Pharmacology Exam 2

seizure

brief episode of abnormal electrical activity in nerve cells of the brain

Convulsion

involuntary spasmodic contractions of any or all voluntary muscles throughout the body, including skeletal, facial, and ocular muscles

Epilepsy

chronic, recurrent pattern of seizures

primary (idiopathic) seizures

cause cannot be determined

secondary (symptomatic)

distinct cause identified (trauma, infection, stroke etc)

general seizures

neuronal activity that originates simultaneously in gray matter of both hemispheres

focal seizures

a localized region of one lobe

status epilepticus

multiple seizures occurring with no recovery between them

result: hypotension, hypoxia, brain damage, and death

true medical emergency

antieplipetic drugs (AEDs)

anticonvulsants

used to control or prevent seizures while maintaining a reasonable quality of life

to minimize adverse effects and drug-induced toxicity

AED therapy is lifelong

serum drug concentrations must be measured

barbiturates

phenobarbital, primidone

hydantoins

phenytoin, fosphenytoin

iminostilbenes

carbamazepine

AED Mechanism of Action

unknown

AED pharmalogic effects

reduce neves ability to be stimulated by incoming electrical or chemical stimulation

suppress transmission of impulses from one nerve to the next

decrease speed of nerve impulse conduction w/in a neuron

Gamma-Aminobutyric Acid (GABA)

inhibitory neurotransmitter

regulates neuron excitability in the brain

low levels r/t seizures

AEDs stabilize neurons and prevent from getting hyperexcited

AEDs Indications

prevention/control of seizure activity

long-term maitenance therapy for chronic, recurring seizures

acute treatment of convulsions and status epilepticus

AEDs adverse effects

vary

nausea, vomiting, diarrhea

often necessitate a change in medication

suicidal thoughts/behavior

AEDs interactions

numerous

many interact with each other

induce hepatic metabolism resulting in reduction of effects of other drugs

interfere with birth control

phenobarbital

used in 3rd world countries d/t low cost

phenobarbital adverse effects

sedation

CV

CNS

GI

skin reactions

phenobarbital serum level

15-40 mcg/mL

phenobarbital half life

long for daily dosing

phenobarbital contraindications

allergy

liver/kidney impairment

respiratory illnesses

phenobarbital route

oral and injectable

Primidone

metabolized in liver into phenobarbital

primidone serum level

lower needed to provide anticonvulsant effect

primidone route

oral

primidone adverse effects

less chance of fatigue and sedation r/t phenobarbital

phenytoin

first line drug for many years and is the prototypical drug

well tolerated, highly effective, inexpensive

phenytoin indications

tonic-clonic seizures

partial seizures

phenytoin contraindication

allergy

heart conditions (bradycardia)

phenytoin adverse effects

lethargy

abnormal movements

mental confusion

cognitive changes

gingival hyperplasia

hirsutism

acne

osteoporosis

dilantin facies (hypertrophy of facial tissue)

phenytoin interactions

interactions with drugs d/t highly bound to plasma protein and induces hepatic p-450 enzymes causing increased metabolism of certain drugs and reduces their blood levels

phenytoin plasma levels

low levels of plasma protein cause high levels of phenytoin in blood d/t malnourishment or chronic renal failure

phenytoin half life

long half life given daily or bid

phenytoin route

PO or parenteral

IV-irritating to veins, not to exceed 50 mg/min, followed by ns flush

fosphenytoin

injectable prodrug of phenytoin

prodrug

inactive drug dosage form that is converted to an active metabolite by various biochemical reactions once inside the body

fosphenytoin rate of admin

150 mg/min

fosphenytoin precautions

fall prevention

ataxia

dizziness

iv incompatabilites

carbamazepine

second most commonly prescribed antiepileptic drug in the US after phenytoin

originally used for treatment of trigeminal neuralgia

chemically related to tricyclic antidepressants

carbamazepine indications

partial seizures

tonic-clonic

may worsen myoclonic or absence seizures

gabapentin

most often used for treatment of neuropathy

can be used as an adjunct drug and prohylactic treatment for partial seizures

gabapentin contraindications

drug allergy

gabapentin adverse effects

CNS (dizziness/drowsiness)

GI (nausea)

visual and speech changed

edema

gabapentin mechanism of action

believed to work by increaing synthesis and synaptic accumulation of GABA between neurons

gabapentin route

oral

Parkinson’s Disease (PD)

chronic, progressive, degenerative disorder

affects dopamine producing nuerons in the brain

caused by an imbalance of 2 neurotransmitters (dopamine and ACh)

PD symptoms

Tremor

Rigidity

Akinesia

Postural instablity

Staggering gait

drooling

on/off phenomenon

rapid swings in response to levodopa

PD worsens when too little dopamine is present

dyskinesia occurs when too much dopamine is present

wearing off phenomenon

medications lose their effectiveness despite max dosing

chorea

irregular, spasmodic, involuntary movements of the limbs or facial muscles

dystonia

abnormal muscle tone leading to impaired or abnormal movements, most notably in head, neck and feet

PD treatment

full explanation of disease to the patient

treatment centers on drug therapy

PT/OT speech therapy

deep brain stimulation (severe)

physical activity is a must

monoamine oxidase enzymes (MAO)

break down catecholamines (dopamine, epinephrine, norepinephrine, serotonin)

highest concentration of MAO enzymes are in liver, kidney, stomach, intestinal wall and brain

MAO inhibitors

cause cheese effect

severe htn r/t ineractions w/ tyramine containing foods (cheese, red wine, beer, yogurt)

selegiline

MAO-B inhibitors

cause and increase in levels of dopaminergic stim in the CNS

no cheese effect

adjunctive therapy with levodopa (reduced dosage of levodopa)

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selegline route

oral, buccal, patch

selegline adverse effects

insomnia, headache, hypotension, confusion, impulse contol disorder

selegline interactions

carbamazepine, oral contraceptives, opiods

entacapone

COMT inhibitor

only works peripherally (bc cannot cross BBB)

taken with levodopa

prolongs duration of levodopa

entacapone adverse effects

GI upset and urine discoloration

entacapone contraindications

allergy

preexisting liver disease

entacapone interactions

not to be taken with nonselective MAOIs

may be given w/ selective MAO-B inhibitor (selelgine)

entacapone route

oral

levodopa and carbidopa

dopamine replacement drug

levodopa crosses BB and is converted into dopamine

large doses required and can cause adverse effects

carbidopa enhances levodopa and allows for lower doses of levodopa reducing adverse effects

levodopa and carbidopa adverse effects

confusion

involuntary movements

GI distress

hypotension

cardiac dysrhythmias

levodopa

5-10 yrs no longer controls PD

levodopa contraindications

angle closure glaucoma

cardiac dysrhytmias

hypotension

muscle cramps

levodopa adverse effects

GI distress

chorea (fidgity/restlessness)

levodopa interactions

pyridoxine (B6)

dietary protein

adrenergic drugs

drugs that stimulate the sympathetic nervous system (SNS)

mimic the effects of the SNS endogenous NTs (catecholamines)

adrenergic agonists

drugs that stimulate and mimic the actions of the sympathetic nervous system

sympathomimetics

adrenergic agonist

catecholamines

produce a sympathomimetic response

endogenous catecholamines

norepinephrine, epinephrine, dopamine

synthetic catecholamines

dobutamine, phenylephrine

alpha 1-adrenergic receptors

located on postsynaptic effector cells (tissue, muscle, or organ that the nerve stimulates)

Alpha 2 adrenergic receptors

located on presynaptic nerve terminals (the nerve that stimulates the effector cells)

alpha-adrenergic responses

control the release of NTs

primary response is vasoconstriction

CNS stimulation-incr alertness and attention, incr energy, incr heart rate, BP, RR

Beta-adrenergic receptors

all are located on postsynaptic effector cells

beta 1 - adrenergic receptors

located primarily in the heart

beat 2 adrenergic receptors

located in smooth muscle of the bronchioles, arterioles, and visceral organs

beta-adrenergic agonist responses

relaxation of: bronchial, GI, uterine smooth muscles

glycogenolysis

cardiac stimulation

dopaminergic receptors

an additional adrenergic receptor

stimulated by dopamine

causes dilation of renal, mesenteric, coronary, and cerebral arteries

**dopamine is the only substance that can stimulate these receptors**

Adrenergic Drugs (MOA)

transmission takes place at the junction between nerve and receptor site of innervated organ/tissue (effector)

direct acting sympathomimetic

indirect acting sympathomimetic

mixed acting sympathomimetic

indirect acting sympathomimetic

causes release of catecholamine from storage sites (vesicles) in nerve endings….catecholamine then binds to receptors and causes a physiologic response (ex: amphetamine)

direct acting sympathomimetic

binds directly to the receptor and causes physiologic response (ex: epinephrine)

mixed acting sympathomimetic

directly stimulates the receptor by binding to it

indirectly stimulates the receptor by causing the relase of stored NTs from vesicles in the nerve endings (ephedrine)

drug effects of alpha adrenergic stimulators

smooth muscle stimulation

vasoconstriction of Blood vessels

relaxation of GI smooth muscles (decreased motility)

constriction/closure of bladder sphincter

contraction of uterus

male ejaculation

mydriasis (dilated pupils)

drug effects of beta 1 adrenergic stimulators

cardiac stimulation

increased force of contraction (positive inotropic effect)

increased heart rate (positive chronotropic) effect

Increased conduction through AV node (positive dromotropic effect)

Increased renin release (when low BP)

Drug effects of beta 2 adrenergic stimulators

Receptors on the airways results in

Bronchodilation (relaxation of the bronchi)

Uterine relaxation

Glycogenolysis in the liver (incr blood glucose)

Relax bladder so it can fill

Relaxation of GI smooth muscles (decr motility)

Relax ciliary eye muscle-(incr visual acuity for distance)

Adrenergic drugs indications

Respiratory: bronchodilator (asthma) (beta)

Nasal congestion (alpha 1)

Opthalamic (alpha)

Overactive bladder

Cardiovascular (failure/shock) (alpha/beta receptors)

Adrenergic drugs Contraindications

Known drug allergy

Severe hypertension

Alphas Adrenergic drugs adverse effects

Headaches, restlessness, excitement, insomnia, euphoria

Chest pain vasoconstriction, htn, reflexive bradycardia, palpitations, dysrhythmias

Anorexia, dry mouth, nausea, vomiting, taste changes

Beta adrenergic drugs adverse effects

Mild tremors, headache, nervousness, dizziness

Increased HR, palpitations, fluctuations of BP

Sweating, nausea, vomiting, muscle cramps

Dobutamine

Vasoactive adrenergic

Beta 1-selective vasoactive adrenergic drug that is structurally similar to the naturally occurring catecholamine dopamine

Stimulates cardiac beta 1 receptors on heart muscle; increases cardiac output by increasing contraction Ty which increases the stroke volume, especially in patient with hear failure

Route: IV

Dopamine

Naturally occurring catecholamine NT

Potent dopaminergic as well as beta 1 and alpha 1 adrenergic receptor activity

Low dosages can dilate BV in the brain, heart, kidneys, and messengers which increases blood flow to these area

Higher infusion fates; improves cardiac contraction Ty and output (beta 1)

Highest doses: vasoconstriction (alpha 1)

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Epinephrine

Endogenous vasoactive catecholamine

Acts directly on both the alpha and beta adrenergic receptors of tissues (beta)

Prototypical non selective adrenergic agonist

Administered in emergency situation

One of the many primary vasoactive drugs used in many advanced cardiac life support protocols

Low dosage: incr force of cardiac contraction and heart rate, acute asthma, and anaphylactic shock

High dosage: vasoconstriction to increase BP

Norepinephrine

Stimulates alpha adrenergic receptors

Causes vasoconstriction

Direct stimulating beta adrenergic effects on the heart (beta 1 adrenergic receptor)

No stimulation to beta 2 adrenergic receptors of the lung

Treatment of hypotension and shock

Administered by continuous infusion