
what drugs can increase TSH secretion/release via thyroiditis
Amiodarone
Amphetamine
metoclopromide
what drugs increase T4/T3 synthesis
Amiodarone
Iodine ingestion
What drugs increase T4/T3 free fraction (inhibit protein binding)
ASA carbamazepine heparin lasix NSAID phenytoin
if a pt with hyperthyroidism develops fever what would you NOT give because it can make it worse
ASA
NSAID
they increase T4/T3 free fraction (inhibits protein binding)
making them more hyperthyroid
Anxiety nervousness dyspnea weight loss heat intolerance N/V menstrual irregularities weakness (proximal muscles and pelvic girdle)
Agitation Tachycardia +- a-fib tremor fever diffuse goiter ophthalmopathy lid retraction or lag
Hyperthyroidism
if someone presents with A-fib, what should you check for
Hyperthyroidism
Hyperthyroidism management
Assumes no thyroitoxicosis or thyroid storm
Thioamides (meds)
Thyroidectomy
Thyroid replacement therapy
Meds for Hyperthyroidism
Methimazole (MMI) (Tapazole) - basically stop synthesis of T4/T3 in the thyroid gland - dosing initially high (30-60mg daily divided into 3 doses for an adult then taper to 5-15mg daily single dose…half life is 6 hours) - not protein bound - so always working bc not protein bound with long half life. Not good for a breastfeeding mom due to no protein binding. liver tox
Agranulocytosis - side effects. No in pregnancy
Propylthiouracil (PTU) -> Half life 1-2 hours
adults give 300-400mg/day in 3 divided doses then taper to 100-150mg/day in divided doses. 60-80% protein bound so technically better for breastfeeding. However, still not good bc it will still get into milk and your newborn needs those thyroid hormones. liver tox, Agranulocytosis - side effects. no in pregnancy
meds are only used in the interim until definitive treatment for hyperthyroid state
Thyrotoxicosis not yet decompensated symptoms
Weakness
weight loss
palpitations
still functioning
Decompensated thyrotoxicosis symptoms
fever
tachycardia
tremors
CV effects of thyrotoxicosis
Sinus tachycardia (most common)
A-fib (2nd most common)
Reduced filling times ->high output heart failure
what do you use to diagnose thyroid storm
and what tool?
clinical diagnosis
Burch & Wartofsky tool
- Thermoregulatory dysfunction
- CNS effects
- GI-hepatic dysfunction
- CV system
score -
<25 unlikely
25-44 - suggestive of impending storm
>45 - highly suggestive
Thyroid workup
Labs - TSH, T4, T3
T3 resin uptake
-assess thyroxine binding globulin levels ->if high means, TBG levels are low
+/- thyroid-stimulating antibodies
CXR
ECG
Differentials:
-Infection, heat exhaustion/stroke, delirium tremens (alcohol withdrawal), malignant hyperthermia, neuroleptic malignant syndrome, pheochromocytoma, cocaine, amphetamine ingestion
Steps in managing thyroid storm
Supportive care - oxygenation (metabolic demand is increased - may need oxygen), fluid resuscitation - if glucose is low use D5NS due to glycogen depletion, temp control (no NSAID or ASA) - ONLY Tylenol
Inhibit new hormone synthesis - usually PTU (this is because it also inhibits T4-T3), can also use Methimazole.
inhibit thyroid secretion - be careful - give the methimazole and PTU first so it can get into the gland. Then you give SSKI (super saturated potassium iodide) - possible to increase but when you give this large of a dose it should inhibit. if pt has iodine allergy- lithium carbonate
Dopamine, Octreotide and steroids
inhibit T4-T3 peripheral conversion (T3 is more potent and biologically active) - PTU, propranolol will also do this
Dexamethasone, Hydrocortisone
inhibit Beta receptors - causing tachycardia and hypertension - propranolol most commonly studied but overall a Beta blocker. Propranolol used frequently bc it also inhibits T4->T3 conversion (also decrease pulse, increase ventricular filling, decreases high output HF)
Thyroid hormone removal - cholestyramine binds enterohepatic reabsorption of thyroxine (can also use plasmapheresis, charcoal hemoperfusion, plasma exchange)
definitive treatment
- Radioactive iodide
- Surgery
what drugs used in thyroid storm treatment block TSH release
Octreotide
Steroids
Dopamine
What drugs used in thyroid storm work on thyroid hormone production
Methimazole
Propylthiouracil
what drugs use in thyroid storm work on thyroid gland activity
Iodine or SSKI
Propylthiouracil
Propranolol
Steroids
these 3 also help with preventing T4-T3
what thyroid lab can you not rely on and why
TSH, takes 6-7 weeks for T3/T4 to effect this number
when you are looking at thyroid storm, what should you consider
differential diagnoses
especially sepsis
In hyperthyroid, caution with giving ____ in failing to recognize high output heart failure
diuretics
Wait at least _____ after thioamide before giving high dose iodine
1 hour
dispo for thyroid storm
Admit to ICU
may take 1-2 weeks to completely recover
TSH high
subclinical Hypothroidism
TSH high
T4 low
overt hypothyroidism
symptomatic
TSH VERY HIGH
T4 VERY low
Myxedema coma
Myxedema coma is more common in who?
women >60yrs old
TSH low
T4 low
secondary hypothyroidism
may be hypothalamus-pituitary axis problem or
sick euthyroid syndrome
autoimmune hypothyroidism
Hashimoto’s Thyroiditis
drugs that decrease TSH secretion
Dopamine
Glucocorticoids
Octreotide
Opiates
Drugs that decrease T4/T3 synthesis
Amiodarone
Lithium
Methimazole (MMI)
Propylthiouracil (PTU)
Drugs that decrease T4/T3 secretion
Amiodarone
Lithium
SSKI
Fatigue weight gain depression constipation shortness of breath cold intolerance infertility
Macroglossia periorbital puffiness hoarseness decreased bowel sounds dry skin delayed relaxation of ankle jerks
Hypothyroidism
Myxedema coma symptoms
AMS bradycardia hypotension hypoventilation hypothermia
metabolic and multi organ dysfunction
what can precipitate myxedema coma
uncorrected hypothyroidism or noncompliance
Infection
trauma
MI
HF
CVA
metabolic problems
Myxedema Coma diagnosis
hypothyroid based on labs (TSH may not be accurate)
Myxedema coma/crisis is a clinical diagnosis
labs for Myxedema
TSH
T4/T3
cortisol level (can be +/-)
BMP - risk of hyponatremia due to increase ADH and risk of hypoglycemia due to decreased gluconeogenesis, decreased insulin clearance and +/- adrenal insufficiency
VBG/ABG - metabolic & resp acidosis - d/t hypotension, hypoventilation, tissue hypoxia
managing hypothyroidism
synthetic T4 (levothyroxine) - gets converted to T3 by the body -99% protein bound -half life depends on thyroid status (euthyroid = 6-7 days, hypothyroid=9-10 days, Hyperthyroid =3-4 days) (pregnant patients have dose increase in 1st trimester)
what factor needs to be taken into consideration when giving levothyroxine for hypothyroidism (pt history)
Cardiovascular disease
If <50 and with or without CVD = 1.6mcg/kg
If > 50 +/- CVD = 12.5-25mcg daily (more conservative approach - too much thyroid hormone can cause sinus tachycardia which can be bad on a diseased heart. This can cause A-fib - could cause a stroke)
Bioavailability of levothyroxine is higher on a empty or full stomach?
empty (however the most important is that they are consistent)
drug interactions with levothyroxine
Decrease Absorption -
-Di- and Tri- valent cations will reduce absorption (Al, Ca, Fe, Mg)
- Cholestyramine (Questran) - can bind to it.
- Sucralfate (carafate) - can chelate with charges
- Fiber supplements - increases peristalsis so transit time changes
Increase Clearance (enzyme inducers)
- Rifampin
- Carbamazepine
- Phenobarbital
- Phenytoin
If you have to change manufacturer for Levothyroxine what do you need to do
re-check TSH, T3, T4 in 6-7 weeks to see if they need dose adjustments
If not able to make T3 in the periphery, what med
Desiccated thyroid (Armour thyroid, Westhroid) (animal brain)
-seen in Congenital hypothyroidism
these are fixed doses of T4 and T3
Liotrix (Thyrolar)
another T4/T3 replacement
Congenital hypothyroidism
not animal sourced
Liothyronine indications
T3 therapy
Hypothyroidism (congenital) Myxedema Myxedema coma cadaveric organ recovery antidepressant augmentation
myxedema coma management
ABC support
Dextrose for hypoglycemia
Free water restriction for hyponatremia
Vasopressors (treat hypotension first with fluids)
Passive warming for hypothermia
Glucocorticoid replacement for stress
IV synthetic T4 (levothyroxine) (onset is 6-8 hours) - don’t wait for labs - high morbidity rate
if initial dose T4 fails, give T3
what happens in pregnancy that a hypothyroid pt needs a dose adjustment
the increase in estrogen increases the thyroid binding globulin secondary to a reduction in its catabolism -> leads to an increase in T4 (bound and free) and T3. Since there is an increase in both, the free fraction and TSH is normal in a euthyroid patient. -> not the case in someone who gets pregnant - need large dose increase in thyroid replacement to avoid problems
