PHARMACOLOGY REVIEW

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OPIOD • MAINLY OBTAINED FROM OPIUM POPPY. • ACT BY BINDING TO SPECIFIC OPIOID RECEPTORS IN THE CNS. • MAINLY USED FOR RELIEVING INTENSE PAIN. • EUPHORIC PROPERTIES • ANTAGONISTS IMPORTANT IN OVERDOSE.

OPIOID RECEPTORS 4 TYPES • Mu ( µ ) • Kappa ( к ) • Delta ( δ ) • Sigma ( σ )

Strong Agonists • Morphine • Fentanyl • Heroin • Meperidine • Methadone • Sufentanil

Moderate Agonists • Codeine • Propoxyphene

Mixed agonist - antagonist • Buprenorphine • Pentazocine

MORPHINE • Main agonist actions on Mu, and also for Kappa and Sigma receptors ACTIONS: - Analgesia – relief of pain without loss of consciousness. - Euphoria - Causes Respiration Depression (This is the most common cause of death in acute opioid overdose)

- Depression of cough reflex • MIOSIS – PINPOINT PUPIL. • Stimulation of the edingerwestphal nucleus of oculomotor nerve which causes parasympathetic stimulation of the eye. • Emesis.—stimulates chemoreceptor trigger zone (CTZ) in area postrema • - GIT : ↓ motility, relieves diarrhea and dysentery - CVS : high doses cause hypotension and bradycardia

METHADONE • MECH: More on Mu receptors • Equal potency to Morphine, but less euphoric and longer duration of action. Actions: • Mostly same as morphine. • Route : oral • Met: Liver • Exe: Urine USES : • Analgesia • Addicts of heroin and morphine – for withdrawal . SE: • Less severe than morphine.

HEROIN • 2-3 times more potent than morphine. • More euphoria • No therapeutic uses • Addiction

PROPOXYPHENE • Derivative of Methadone • Analgesic for mild to moderate pain • Sometimes used in combination with aspirin or acetaminophen - ↑ analgesia • Also has antitussive action (used for cough)

CODEINE • Good antitussive, • Less analgesic than morphine • Causes euphoria • Sedation • Addiction • So, many of the newer cough medications do not contain codeine • It has been replaced by dextrometharphan

FENTANYL • AROUND 100 TIMES MORE POWERFUL ANALGESIC THAN MORPHINE, SO USED during ANESTHESIA • Rapid action and short duration of action. • Main action is on Mu, and also on kappa sigma receptors.

NALOXONE • OPIOID ANTAGONIST • Rapidly reverse the effects of opioids, which can increase withdrawal symptoms • Reverse the coma and resp depression of opioid overdose. • IV route – In 30 sec shows significant changes in resp depression and coma. • Precipitates the withdrawal symptoms in morphine and heroin abusers.

NALTREXONE • SAME AS NALOXONE • Longer duration of action than naloxone • Oral route • Used in opiate dependence maintainance programs.

DEPRESSION • INTENSE FEELINGS OF SADNESS • HOPELESSNESS • DESPAIR • INABILITY TO EXPERIENCE PLEASURE IN USUAL ACTIVITIES.. • Weight loss/weight gain • Changes in sleep pattern • Recurrent thoughts of death • Suicidal tendencies

MANIA • OPPOSITE BEHAVIOR • ENTHUSIASM • RAPID THOUGHT AND SPEECH . • IMPAIRED JUDGEMENT.

Tricyclic antidepressants (TCAs) • Amitriptyline • Imipramine - NOREPINEPHRINE • Desipramine • Doxepin • Clomipramine - SEROTONIN • Nortriptyline • Protriptyline • Maprotiline – Second generation • Amoxapine -- Second generation

MODE OF ACTION • These drugs are thought to increase levels of norepinephrine and serotonin in the synaptic cleft by blocking neuronal reuptake. • They also block histamine, cholinergic and alpha-adrenergic receptors. Which accounts for a large proportion of their side effects

Actions • Elevate mood • Improve mental alertness • ↑ physical activity • More than 2 weeks need..

Clinical indications for tricyclics • Mood disorders • Panic disorder • Generalized anxiety disorder • Posttraumatic stress disorder(clomipramine) • Pain disorders • Enuresis in children(imipramine)

Serotonin- specific reuptake inhibitors (SSRIS) • FLUOXETINE (PROZAC) • SERTRALINE (ZOLOFT) • PAROXETINE( PAXIL) • FLUVOXAMINE (LUVOX)

Action • New group • Selectively inhibit serotonin reuptake. • Fewer anticholinergic and lower cardiac toxicity. • USES: endogenous depression • obsessive-compulsive disorder • obesity • bulimia nervosa – (Fluoxetine)

EPILEPSY PRIMARY or IDIOPATHIC SECONDARY KNOWN CAUSES: • HEAD INJURY • TUMORS • MENINGITIS • HYPOGLYCEMIA • DRUG WITH DRAWAL

The two main categories of seizures include • Partial seizures – no loss of consciousness • and • Generalized seizures – loss of consciousness • A partial seizure can evolve to a generalized seizure.

Simple Partial • These produce symptoms associated with the area of abnormal neural activity in the brain confined to single locus: • The electrical discharge does not spread • Can occur at any age • motor signs, sensory symptoms, autonomic signs and symptoms • There is no impairment of consciousness in simple partial seizures.

Complex Partial • Impairment of consciousness, characteristic of complex partial seizures (CPS) • results in the inability to respond to or carry out simple commands or to execute willed movement, and a lack of awareness of one’s surroundings and events. • Exhibit complex sensory hallucinations, mental distortion and motor dysfunction • Experience initial seizures before age of 20 yrs

Generalized Seizures • At the onset, seizure activity occurs simultaneously in large areas of the brain, often in both hemispheres. • Begin locally and rapidly spread to both the hemispheres. • Loss of consciousness • Seizures can be convulsive or nonconvulsive. • The two most common types are tonic-clonic (grand mal) and • Absence (Petit mal).

Status Epilepticus was defined as 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness between the seizures

CLASSIFICATION Seizures • PARTIAL / FOCAL • SIMPLE • COMPLEX • GENERALIZED • GRAND MAL ( tonic clonic) • PETIT MAL ( Absence) • MYOCLONIC • FEBRILE • STATUS EPILEPTICUS

INHALED AGENTS HALOTHANE ENFLURANE ISOFLURANE SEVOFLURANE NITROUS OXIDE There potency is defined base on the concept of minimum alveolar concentration ( MAC)

Definition • Elevation of arterial blood pressure above 140/90 mm Hg. Can be caused by: • - idiopathic process (primary or essential hypertension) • an underlying disease process (secondary hypertension) • Renal artery stenosis • Hyperaldosteronism • pheochromocytoma

ANTI-HYPERTENSIVE DRUG CLASSES • Diuretics • Beta blockers • Vasodilators • Calcium Channel Blockers • Angiotensin Converting Enzyme (ACE) Inhibitor • Alpha blockers

ACE INHIBITORS • ENALAPRIL • CAPTOPRIL • LISINOPRIL • QUINAPRIL • FOSINOPRIL • BENAZEPRIL • MOEXIPRIL

USES • HTN • CHF • POST MI • Considered best drugs for HTN with DM.

VASODILATORS • HYDRALAZINE • MINOXIDIL

USES HTN, CHF. SE: whose main side effect is a lupus-like syndrome SLE NAUSEA VOMITING HEADACHE FLUID RETENTION ARRHYTHMIA ANGINA HYDRALAZINE

MINOXIDIL SE: • SODIUM AND WATER RETENTION • VOLUME OVERLOAD • LEADING TO EDEMA & CHF • USED FOR TREATING REFRACTORY HTN • HYPERTRICHOSIS • For baldness

DRUGS • ORGANIC NITRATES • BETA BLOCKERS • CALCIUM CHANNEL BLOCKERS

Therapeutic uses • Acute angina attacks- use the sublingual form of nitroglycerin because the onset of action in seconds to minutes • Prevention of attacks- use the oral or transdermal form of nitroglycerin

SIDE EFFECTS • MC: Headache The most common side effect of nitrates is headache. For most people, headaches subside after a few days • Dizziness, weakness due to postural hypotension. • Drug rash, especially with Pentaerythritol tetra nitrate.

CALCIUM CHANNEL BLOCKERS • MECH –Inhibit the entrance of Ca into cardiac & smooth muscle cells of the coronary and systemic arterial beds. • GREATER EFFECT ON ARTERIOLES • DECREASES AFTER LOAD • DECRASES OXY. DEMAND

USES • VARIANT ANGINA OR PRINZMENTAL’S ANGINA – DUE TO VASOSPASM • EXERTIONAL ANGINA • RAYNAUDS DISEASE

PHARMACOLOGY REVIEW