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Pharmacokinetics
Pharmacodynamics
Clinical Pharmacology
Pharmacokinetics: Ethanol- Absorption and Distribution
Small water soluble easily absorbed
Rapid GIT absorption (esp. empty stomach)
Food: Absorption retardant (slow gastric empting
time)
A little in brain
Jcelimpin
Jmmission
as of 1/11/12
NADH metabolic
alcoholism-
abnormalities
in
chronic
Jcelimpin
Jmmission
as of 1/11/12
Pharmacodynamics: CNS
-
Sedative
Anxiolytic
Slurred speech
Ataxia
Jcelimpin
Jmmission
as of 1/11/12
Chronic pancreatitis
Gastritis
Anemia
Protein malnutrition
cytokine-induced injuries
Chronic Alcohol Consumption in large amounts
INCREASED RISK OF DEATH
liver disease
cancer
accidents
suicides
Liver and the GIT
Most common medical complication
Alcoholic fatty liver, alcoholic hepatitis, cirrhosis,
liver failure
Risk is related to amount and duration of use
Susceptibility to hepatotoxicity : Female >Male
2.
3.
Nervous System
-
neurotoxic
Jcelimpin
Jmmission
as of 1/11/12
Hypertension
Coronary Heart Disease
#1 dilated cardiomyopathy, ventricular hypertrophy, fibrosis.
Alcohol induced changes in heart cells- membrane disruption,
depressed function of mitochondria and sarcoplastic
reticulum, intracellular accumulation of phospholipids and
fatty acids, upregulation of voltage dependent calcium
channels
#2 atrial and ventricular arr., reflects abnormalities of
potassium and magnesium metabolism and enhanced release
of catecholamines
#3 independent of obesity, salt intake, coffee intake, cigarette
smoking
#4 cardioprotective effects of moderate drinking is still
unestablished-based on ROH ability to raise HDL
Blood
Mild anemia (folic acid deficiency)
IDA from gastrointestinal bleeding
Hemolytic syndrome
-
Nervous System
Neurotoxicity
generalized symmetric peripheral nerve injury
(distal paresthesias of hands and feet)
gait disturbances and ataxia motor and gait
abnormality
dementia
Potassium depletion
demyelinating disease
Hypoglycemia
Jcelimpin
Jmmission
as of 1/11/12
Immune System
-
FAS
Mouth, pharynx, larnyx, esophagus, liver, breast
-
IUGR
Microcephaly
Poor coordination
Mental retardation
FAS Mechanism
Jcelimpin
Jmmission
as of 1/11/12
Seizure:
common
withdrawal syndrome
manifestation
Abrupt drop
syndrome
lead to withdrawal
of
as
Thiamine
caution
of
Jcelimpin
Jmmission
as of 1/11/12
Slow elimination
Other Drugs
Topiramate
Ondansetron anti-emetic
Jcelimpin
Jmmission
as of 1/11/12
Drug of Abuse
J. Ona Cruz, MD, MHPED, FPOGS
A.
Physical dependence
Psychological dependence
Triggers: cravings
Dopaminergic Pathway:
The mesolimbic dopamine sysytem consists of
dopaminergic neurons that originate in the VTA (ventral tegmental
area) and terminate in the nucleus accumbens.
Jcelimpin
Jmmission
as of 1/11/12
o
o
B.
Note the RR
o It represents the potential for addiction
o 5 highest, 1-lowest addictive drug
The vulnerability for addiction can be inherited
o the higher the RR of the drug, the more likely you
are to transmit this vulnerability to your children
LSDs, Mescaline, Psilocybin
o They have RR of 1
o Because they are anaesthetics that are usually
abused
o
There potential is low because they affect the
serotonin system
Phencyclidine, Ketamine
o They are anaesthetic
10
Jcelimpin
Jmmission
Tolerance
Withdrawal
Symptoms:
o MILD- anxiousness, abdominal pain, diarrhea,
insomnia, headache, nausea, vomiting, tremors
o SERIOUS- rapid pulse, fever, palpitations,
excessive sweating, difficulty in walking, rapid
breathing, hallucinations, confusion, seizures
Dependence: Mechanism (e.g. Opiods)
as of 1/11/12
Triggered by:
o Stress
o Drug re-exposure
o Condition/context that recalls prior drug use
Mechanism of Relapse
Environment + genetics
LSD, Phencyclidine
11
Jcelimpin
Jmmission
Opioids
Agonists at
Opioids Withdrawal
Dysphoria
Muscle aches
Lacrimation
Rhinorrhea
Mydriasis
Piloerection goosebumps
Sweating
Diarrhea
Yawning
Fever
Treatment
as of 1/11/12
b.
Cannabinoids
Half-life- 4 hours
Onset-minutes
RR=2
Hallucinogens, Psychotomimetics
Somatic symptoms, Flashbacks (hallucination)
Not usually addictive but repetitive exposure
may lead to tolerance (tachyphylaxis)
Non-rewarding: does not stimulate dopamine
release, increase cortical glutamate release
Cannabinoid Withdrawal
c.
GHB
Rapid absorption
GHB: Target
d.
12
a.
Jcelimpin
Jmmission
as of 1/11/12
Nicotine Withdrawal
Irritability, sleeplessness
RR=4
o More addictive than alcohol and
marijuana
RR=1
Treatment
Bupropion
Behavior therapy
Not successful
b.
d.
Benzodiazepine
Commonly used as anxiolytic and sleep agent
Moderate risk of addiction (euphoric effects)
RR 3
Usually abused with other drugs (increase RR)
Note:
Barbiturates were the most commonly abused
prescribed sedative before the benzodiazepines
but they are now rarely prescribed and therefore
is less of a problem today in terms of prescribed
abused drugs. Street versions however continue.
Withdrawal and addiction is similar to the BZs.
Benzodiazepine: Mechanism
Inhalants
Abuse: recreational exposure to chemical
vapors*which are present in many common
household and industrial products
Hydrocarbons sweet smelling
sniffing, huffing, bagging
Inhalant abuse common in children and young
adults
Inhalants: Mechanism
Largely unknown
3.
Benzodiazepine: Withdrawal
13
Jcelimpin
Jmmission
as of 1/11/12
a.
Cocaine
Alkaloid from Erythroxylon coca
Initially used as local anesthetic and mydriatic
Highly addictive at RR=5
Water soluble, can be absorbed through mucosal
surfaces (nasal snorting) or injected
heated in alkaline solution smoked (crack cocaine)
swift distribution to brain rush
Cocaine Mechanism
No specific antagonists
14
Amphetamines
Synthetic, indirect-acting sympathomimetics
Substrates of DAT and competes with dopamine
Jcelimpin
Jmmission
Tachycardia, dysrhythmias
Dysphoria
Drowsiness
Insomnia
Irritability
c.
Ecstasy (MDMA)
Derivatives of methylmedioxymethamphetamine
(MDMA)
Same mechanism as amphetamines
Designer drug
Oral
Ecstasy: Effects
NEUROTOXIC - most
as of 1/11/12
Serotonin syndrome**
o All serotonin gets thrown in the synapse,
nothing is left on the cell
*Profound effect leading to depletion of intracellular
serotonin for 24 h after a single dose and repeated
exposure may lead to permanent serotonin depletion:
Neurotoxic- long term cognitive impairment
**autonomic hyperactivity, mental status changes,
neuromuscular abnormalities
Severe acute toxic effects (hyperthermia,
dehydration)
Seizures
Ecstasy Withdrawal
Increased aggression
15
Jcelimpin
Jmmission
as of 1/11/12