Pcol Finals Compre
Pcol Finals Compre
Pcol Finals Compre
1|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
Norepinephrine Contraction of
intestin Relaxation of
- Primary transmitter at sympathetic sphincters
al tract sphincters
postganglionic synapses (alpha)
- Synthesis
o Tyrosine DOPA by tyrosine
Sympatheti Parasympat
hydroxylase
Organ c hetic
o Decarboxylated to: Dopamine
Stimulation Stimulation
o Hydroxylated to: NE
- Storage Glycogenoly
o MAO inactivates NTA in the sis (beta2&
cytoplasm alpha)
- Release
o Same as ACh
Gluconeogen Glycogen
o Metabolism – not responsible for Liver
esis (beta2& synthesis
termination
alpha)
o Diffusion and Reuptake 1
Reduce the concentration
Lipolysis
Stop action
(beta2&
alpha)
DRUG EFFECTS
Renin
Used in several diseases; only block
Kidney secretion
sympathetic
(beta2)
- Metyrosine– Synthesis of NE
Detrussor
- Reserpine – Storage of NE Detrussor
relaxation
- Guanethedine– Release of NE contraction
(beta2)
- MAO Inhibitors – Metabolism of NE Bladder
Contraction
Relaxation of
of sphincter
sphincter
(alpha)
Parasympat Contraction
Sympathetic
Organ hetic of pregnant
Stimulation
Stimulation uterus
↑ heart rate (alpha)
↓ heart rate
beta1 (& beta2) Relaxation of
↑ force of Uterus
↓ force of pregnant
Heart contraction and non-
contraction
beta1 (& beta2) pregnant
↑ conduction ↓ conduction uterus
velocity velocity (beta2)
Constriction Constricts
Arteries (alpha1) Dilation pupil
Dilates pupil
Dilation (beta2) Eye ↓ lacrimal
(alpha)
Constriction gland
Veins (alpha1) secretions
Dilation (beta2) Submandi Viscous
Bronchial Watery
bular & salivary
Bronchial muscle salivary
parotid secretions
muscle contraction secretions
Lungs glands (alpha)
relaxation ↓ bronchial
(beta2) gland INTRO TO CNS
secretions
Gastro- ↓ motility (beta2) ↓ motility
2|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
EPSP IPSP - Oxidized in the liver
- Excretion: excreted partly unchanged
Excitatory Inhibitory
in the urine
Postsynaptic Postsynaptic
- Alkalinize urine
Potentials Potentials
- Half-life: 4-5 days
Depolarizing Hyperpolarizing - Require loading dose
Open K & Cl
Open Na, Ca
(Postsynaptic) ANTISEIZURE DRUGS
Close Ca PHENYTOIN
Close K
(Presynaptic) - Mephenytoin
↑ Na Ca, ↓ K ↑ K Cl, ↓ Ca o Congener of phenytoin
o Metabolized to 5,5-
SEDATIVE HYPNOTICS ethylphenylhydantoin
(demethylation)
BENZODIAZEPINES o Nirvanol
- Triazolam (Short) Contributes most of the
- Alprazolam (Intermediate) antiseizure activity of
- Flurazepam (Long Acting) mephenytoin
Therapeutic blood level:
BARBITURATES 25-40 mcg/mL
- Thiopental (Ultra-short) o Hydroxylated
- Secobarbital (Short) o Undergo conjugation and
- Phenobarbital (Long Action) excretion
o Therapeutic Level: 5-16 mcg/mL
MISCELLANEOUS o Above 20 mcg/mL – toxic
- Buspirone
- Ramelteon OXCARBAZEPINE
- Ezopiclone - Half-life of 8-12 hrs
- Chloral Hydrate - 10-hydroxy metabolite
- Zaleplon o Activity resides here
- Zolpidem
o Same half-life
o Drug is mostly excreted as the
BARBITURATES
- Eluxtensively metabolized glucuronide of 10-hydroxy
- Depress neuronal activity metabolite
- Facilitate & prolongs inhibitory effect
of GABA and Glycine OPOID ANALGESICS
- Blocks excitatory transmitter MORPHINE
glutamic acid Metabolism
- Block Na Channels at high - Metabolized by hepatic enzymes
concentration - Eliminated by the kidney
- Bind to multiple isoforms of GABAA - Converted to inactive glucuronide
- Not antagonized by flumazenil conjugates
- Except:
Thiopental o Morphine-6-Glucoronide
- Highest lipid solubility Analgesic activity is
- Enter CNS rapidly similar to Morphine
- Induction agent in anesthesia o Morphine-3-Glucoronide
- Metabolism occur: Primary Metabolite
o Oxidation Neuroexcitatory
o Glucoronidation
MECHANISM OF ACTION
Phenobarbital A. RECEPTORS
Location of some opioid analgesics
3|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
- Ascending Pathways - Quetiapine
o Primary afferents - Risperidone
o Spinal cord transmission - Ziprasidone
neurons - Aripiprazole
- Descending Pathways
o Neurons in the: SCHIZOPHRENIA
Midbrain - Symptoms:
Medulla o Thought disorders
Modulate pain modulation o Emotional withdrawal
o Hallucination
B. OPIOID PEPTIDES
o Delusions
- Modulate transmission in the:
- Not cured by drug therapy
o Brain, spinal cord, & primary
- Beneficial effects may take several
afferents
weeks to develop
o Also found in: adrenal medulla
- Individual patients – respond to
and gut specific drugs
o Unclear if they function as NTAs - Older drugs – lower cost
- Ameliorated by antipsychotic drugs
C. IONIC MECHANISMS
- POSTSYNAPTIC Treatment of Schizophrenia
o Open K Channels - Reduce some positive symptoms
o Cause membrane o Hyperactivity
hyperpolarization (IPSPs) o Bizarre ideation
- PRESYNAPTIC o Hallucination
o Close Voltage gated Ca o Delusions
o Inhibit NTA Release - Facilitate functioning in out and
Serotonin inpatients
Acetylcholine - Negative Symptoms
NE o Older drugs – not much effect
Glutamate o Newer (Atypical) improve
Substance P
Emotional blunting
Social Withdrawal
ANTIPSYCHOTIC DRUGS
Antipsychotics Bipolar Drugs MECHANISM OF ACTION
Old
New A. DOPAMINE HYPOTHESIS
Old (D2) (Classic New
(5HT2) - Relative excess of functional activity of
)
Chlorproma
Clozapine Lithium
Carbamazep dopamine
zine ine - Not full satisfactory
Fluphenazin - Antipsychotic drugs – partly effective
Olanzapine Clonazepam
e
Haloperidol Quetiapine Olanzapine in most px
Risperidon - Many effective drugs have a higher
Thioridazine Valproic Acid
e affinity for other receptors other than
Trifluoperzin Ziprasidon D2
e e - Based on the ff:
o Antipsychotics block dopamine
receptors
Those with D2 receptors
Newer Drugs o Dopamine agonists –
Heterocyclic exacerbate schizophrenia
- Clozapine Amphetamine
- Loxapine Levodopa
- Olanzapine
4|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
o Increased density of dopamine o Haloperidol
recptors have been detected in o Fluphenazine
untreated schizophrenia o Trifluophenazine
- Clozapine – Less frequent
B. DOPAMINE RECEPTORS - Newer Drugs – Less common
- 5 receptors (D1-D5) - Other neurologic dysfunction cause:
- G protein coupled o Akathisia
- Therapeutic efficacy of most older o Dystonia
antipsychotic drugs correlate with o Respond to:
relative affinity to D2 Diphenhydramine
- Correlation between blocking: Muscarinic blocking
o D2 receptors agents
o Extrapyramidal dysfunction
B. TARDIVE DYSKINESIA
C. OTHER RECEPTORS - Choreoathethoid movements of the
- Newer Atypical AP muscles of the lips and buccal
o Have higher affinities for other activity
receptors - Irreversible
than for D2 receptors - Develop after years of therapy
o 5HT2 receptors - Appear as early as 6 years
- Alpha Adrenoreceptor Blockade - No effective drug for treatment
o Responsible for the - Antimuscarinic drugs
antipsychotic effect o Increase severity of symptoms
o Olanzapine, Quetiapine, - Switching to clozapine
Risperidone o Does not exacerbate the
New condition
High affinity for 5HT2 - Maybe caused by dopamine
May also interact with D2 receptor sensitization
o Clozapine - Improved by: increasing neuroleptic
D4 and 5HT2 receptor dosage
blocking
Low affinity for D2 C. AUTONOMIC EFFECTS
Less extrapyramidal
- Due to: blockade of peripheral
dysfunction
muscarinic receptors and alpha
- H1 Receptor Blockade
adrenoceptors
o All antipsychotic except
- Thioridazine– strongest autonomic
haloperidol effects
- Haloperidol – weakest
SIDE EFFECTS/TOXICITY - Clozapine and Atypical –
intermediate
A. REVERSIBLE NEUROLOGICAL EFFECTS - Cause: Atropine like effects
- Dose dependent extrapyramidal o Dry mouth
effects
o Constipation
o Parkinson-like syndrome
o Urinary retention
Rigidity
o Visual problems
Akinesia
Flat faces - Not a problem with ziprasidone and
Tremor aripiprazole
- Solution: - Alpha receptor blockade
o Decrease in dose o Cause postural hypotension
o Antagonized with muscarinic o All atypical
blocking agents - Phenothiazines(Chlorpromazine,
- Occur frequently with: Thioridazine, Triflu, Fluo)
5|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
o Failure to ejaculate
OPIOID ANALGESICS
D. ENDOCRINE AND METABOLIC EFFECTS MORPHINE
- D2 receptor blockade in pituitary Metabolism
- Cause: - Metabolized by hepatic enzymes
o Hyperprolactinemia - Eliminated by the kidney
o Gynecomastesia - Converted to inactive glucuronide
o Amenorrhea-galactorrhea conjugates
syndrome - Except:
o Infertility o Morphine-6-Glucoronide
- Clozapine & Olanzapine Analgesic activity is
o Weight gain similar to Morphine
o Hyperglycemia o Morphine-3-Glucoronide
Primary Metabolite
Neuroexcitatory
E. NEUROLEPTIC MALIGNANT
SYNDROME (NMS)
MECHANISM OF ACTION
- Signs and symptoms:
A. RECEPTORS
o Muscle rigidity
Location of some opioid analgesics
o Impairment of sweating
o Hyperprexia - Ascending Pathways
o Primary afferents
o Autonomic instability
o Spinal cord transmission
- Developed by those who are sensitive
to extrapyramidal effects neurons
- Life threatening - Descending Pathways
- Treated by: o Neurons in the:
o Dantrolene Midbrain
o Dopamine agonists Medulla
Modulate pain modulation
F. SEDATION
B. OPIOID PEPTIDES
- Phenothiazines (Chlorpromazine)
- Modulate transmission in the:
o More marked sedation
o Brain, spinal cord, & primary
- Fluphenazine& Haloperidol
afferents
o Less sedating among older
o Also found in: adrenal medulla
- Aripiprazole
and gut
o Less sedating among newer
o Unclear if they function as NTAs
G. MISCELLANEOUS TOXICITIES
- Thioridazine
o Visual impairment due to retinal
C. IONIC MECHANISMS
deposits
- POSTSYNAPTIC
o Fatal ventricular arrhythmias (at
o Open K Channels
high doses)
o Cause membrane
- Ziprasidone – arrhythmias
hyperpolarization (IPSPs)
- Clozapine
- PRESYNAPTIC
o at high doses: agranulocytosis &
o Close Voltage gated Ca
seizure
o Inhibit NTA Release
H. OVERDOSAGE TOXICITY Serotonin
- Not fatal Acetylcholine
- Cardiotoxicity – difficult to treat NE
- Hypotension – fluid replacement Glutamate
- Seizures – diazepam/phenytoin Substance P
6|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
- Well absorbed most sites of
administration
CHOLINOMIMETIC/SYMPATHETIC DRUGS
- Excreted chiefly by kidneys
- Mimic acetylcholine - Aidification of urine accelerates
clearance of these amines
Classified by:
PILOCARPINE
o Spectrum of Action (type of NICOTINE
receptor activated) MUSCARINE
- Muscarinic LOBELINE
- Nicotinic NICOTINE
o MOA
- Direct-acting: - Liquid, lipid-soluble: absorbed across
Binding/activate the skin
cholinoceptor MUSCARINE
- Indirect-acting: Inhibit
hydrolysis of endogenous - Quaternary amine
ACh - Less completely absorbed from GIT
- Toxic when ingested
BASIC PHARMACOLOGY OF DIRECT- - Eg. In certain mushrooms
ACTING CHOLINOMIMETICS - Enters the brain
7|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
- Increases peristaltic activity - Diminish its secretion
- Relaxation of Sphincters PILOCARPINE
5. Blood Vessels ECHOTHIOPHATE (long-acting
- EDRF (Endothelium Derived effect)
Relaxing Factor)
- Dilation of Arteries 2. GIT & GUT
Post-Op Ileus
- Dilation of Veins
Urinary Retention Post-Op
- Constriction Disorders that involve depression of
6. GUT smooth muscle activity w/o
- Stimulate the detrusor muscle obstruction
- Relax trigone& sphincter BETHANECOL
- Promote voiding 3. Neuromuscular Junction
7. GLANDS - Myasthenia Gravis
- Stimulate thermoegulatory sweat, - Disease affecting skeletal muscles
lacrimal & nasopharyngeal neuromuscular junc.
glands - Autoimmune process
INDIRECT-ACTING CHOLINOMIMETIC - Production of antibodies that decrease
DRUGS the functional nicotinic receptors at
postjunctional end plates
SIMPLE ALCOHOLS
Cholinesterase inhibitors are used for
- Quaternary NH4 group therapy
- 2-10 mins.
EDROPHONIUM – diagnostic test
- Reversible
- EDROPHONIUM NEOSTIGMINE, PYRIDOSTIGMINE – long
term therapy
CARBAMIC ACID ESTERS OF ALCOHOL
4. Heart
- Quaternary or tertiary NH4 group - Supraventricular Tachycardia
- 30mins to 6 hrs - Treated by short-acting cholinesterase
- Reversible inhibitor (Edrophonium)
- Carbamates - Replaced by newer drugs (Ca+2
NEOSTIGMINE Channel blockers)
PHYSOSTIGMINE 5. Antimuscarinic Drug Intoxication
Exception, Lipid-soluble - ATROPINE intoxication
ORGANIC DERIVATIVES OF PHOSPHORIC ACID - Lethal in children
- Prolonged sever behavioral
Highly lipid soluble disturbances and arrhythmias in adults
Very long duration - Severe muscarinic bloackade
Irreversible PHYSOSTIGMINE
ECHOTHIOPHATE -Antidote of Atropine poisoning
ORGAN SYSTEM EFFECTS 6. CNS
1. Eye - Alzheimer’s isease
- Glaucoma - Tacrine
- Reduce IO pressure - w/ anticholinesterase activity
- Contraction of the ciliary body - w/ cholinomimetic action
- used for therapy
- Facilitate outflow of aq. Humore
8|A s t o r, G a r c i a , M e d i n a [ 3 G - P H ]
TOXICITY - Competitive (surmountable)
A. Direct-Acting Muscarinic Stimulants pharmacologic antagonists
o Nausea & Vomiting - Reversible blockade of
o Diarrhea cholinomimetic actions at the
o Salivation muscarinic receptors
o Sweating - Blocking effects, overcome by
o Cutaneous vasodilation increase conc. of muscarinic
o Bronchial constriction agonists
o Excitation
o Lacrimation ORGAN SYSTEM EFFECTS
o Blocked by ATROPINE - Peripheral effects mostly
Acute Toxicity predictable
o 4omg or 1drop of pure liquid is fatal
- Ocular, GIT, GUT & secretory
(2 cigarettes)
effects
CHOLINOCEPTOR BLOCKING DRUGS - CNS effects are less predictable
- ANTIMUSCARINIC
EFFECTS OF INCREASE DOSE OF
- ANTINICOTIC ATROPINE
- Decrease bronchial & salivary
Muscarinic Antagonists
secretions
o M1 receptor
- Decrease sweating
- Selective
- MYDRIASIS
- Only few receptor-selective
- Tachycardia
M1 antagonists reached clinical trial
PIRENZIPINE - Urinary hesitancy
o Non-selective - Decrease Intestinal Motility
- Most of drugs in market - Decrease gastric secretion
NOREPINEPHRINE
- Pressor agent
CLINICAL USES ISOPROTERENOL
o ANAPHYLAXIS
- Potent vasodilator
EPINEPHRINE
- For immediate Tx of Anaphylactic DOBUTAMINE
shock
- Rapid acting - Congestive heart failure
- Pressor agent - Inotropic effect
- For Cardiac arrest DOPAMINE
o CNS - Inotropic
AMPHETAMINES - Low dose: renal vasodilation
(PHENYLISOPROPYLAMINES) - High: Vasoconstriction
- Narcolepsy
NON-CATHECOLAMINES
- Attention Deficit Disorder
- Weigh reduction (approp. Control) PHENYLEPRHINE
12 | A s t o r , G a r c i a , M e d i n a [ 3 G - P H ]
- Local vasoconstrictive Intrinsic sympathomimetic activity (ISA)
- Anesthetic effect - Partial agonist action by adrenoceptor
blockers; typical of several β blockers (eg,
TYRAMINE pindolol, acebutolol)
- Byproductpf Tyrosine Irreversible blocker - A nonsurmountable
- Increase P inhibitor, usually because of covalent bond
- Found in Cheese and Wine: not formation (eg, phenoxybenzamine)
advised when taking MAO Membrane-stabilizing activity (MSA) -
Local anesthetic action; typical of several β
blockers (eg, propranolol)
TOXICITY
Orthostatic hypotension - Hypotension
- Little CNS toxicity when given that is most marked in the upright position;
systematically caused by venous pooling (typical of α
- Periphery: Excess vasoconstriction, blockade) or inadequate blood volume
cardiac arrhythmias, MI, (caused by blood loss or excessive diuresis)
Pulmonary edema or hemorrhage
Partial agonist - A drug (eg, pindolol) that
- Apha agonists Hypertension
produces a smaller maximal effect than a full
- B1 agonists sinus tachycardia & agonist and therefore can inhibit the effect of
serious arrthmia a full agonist
- B2 agonists skeletal muscle
tremor Pheochromocytoma A tumor consisting of
cells that release varying amounts of
ADRENOCEPTOR BLOCKERS norepinephrine and epinephrine into the
circulation
Adrenoceptor antagonists
o Alpha blockers ANTIHYPERTENSIVE AGENTS
Alpha1-selective (PRAZOSIN) Drugs used in hypertension
Alpha2-selective (YOHIMBINE)
o Diuretics
o Nonselective o Sympathoplegics— blockers of
Reversible (PHENTOLAMINE) - Alpha or Beta receptors
Irreversible (PHENOXYBENZAMINE) (PRAZOSIN, PROPANOLOL)
- Nerve terminals (GUANETHEDINE<
o Beta blockers
RESERPINE)
Nonselective (PROPRANOLOL)
Beta2-selective (BUTOXAMINE) - GANGLIA (HEXAMETHONIUM)
Beta1-selective (ATENOLOL) - CNS SYMPHATHETIC OUTFLOW
(CLONIDINE)
Competitive blocker - A surmountable o Vasodilators
antagonist (eg, phentolamine); one that can - Older Oral Vasodilators
be overcome by increasing the dose of (HYDRALAZINE)
agonist
- CALCIUM BLOCKERS (NIFEDIPINE)
Epinephrine reversal - Conversion of the - Parenteral vasodilators
pressor response to epinephrine (typical of (NITROPUSSIDE)
large doses) to a blood pressure– lowering o Angiotensin antagonists
effect; caused by α blockers, which unmask - ACE inhibitors (CAPTOPRIL)
the β2 vasodilating effects of epinephrine - Receptor blockers (LOSARTAN)
- Renin Inhibitor (ALISKIREN)
13 | A s t o r , G a r c i a , M e d i n a [ 3 G - P H ]
Systolic/Diastol Category Minoxidil sulfate, its metabolite is a
ic Pressure potassium channel opener that
(mm/Hg) hyperpolarizes and relaxes vascular
<120/80 Normal smooth muscle
120-139/80-89 Pre— Extremely efficacious
hypertension Reserved for severe hypertension
≥ 140/90 Hypertension Toxicity
140-159/90-99 Stage 1 Severe compensatory responses
≥ 160/100 Stage 2 Hirsutism
Pericardial abnormalities
17 | A s t o r , G a r c i a , M e d i n a [ 3 G - P H ]